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A Note on Heart Failure in H7N9 Bird Flu
30 Nov 2013 08:19 pm
Publication date: November 2013
Source:Journal of Cardiac Failure, Volume 19, Issue 11
Author(s): Viroj Wiwanitkit
A Simplified Echocardiographic Strategy for Heart Failure Diagnosis and Management
Within an Integrated Noncommunicable Disease Clinic at District Hospital Level for SubSaharan Africa
01 Dec 2013 07:00 am
Publication date: June 2013
Source:JACC: Heart Failure, Volume 1, Issue 3
Author(s): Gene F. Kwan , Alice K. Bukhman , Ann C. Miller , Gedeon Ngoga , Joseph Mucumbitsi ,
Charlotte Bavuma , Symaque Dusabeyezu , Michael L. Rich , Francis Mutabazi , Cadet Mutumbira , Jean
Paul Ngiruwera , Cheryl Amoroso , Ellen Ball , Hamish S. Fraser , Lisa R. Hirschhorn , Paul Farmer ,
Emmanuel Rusingiza , Gene Bukhman
Objectives This study sought to describe a decentralized strategy for heart failure diagnosis and
management and report the clinical epidemiology at district hospitals in rural Rwanda. Background Heart
failure contributes significantly to noncommunicable disease burden in sub-Saharan Africa. Specialized
care is provided primarily at referral hospitals by physicians, limiting patients' access. Simplifying clinical
strategies can facilitate decentralization of quality care to the district hospital level and improve care
delivery. Methods Heart failure services were established within integrated advanced noncommunicable
disease clinics in 2 rural district hospitals in Rwanda. Nurses, supervised by physicians, were trained to use
simplified diagnostic and treatment algorithms including echocardiography with diagnoses confirmed by a
cardiologist. Data on 192 heart failure patients treated between November 2006 and March 2011 were
reviewed from an electronic medical record. Results In our study population, the median age was 35 years,
70% were women, 63% were subsistence farmers, and 6% smoked tobacco. At entry, 47% had New York
Heart Association class III or IV functional status. Of children age <18 years (n = 54), rheumatic heart
disease (48%), congenital heart disease (39%), and dilated cardiomyopathy (9%) were the leading
diagnoses. Among adults (n = 138), dilated cardiomyopathy (54%), rheumatic heart disease (25%), and
hypertensive heart disease (8%) were most common. During follow-up, 62% were retained in care, whereas
9% died and 29% were lost to follow-up. Conclusions In rural Rwanda, the causes of heart failure are
almost exclusively nonischemic even though patients often present with advanced symptoms. Training
nurses, supervised by physicians, in simplified protocols and basic echocardiography is 1 approach to
integrated, decentralized care for this vulnerable population.
A Trial of Family Partnership and Education Interventions in Heart Failure
30 Nov 2013 08:19 pm
Publication date: Available online 29 October 2013
Source:Journal of Cardiac Failure
Author(s): Sandra B. Dunbar , Patricia C. Clark , Carolyn M. Reilly , Rebecca A. Gary , Andrew Smith ,
Frances McCarty , Melinda Higgins , Daurice Grossniklaus , Nadine Kaslow , Jennifer Frediani , Carolyn
Dashiff , Richard Ryan
Background Lowering dietary sodium and adhering to medication regimens are difficult for persons with
heart failure (HF). Because these behaviors often occur within the family context, this study evaluated the
effects of family education and partnership interventions on dietary sodium (NA) intake and medication
adherence (MA). Methods HF patients and family member (FM) dyads (N = 117) were randomized to: usual
care (UC), Patient-FM education (PFE), or a family partnership intervention (FPI). Dietary NA (3-day food
record), Urine NA (24-hour urine) and MA (MEMS®) were measured at baseline (BL) prior to
randomization, and at 4 and 8 months (M). Results FPI and PFE reduced Urine NA at 4 M, and FPI differed
from UC at 8 M (p=.016). Dietary NA decreased from BL to 4M with both PFE (p=.04) and FPI (p=.018)
lower than UC. The proportion of subjects adherent to NA intake ( < 2500 mg/day) was higher at 8 M in
PFE and FPI vs UC (χ2 (2) =7.076, p=.029). MA did not differ among groups across time. Both FPI and PFE
groups increased HF knowledge immediately after intervention. Conclusions Dietary NA intake, but not MA,
was improved by the PFE and FPI interventions compared with UC. UC was less likely to be adherent with
dietary NA. Greater efforts to study and incorporate family-focused education and support interventions into
HF care are warranted.
Acute Effects of Multisite Left Ventricular Pacing on Mechanical Dyssynchrony in Patients
Receiving Cardiac Resynchronization Therapy
30 Nov 2013 08:19 pm
Publication date: November 2013
Source:Journal of Cardiac Failure, Volume 19, Issue 11
Author(s): C. Aldo Rinaldi , Wolfgang Kranig , Christophe Leclercq , Salem Kacet , Tim Betts , Pierre
Bordachar , Klaus-Jürgen Gutleben , Anoop Shetty , Allen Keel , Kyungmoo Ryu , Taraneh G. Farazi ,
MARCUS SIMON , Tasneem Z. Naqvi
Background A novel quadripolar left ventricular (LV) pacing lead has the ability to deliver multisite LV pacing
(MSLV). We set out to characterize the safety and changes in acute mechanical dyssynchrony with MSLV
in cardiac resynchronization therapy (CRT) patients. Methods and Results Prospective multicenter study in
52 patients receiving CRT. An acute pacing protocol comprising 8 MSLV configurations covering a range of
delays was compared with conventional CRT (baseline). Transthoracic tissue Doppler imaging (TDI) was
used to measure the standard deviation of time to peak contraction of 12 LV segments (Ts-SD) and delayed
longitudinal contraction. No ventricular arrhythmia occurred in any of the 52 patients. Complete TDI
datasets were collected in 41 patients. Compared with baseline: 1) The mean Ts-SD was significantly lower
for the optimal MSLV configuration (35.3 ± 36.4 vs 50.2 ± 29.1 ms; P < .001); 2) at least 1 MSLV
configuration exhibited a significant dyssynchrony improvement in 63% of patients; and 3) the mean
number of LV segments with delayed longitudinal contractions was significantly reduced with the optimal
MSLV configuration (0.37 ± 7.99 vs 2.20 ± 0.19; P < .001). Conclusions Acute MSLV was acutely safe,
and a proportion of MSLV vectors resulted in a significant reduction in echocardiographic dyssynchrony
compared with conventional CRT.
Acute decompensated heart failure and pulmonary hypertension
30 Nov 2013 08:19 pm
Publication date: Available online 27 November 2013
Source:Journal of Cardiac Failure
Author(s): Doron Aronson , Robert Dragu , Zaher S. Azzam
Acute heart failure
01 Sep 2014 01:00 am
This is the clinical guideline in development on using Acute heart failure.
Adherence and Persistence in the Use of Warfarin After Hospital Discharge Among Patients
With Heart Failure and Atrial Fibrillation
30 Nov 2013 08:19 pm
Publication date: Available online 22 November 2013
Source:Journal of Cardiac Failure
Author(s): Zubin J. Eapen , Xiaojuan Mi , Laura G. Qualls , Bradley G. Hammill , Gregg C. Fonarow , Mintu
P. Turakhia , Paul A. Heidenreich , Eric D. Peterson , Lesley H. Curtis , Adrian F. Hernandez , Sana M. AlKhatib
Background Postdischarge adherence and long-term persistence in the use of warfarin among patients with
heart failure and atrial fibrillation without contraindications have not been fully described. Methods and
Results We identified patients with heart failure and atrial fibrillation who were 65 years or older, eligible for
warfarin, and discharged home from hospitals in the Get With the Guidelines-Heart Failure registry between
January 1, 2006, and December 31, 2009. We used linked Medicare prescription drug event data to
measure adherence and persistence. The main outcome measures were rates of prescription at discharge,
outpatient dispensing, discontinuation, and adherence as measured by the medication possession ratio. We
hypothesized that adherence to warfarin would differ according to whether patients received the prescription
at discharge. Among 2691 eligible patients, 1856 (69.0%) were prescribed warfarin at discharge. Patients
prescribed warfarin at discharge had significantly higher prescription fill rates within 90 days (84.5% vs
12.3%; P < .001) and 1 year (91.6% vs 16.8%; P < .001) and significantly higher medication possession
ratios (0.78 vs 0.63; P < .001). Among both previous non-users and existing users, fill rates at 90 days
and 1 year and possession ratios were significantly higher among those prescribed warfarin at discharge.
Conclusions One-third of eligible patients with heart failure and atrial fibrillation were not prescribed warfarin
at discharge from a heart failure hospitalization, and few started therapy as outpatients. In contrast, most
patients who were prescribed warfarin at discharge filled the prescription within 90 days and remained on
therapy at 1 year.
Adrenergic Activation, Fuel Substrate Availability, and Insulin Resistance in Patients With
Congestive Heart Failure
01 Dec 2013 07:00 am
Publication date: August 2013
Source:JACC: Heart Failure, Volume 1, Issue 4
Author(s): Nir Uriel , Jose Gonzalez-Costello , Andrea Mignatti , Kerry A. Morrison , Nadav Nahumi , Paolo
C. Colombo , Ulrich P. Jorde
Objectives This study sought to investigate plasma levels of glucose and free fatty acids (FFA) and their
relationship with adrenergic activation and insulin resistance (IR) in patients with advanced congestive heart
failure (CHF). Background Adrenergic activation and IR are hallmarks of advanced heart failure. The
resulting changes in fuel substrate availability and their implications for exercise capacity have not been
elucidated. Methods Subjects with CHF underwent maximal exercise testing. Plasma glucose, FFA, insulin,
and norepinephrine (NE) levels were measured at rest and at peak exercise. Beta-receptor sensitivity to NE
was assessed using the Chronotropic Responsiveness Index (CRI). Homeostasis Model Assessment Index
>2.5 defined IR. Left ventricular ejection fraction was estimated by 2-dimensional echocardiography.
Results Ninety-six subjects were enrolled. CHF subjects without IR (CHF/No-IR), but not those with IR
(CHF/IR), significantly increased glucose and insulin in response to exercise. Only CHF/No-IR subjects
increased FFA in response to exercise (0.14 ± 0.27 mmol/l; p = 0.027). NE increased significantly less with
exercise, and CRI was lower in CHF/IR subjects compared with CHF/No-IR subjects (1.3 ± 1.4 vs. 2.5 ± 2.1;
6.4 ± 2.6 vs. 8.5 ± 3.4; p = 0.069). CRI correlated with the exercise-induced increase in FFA (r = 0.41; p <
0.005). These results stayed the same after excluding diabetic patients from the CHF/IR group. Conclusions
Circulating FFA levels increased during exercise in CHF subjects without IR, but not in those with IR or DM.
Increased FFA availability during exercise may represent a catecholamine-dependent compensatory fuel
shift in CHF.
Association of low body temperature and poor outcomes in patients admitted with
worsening heart failure: a substudy of the Efficacy of Vasopressin Antagonism in Heart
Failure Outcome Study with Tolvaptan (EVEREST) trial
20 Nov 2013 03:29 pm
Aims
Risk stratification in patients admitted with worsening heart failure (HF) is essential for tailoring therapy and
counselling. Risk models are available but rarely used, in part because many require laboratory and
imaging results that are not routinely available. Body temperature is associated with prognosis in other
illnesses, and we hypothesized that low body temperature would be associated with worse outcomes in
patients admitted with worsening HF.
Methods and results
The Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial
was an event-driven, randomized, double-blind, placebo-controlled study of tolvaptan in 4133 patients
hospitalized for worsening HF with an EF <40%. Co-primary endpoints were all-cause mortality and
cardiovascular (CV) death or HF rehospitalization. Body temperature was measured orally at randomization
and entered in analyses both as a continuous variable and categorized into three groups (<36°C, 36–
36.5°C, and >36.5°C) using Cox regression models. The composite of CV death or HF rehospitalization
occurred in 1544 patients within 1 year. For every 1°C decrease in body temperature, the risk of adverse
outcomes increased by 16% [hazard raio (HR) 1.16, 95% confidence interval (CI) 1.04–1.28], after
adjustment for age, gender, race, systolic blood pressure, EF, blood urea nitrogen, and serum sodium. In
fully adjusted analysis, the risk of adverse outcomes in the lowest body temperature group (<36°C) was
51% higher than that of the index group (>36.5°C) (HR 1.35, 95% CI 1.15–1.58).
Conclusions
Low body temperature is an independent marker of poor cardiovascular outcomes in patients admitted with
worsening HF and reduced EF.
Associations Between Use of the Hospitalist Model and Quality of Care and Outcomes of
Older Patients Hospitalized for Heart Failure
01 Dec 2013 07:00 am
Publication date: October 2013
Source:JACC: Heart Failure, Volume 1, Issue 5
Author(s): Robb D. Kociol , Bradley G. Hammill , Gregg C. Fonarow , Paul A. Heidenreich , Alan S. Go ,
Eric D. Peterson , Lesley H. Curtis , Adrian F. Hernandez
Objectives This study sought to examine the associations of hospitalist and cardiologist care of patients with
heart failure with outcomes and adherence to quality measures. Background The hospitalist model of
inpatient care has grown nationally, but its associations with quality of care and outcomes of patients
hospitalized with heart failure are not known. Methods We analyzed data from the Get With the GuidelinesHeart Failure registry linked to Medicare claims for 2005 through 2008. For each hospital, we calculated the
percentage of heart failure hospitalizations for which a hospitalist was the attending physician. We
examined outcomes and care quality for patients stratified by rates of hospitalist use. Using multivariable
models, we estimated associations between hospital-level use of hospitalists and cardiologists and 30-day
risk-adjusted outcomes and adherence to measures of quality care. Results The analysis included 31,505
Medicare beneficiaries in 166 hospitals. Across hospitals, the use of hospitalists varied from 0% to 83%.
After multivariable adjustment, a 10% increase in the use of hospitalists was associated with a slight
increase in mortality (risk ratio: 1.03; 95% confidence interval [CI]: 1.00 to 1.06) and decrease in length of
stay (0.09 days; 95% CI: 0.02 to 0.16). There was no association with 30-day readmission. Increased use of
hospitalists in hospitals with high use of cardiologists was associated with improved defect-free adherence
to a composite of heart failure performance measures (risk ratio: 1.03; 95% CI: 1.01 to 1.06). Conclusions
Hospitalist care varied significantly across hospitals for heart failure admissions and was not associated
with improved 30-day outcomes. Comanagement by hospitalists and cardiologists may help to improve
adherence to some quality measures, but it remains unclear what care model improves 30-day clinical
outcomes.
Atrial Fibrillation Impairs the Diagnostic Performance of Cardiac Natriuretic Peptides in
Dyspneic Patients Results From the BACH Study (Biomarkers in ACute Heart Failure)
01 Dec 2013 07:00 am
Publication date: June 2013
Source:JACC: Heart Failure, Volume 1, Issue 3
Author(s): Mark Richards , Salvatore Di Somma , Christian Mueller , Richard Nowak , W. Frank Peacock ,
Piotr Ponikowski , Martin Mockel , Christopher Hogan , Alan H.B. Wu , Paul Clopton , Gerasimos S.
Filippatos , Inder Anand , Leong Ng , Lori B. Daniels , Sean-Xavier Neath , Kevin Shah , Robert
Christenson , Oliver Hartmann , Stefan D. Anker , Alan Maisel
Objectives The purpose of this study was to assess the impact of atrial fibrillation (AF) on the performance
of mid-region amino terminal pro-atrial natriuretic peptide (MR-proANP) in comparison with the B-type
peptides (BNP and NT-proBNP) for diagnosis of acute heart failure (HF) in dyspneic patients. Background
The effects of AF on the diagnostic and prognostic performance of MR-proANP in comparison with the B
type natriuretic peptides have not been previously reported. Methods A total of 1,445 patients attending the
emergency department with acute dyspnea had measurements taken of MR-proANP, BNP, and NTproBNP values on enrollment to the BACH trial and were grouped according to presence or absence of AF
and HF. Results AF was present in 242 patients. Plasma concentrations of all three peptides were lowest in
those with neither AF nor HF and AF without HF was associated with markedly increased levels (p &lt;
0.00001). HF with or without AF was associated with a significant further increment (p &lt; 0.00001 for all
three markers). Areas under receiver operator characteristic curves (AUCs) for discrimination of acute HF
were similar and powerful for all peptides without AF (0.893 to 0.912; all p &lt; 0.001) with substantial and
similar reductions (0.701 to 0.757) in the presence of AF. All 3 peptides were independently prognostic but
there was no interaction between any peptide and AF for prediction of all-cause mortality. Conclusions AF is
associated with increased plasma natriuretic peptide (MR-proANP, BNP and NT-proBNP) levels in the
absence of HF. The diagnostic performance of all three peptides is impaired by AF. This warrants
consideration of adjusted peptide thresholds for diagnostic use in AF and mandates the continued search
for markers free of confounding by AF.
Biochemical Evidence of Mild Hepatic Dysfunction Identifies Decompensated Heart Failure
Patients With Reversible Renal Dysfunction
30 Nov 2013 08:19 pm
Publication date: November 2013
Source:Journal of Cardiac Failure, Volume 19, Issue 11
Author(s): Meredith A. Brisco , Brian D. McCauley , Jennifer Chen , Chirag R. Parikh , Jeffrey M. Testani
Background Differentiation of HF-induced renal dysfunction (RD) from irreversible intrinsic kidney disease is
challenging, likely related to the multifactorial pathophysiology underlying HF-induced RD. In contrast, HFinduced liver dysfunction results in characteristic laboratory abnormalities. Given that similar
pathophysiologic factors are thought to underlie both conditions, and that the liver and kidneys share a
common circulatory environment, patients with laboratory evidence of HF-induced liver dysfunction may
also have a high incidence of potentially reversible HF-induced RD. Methods and Results Hospitalized
patients with a discharge diagnosis of HF were reviewed (n = 823). Improvement in renal function (IRF) was
defined as a 20% improvement in estimated glomerular filtration rate (eGFR). An elevated international
normalized ratio (INR; odds ratio [OR] 2.8; P &lt; .001), bilirubin (BIL; OR 2.2; P &lt; .001), aspartate
aminotransferase (AST; OR 1.8; P = .004), and alanine aminotransferase (ALT; OR 2.1; P = .001) were all
significantly associated with IRF. Among patients with baseline RD (eGFR ≤45 mL min−1 1.73 m−2),
associations between liver dysfunction and IRF were particularly strong (INR: OR 5.7 [ P &lt; .001]; BIL: OR
5.1 [ P &lt; .001]; AST: OR 2.9 [ P = .005]; ALT: OR 4.8 [ P &lt; .001]). Conclusions Biochemical evidence of
mild liver dysfunction is associated with reversible RD in decompensated HF patients. In the absence of
methodology to directly identify HF-induced RD, signs of HF-induced dysfunction of other organs may serve
as an accessible method by which HF-induced RD is recognized.
Biomarkers of Acute Kidney Injury in Chronic Heart Failure What Do the Signals Mean?∗
01 Dec 2013 07:00 am
Publication date: October 2013
Source:JACC: Heart Failure, Volume 1, Issue 5
Author(s): Jeffrey M. Testani , W. H. Wilson Tang
Biomarkers of heart failure with normal ejection fraction: a systematic review
20 Nov 2013 03:29 pm
Aims
Heart failure with normal ejection fraction (HFNEF) is a major and growing public health problem, currently
representing half of the heart failure burden. Although many studies have investigated the diagnostic and
prognostic value of new biomarkers in heart failure, limited data are available on biomarkers other than
natriuretic peptides in HFNEF. We performed a systematic review of epidemiological studies on the
associations of biomarkers with the occurrence of HFNEF and with the prognosis of HFNEF patients.
Methods and results
Biomarkers examined most extensively in HFNEF include biomarkers of myocyte stress, inflammation, and
extracellular matrix remodelling. Some biomarkers have been shown to be increased to a different extent in
HFNEF compared with heart failure with reduced ejection fraction (HFREF). Several biomarkers, including
biomarkers of myocyte stress, inflammation, extracellular matrix remodelling, growth differentiation factor 15
(GDF-15), cystatin C, resistin, and galectin-3, were associated with development of HFNEF and with clinical
outcomes of HFNEF patients in terms of morbidity and mortality.
Conclusion
Several biomarkers, including biomarkers of myocyte stress, inflammation, extracellular matrix remodelling,
GDF-15, cystatin C, resistin, and galectin-3, appeared to be promising diagnostic and prognostic tools in
patients with HFNEF. Investigation of the incremental diagnostic and prognostic value of these biomarkers,
or a combination thereof, over established clinical covariates and imaging techniques in large, prospective
studies is warranted.
CG172: Myocardial infarction: secondary prevention
13 Nov 2013 12:01 am
The summary of the published clinical guideline on Myocardial infarction: secondary prevention. It links to
the published guidance and key documents.
CPAP and Short-Term Mortality in Acute Cardiac Pulmonary Edema: Now, What Can We
Be Expecting?
30 Nov 2013 08:19 pm
Publication date: October 2013
Source:Journal of Cardiac Failure, Volume 19, Issue 10
Author(s): Antonio M. Esquinas , Andrea Bellone
Cardiac Allograft Vasculopathy by Intravascular Ultrasound in Heart Transplant Patients
Substudy From the Everolimus Versus Mycophenolate Mofetil Randomized, Multicenter
Trial
01 Dec 2013 07:00 am
Publication date: October 2013
Source:JACC: Heart Failure, Volume 1, Issue 5
Author(s): Jon A. Kobashigawa , Daniel F. Pauly , Randall C. Starling , Howard Eisen , Heather Ross ,
Shoei-Shen Wang , Bernard Cantin , James A. Hill , Patricia Lopez , Gaohong Dong , Stephen J. Nicholls
Objectives A pre-planned substudy of a larger multicenter randomized trial was undertaken to compare the
efficacy of everolimus with reduced-dose cyclosporine in the prevention of cardiac allograft vasculopathy
(CAV) after heart transplantation to that of mycophenolate mofetil (MMF) with standard-dose cyclosporine.
Background CAV is a major cause of long-term mortality following heart transplantation. Everolimus has
been shown to reduce the severity and incidence of CAV as measured by first year intravascular ultrasound
(IVUS). MMF, in combination with cyclosporine, has also been shown to have a beneficial effect in slowing
the progression of CAV. Methods Study patients were a pre-specified subgroup of the 553 - patient
Everolimus versus mycophenolate mofetil in heart transplantation: a randomized, multicenter trial who
underwent heart transplantation and were randomized to everolimus 1.5 mg or MMF 3 g/day. IVUS was
performed at baseline and at 12 months. Evaluable IVUS data were available in 189 patients (34.6%).
Results Increase in average maximal intimal thickness (MIT) from baseline to month 12 was significantly
smaller in the everolimus 1.5 mg group compared with the MMF group (0.03 mm vs. 0.07 mm, p &lt; 0.001).
The incidence of CAV, defined as an increase in MIT from baseline to month 12 of greater than 0.5 mm,
was 12.5% with everolimus versus 26.7% with MMF (p = 0.018). These findings remained irrespective of
sex, age, diabetic status, donor disease, and across lipid categories. Conclusions Everolimus was
significantly more efficacious than MMF in preventing CAV as measured by IVUS among heart-transplant
recipients after 1 year, a finding, which was maintained in a range of patient subpopulations. CV surgery:
transplantation, ventricular assistance, cardiomyopathy
Cardiac Rehabilitation Exercise and Self-Care for Chronic Heart Failure
01 Dec 2013 07:00 am
Publication date: Available online 24 October 2013
Source:JACC: Heart Failure
Author(s): Philip A. Ades , Steven J. Keteyian , Gary J. Balady , Nancy Houston-Miller , Dalane W. Kitzman
, Donna M. Mancini , Michael W. Rich
Chronic heart failure (CHF) is highly prevalent in older individuals and is a major cause of morbidity,
mortality, hospitalizations, and disability. Cardiac rehabilitation (CR) exercise training and CHF self-care
counseling have each been shown to improve clinical status and clinical outcomes in CHF. Systematic
reviews and meta-analyses of CR exercise training alone (without counseling) have demonstrated
consistent improvements in CHF symptoms in addition to reductions in cardiac mortality and number of
hospitalizations, although individual trials have been less conclusive of the latter 2 findings. The largest
single trial, HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training),
showed a reduction in the adjusted risk for the combined endpoint of all-cause mortality or hospitalization
(hazard ratio: 0.89, 95% confidence interval: 0.81 to 0.99; p = 0.03). Quality of life and mental depression
also improved. CHF-related counseling, whether provided in isolation or in combination with CR exercise
training, improves clinical outcomes and reduces CHF-related hospitalizations. We review current evidence
on the benefits and risks of CR and self-care counseling in patients with CHF, provide recommendations for
patient selection for third-party payers, and discuss the role of CR in promoting self-care and behavioral
changes.
Cardiac Resynchronization Therapy in Patients With Atrial Fibrillation The CERTIFY Study
01 Dec 2013 07:00 am
Publication date: Available online 23 October 2013
Source:JACC: Heart Failure
Author(s): Maurizio Gasparini , Christophe Leclercq , Maurizio Lunati , Maurizio Landolina , Angelo
Auricchio , Massimo Santini , Giuseppe Boriani , Barbara Lamp , Alessandro Proclemer , Antonio Curnis ,
Catherine Klersy , Francisco Leyva
Objectives The purpose of this study is to determine whether, in patients with atrial fibrillation (AF)
undergoing cardiac resynchronization therapy (CRT), atrioventricular junction ablation (AVJA) is associated
with a better outcome than treatment with rate-slowing drugs. Background Different trials have
demonstrated that CRT is effective in treating heart failure (HF) patients who are in sinus rhythm (SR). No
trials have addressed whether CRT confers similar benefits on AF patients, with or without AVJA. Methods
The clinical outcomes of CRT for patients with permanent AF undergoing CRT combined with either AVJA
(n = 443) or rate-slowing drugs (n = 895) were compared with those of SR patients (n = 6,046). Results
Median follow-up was 37 months. Total mortality (6.8 vs. 6.1 per 100 person-years) and cardiac mortality
(4.2 vs. 4.0) were similar for patients with AF+AVJA and patients in SR (both p = not significant). In
contrast, the AF+drugs group had a higher total and cardiac mortality than the SR group and the AF+AVJA
group (11.3 and 8.1, respectively; p &lt; 0.001). On multivariable analysis, AF+AVJA had total mortality
(hazard ratio [HR]: 0.93, 95% confidence interval [CI]: 0.74 to 1.67) and cardiac mortality (HR: 0.88, 95%
CI: 0.66 to 1.17) similar to that of the SR group, independent of known confounders. The AF+drugs group,
however, had a higher total mortality (HR: 1.52, 95% CI: 1.26 to 1.82) and cardiac mortality (HR: 1.57, 95%
CI: 1.27 to 1.94) than both the SR group and the AF+AVJA group (both p &lt; 0.001). Conclusions Longterm survival after CRT among patients with AF+AVJA is similar to that observed among patients in SR.
Mortality is higher for AF patients treated with rate-slowing drugs.
Cardiac Structure and Function in Heart Failure With Preserved Ejection Fraction: Baseline
Findings From the Echocardiographic Study of the Treatment of Preserved Cardiac
Function Heart Failure With an Aldosterone Antagonist Trial [Original Articles]
18 Nov 2013 05:55 pm
Background—Heart failure with preserved ejection fraction (HFpEF) is associated with substantial
morbidity and mortality. Existing data on cardiac structure and function in HFpEF suggest significant
heterogeneity in this population.
Methods and Results—Echocardiograms were obtained from 935 patients with HFpEF (left ventricular
ejection fraction ≥45%) enrolled in the Treatment of Preserved Cardiac Function Heart Failure with an
Aldosterone Antagonist (TOPCAT) trial before initiation of randomized therapy. Average age was 70±10
years, 49% were women, 14% were of African descent, and comorbidities were highly prevalent.
Centralized quantitative analysis in a blinded core laboratory demonstrated a mean left ventricular ejection
fraction of 59.3±7.9%, with prevalent concentric left ventricular remodeling (34%) and hypertrophy (43%),
and left atrial enlargement (53%). Diastolic dysfunction was present in 66% of gradable participants and
was significantly associated with greater left ventricular hypertrophy and a higher prevalence of left atrial
enlargement. Doppler evidence of pulmonary hypertension was present in 36%. At least 1 measure of
structural heart disease was present in 93% of patients.
Conclusions—Patients enrolled in TOPCAT demonstrated heterogeneous patterns of ventricular
remodeling, with high prevalence of structural heart disease, including left ventricular hypertrophy and left
atrial enlargement, in addition to pulmonary hypertension, each of which has been associated with adverse
outcomes in HFpEF. Diastolic function was normal in approximately one third of gradable participants,
highlighting the heterogeneity of the cardiac phenotype in this syndrome. These findings deepen our
understanding of the TOPCAT trial population and expand our knowledge of the diversity of the cardiac
phenotype in HFpEF.
Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00094302.
Cardiovascular Effects of 1 Year of Alagebrium and Endurance Exercise Training in Healthy
Older Individuals [Original Articles]
19 Nov 2013 09:01 pm
Background—
Lifelong exercise training maintains a youthful compliance of the left ventricle (LV), whereas a year of
exercise training started later in life fails to reverse LV stiffening, possibly because of accumulation of
irreversible advanced glycation end products. Alagebrium breaks advanced glycation end product
crosslinks and improves LV stiffness in aged animals. However, it is unclear whether a strategy of exercise
combined with alagebrium would improve LV stiffness in sedentary older humans.
Methods and Results—
Sixty-two healthy subjects were randomized into 4 groups: sedentary+placebo; sedentary+alagebrium (200
mg/d); exercise+placebo; and exercise+alagebrium. Subjects underwent right heart catheterization to define
LV pressure–volume curves; secondary functional outcomes included cardiopulmonary exercise testing and
arterial compliance. A total of 57 of 62 subjects (67±6 years; 37 f/20 m) completed 1 year of intervention
followed by repeat measurements. Pulmonary capillary wedge pressure and LV end-diastolic volume were
measured at baseline, during decreased and increased cardiac filling. LV stiffness was assessed by the
slope of LV pressure–volume curve. After intervention, LV mass and end-diastolic volume increased and
exercise capacity improved (by 8%) only in the exercise groups. Neither LV mass nor exercise capacity was
affected by alagebrium. Exercise training had little impact on LV stiffness (trainingxtime effect, P=0.46),
whereas alagebrium showed a modest improvement in LV stiffness compared with placebo
(medicationxtime effect, P=0.04).
Conclusions—
Alagebrium had no effect on hemodynamics, LV geometry, or exercise capacity in healthy, previously
sedentary seniors. However, it did show a modestly favorable effect on age-associated LV stiffening.
Clinical Trial Registration—
URL: http://www.clinicaltrials.gov. Unique identifier: NCT01014572.
Characteristics and Outcomes of Heart Failure–Related Intensive Care Unit Admissions in
Children With Cardiomyopathy
30 Nov 2013 08:19 pm
Publication date: October 2013
Source:Journal of Cardiac Failure, Volume 19, Issue 10
Author(s): Pirouz Shamszad , Matthew Hall , Joseph W. Rossano , Susan W. Denfield , Jarrod D. Knudson
, Daniel J. Penny , Jeffrey A. Towbin , Antonio G. Cabrera
Objective The purpose of this study was to describe patient characteristics and outcomes of heart failure
(HF)–related intensive care unit (ICU) hospitalizations in children with cardiomyopathy (CM). Methods and
Results A query of the Pediatric Health Information System database, a large administrative and billing
database of 43 tertiary children’s hospitals, was performed. A total of 17,309 HF-related ICU
hospitalizations from 2005 to 2010 of 14,985 children ≤18 years old were analyzed. Of those, 2,058 (12%)
hospitalizations for CM-HF in 1,599 (11%) children were identified. Classification into CM subtypes was not
possible owing to database limitations. The number of yearly CM-HF hospitalizations significantly increased
during the study period ( P = .036). Overall mortality was 11%, and cardiac transplantation occurred in 20%
of hospitalizations. Mechanical circulatory support (MCS) was used in 261 (13%) of hospitalizations. Renal
failure, MCS, respiratory failure, sepsis, and vasoactive medications were associated with mortality on
multivariable analysis. Significant comorbidities associated with these hospitalizations included arrhythmias
in 42%, renal failure in 13%, cerebrovascular disease in 6%, and hepatic impairment in 5%. Conclusions
HF-related ICU hospitalizations in children with cardiomyopathy are increasing. These children are at high
risk for poor outcomes with an in-hospital mortality of 11%.
Characteristics, Adverse Events, and Racial Differences Among Delivering Mothers With
Peripartum Cardiomyopathy
01 Dec 2013 07:00 am
Publication date: October 2013
Source:JACC: Heart Failure, Volume 1, Issue 5
Author(s): David P. Kao , Eileen Hsich , JoAnn Lindenfeld
Objectives The aim of this study was to identify clinical features associated with peripartum cardiomyopathy
(PPCM) and possible racial differences and to quantify in-hospital outcomes in delivering mothers with
PPCM. Background Investigation of patient characteristics and outcomes in PPCM has been limited to
small cohorts. Hospital discharge data allow assembly of the largest number of PPCM cases to date.
Methods Hospital records from 6 states were screened for PPCM. Clinical profiles, maternal, and fetal
outcomes in delivering mothers with and without PPCM were compared and stratified by race. A maternal
major adverse event (MAE) was defined as death, cardiac arrest, heart transplantation, or mechanical
circulatory support. Logistic regression was used to identify variables associated with PPCM. Results In
total, 535 of 4,003,914 records of delivering mothers specified a diagnosis of PPCM. Prevalence of PPCM
was highest among African Americans and similar in Caucasians and Hispanics. Established risk factors
including age ≥30 years, African- American race, hypertension, preeclampsia/eclampsia, and
multigestational status were associated with PPCM, and novel associations such as anemia and asthma
were identified. Autoimmune disease and substance abuse, which can cause cardiomyopathy
independently, were also associated with PPCM. Maternal MAE (odds ratio: 436, p &lt; 0.0001) and stillbirth
(odds ratio: 3.8, p &lt; 0.0001) occurred more frequently among women with PPCM. Conclusions The
prevalence of PPCM at the time of delivery in Hispanics was similar to Caucasians and lower than African
Americans. Autoimmune disease, substance abuse, anemia and asthma were conditions associated with
PPCM not consistently identified in smaller cohorts. Peripartum cardiomyopathy was also associated with
increased risk of stillbirth and maternal MAEs at delivery.
Circulating angiopoietin-2, its soluble receptor Tie-2, and mortality in the general population
20 Nov 2013 03:29 pm
Aims
To assess the association of circulating concentrations of angiopoietin-2 (Ang-2) and its soluble receptor
Tie-2 (sTie-2) with all-cause, cardiovascular, and cancer mortality in a population-based sample.
Methods and results
Angiopoietin-2 and sTie-2 were measured in 3220 participants (1665 women; mean age 54.4 years) in the
Study of Health in Pomerania (SHIP). Multivariable adjusted hazard ratios (HRs) for mortality were
estimated using Cox proportional hazard models. During a median follow-up of 6.2 years, 217 participants
died. Ang-2 levels were positively associated with all-cause mortality [HR 1.29; 95% confidence interval (CI)
1.19–1.39 per 1 SD increment; P < 0.001] and cardiovascular mortality (HR 1.32; 95% CI 1.18–1.49; P <
0.001), but not with cancer mortality (HR 1.08; 95% CI 0.89–1.32; P = 0.416). Levels of sTie-2 were not
significantly related to all-cause mortality (HR 1.12; 95% CI 0.98–1.27; P = 0.102). Adding Ang-2 to a
prediction model for all-cause mortality with standard risk factors slightly improved discrimination ( Harrell's
C, 0.008; P < 0.001) but not risk reclassification (continuous net reclassification improvement, –0.015; P =
0.571).
Conclusion
In our community-based sample, higher serum Ang-2 concentrations were associated with greater risk for
all-cause and cardiovascular mortality, suggesting that subtle increases in Ang-2 levels might reflect
processes such as vascular remodelling that are associated with higher mortality risk. Adding Ang-2 to a
mortality prediction model only modestly improved discrimination.
Circulation: Heart Failure Editors' Picks: Most Important Articles in Heart Failure in Children
[Circulation: Heart Failure Topic Review]
19 Nov 2013 09:01 pm
Clinical Features, Hemodynamics, and Outcomes of Pulmonary Hypertension Due to
Chronic Heart Failure With Reduced Ejection Fraction Pulmonary Hypertension and Heart
Failure
01 Dec 2013 07:00 am
Publication date: August 2013
Source:JACC: Heart Failure, Volume 1, Issue 4
Author(s): Wayne L. Miller , Diane E. Grill , Barry A. Borlaug
Objectives The purpose of this study was to assess the clinical, functional, and hemodynamic
characteristics of passive and mixed pulmonary hypertension (PH), compare outcomes, and contrast
conventional and novel hemodynamic partition values in patients with chronic heart failure of reduced left
ventricular ejection fraction (HFREF). Background PH in HFREF may develop from left-sided venous
congestion (passive PH) or the combination of pulmonary arterial disease and venous congestion (mixed
PH). Subgroup outcomes are not well defined, and the partition values used to define risk are based largely
on consensus opinion rather than outcome data. Methods Ambulatory patients referred for hemodynamic
catheterization were analyzed retrospectively (N = 463). Results Comparing patients with no PH to those
with passive PH and mixed PH, a progressive gradient of more severely deranged hemodynamics, diastolic
dysfunction, and mitral regurgitation was observed. In multivariate analysis, the presence of any PH or
mixed PH was associated with older age, diuretic use, atrial fibrillation, and lower pulmonary artery
compliance (PAC). Over a median follow-up of 2.1 years, patients with PH displayed greater risk of death
(hazard ratio [HR]: 2.24; confidence limits [95% CL]: 1.39, 3.98; p &lt; 0.001) with mixed PH demonstrating
greater risk than passive PH (HR: 1.55; 95% CL: 1.11, 2.20; p &lt; 0.001). Partition values identifying
highest risk were pulmonary vascular resistance &gt;4 Wood units, systolic pulmonary artery pressure
&gt;35 mm Hg, pulmonary wedge pressure &gt;25 mm Hg, and PAC &lt;2.0 ml/mm Hg. Conclusions Among
stable HFREF outpatients, PH was associated with markers of greater disease severity and risk of death.
However, the presence of pulmonary arterial disease (mixed PH) carries incremental risk. Abnormalities in
pulmonary vascular resistance and compliance may serve as novel therapeutic targets.
Clinical Outcomes and Cardiovascular Responses to Different Exercise Training Intensities
in Patients With Heart Failure A Systematic Review and Meta-Analysis
01 Dec 2013 07:00 am
Publication date: Available online 23 October 2013
Source:JACC: Heart Failure
Author(s): Hashbullah Ismail , James R. McFarlane , A. Hadi Nojoumian , Gudrun Dieberg , Neil A. Smart
Objectives The aim of this study was to establish whether aerobic exercise training intensity produces
different effect sizes for fitness, adherence, event rates, mortality rates, and hospitalization rates in patients
with heart failure. Background Intuitively, greater exercise intensity is considered to result in higher risk for
serious events, but intensity may be the primary stimulus for physical adaptation. Methods A MEDLINE
search (1985 to 2012) was conducted for exercise-based rehabilitation trials in heart failure, using the
search terms “exercise training,” “left ventricular dysfunction,” “peak V o 2 ,” “cardio-myopathy,” and
“systolic heart dysfunction.” Seventy-four studies were included, producing 76 intervention groups; 9
(11.8%) were high-intensity, 38 (50%) vigorous-intensity, 24 (31.6%) moderate-intensity, and 5 (6.6%) lowintensity groups, providing a total of 3,265 exercising subjects and 2,612 control subjects. Results Peak
oxygen consumption increased by a mean difference of 3.33 ml · kg−1 · min−1 (95% confidence interval [CI]:
0.53 to 6.13 ml · kg−1 · min−1; p = 0.02) with high-intensity training in exercise groups compared with control
groups, equating to a 23% improvement from baseline. For vigorous intensity, the mean difference was
2.27 ml · kg−1 · min−1 (95% CI: 1.70 to 2.84 ml · kg−1 · min−1; p &lt; 0.00001), with an 8% weighted mean; for
moderate intensity, the mean difference was 2.17 ml · kg−1 · min−1(95% CI: 1.34 to 2.99 ml · kg−1 · min−1;
p &lt; 0.00001), with a weighted mean of 13%; and for low intensity, the mean difference was 1.04 ml ·
kg−1 · min−1 (95% CI: −2.50 to 4.57 ml · kg−1 · min−1; p = 0.57), with a weighted mean of 7%. In 123,479
patient-hours of training, not a single death was directly attributable to exercise. Conclusions As exercise
training intensity rises, so may the magnitude of improvement in cardiorespiratory fitness, accompanied by
lower study withdrawal in exercising patients. Total exercise time may be a confounder.
Comparable Performance of the Kansas City Cardiomyopathy Questionnaire in Patients
With Heart Failure With Preserved and Reduced Ejection Fraction [Original Articles]
19 Nov 2013 09:01 pm
Background—
Despite the growing epidemic of heart failure with preserved ejection fraction (HFpEF), no valid measure of
patients’ health status (symptoms, function, and quality of life) exists. We evaluated the Kansas City
Cardiomyopathy Questionnaire (KCCQ), a validated measure of HF with reduced EF, in patients with
HFpEF.
Methods and Results—
Using a prospective HF registry, we dichotomized patients into HF with reduced EF (EF≤ 40) and HFpEF
(EF≥50). The associations between New York Heart Association class, a commonly used criterion standard,
and KCCQ Overall Summary and Total Symptom domains were evaluated using Spearman correlations
and 2-way ANOVA with differences between patients with HF with reduced EF and HFpEF tested with
interaction terms. Predictive validity of the KCCQ Overall Summary scores was assessed with Kaplan–
Meier curves for death and all-cause hospitalization. Covariate adjustment was made using Cox
proportional hazards models. Internal reliability was assessed with Cronbach’s α. Among 849 patients, 200
(24%) had HFpEF. KCCQ summary scores were strongly associated with New York Heart Association class
in both patients with HFpEF (r=–0.62; P<0.001) and HF with reduced EF (r=–0.55;P=0.27 for interaction).
One-year event-free rates by KCCQ category among patients with HFpEF were 0 to 25=13.8%, 26 to
50=59.1%, 51 to 75=73.8%, and 76 to 100=77.8% (log rank P<0.001), with no significant interaction by EF
(P=0.37). The KCCQ domains demonstrated high internal consistency among patients with HFpEF
(Cronbach’s α=0.96 for overall summary and ≥0.69 in all subdomains).
Conclusions—
Among patients with HFpEF, the KCCQ seems to be a valid and reliable measure of health status and
offers excellent prognostic ability. Future studies should extend and replicate our findings, including the
establishment of its responsiveness to clinical change.
Complete atrioventricular block does not reduce long-term mortality in patients with
permanent atrial fibrillation treated with cardiac resynchronization therapy
20 Nov 2013 03:29 pm
Aims
A maximum percentage of ventricular pacing is mandatory to obtain a good response to CRT.
Atrioventricular junction (AVJ) ablation has been recommended to attain this objective in patients with AF.
The aims of our study were: (i) to determine whether the presence of complete AVJ block (induced or
spontaneous) improves survival in patients with permanent AF treated with CRT and (ii) to analyse the
predictors of mortality in AF patients treated with CRT.
Methods and results
From a series of 608 patients treated with CRT in our centre from 2000 to 2011, a cohort of 155 patients
with permanent AF was analysed. Patients in AF were divided into two groups, AF + AVJ block [76 (49%)]
and AF non-AVJ block [79 (51%)]. Mean follow-up was 30 months (interquartile range 13–51 months).
During the follow-up, 62 patients died. Overall and cardiovascular mortality were similar between both
groups: hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.51–1.39, P = 0.51 and HR 0.94, 95% CI
0.52–1.68, P = 0.82. Multivariate analysis identified three independent predictors of mortality: basal NYHA
functional class IV (HR 2.25, 95% CI 1.12–4.22, P = 0.03), glomerular filtration rate (HR 0.98, 95% CI 0.96–
0.99, P = 0.03), and LVEF (HR 0.94, 95% CI 0.89–0.99, P = 0.02).
Conclusions
AVJ block did not improve survival for patients in AF treated with CRT. Basal NYHA functional class IV,
poor renal function, and LVEF were the independent predictors of mortality.
Continuous Ultrafiltration for Congestive heart failure the Cuore Trial
30 Nov 2013 08:19 pm
Publication date: Available online 20 November 2013
Source:Journal of Cardiac Failure
Author(s): Giancarlo Marenzi , Manuela Muratori , Eugenio R. Cosentino , Elisa R. Rinaldi , Valeria Donghi ,
Valentina Milazzo , Emiliana Ferramosca , Claudio Borghi , Antonio Santoro , Piergiuseppe Agostoni
Background There are limited data comparing ultrafiltration with standard medical therapy as first-line
treatment in patients with severe congestive heart failure (HF). We compared ultrafiltration vs. conventional
therapy in patients hospitalized for HF and overt fluid overload. Methods and Results Patients with
congestive HF were randomized to receive standard medical therapy (Control group) or ultrafiltration
(Ultrafiltration group). The primary end point of the study was re-hospitalizations for congestive HF during a
1-year follow-up. Fifty-six patients were randomized to ultrafiltration (n=27) or standard therapy (n=29).
Despite similar body weight reduction at hospital discharge in the two groups (7.5±4.5 and 7.9±5.0 kg,
respectively; P=0.75), a lower incidence of re-hospitalizations for HF was observed in the ultrafiltrationtreated patients during the following year (hazard ratio 0.14, 95% confidence interval 0.04-0.48; P=0.002).
Ultrafiltration-induced benefit was associated with a more stable renal function, unchanged furosemide
dose, and lower BNP levels. At one year, 7 (30%) deaths occurred in the ultrafiltration group, and 11 (44%)
in the Control group (P=0.33). Conclusions In HF patients with severe fluid overload, first-line treatment with
ultrafiltration is associated with a prolonged clinical stabilization and a greater freedom from rehospitalization for congestive HF.
Coronary microvascular dysfunction is an early feature of cardiac involvement in patients
with Anderson-Fabry disease
20 Nov 2013 03:29 pm
Aims
Male patients with Anderson–Fabry disease (AFD) often exhibit cardiac involvement, characterized by LV
hypertrophy (LVH), associated with severe coronary microvascular dysfunction (CMD). Whether CMD is
present in patients without LVH, particularly when female, remains unresolved. The aim of the study was to
investigate the presence of CMD by positron emission tomography (PET) in AFD patients of both genders,
with and without evidence of LVH.
Methods and results
We assessed myocardial blood flow following dipyridamole infusion (Dip-MBF) with13N-labelled ammonia by
PET in 30 AFD patients (age 51 ± 13 years; 18 females) and in 24 healthy controls. LVH was defined as
echocardiographic maximal LV wall thickness ≥13 mm. LVH was present in 67% of patients (n = 20; 10
males and 10 females). Dip-MBF was reduced in all patients compared with controls (1.8 ± 0.5 and 3.2 ±
0.5 mL/min/g, respectively, P < 0.001). For both genders, flow impairment was most severe in patients with
LVH (1.4 ± 0.5 mL/min/g in males and 1.9 ± 0.5 mL/min/g in females), but was also evident in those without
LVH (1.8 ± 0.3 mL/min/g in males and 2.1 ± 0.4 mL/min/g in females; overall P = 0.064 vs. patients with
LVH). Analysis of variance (ANOVA) for the 17 LV segments showed marked regional heterogeneity of
MBF in AFD (F = 4.46, P < 0.01), with prevalent hypoperfusion of the apical region. Conversely, controls
showed homogeneous LV perfusion (F = 1.25, P = 0.23).
Conclusions
Coronary microvascular function is markedly impaired in AFD patients irrespective of LVH and gender.
CMD may represent the only sign of cardiac involvement in AFD patients, with potentially important
implications for clinical management.
DUCCS and SWANS: When U.S. Site-Based Research Was Highly Successful
01 Dec 2013 07:00 am
Publication date: August 2013
Source:JACC: Heart Failure, Volume 1, Issue 4
Author(s): Christopher O'Connor
Delta-6-desaturase Links PUFA Metabolism with Phospholipid Remodeling and Disease
Progression in Heart Failure [Original Articles]
27 Nov 2013 06:38 pm
Background—Remodeling of myocardial phospholipids has been reported in various forms of heart failure
for decades, but the mechanism and pathophysiological relevance of this phenomenon have remained
unclear. We examined the hypothesis that delta-6 desaturase (D6D), the rate limiting enzyme in long-chain
polyunsaturated fatty acid (PUFA) biosynthesis, mediates the signature pattern of fatty acid redistribution
observed in myocardial phospholipids following chronic pressure overload, and explored plausible links
between this process and disease pathogenesis.
Methods and Results—Compositional analysis of phospholipids from hearts explanted from patients with
dilated cardiomyopathy revealed elevated PUFA product/precursor ratios reflective of D6D hyperactivity,
manifesting primarily as lower levels of linoleic acid with reciprocally higher levels of arachidonic and
docosahexaenoic acids. This pattern of remodeling was attenuated in failing hearts chronically unloaded
with a left ventricular assist device. Chronic inhibition of D6D in vivo reversed similar patterns of myocardial
PUFA redistribution in rat models of pressure overload and hypertensive heart disease, and significantly
attenuated cardiac hypertrophy, fibrosis and contractile dysfunction in both models. D6D inhibition also
attenuated myocardial elevations in pathogenic eicosanoid species, lipid peroxidation, and ERK1/2
activation; normalized cardiolipin composition in mitochondria; reduced circulating levels of inflammatory
cytokines; and elicited model-specific effects on cardiac mitochondrial respiratory efficiency, NFB activation
and caspase activities.
Conclusions—These studies demonstrate a pivotal role of essential fatty acid metabolism though D6D in
myocardial phospholipid remodeling induced by hemodynamic stress, and reveal novel links between this
phenomenon and the propagation of multiple pathogenic systems involved in maladaptive cardiac
remodeling and contractile dysfunction.
Diagnostic and prognostic value of osteopontin in patients with acute congestive heart
failure
20 Nov 2013 03:29 pm
Aims
To evaluate the diagnostic and prognostic value of osteopontin in patients with acute dyspnoea and/or
peripheral oedema suspected of having acute congestive heart failure (aCHF).
Methods and results
A total of 401 patients presenting with acute dyspnoea and/or peripheral oedema to the emergency
department were prospectively enrolled and followed up for up to 5 years. Blood samples for biomarker
measurements were collected on admission to the emergency department. Osteopontin combined with NTproBNP vs. NT-proBNP alone for diagnosis of aCHF was tested. Additionally, osteopontin vs. NT-proBNP
for prognostic outcomes (i.e. all-cause mortality, aCHF-related rehospitalization, and both in combination)
was tested. The diagnostic and prognostic capacity of osteopontin was tested by C-statistics,
reclassification indices, and multivariable Cox prediction models. Osteopontin plus NT-proBNP improved
the diagnostic capacity for aCHF diagnosis [accuracy 76%, 95% confidence interval (CI) 72–80%;
specificity 74%, 95% CI 69–79%, net reclassification improvement (NRI) +0.10] compared with NT-proBNP
alone in the emergency department (P = 0.0001). Osteopontin independently predicted all-cause mortality
and aCHF-related rehospitalization after 1 and 5 years. Compared with NT-proBNP, osteopontin was of
superior prognostic value, specifically in aCHF patients and for the prognostic outcome of aCHF-related
rehospitalization.
Conclusion
Osteopontin improves aCHF diagnosis when combined with NT-proBNP. Osteopontin identifies aCHF
patients with high 1- and 5-year mortality and rehospitalization risk, and adds prognostic value to NTproBNP.
Trial registration
NCT00143793
Diet Prevention and Therapy for Heart Failure? [Editorials]
19 Nov 2013 09:01 pm
Differences in Blood Volume Components Between Hyporesponders and Responders to
Erythropoietin Alfa: The Heart Failure With Preserved Ejection Fraction (HFPEF) Anemia
Trial
30 Nov 2013 08:19 pm
Publication date: October 2013
Source:Journal of Cardiac Failure, Volume 19, Issue 10
Author(s): Margarita Borovka , Sergio Teruya , Julissa Alvarez , Stephen Helmke , Mathew S. Maurer
Background Hyporesponders to erythropoietin-stimulating agents (ESAs) have been associated with
an increased subsequent risk of death or cardiovascular events. We hypothesized that subjects who are
hyporesponsive to erythropoietin alfa would have higher plasma volumes and lower red cell deficits than
subjects who are responsive to therapy. Methods As part of a prospective, single blind, randomized,
placebo-controlled study comparing erythropoietin alfa with placebo in older adults (n = 56) with heart failure
and a preserved ejection fraction (HFPEF), we performed blood volume analysis with the use of an indicator
dilution technique with 131iodine-labeled albumin. We evaluated differences in plasma volumes and red cell
volumes in hyporesponders (eg, &lt;1 g/dL increase in hemoglobin within the first 4 weeks of treatment with
erythropoetin alfa) compared with subjects who were responders and controls. Results Nine of 28 subjects
(32%) assigned to ESA were hyporesponders. Hyporesponders did not differ from responders nor control
subjects by any baseline demographic, clinical, or laboratory parameter, including hemoglobin.
Hyporesponders had a greater total blood volume expansion (1,264.7 ± 387 vs 229 ± 206 mL; P = .02) but
less of a red cell deficit (−96.2 ± 126 vs −402.5 ± 80.6 mL; P = .04) and a greater plasma volume
expansion (+1,360.8 ± 264.5 vs +601.1 ± 165.5 mL; P = .01). Among responders, the increase in
hemoglobin with erythropoietin alfa was associated primarily with increases in red cell volume ( r = 0.91; P
&lt; .0001) as well as a decline in plasma volume ( r = −0.55; P = .06). Conclusions Among older adults
with HFPEF and anemia, hyporesponders to erythropoietin alfa had a hemodilutional basis of their anemia,
suggesting that blood volume analysis can identify a cohort likely to respond to therapy.
Differences in Treatment, Outcomes, and Quality of Life Among Patients With Heart Failure
in Canada and the United States
01 Dec 2013 07:00 am
Publication date: Available online 23 October 2013
Source:JACC: Heart Failure
Author(s): Padma Kaul , Shelby D. Reed , Adrian F. Hernandez , Jonathan G. Howlett , Justin A. Ezekowitz
, Yanhong Li , Yinggan Zheng , Jean L. Rouleau , Randall C. Starling , Christopher M. O'Connor , Robert M.
Califf , Paul W. Armstrong
Objectives The aim of this study was to compare clinical outcomes, resource utilization, and health-related
quality of life between Canadian and U.S. patients enrolled in ASCEND-HF (Acute Study of Clinical
Effectiveness of Nesiritide in Decompensated Heart Failure). A further aim was to supplement the withintrial analysis with a contemporaneous population-based comparison of all patients hospitalized with primary
diagnoses of heart failure (HF) in the 2 countries. Background Little is known about intercountry differences
in outcomes of patients with HF in Canada and the United States. Methods Trial patients consisted of 465
Canadian and 2,684 U.S. patients enrolled in ASCEND-HF. Population-level cohorts consisted of 1.9 million
U.S. and 81,016 Canadians hospitalized for HF in 2007 and 2008. Results Canadian patients in ASCENDHF were older, were more likely to be white, and had lower body weights and blood pressures than U.S.
patients. Canadians also had lower baseline-adjusted odds of 30-day mortality (odds ratio: 0.46; 95%
confidence interval: 0.23 to 0.92) and better health-related quality of life than U.S. patients. In both
countries, trial patients differed significantly from population-level cohorts. In contrast to ASCEND-HF,
unadjusted in-hospital mortality at the population level was significantly lower in the United States (3.4%)
compared with Canada (11.1%) (p &lt; 0.01). Conclusions Intercountry differences in outcomes of patients
hospitalized with HF differed significantly between trial and population cohorts. Further study on how
cardiac care is delivered in the 2 countries and how it influences the results of clinical trials and populationlevel outcomes, especially in the long term, is warranted. (A Study Testing the Effectiveness of Nesiritide in
Patients With Acute Decompensated Heart Failure; NCT00475852 )
Disaster Hypertension
30 Nov 2013 08:19 pm
Publication date: October 2013
Source:Journal of Cardiac Failure, Volume 19, Issue 10, Supplement
Author(s): Hoshide Satoshi
Do Outcomes for Patients With Heart Failure Vary by Emergency Department Volume?
[Original Articles]
19 Nov 2013 09:01 pm
Background—
Heart failure is a common Emergency Department (ED) presentation but whether ED volume influences
patient outcomes is unknown.
Methods and Results—
Retrospective cohort of all adults presenting to 93 EDs between 1999 and 2009 with a most responsible
diagnosis of heart failure (n=44 925 ED visits; mean age, 76.4 years). Cases seen in low-volume EDs had
less comorbidities and were less likely to be hospitalized (54.5%) than those seen in medium (61.8%;
adjusted odds ratio [aOR] 1.16, [95% confidence interval {CI} 1.10–1.23]) or high-volume EDs (73.6%; aOR,
1.95 [95% CI, 1.83–2.07]). Of patients treated and released, low-volume ED cases exhibited higher risk of
death/hospitalization/ED visit in the subsequent 7 (22.0%) and 30 days (44.9%) than medium (16.3%; aOR,
0.81 [95% CI, 0.73–0.90], and 35.3%; aOR, 0.79 [95% CI, 0.73–0.86]) or high-volume ED cases (13.0%;
aOR, 0.69 [95% CI, 0.61–0.78], and 30.2%; aOR, 0.67 [95% CI, 0.61–0.74]). Of patients hospitalized at the
time of their index ED visit, low-volume ED cases exhibited a higher risk of 30-day death/all-cause
readmission (24.3%) than those seen in medium (21.9%; aOR, 0.83 [95% CI, 0.76–0.91]) or high-volume
EDs (18.1%; aOR, 0.77 [95% CI, 0.70–0.85]).
Conclusions—
Low-volume EDs were more likely to discharge patients with heart failure home, but low-volume ED cases
exhibited worse outcomes (driven largely by readmissions or repeat ED visits). Interventions to improve
management of acute heart failure are required at low-volume sites.
Drug Therapy to Reduce Early Readmission Risk in Heart Failure Ready for Prime Time?
01 Dec 2013 07:00 am
Publication date: August 2013
Source:JACC: Heart Failure, Volume 1, Issue 4
Author(s): Muthiah Vaduganathan , Gregg C. Fonarow , Mihai Gheorghiade
Readmission for heart failure remains a major focus of policymakers, clinicians, and patients. Despite
meeting key national performance measures and frequent use of evidence-based therapies, rates of 30-day
post-discharge rehospitalization may be as high as 25%. Digoxin and mineralocorticoid antagonists are
known to reduce admissions for heart failure, but are significantly underused in current clinical practice
despite their proven benefits.
Dynamic Nature of Pulmonary Artery Systolic Pressure in Decompensated Heart Failure
With Preserved Ejection Fraction: Role of Functional Mitral Regurgitation
30 Nov 2013 08:19 pm
Publication date: November 2013
Source:Journal of Cardiac Failure, Volume 19, Issue 11
Author(s): Pierre Vladimir Ennezat , Sylvestre Maréchaux , Nadia Bouabdallaoui , Thierry H. Le Jemtel
Background Pulmonary hypertension (PH) is prevalent in decompensated heart failure with preserved
ejection fraction (HFpEF). We investigated the effect of a return to a compensated state on pulmonary
artery systolic pressure (PASP) and functional mitral regurgitation (FMR). Methods and Results Twodimensional Doppler echocardiography was prospectively performed before initiation of standard therapy
and 48 hours later in 37 patients hospitalized for HFpEF-related dyspnea and in 26 patients hospitalized for
non-HFpEF–related dyspnea. Left atrial volume index, and E/e′ ratio, and PASP were significantly greater
and E-wave deceleration time significantly shorter in HFpEF than in non-HFpEF patients. Thirty-two of the
37 HFpEF had FMR on admission whereas none of the non-HFpEF patients had FMR. After 48 hours of
therapy, the reduction in PASP was significantly greater in the 26 HFpEF patients who improved than in the
11 HFpEF patients who did not (−24 vs −9 mm Hg, respectively; P &lt; .0001), whereas PASP remained
unchanged in non-HFpEF patients. The decrease in PASP correlated in HFpEF patients with reductions in
blood pressure, heart rate, left ventricular end-diastolic volume, inferior vena cava diameter, E/A ratio, E/e′
ratio, mitral effective regurgitant orifice area (EROA), and E-wave deceleration time. The correlation
between PASP and mitral EROA was the only one that remained significant by multivariate analysis.
Conclusions Noninvasive monitoring of PASP and FMR during an episode of HFpEF decompensation
reveals that the return to a compensated state is associated with a significant reduction in PASP and FMR.
Dynamic Pulmonary Hypertension in Decompensated Heart Failure With Preserved
Ejection Fraction: Is Functional Mitral Regurgitation the Driver?
30 Nov 2013 08:19 pm
Publication date: November 2013
Source:Journal of Cardiac Failure, Volume 19, Issue 11
Author(s): Patricia Campbell
Editorial Board
30 Nov 2013 08:19 pm
Publication date: November 2013
Source:Journal of Cardiac Failure, Volume 19, Issue 11
Effect of Amlodipine on the Survival of Patients With Severe Chronic Heart Failure Due to a
Nonischemic Cardiomyopathy Results of the PRAISE-2 Study (Prospective Randomized
Amlodipine Survival Evaluation 2)
01 Dec 2013 07:00 am
Publication date: August 2013
Source:JACC: Heart Failure, Volume 1, Issue 4
Author(s): Milton Packer , Peter Carson , Uri Elkayam , Marvin A. Konstam , Gordon Moe , Christopher
O'Connor , Jean-Lucien Rouleau , Douglas Schocken , Susan A. Anderson , David L. DeMets
Objectives This study was designed to test the hypothesis of whether amlodipine reduces the risk for death
in patients with heart failure due to a nonischemic cardiomyopathy. Background A pre-specified subgroup
analysis in an earlier, large-scale, placebo-controlled study suggested that amlodipine might reduce the risk
for death in patients with heart failure due to a nonischemic cardiomyopathy. Methods To evaluate this
hypothesis, 1654 patients with severe heart failure due to a nonischemic cardiomyopathy (ejection
fraction &lt;30%) were randomly assigned to amlodipine (target dose: 10 mg/d) or placebo added to
conventional therapy for heart failure for a median of 33 months. Results There were 278 deaths in the
amlodipine group and 262 deaths in the placebo group (hazard ratio: 1.09; 95% confidence interval [CI]:
0.92 to 1.29; p = 0.33). The differences between the 2 groups in the risks for cardiovascular death and
hospitalization were also not significant. When the results from patients with a nonischemic cardiomyopathy
in both the earlier trial and in the current study were combined, there was no evidence of a favorable or
unfavorable effect of amlodipine on mortality (hazard ratio: 0.97; 95% CI: 0.83 to 1.13; p = 0.66). Both trials,
however, observed higher frequencies of peripheral edema and pulmonary edema and lower frequencies of
uncontrolled hypertension and chest pain in patients treated with amlodipine. Conclusions These results of
the current trial, viewed together with the results from the earlier study, indicate that amlodipine does not
exert favorable effects on the clinical course of patients with heart failure, regardless of the presence or
absence of underlying coronary artery disease. These findings indicate the need for great caution when
striking benefits are observed in subgroups of patients or in trials not primarily designed to assess such
effects.
Effect of cardiac resynchronization therapy on left ventricular diastolic function: Implications
for clinical outcome
30 Nov 2013 08:19 pm
Publication date: Available online 8 November 2013
Source:Journal of Cardiac Failure
Author(s): A. Doltra , B. Bijnens , J.M. Tolosana , L. Gabrielli , M.A. Castel , A. Berruezo , J. Brugada , L.
Mont , M. Sitges
Background The definition of response to cardiac resynchronization therapy (CRT) remains controversial,
with variable rates of response depending on the criteria used. Our aim was to analyze the impact of CRT
on diastolic function in different degrees of response, particularly in patients with positive clinical but no
echocardiographic response. Methods and Results In 250 CRT patients clinical evaluation and
echocardiography were performed before and after CRT. Absolute response to CRT was defined as a
reduction in left ventricular (LV) end-systolic volume ≥ 15% at 1-year follow-up. Additionally, patients were
classified in four subgroups according to their amount of response: extensive reverse remodeling (RR),
slight RR, clinical response without RR and neither clinical response nor RR. An improvement in estimates
of LV filling pressure and a decrease in left atrium (LA) dimensions were observed only in responders to
CRT. Patients with clinical but no echo response had significant improvement in E-wave and deceleration
time, and non-significant improvement in other parameters. Conclusions LV diastolic function improves with
CRT. Clinical responders without echo response show improvement in parameters of diastolic function.
That suggests that clinical-only response to CRT is secondary to a real effect of the therapy, rather than a
placebo effect.
Effects of Losartan on Left Ventricular Hypertrophy and Fibrosis in Patients With
Nonobstructive Hypertrophic Cardiomyopathy
01 Dec 2013 07:00 am
Publication date: Available online 24 October 2013
Source:JACC: Heart Failure
Author(s): Yuichi J. Shimada , Jonathan J. Passeri , Aaron L. Baggish , Caitlin O’Callaghan , Patricia A.
Lowry , Gia Yannekis , Suhny Abbara , Brian B. Ghoshhajra , Richard D. Rothman , Carolyn Y. Ho , James
L. Januzzi , Christine E. Seidman , Michael A. Fifer
Objectives The aim of this study was to evaluate the effects of losartan on left ventricular (LV) hypertrophy
and fibrosis in patients with nonobstructive hypertrophic cardiomyopathy (HCM). Background Despite
evidence that myocardial hypertrophy and fibrosis are mediated by angiotensin II and are important
determinants of morbidity and mortality in patients with HCM, no prior studies have evaluated the effects of
angiotensin receptor blockers on LV hypertrophy and fibrosis with cardiac magnetic resonance imaging.
Methods In double-blind fashion, 20 patients (3 women, 17 men; age: 51 ± 13 years) with HCM were
randomly assigned to receive placebo (n = 9) or losartan 50 mg twice a day (n = 11) for 1 year. Cardiac
magnetic resonance imaging was performed at baseline and 1 year to measure LV mass and extent of
fibrosis as assessed by late gadolinium enhancement. Results There was a trend toward a significant
difference in the percent change in LV mass (median [interquartile range]: +5% [−4% to +21%] with placebo
vs. −5% [−11% to −0.9%] with losartan; p = 0.06). There was also a significant difference in the percent
change in extent of late gadolinium enhancement, with the placebo group experience a larger increase
(+31% ± 26% with placebo vs. −23% ± 45% with losartan; p = 0.03). Conclusions This pilot study suggests
attenuation of progression of myocardial hypertrophy and fibrosis with losartan in patients with
nonobstructive HCM. Confirmation of these results in a larger trial is required to confirm a place for
angiotensin receptor blockers in the management of patients with HCM. (Effect of Losartan in Patients With
Nonobstructive Hypertrophic Cardiomyopathy; NCT01150461 ).
Effects of Respiratory Exchange Ratio on the Prognostic Value of Peak Oxygen
Consumption and Ventilatory Efficiency in Patients With Systolic Heart Failure
01 Dec 2013 07:00 am
Publication date: October 2013
Source:JACC: Heart Failure, Volume 1, Issue 5
Author(s): Paul J. Chase , Aarti Kenjale , Lawrence P. Cahalin , Ross Arena , Paul G. Davis , Jonathan
Myers , Marco Guazzi , Daniel E. Forman , Euan Ashley , Mary Ann Peberdy , Erin West , Christopher T.
Kelly , Daniel R. Bensimhon
Objectives The purpose of this analysis was to evaluate the prognostic characteristics of peak oxygen
consumption (V o 2 ) and the minute ventilation/carbon dioxide (VE/V co 2 ) slope of different peak
respiratory exchange ratios (RERs) obtained from cardiopulmonary exercise testing in patients with heart
failure (HF). Background For patients with HF, peak V o 2 and the VE/V co 2 slope are used for assessing
prognosis. Peak V o 2 is assessed in association with peak RER ≥1.10, indicating maximal effort and
prognostic sensitivity. Conversely, the VE/V co 2 slope provides effort-independent prognostic
discrimination. Methods Patients with HF scheduled to undergo cardiopulmonary exercise testing were
enrolled. Patients were subclassified by peak RER (RER &lt;1.00, RER 1.00 to 1.04, RER 1.05 to 1.09,
RER ≥1.10) and followed for up to 3 years for major cardiac-related events (death, left ventricular assist
device implantation, or cardiac transplantation). Results Included were 1,728 patients with HF (75% males;
40% ischemic etiology; age: 55 ± 14 years; left ventricular ejection fraction: 28 ± 10%). Two hundred
seventy major events occurred, with no proportional differences across the RER subgroups. Multivariate
Cox regression analysis indicated that the VE/V co 2 slope and peak V o 2 remained prognostic within each
subgroup; the VE/V co 2 slope remained the strongest predictor. Receiver-operating characteristic analysis
demonstrated equitable prognostic cutoffs for the VE/V co 2 slope (range: 34.9 to 35.7; area under the
curve [AUC] range: 0.69 to 0.75) and peak V o 2 (range: 13.8 to 14.0 ml·kg–1·min–1; AUC range: 0.68 to
0.75). Conclusions Peak V o 2 provided a sensitive assessment of prognosis in patients with HF in all RER
subgroups. The VE/V co 2 slope provided greater prognostic discrimination in all RER subgroups. Clinical
consideration may be warranted for patients with low RER, low peak V o 2 , and an elevated VE/V co 2
slope.
Efficacy and Safety of Angiotensin-Converting Enzyme Inhibitors in Patients With Left
Ventricular Systolic Dysfunction and Hyponatremia
30 Nov 2013 08:19 pm
Publication date: November 2013
Source:Journal of Cardiac Failure, Volume 19, Issue 11
Author(s): Louise Balling , Lars Kober , Morten Schou , Christian Torp-Pedersen , Finn Gustafsson
Background The presence of hyponatremia has been perceived to increase the risk of adverse events on
initiation of treatment with angiotensin-converting enzyme inhibition in heart failure patients. The aim of this
study was to investigate if baseline hyponatremia (plasma Na+ &lt;135 mmol/L) predicts development of
hypotension and renal impairment in patients with myocardial infarction (MI) and left ventricular dysfunction
(LVD) treated with angiotensin-converting enzyme inhibitors. Methods and Results A retrospective analysis
was performed with data from the Trandolapril Cardiac Evaluation (TRACE) a double-blind randomized
study. Plasma sodium levels were available in 1,731 patients, who were considered as the study
population. Patients 3–7 days after MI with left LVD (LVEF ≤0.35), were randomized to trandolapril
(n = 876) or placebo (n = 873). Baseline hyponatremia did not predict development of hypotension or
worsening renal function after 1 month in patients treated with trandolapril compared with placebo
(122 ± 19.1 mm Hg vs 123.2 ± 20.4 mm Hg [ P = .84]; and creatinine clearance 57.4 ± 21.4 mL/min vs
55.2 ± 21.0 mL/min [ P = .8]). There was no interaction between hyponatremia and the effect of trandolapril
( P = .68). Conclusions Mild hyponatremia was not a contraindication for the initiation of treatment with
angiotensin-converting enzyme inhibitors in patients with post-MI heart failure.
Extracellular Matrix Turnover Biomarkers Predict Long-Term Left Ventricular Remodeling
After Myocardial Infarction: Insights From the REVE-2 Study [Original Articles]
19 Nov 2013 09:01 pm
Background—
Extracellular matrix turnover plays a key role in wound repair after myocardial infarction (MI). The aim of the
study was to evaluate whether biomarkers of myocardial fibrosis measurements 1 month after MI may
predict left ventricular (LV) remodeling.
Methods and Results—
This prospective multicenter study included 246 patients with a first anterior Q-wave MI. Echocardiographic
studies were performed at hospital discharge and 12 months after MI. Brain natriuretic peptide as well as
biomarkers of myocardial fibrosis (type 1 collagen telopeptide, aminoterminal propeptide of type I
procollagen, aminoterminal propeptide of type III procollagen) were measured 1 month after MI in 218
patients. In multivariate analysis, aminoterminal propeptide of type III procollagen/type 1 collagen
telopeptide ratio ≤1 (odds ratio [95% confidence interval], 1.86 [1.02–3.39]; P=0.043) 1 month after MI and
brain natriuretic peptide >100 pg/mL (2.35 [1.28–4.31]; P=0.006) were associated with a pejorative LV
remodeling, whereas LV ejection fraction at discharge (per 5% increment; 0.78 [0.65–0.94]; P=0.01) was
independently associated with lower rates of detrimental LV remodeling at 12 months. Patients with high
brain natriuretic peptide and aminoterminal propeptide of type III procollagen/type 1 collagen telopeptide
ratio ≤1, measured 1 month after MI, had the highest risk of developing a primary composite event
(cardiovascular death or hospitalization for worsening heart failure; 14 events per 216 patients; P=0.0001)
during a 3-year follow-up.
Conclusions—
Myocardial fibrosis turnover after MI is associated with LV remodeling. Low aminoterminal propeptide of
type III procollagen/type 1 collagen telopeptide ratio (≤1) at 1 month is predictive, in addition to brain
natriuretic peptide and LV ejection fraction, of detrimental LV remodeling as well as cardiovascular deaths
and hospitalizations for heart failure.
Follow-up of Earthquake-induced Acute Decompensated Heart Failure and Related Risk
Factors in the Great East Japan Earthquake
30 Nov 2013 08:19 pm
Publication date: October 2013
Source:Journal of Cardiac Failure, Volume 19, Issue 10, Supplement
Author(s): Hitoshi Suzuki , Hiroyuki Yamauchi , Takashi Owada , Akiomi Yoshihisa , Yasuchika Takeishi
Four-Variable Risk Model in Men and Women with Heart Failure [Original Articles]
26 Nov 2013 06:51 pm
Background—Risk stratification is an integral component of clinical decision-making in heart failure (HF).
Women with HF have unique characteristics compared to men, and it is unknown whether common
prognostic factors are equally useful in both populations. We aimed to investigate whether sex-specific risk
models are more accurate for risk prediction in patients with advanced HF.
Methods and Results—Advanced HF patients referred to UCLA (n=2,255) were stratified by sex into
derivation (referred in 2000-2007) and validation (referred in 2008-2011) cohorts. Cox regression analysis
was used to ascertain key variables predictive of the primary end point of death/urgent
transplantation/ventricular assist device in the derivation cohorts and confirmed in the validation cohorts in
men, women, and the total population. Women were younger, with higher ejection fraction, and better
event-free survival. Despite differences in baseline characteristics, the four strongest predictors of outcome
in both women and men, as well as in the total cohort, were B-type natriuretic peptide (BNP), peak oxygen
consumption by cardiopulmonary exercise testing (pkVO2), New York Heart Association (NYHA)
classification, and use of angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker
(ARB). Additionally, the UCLA model performed better than the Seattle Heart Failure Model (SHFM) and the
Heart Failure Survival Score (HFSS) in our cohort (c-indexes of 0.791[UCLA] vs. 0.758 [SHFM], 0.607 [noninvasive HFSS], and 0.625 [invasive HFSS]).
Conclusions—A simple risk model assessing four clinical variables - BNP, pkVO2, NYHA, and ACEI/ARB
use - is well-suited to provide prognostic information in both men and women with advanced HF.
Gremlin-1 Identifies Fibrosis and Predicts Adverse Outcome in Patients With Heart Failure
Undergoing Endomyocardial Biopsy
30 Nov 2013 08:19 pm
Publication date: October 2013
Source:Journal of Cardiac Failure, Volume 19, Issue 10
Author(s): Karin A.L. Mueller , Elli Tavlaki , Martina Schneider , Rezo Jorbenadze , Tobias Geisler ,
Reinhard Kandolf , Meinrad Gawaz , Christine S. Zuern , Iris I. Mueller
Background Gremlin-1 (Grem1), an antagonist of bone morphogenetic proteins, is involved in fibrotic tissue
formation in kidney and lung. The impact of myocardial Grem1 expression is unknown. We investigated the
prognostic value of Grem1 expression in 214 consecutive patients with nonischemic heart failure (HF)
undergoing endomyocardial biopsy. Methods In all patients, the following risk factors were assessed:
Grem1 expression (semiquantitative score scheme ranging from 1 to 4), presence of inflammatory markers,
detection of viral genome, left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter
(LVEDD), New York Heart Association functional class (NYHA), troponin I, and B-type natriuretic peptide.
Degree of myocardial fibrosis was defined as an index. Study end point was a combination of all-cause
death and HF-related rehospitalization within 3 years of follow-up. Results Grem1 expression significantly
correlated with the degree of myocardial fibrosis (correlation coefficient r = 0.619; P &lt; .0001). Patients
with the highest Grem1 expression (score 4) showed the most severely impaired LVEF and highest LVEDD
( P &lt; .0001 and P = .030, respectively, for comparison of semiquantitative scores). During follow-up, 33
patients (15.4%) reached the study end point. Grem1 expression and NYHA ≥II were independent
predictors of the end point (Grem1: hazard ratio [HR] 7.5, 95% confidence interval [CI] 1.8-32.2; P = .006;
NYHA ≥II: HR 2.0, 95% CI 1.0-4.1; P = .048). Conclusions Grem1 correlates with the degree of myocardial
fibrosis and left ventricular dysfunction and is an independent predictor of adverse outcome in patients with
nonischemic HF.
Growth Hormone Replacement Delays the Progression of Chronic Heart Failure Combined
With Growth Hormone Deficiency An Extension of a Randomized Controlled Single-Blind
Study
01 Dec 2013 07:00 am
Publication date: August 2013
Source:JACC: Heart Failure, Volume 1, Issue 4
Author(s): Antonio Cittadini , Alberto M. Marra , Michele Arcopinto , Emanuele Bobbio , Andrea Salzano ,
Domenico Sirico , Raffaele Napoli , Annamaria Colao , Salvatore Longobardi , Ragavendra R. Baliga ,
Eduardo Bossone , Luigi Saccà
Objectives This study sought to evaluate the efficacy and safety of long-term growth hormone (GH)
replacement therapy in GH-deficient patients with chronic heart failure (CHF). Background Recent evidence
indicates that growth hormone deficiency (GHD) affects as many as 40% of patients with CHF, and shortterm GH replacement causes functional benefit. Whether long-term GH replacement also affects CHF
progression is unknown. Methods The study is an extension of a previous randomized, controlled singleblind trial that screened 158 consecutive CHF patients (New York Heart Association classes II to IV) and
identified 63 who had GHD by the growth hormone releasing hormone plus arginine test. Fifty-six patients
were randomized to receive either GH therapy or standard CHF therapy. Patients were evaluated at
baseline and after a 4-year follow-up. The primary endpoint was peak oxygen consumption (VO 2 ).
Secondary endpoints included left ventricular (LV) ejection fraction and volumes, serum amino terminal
fragment of the pro-hormone brain-type natriuretic peptide, quality of life, and safety. Results Seventeen
patients in the GH group and 14 in the control group completed the study. In the GH group, peak VO 2
improved over the 4-year follow-up. The treatment effect was 7.1 ± 0.7 ml/kg/min versus −1.8 ± 0.5
ml/kg/min in the GH and control groups, respectively. At 4 years, LV ejection fraction increased by 10 ± 3%
in the GH group, whereas it decreased by 2 ± 5% in control patients. The treatment effect on LV endsystolic volume index was −22 ± 6 ml and 8 ± 3 ml/m2 in the GH and control groups, respectively (all p &lt;
0.001). No major adverse events were reported in the patients who received GH. Conclusions Although this
is a preliminary study, the finding suggests a new therapeutic approach to a large proportion of GHD
patients with CHF.
Guideline Concordance of Testing for Hyperkalemia and Kidney Dysfunction During
Initiation of Mineralocorticoid Receptor Antagonist Therapy in Patients with Heart Failure
[Original Articles]
26 Nov 2013 07:49 pm
Background—Mineralocorticoid receptor antagonists (MRA) reduce morbidity and mortality in heart failure
with reduced ejection fraction (HFREF), but can cause hyperkalemia and acute kidney injury. Guidelines
recommend measurement of serum potassium (K) and creatinine (Cr) before and serially after MRA
initiation, but the extent to which this occurs is unknown.
Methods and Results—Using electronic data from 3 health systems 2005-2008, we performed a
retrospective review of laboratory monitoring among 490 patients hospitalized for HFREF who were
subsequently initiated on MRA therapy. Median age at time of MRA initiation was 73 years and 37.1% were
female. Spironolactone accounted for 99.4% of MRA use. Initial ambulatory MRA dispensing occurred at
hospital discharge in 70.0% of cases. In the 30 days before MRA initiation, 94.3% of patients had a K or Cr
measurement. Pre-initiation K was >5.0 mmol/L in 1.4% and Cr >2.5 mg/dL in 1.7%. In the 7 days after
MRA initiation among patients who remained alive and out of the hospital, 46.5% had no evidence of K
measurement; by 30 days, 13.6% remained untested. Patient factors explained a small portion of postinitiation K testing (c-statistic 0.67).
Conclusions—While laboratory monitoring prior to MRA initiation for HFREF is common, laboratory
monitoring following MRA initiation frequently does not meet guideline recommendations, even in patients
at higher risk for complications. Quality improvement efforts that encourage the use of MRA should also
include mechanisms to address recommended monitoring.
Haemoconcentration, renal function, and post-discharge outcomes among patients
hospitalized for heart failure with reduced ejection fraction: insights from the EVEREST trial
20 Nov 2013 03:29 pm
Aims
Haemoconcentration has been studied as a marker of decongestion in patients with hospitalization for heart
failure (HHF). We describe the relationship between haemoconcentration, worsening renal function, postdischarge outcomes, and clinical and laboratory markers of congestion in a large multinational cohort of
patients with HHF.
Methods and results
In 1684 patients with HHF with ejection fraction (EF) ≤40% assigned to the placebo arm of the Efficacy of
Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial, absolute inhospital haematocrit change was calculated as the change between baseline and discharge or day 7
(whichever occurred first). Patient characteristics, changes in renal function, and outcomes over a median
follow-up of 9.9 months were compared by in-hospital haematocrit change. Overall, 26% of patients had
evidence of haemoconcentration (i.e. ≥3% absolute increase in haematocrit). Patients with greater
increases in haematocrit tended to have better baseline renal function. Haemoconcentration correlated with
greater risk of in-hospital worsening renal function, but renal parameters generally returned to baseline
within 4 weeks post-discharge. Patients with haemoconcentration were less likely to have clinical
congestion at discharge, and experienced greater in-hospital decreases in body weight and natriuretic
peptide levels. After adjustment for baseline clinical risk factors, every 5% increase of in-hospital
haematocrit change was associated with a decreased risk of all-cause death [hazard ratio (HR) 0.81, 95%
confidence interval (CI) 0.70–0.95]. Haematocrit change was also associated with decreased
cardiovascular mortality or heart failure (HF) hospitalization at ≤100 days post-randomization (HR 0.73, 95%
CI 0.71–0.76).
Conclusion
In this large cohort of patients with HHF with reduced EF, haemoconcentration was associated with greater
improvements in congestion and decreased mortality and HF re-hospitalization despite an increased risk of
in-hospital worsening renal function.
Harmonization between Pharmacotherapy and Non-pharmacotherapy
30 Nov 2013 08:19 pm
Publication date: October 2013
Source:Journal of Cardiac Failure, Volume 19, Issue 10, Supplement
Author(s): Shin-Ichi Momomura
Heart Failure Complicating Non–ST-Segment Elevation Acute Coronary Syndrome Timing,
Predictors, and Clinical Outcomes
01 Dec 2013 07:00 am
Publication date: June 2013
Source:JACC: Heart Failure, Volume 1, Issue 3
Author(s): Maria Cecilia Bahit , Renato D. Lopes , Robert M. Clare , L. Kristin Newby , Karen S. Pieper ,
Frans Van de Werf , Paul W. Armstrong , Kenneth W. Mahaffey , Robert A. Harrington , Rafael Diaz , E.
Magnus Ohman , Harvey D. White , Stefan James , Christopher B. Granger
Objectives This study sought to describe the occurrence and timing of heart failure (HF), associated clinical
factors, and 30-day outcomes in patients with non–ST-segment elevation acute coronary syndromes
(NSTE-ACS). Background Little is known about HF-complicating NSTE-ACS. Methods Using pooled
patient-level data from 7 clinical trials from 1994 to 2008, we describe the occurrence and timing of HF,
associated clinical factors, and 30-day outcomes in NSTE-ACS patients. HF at presentation was defined as
Killip classes II to III; patients with Killip class IV or cardiogenic shock were excluded. New in-hospital cases
of HF included new pulmonary edema. After adjusting for baseline variables, we created logistic regression
models to identify clinical factors associated with HF at presentation and to determine the association
between HF and 30-day mortality. Results Of 46,519 NSTE-ACS patients, 4,910 (10.6%) had HF at
presentation. Of the 41,609 with no HF at presentation, 1,194 (2.9%) developed HF during hospitalization.
A total of 40,415 (86.9%) had no HF at any time. Patients presenting with or developing HF during
hospitalization were older, more often female, and had a higher risk of death at 30 days than patients
without HF (adjusted odds ratio [OR]: 1.74; 95% confidence interval: 1.35 to 2.26). Older age, higher
presenting heart rate, diabetes, prior myocardial infarction (MI), and enrolling MI were significantly
associated with HF during hospitalization. Conclusions In this large cohort of NSTE-ACS patients,
presenting with or developing HF during hospitalization was associated with an increased risk of 30-day
mortality. Research targeting new strategies to prevent and manage HF in this high-risk population is
needed.
Heart Failure Therapy Induced Early ST2 Changes May Offer Long-term Therapy Guidance
30 Nov 2013 08:19 pm
Publication date: Available online 14 November 2013
Source:Journal of Cardiac Failure
Author(s): Tobias Breidthardt , Cathrin Balmelli , Raphael Twerenbold , Tamina Mosimann , Jaqueline
Espinola , Philip Haaf , Gregor Thalmann , Berit Moehring , Mira Mueller , Bernadette Meller , Tobias
Reichlin , Karsten Murray , Ronny Ziller , Pascal Benkert , Stefan Osswald , Christian Mueller
Background Biomarkers may help to monitor and tailor treatment in patients with acute heart failure (AHF).
Methods Levels of ST2, a novel biomarker integrating hypervolemic cardiac strain and proinflammatory
signals, were measured at presentation to the emergency department (ED) and after 48 hours in 207
patients with AHF. Patients were stratified according to their early ST2 response (responders: ST2
decrease ≥25%; non-responders: ST2 decrease &lt; 25%) and beta-blocker, RAAS blockade or diuretic
treatment status at hospital discharge. We assessed the utility of ST2 levels and its changes to predict longterm mortality and the interaction between ST2 levels, treatment at discharge and one-year mortality.
Results ST2 levels were higher in decedents than in survivors (median 108 vs. 69 ng mL -1, p&lt;0.01) and
decreased significantly during the first 48 hours (median decrease 33%). ST2 decrease was less in
decedents compared to survivors (median change: -25% versus -42%, p&lt;0.01). In Cox regression early
ST2 changes independently predicted one-year mortality (HR 1.07 for every increase of 10%; p=0.02).
RAAS blockers at discharge were associated with survival independent of ST2 response, whereas the
association of beta-blockers with survival differed markedly according to ST2 response with beneficial
effects restricted to ST2 non-responders (p for interaction=0.04). A similar albeit non-significant trend was
observed for diuretics (p for interaction =0.11). Conclusion ED and serial ST2 measurements are
independent predictors of one- year mortality in AHF.
Impact of Ejection Fraction on the Clinical Response to Cardiac Resynchronization Therapy
in Mild Heart Failure [Original Articles]
19 Nov 2013 09:01 pm
Background—
Current guidelines recommend cardiac resynchronization therapy (CRT) in mild heart failure (HF) patients
with QRS prolongation and ejection fraction (EF) ≤30%. To assess the effect of CRT in less severe systolic
dysfunction, outcomes in the REsynchronization reVErses Remodeling in Systolic left vEntricular
dysfunction (REVERSE) study were evaluated in which patients with left ventricular (LV) ejection fraction
(LVEF) >30% were included.
Methods and Results—
The results of patients with baseline EF >30% (n=177) and those with EF ≤30% (n=431), as determined by
a blinded core laboratory, were compared. In the LVEF >30% subgroup, there was a trend for improvement
in the clinical composite response with CRT ON versus CRT OFF (P=0.06) and significant reductions in LV
end systolic volume index (–6.7±21.1 versus 2.1±17.6 mL/m2; P=0.01) and LV mass (–20.6±50.5 versus
5.0±42.4 g; P=0.04) after 12 months. The time to death or first HF hospitalization was significantly
prolonged with CRT (hazard ratio, 0.26; P=0.012). In the LVEF <30% subgroup, significant improvements in
clinical composite response (P=0.02), reverse remodeling parameters, and time to death or first HF
hospitalization (hazard ratio, 0.58; P=0.047) were observed. After adjusting for important covariates, the
CRT ON assignment remained independently associated with improved time to death or first HF
hospitalization (hazard ratio, 0.54; P=0.035), whereas there was no significant interaction with LVEF.
Conclusions—
Among subjects with mild HF, QRS prolongation, and LVEF >30%, CRT produced reverse remodeling and
similar clinical benefit compared with subjects with more severe LV systolic dysfunction.
Clinical Trial Registration—
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00271154.
Impact of QRS Morphology and Duration on Outcomes After Cardiac Resynchronization
Therapy: Results From the Resynchronization-Defibrillation for Ambulatory Heart Failure
Trial (RAFT) [Original Articles]
19 Nov 2013 09:01 pm
Background—
The impact of QRS morphology and duration on the effectiveness of cardiac resynchronization therapy
(CRT) has been usually assessed separately. The interaction between these 2 simple ECG parameters and
their effect on CRT has not been systematically assessed in a large-scale clinical trial.
Methods and Results—
The Resynchronization–Defibrillation for Ambulatory Heart Failure Trial showed that implantable
cardioverter defibrillator-CRT was associated with a significant reduction in the primary end point of allcause mortality or heart failure hospitalization. For this substudy, we excluded patients in atrial fibrillation
and those with a previous pacemaker. All baseline ECGs were reviewed by a panel of 3 experienced
electrocardiographers. A total of 1483 patients were included in this study. Of these, 1175 had left bundlebranch block (LBBB) and 308 had non-LBBB. In patients with LBBB receiving implantable cardioverter
defibrillator-CRT, there was a reduction in the primary outcome and in each individual component of the
primary outcome. Furthermore, there was continuous relationship between QRS duration and extent of
benefit. In patients with non-LBBB and QRS ≥160 ms, the hazard ratio for the primary outcome was 0.52
(0.29–0.96; P=0.033); in patients with QRS <160 ms, the hazard ratio was 1.38 (0.88–2.14; P=0.155).
Conclusions—
In patients with LBBB, there was a continuous relationship between broader QRS and greater benefit from
implantable cardioverter defibrillator-CRT. However, our data do not support the use of implantable
cardioverter defibrillator-CRT in patients with non-LBBB, especially when the QRS duration is <160 ms.
There may be some delayed benefit when the QRS is ≥160 ms, but this needs further investigation.
Clinical Trial Registration—
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00251251.
Impairment of Subendocardial Perfusion Reserve and Oxidative Metabolism in NonIschemic Dilated Cardiomyopathy
30 Nov 2013 08:19 pm
Publication date: Available online 29 October 2013
Source:Journal of Cardiac Failure
Author(s): Susan P. Bell , Douglas W. Adkisson , Henry Ooi , Douglas B. Sawyer , Mark A. Lawson , Marvin
W. Kronenberg
Background Cardiac magnetic resonance (CMR) and [11C] acetate positron emission tomography (PET)
were used to assess the hypothesis that patients with nonischemic dilated cardiomyopathy (NIDCM) have
decreased subendocardial perfusion reserve and impaired oxidative metabolism, consistent with the
concept of “energy starvation” in heart failure (HF). Methods and results CMR myocardial perfusion was
evaluated in 13 NIDCM patients and 15 control subjects with coronary risk factors and normal myocardial
perfusion. The NIDCM patients underwent [11C] acetate PET. The myocardial perfusion index (MPI) was
calculated as the normalized rate of myocardial signal augmentation following gadolinium contrast injection.
Hyperemic transmural, subendocardial and subepicardial MPI were reduced in NIDCM compared to control
subjects [0.13 vs. 0.18 (P&lt;0.001), 0.13 vs. 0.17 (P&lt; 0.001), and 0.13 vs. 0.17 (P= 0.008), respectively].
The subendocardial perfusion reserve was 1.59 ± 0.21 vs. 1.86 ± 0.32 for the subepicardium (P= 0.002)
demonstrating reduced perfusion reserve. The myocardial oxidative metabolic rate (k mono ) per unit
demand (rate-pressure product) was reduced proportional to perfusion reserve (P=0.02) Conclusions
Impaired subendocardial perfusion reserve in NIDCM confirmed results previously attained only in animal
models. Impaired perfusion and impaired oxidative metabolism are consistent with subendocardial energy
starvation in HF.
Implant Strategies Change Over Time and Impact Outcomes Insights From the
INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support)
01 Dec 2013 07:00 am
Publication date: October 2013
Source:JACC: Heart Failure, Volume 1, Issue 5
Author(s): Jeffrey J. Teuteberg , Garrick C. Stewart , Mariell Jessup , Robert L. Kormos , Benjamin Sun ,
O.H. Frazier , David C. Naftel , Lynne W. Stevenson
Objectives This study investigated how the initial intended strategy at left ventricular assist device (LVAD)
implantation influenced patient outcomes. Background Left ventricular assist device implantation strategy
impacts candidate selection, reimbursement, and clinical trial design; however, concepts of device strategy
are continuing to evolve. Methods For patients entered in the INTERMACS (Interagency Registry for
Mechanically Assisted Circulatory Support) receiving a primary continuous flow LVAD between March 2006
and March 2011, initial strategies were bridge to transplant (BTT), bridge to candidacy (BTC) for transplant,
and destination therapy (DT). Primary analyses compared BTT, BTC, and DT outcomes at 6, 12, and 24
months. Results Among 2,816 primary LVAD recipients, implant strategy was 1,060 (38%) BTT, 1,162
(42%) BTC (likely to be listed 796, moderately likely 282, unlikely 84), and 553 (20%) DT. Compared with
BTC/DT, those listed at implant (BTT) had similar degrees of ventricular dysfunction and hemodynamic
derangement but generally less comorbidity. Survival (alive with LVAD or transplanted) was superior at 24
months for BTT versus BTC versus DT (77.7% vs.70.1% vs. 60.7%, respectively, p &lt; 0.0001). Strategic
intent changed over time, at 2 years 43.5% of BTT patients were no longer listed for transplant, but 29.3%
of BTC patients were listed for transplant. Conclusions The currently accepted indications only account for
58% of LVAD implants. Across indications, patients differ by the number and types of comorbidities rather
than the need for hemodynamic support. Regardless of initial implant strategy, patients often have long
durations of support, and strategies often change over time, challenging the regulatory categorization of
LVAD recipients as either BTT or DT.
Incidence and Predictors of End-Stage Renal Disease in Outpatients With Systolic Heart
Failure [Original Articles]
19 Nov 2013 09:01 pm
Background—
Renal dysfunction is an important prognostic factor in heart failure (HF), but whether this dysfunction
progresses to end-stage renal disease (ESRD) is unknown. Therefore, we examined incidence and
predictors of ESRD in outpatients with HF.
Methods and Results—
Patients with systolic HF were identified in The Danish Heart Failure database and new-onset ESRD from
the Danish Registry on Dialysis. Renal function was estimated by The Chronic Kidney Disease
Epidemiology Collaboration equation and patients grouped by estimated glomerular filtration rate (eGFR)—
group I: ≥60 mL/min per 1.73 m2, group II: 30 to 59 mL/min per 1.73 m 2, group III: 15 to 29 mL/min per 1.73
m2, group IV: <15 mL/min per 1.73 m 2. Cox hazard models for time to ESRD, to death, and the composite
end point of ESRD or death were constructed and predictors of ESRD identified. A total of 8204 patients
were included in the analyses. Median age was 70 years (Q, 61–77), 28% were women, median left
ventricular ejection fraction was 30% (Q, 24–40), and median eGFR was 68 (Q, 51–85) mL/min per 1.73
m2. Forty-one patients developed ESRD (1.3/1000 patient-years). Baseline eGFR group II (P<0.001), eGFR
group III (P<0.001), eGFR group IV (P<0.001), uncontrolled hypertension (P=0.049), need of diuretics, and
age <60 years (P=0.016) were associated with time to ESRD.
Conclusions—
ESRD is rare in outpatients with systolic HF and is mainly observed in patients with an eGFR <30 mL/min
per 1.73 m2. A low eGFR, age <60 years, need of diuretics, and uncontrolled hypertension identify patients
with an increased risk for ESRD.
Information for Authors
30 Nov 2013 08:19 pm
Publication date: November 2013
Source:Journal of Cardiac Failure, Volume 19, Issue 11
Inside This Issue
01 Dec 2013 07:00 am
Publication date: October 2013
Source:JACC: Heart Failure, Volume 1, Issue 5
Insulin Resistance and Incident Heart Failure The Atherosclerosis Risk in Communities
Study
01 Dec 2013 07:00 am
Publication date: Available online 24 October 2013
Source:JACC: Heart Failure
Author(s): Orly Vardeny , Deepak K. Gupta , Brian Claggett , Stuart Burke , Amil Shah , Laura Loehr , Laura
Rasmussen-Torvik , Elizabeth Selvin , Patricia P. Chang , David Aguilar , Scott D. Solomon
Objectives This study was designed to assess the relationship between insulin resistance and incident heart
failure (HF) in a community-based cohort. Background Diabetes mellitus increases the risk for HF, but the
association between insulin resistance and HF in individuals without diabetes is unclear. Methods We
prospectively analyzed 12,606 participants without diabetes mellitus, prevalent HF, or history of myocardial
infarction at baseline (1987 to 1989) from the ARIC (Atherosclerosis Risk in Communities) study. We
assessed the relationship between insulin resistance and incident HF using the homeostatic model
assessment of insulin resistance (HOMA-IR) equation, adjusting for age, sex, race, body mass index,
smoking, hypertension, center, and interim myocardial infarction. We tested for interactions by age, sex,
obesity, and race. Results Participants with insulin resistance, defined as HOMA-IR ≥2.5 (n = 4,810, 39%),
were older, more likely female, African American, hypertensive, and had a higher body mass index as
compared with those without insulin resistance. There were 1,455 incident HF cases during a median of
20.6 years of follow-up. Insulin resistance defined by this threshold was not significantly associated with an
increased risk for incident HF after adjustment (hazard ratio: 1.08, 95% confidence interval: 0.95 to 1.23).
However, when analyzed continuously, this relationship was nonlinear, which indicated that risk increased,
and was significantly associated with incident HF between HOMA-IR of 1.0 to 2.0, adjusting for baseline
covariates; however, values over 2.5 were not associated with additional increased risk in adjusted models.
Conclusions In a community cohort, insulin resistance, defined by lower levels of HOMA-IR than previously
considered, was associated with an increased risk for HF.
Is Dual Renin-Angiotensin-System Blockade Associated With Increased Risk of Stroke?
01 Dec 2013 07:00 am
Publication date: October 2013
Source:JACC: Heart Failure, Volume 1, Issue 5
Author(s): Harikrishna Makani , Sripal Bangalore , Peter Sever , Franz H. Messerli
JACC: Heart Failure Fellows Program: Training the Next Generation
01 Dec 2013 07:00 am
Publication date: October 2013
Source:JACC: Heart Failure, Volume 1, Issue 5
Author(s): Christopher O'Connor
Kaplan-Meier survival curves: interpretation and communication of risk
29 Nov 2013 11:27 am
Researchers investigated whether specialist nurse intervention reduced morbidity and mortality in patients
with chronic heart failure. A randomised controlled trial study design was used. The...
Left Bundle Branch Block Predicts Better Survival in Women Than Men Receiving
Cardiac Resynchronization Therapy Long-Term Follow-Up of ∼145,000 Patients
01 Dec 2013 07:00 am
Publication date: June 2013
Source:JACC: Heart Failure, Volume 1, Issue 3
Author(s): Zak Loring , Daniel A. Caños , Kimberly Selzman , Naomi D. Herz , Henry Silverman , Thomas E.
MaCurdy , Christopher M. Worrall , Jeffrey Kelman , Mary E. Ritchey , Ileana L. Piña , David G. Strauss
Objectives The goal of this study was to test the hypothesis that in recipients of cardiac resynchronization
therapy defibrillators (CRT-D), conventional left bundle branch block (LBBB) diagnosis predicts better
survival in women than in men. Background New York Heart Association class I and II patients without
LBBB do not benefit from CRT-D, and women have better survival after CRT-D than men. Separate
analysis suggests that QRS duration thresholds for LBBB diagnosis differ according to sex, and
conventional LBBB electrocardiographic criteria are falsely positive in men more frequently than in women.
Methods We analyzed Medicare records from 144,642 CRT-D recipients between 2002 and 2008 that were
followed up for up to 90 months. Medicare billing data were used to determine age, sex, race, and
comorbidities. Hazard ratios (HRs) were calculated to assess if conventional LBBB diagnosis had different
prognostic significance according to sex. Results In univariate analysis, LBBB was associated with a 31%
reduction in death in women (HR: 0.69 [95% confidence interval (CI): 0.67 to 0.71]) but only a 16%
reduction in death in men (HR: 0.84 [95% CI: 0.82 to 0.85]). In multivariable analyses controlling for
comorbidities, LBBB was associated with a 26% reduction in death in women (HR: 0.74 [95% CI: 0.71 to
0.77]) and a 15% reduction in death in men (HR: 0.85 [95% CI: 0.83 to 0.87]). A significant interaction (p &lt;
0.0001) between sex and LBBB was seen. Conclusions LBBB diagnosis is associated with greater survival
in women than in men receiving CRT-D, and this discrepancy is not explained by differences in measured
comorbidities. Possible explanations for this difference include that LBBB may have different prognostic
significance according to sex or that LBBB diagnosis is more often false-positive in men compared with
women.
Left Ventricular Assist Device Implantation Induced Tricuspid Valve Prolapse [Images and
Case Reports in Heart Failure]
19 Nov 2013 09:01 pm
Levosimendan in End-Stage Heart Failure
01 Dec 2013 07:00 am
Publication date: August 2013
Source:JACC: Heart Failure, Volume 1, Issue 4
Author(s): Poh Shuan Daniel Yeo
Long-Term Trajectory of Two Unique Cardiac Biomarkers and Subsequent Left Ventricular
Structural Pathology and Risk of Incident Heart Failure in Community-Dwelling Older Adults
at Low Baseline Risk
01 Dec 2013 07:00 am
Publication date: August 2013
Source:JACC: Heart Failure, Volume 1, Issue 4
Author(s): Danielle Glick , Christopher R. deFilippi , Robert Christenson , John S. Gottdiener , Stephen L.
Seliger
Objectives This study sought to determine whether the combined trajectories of cardiac biomarkers identify
those older adults with initial low levels who have an increased risk for structural heart disease, incident
heart failure (HF), and cardiovascular (CV) death. Background Initial low levels of high-sensitivity cardiac
troponin T (hs-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) identify older adults at lower
risk for CV events. Methods We performed an observational study among older adults without prevalent HF
in the CHS (Cardiovascular Health Study). NT-proBNP and hs-cTnT were measured at baseline and after 2
to 3 years. In those with low baseline levels, a significant increase was defined as cardiac troponin T (cTnT)
&gt;50% and NT-proBNP &gt;25% increase to &gt;190 pg/ml. Left ventricular ejection fraction and left
ventricular mass were measured by echocardiography at baseline and 5 years. Cox regression was used to
estimate the association of change in biomarkers with HF and CV mortality. Results Among 2,008
participants with initially low biomarker concentrations, significant increases occurred in 14.8% for cTnT
only, 13.2% for NT-proBNP only, and 6.1% for both. After 10 years, cumulative HF incidence was 50.4%
versus 12.2% among those with both biomarkers versus neither biomarker increased. The adjusted relative
risk comparing those with increases in both biomarkers versus neither biomarker was 3.56 for incident HF
(95% confidence interval: 2.56 to 4.97) and 2.98 for CV mortality (95% confidence interval: 2.98 to 4.26).
Among 1,340 participants with serial echocardiography, the frequency of new abnormal left ventricular
ejection fraction was 11.8% versus 4% for those with increases in both biomarkers versus neither biomarker
(p = 0.007). Conclusions Among older adults without HF with initially low cTnT and NT-proBNP, the longterm trajectory of both biomarkers predicts systolic dysfunction, incident HF, and CV death.
Long-term Effects of the 2011 Japan Earthquake and Tsunami on the Incidence of Heart
Failure: A Community-based Study
30 Nov 2013 08:19 pm
Publication date: October 2013
Source:Journal of Cardiac Failure, Volume 19, Issue 10, Supplement
Author(s): Motoyuki Nakamura , Fumitaka Tanaka , Hiroshi Endof , Mikio Kawakami , Tatsuya Matsumoto ,
Osamu Nishiyama , Toshiyuki Onoda
Longitudinal Study of Post-Traumatic Stress Disorder after the Great East Japan
Earthquake Disaster in Cardiovascular Disease Patients - The CHART-2 Study30 Nov 2013 08:19 pm
Publication date: October 2013
Source:Journal of Cardiac Failure, Volume 19, Issue 10, Supplement
Author(s): Kotaro Nochioka , Yasuhiko Sakata , Satoshi Miyata , Jun Takahashi , Masanobu Miura ,
Tsuyoshi Takada , Soichiro Tadaki , Ryouichi Ushigome , Tsuyoshi Yamauchi , Hiroaki Shimokawa
Low-Sodium DASH Diet Improves Diastolic Function and Ventricular-Arterial Coupling in
Hypertensive Heart Failure With Preserved Ejection Fraction [Original Articles]
19 Nov 2013 09:01 pm
Background—
Heart failure with preserved ejection fraction (HFPEF) involves failure of cardiovascular reserve in multiple
domains. In HFPEF animal models, dietary sodium restriction improves ventricular and vascular stiffness
and function. We hypothesized that the sodium-restricted dietary approaches to stop hypertension diet
(DASH/SRD) would improve left ventricular diastolic function, arterial elastance, and ventricular–arterial
coupling in hypertensive HFPEF.
Methods and Results—
Thirteen patients with treated hypertension and compensated HFPEF consumed the DASH/SRD (target
sodium, 50 mmol/2100 kcal) for 21 days. We measured baseline and post-DASH/SRD brachial and central
blood pressure (via radial arterial tonometry) and cardiovascular function with echocardiographic measures
(all previously invasively validated). Diastolic function was quantified via the parametrized diastolic filling
formalism that yields relaxation/viscoelastic (c) and passive/stiffness (k) constants through the analysis of
Doppler mitral inflow velocity (E-wave) contours. Effective arterial elastance (Ea) end-systolic elastance (Ees)
and ventricular–arterial coupling (defined as the ratio Ees:Ea) were determined using previously published
techniques. Wilcoxon matched-pairs signed-rank tests were used for pre–post comparisons. The
DASH/SRD reduced clinic and 24-hour brachial systolic pressure (155±35 to 138±30 and 130±16 to 123±18
mm Hg; both P=0.02), and central end-systolic pressure trended lower (116±18 to 111±16 mm Hg; P=0.12).
In conjunction, diastolic function improved (c=24.3±5.3 to 22.7±8.1 g/s; P=0.03; k=252±115 to 170±37
g/s2; P=0.03), Eadecreased (2.0±0.4 to 1.7±0.4 mm Hg/mL; P=0.007), and ventricular–arterial coupling
improved (Ees:Ea=1.5±0.3 to 1.7±0.4; P=0.04).
Conclusions—
In patients with hypertensive HFPEF, the sodium-restricted DASH diet was associated with favorable
changes in ventricular diastolic function, arterial elastance, and ventricular–arterial coupling.
Clinical Trial Registration—
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00939640.
Masthead
30 Nov 2013 08:19 pm
Publication date: November 2013
Source:Journal of Cardiac Failure, Volume 19, Issue 11
Mechanisms of Diastolic Dysfunction in Heart Failure With a Preserved Ejection Fraction: If
It's Not One Thing It's Another [Editorials]
19 Nov 2013 09:01 pm
Mediterranean and DASH Diet Scores and Mortality in Women With Heart Failure: The
Women's Health Initiative [Original Articles]
19 Nov 2013 09:01 pm
Background—
Current dietary recommendations for patients with heart failure (HF) are largely based on data from non-HF
populations; evidence on associations of dietary patterns with outcomes in HF is limited. We therefore
evaluated associations of Mediterranean and Dietary Approaches to Stop Hypertension (DASH) diet scores
with mortality among postmenopausal women with HF.
Methods and Results—
Women’s Health Initiative participants were followed up from the date of HF hospitalization through the date
of death or last participant contact before August 2009. Mediterranean and DASH diet scores were
calculated from food-frequency questionnaires. Cox proportional hazards models adjusted for
demographics, health behaviors, and health status were used to calculate hazard ratios and 95%
confidence intervals (CI). For a median of 4.6 years of follow-up, 1385 of 3215 (43.1%) participants who
experienced a HF hospitalization died. Multivariable-adjusted hazard ratios were 1 (reference), 1.05 (95%
CI, 0.89–1.24), 0.97 (95% CI, 0.81–1.17), and 0.85 (95% CI, 0.70–1.02) across quartiles of the
Mediterranean diet score (P trend=0.08) and 1 (reference), 1.04 (95% CI, 0.89–1.21), 0.83 (95% CI, 0.70–
0.98), and 0.84 (95% CI, 0.70–1.00) across quartiles of the DASH diet score (P trend=0.01). Diet score
components, vegetables, nuts, and whole grain intake, were inversely associated with mortality.
Conclusions—
Higher DASH diet scores were associated with modestly lower mortality in women with HF, and there was a
nonsignificant trend toward an inverse association with Mediterranean diet scores. These data provide
support for the concept that dietary recommendations developed for other cardiovascular conditions or
general populations may also be appropriate in patients with HF.
Clinical Trial Registration—
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000611.
Meta-analysis of symptomatic response attributable to the pacing component of cardiac
resynchronization therapy
20 Nov 2013 03:29 pm
Aims
Prognostic benefit from CRT compared with controls is well established. Symptomatic response rates,
however, are controversial and have never been systematically evaluated with standard subtraction of
control rates to establish the incremental symptomatic response effect of CRT pacing.
Methods and results
First, we identified 150 consecutive CRT papers and assessed researchers' perceptions of the symptomatic
response to CRT. The mean quoted response rate was 66%. Only 26 studies acknowledged the existence
of response without the device. Secondly, we examined actual symptomatic response rates in the
randomized trials (CARE-HF, COMPANION, CONTAK-CD, MIRACLE, MIRACLE-ICD, MIRACLE-ICD II,
MUSTIC, and REVERSE) totalling 3904 patients. The NYHA status improved in 51% of those randomized
to CRT vs. 35% of controls (incremental effect 16%). This incremental improvement was significantly
greater in open studies (with no device for controls) than in blinded studies (control arm receiving a device
but no CRT, such as a defibrillator or a CRT programmed off), 20% vs. 13%, P < 0.001.
Conclusions
Quoting CRT responder rates in isolation without recognizing spontaneous ‘response’ is common but
unwise. The incremental symptomatic response rate from CRT pacing is ~16%, much lower than widely
reported. This value is similar to that for drugs in heart failure and should not be considered disappointing:
they both exert powerful prognostic benefits. For scientific purposes, e.g. to explore potential improvements,
symptomatic benefit from CRT should be quantified, like all other effects, by comparison with a control.
Mid-region pro-adrenomedullin adds predictive value to clinical predictors and Framingham
risk score for long-term mortality in stable outpatients with heart failure
20 Nov 2013 03:29 pm
Aims
The aim of this study was to evaluate the long-term prognostic utility of mid-region prohormone
adrenomedullin (MR-proADM) in stable outpatients with heart failure (HF).
Methods and results
Echocardiogram and serum for MR-proADM and BNP levels were obtained in 724 stable outpatients. These
patients were followed for up to 6 years for the primary endpoint of all-cause mortality. There were 198
stage A patients, 328 stage B patients, and 200 stage C/D patients, with an average age of 68 ± 12 years.
There were 195 deaths during the 6-year follow-up period. MR-proADM was predictive of mortality in the
overall patient population. The predictive value of MR-proADM for long-term mortality was independent of
BNP, echocardiographic indices of structural heart disease, clinical predictors of mortality, and the
Framingham risk score. Patients with elevated MR-proADM had significantly increased risk for mortality in
stage A and stage C/D HF, with hazard ratio (HR) 3.780, P < 0.001 and HR 2.744, P < 0.001, respectively.
There was a trend toward increased mortality in patients with elevated MR-proADM and stage B HF (HR
1.579, P = 0.05005). MR-proADM added incremental predictive value to clinical predictors and the
Framingham risk score.
Conclusions
MR-proADM was a potent independent predictor of long-term all-cause mortality in stable outpatients with
stage A–D HF, especially in patients in stage A and stage C/D HF. MR-proADM added incremental
predictive value to clinical predictors and the Framingham risk score.
Mixed Messages
01 Dec 2013 07:00 am
Publication date: Available online 23 October 2013
Source:JACC: Heart Failure
Author(s): Heinrich Taegtmeyer
Moving Beyond “Bridges”∗
01 Dec 2013 07:00 am
Publication date: October 2013
Source:JACC: Heart Failure, Volume 1, Issue 5
Author(s): James C. Fang , Joseph Stehlik
Moving Toward Comprehensive Acute Heart Failure Risk Assessment in the Emergency
Department The Importance of Self-Care and Shared Decision Making
01 Dec 2013 07:00 am
Publication date: August 2013
Source:JACC: Heart Failure, Volume 1, Issue 4
Author(s): Sean P. Collins , Alan B. Storrow
Nearly 700,000 emergency department (ED) visits were due to acute heart failure (AHF) in 2009. Most visits
result in a hospital admission and account for the largest proportion of a projected $70 billion to be spent on
heart failure care by 2030. ED-based risk prediction tools in AHF rarely impact disposition decision making.
This is a major factor contributing to the 80% admission rate for ED patients with AHF, which has remained
unchanged over the last several years. Self-care behaviors such as symptom monitoring, medication taking,
dietary adherence, and exercise have been associated with decreased hospital readmissions, yet self-care
remains largely unaddressed in ED patients with AHF and thus represents a significant lost opportunity to
improve patient care and decrease ED visits and hospitalizations. Furthermore, shared decision making
encourages collaborative interaction between patients, caregivers, and providers to drive a care path based
on mutual agreement. The observation that “difficult decisions now will simplify difficult decisions later” has
particular relevance to the ED, given this is the venue for many such issues. We hypothesize patients as
complex and heterogeneous as ED patients with AHF may need both an objective evaluation of physiologic
risk as well as an evaluation of barriers to ideal self-care, along with strategies to overcome these barriers.
Combining physician gestalt, physiologic risk prediction instruments, an evaluation of self-care, and an
information exchange between patient and provider using shared decision making may provide the critical
inertia necessary to discharge patients home after a brief ED evaluation.
Myocardial Titin Hypophosphorylation Importantly Contributes to Heart Failure With
Preserved Ejection Fraction in a Rat Metabolic Risk Model [Original Articles]
19 Nov 2013 09:01 pm
Background—
Obesity and diabetes mellitus are important metabolic risk factors and frequent comorbidities in heart failure
with preserved ejection fraction. They contribute to myocardial diastolic dysfunction (DD) through collagen
deposition or titin modification. The relative importance for myocardial DD of collagen deposition and titin
modification was investigated in obese, diabetic ZSF1 rats after heart failure with preserved ejection fraction
development at 20 weeks.
Methods and Results—
Four groups of rats (Wistar-Kyoto, n=11; lean ZSF1, n=11; obese ZSF1, n=11, and obese ZSF1 with highfat diet, n=11) were followed up for 20 weeks with repeat metabolic, renal, and echocardiographic
evaluations and hemodynamically assessed at euthanization. Myocardial collagen, collagen cross-linking,
titin isoforms, and phosphorylation were also determined. Resting tension (F passive)–sarcomere length
relations were obtained in small muscle strips before and after KCl–KI treatment, which unanchors titin and
allows contributions of titin and extracellular matrix to Fpassive to be discerned. At 20 weeks, the lean ZSF1
group was hypertensive, whereas both obese ZSF1 groups were hypertensive and diabetic. Only the obese
ZSF1 groups had developed heart failure with preserved ejection fraction, which was evident from
increased lung weight, preserved left ventricular ejection fraction, and left ventricular DD. The underlying
myocardial DD was obvious from high muscle strip stiffness, which was largely (±80%) attributable to titin
hypophosphorylation. The latter occurred specifically at the S3991 site of the elastic N2Bus segment and at
the S12884 site of the PEVK segment.
Conclusions—
Obese ZSF1 rats developed heart failure with preserved ejection fraction during a 20-week time span. Titin
hypophosphorylation importantly contributed to the underlying myocardial DD.
Nitrate Therapy for Heart Failure Benefits and Strategies to Overcome Tolerance
01 Dec 2013 07:00 am
Publication date: June 2013
Source:JACC: Heart Failure, Volume 1, Issue 3
Author(s): Divya Gupta , Vasiliki V. Georgiopoulou , Andreas P. Kalogeropoulos , Catherine N. Marti , Clyde
W. Yancy , Mihai Gheorghiade , Gregg C. Fonarow , Marvin A. Konstam , Javed Butler
Combination therapy with hydralazine and nitrates can improve outcomes in patients with heart failure and
low ejection fraction. However, this combination is underused in clinical practice for several reasons,
including side effects related to hydralazine and polypharmacy. Some of the benefits seen with hydralazine,
including afterload reduction and attenuation of nitrate tolerance, have also been observed with
angiotensin-converting enzyme inhibitors. Demonstrating similar clinical benefits with nitrates plus
angiotensin-converting enzyme inhibitor therapy alone, in the absence of hydralazine, may represent an
opportunity to improve heart failure care by increasing the use of nitrates. In this paper, we summarize data
that support studying such an approach.
Nitroxyl (HNO): A Novel Approach for the Acute Treatment of Heart Failure [Original
Articles]
19 Nov 2013 09:01 pm
Background—
The nitroxyl (HNO) donor, Angeli’s salt, exerts positive inotropic, lusitropic, and vasodilator effects in vivo
that are cAMP independent. Its clinical usefulness is limited by chemical instability and cogeneration of
nitrite which itself has vascular effects. Here, we report on effects of a novel, stable, pure HNO donor (CXL1020) in isolated myoctyes and intact hearts in experimental models and in patients with heart failure (HF).
Methods and Results—
CXL-1020 converts solely to HNO and inactive CXL-1051 with a t1/2 of 2 minutes. In adult mouse ventricular
myocytes, it dose dependently increased sarcomere shortening by 75% to 210% (50–500 μmol/L), with a
30% rise in the peak Ca2+transient only at higher doses. Neither inhibition of protein kinase A nor soluble
guanylate cyclase altered this contractile response. Unlike isoproterenol, CXL-1020 was equally effective in
myocytes from normal or failing hearts. In anesthetized dogs with coronary microembolization-induced HF,
CXL-1020 reduced left ventricular end-diastolic pressure and myocardial oxygen consumption while
increasing ejection fraction from 27% to 40% and maximal ventricular power index by 42% (both P<0.05). In
conscious dogs with tachypacing-induced HF, CXL-1020 increased contractility assessed by end-systolic
elastance and provided venoarterial dilation. Heart rate was minimally altered. In patients with systolic HF,
CXL-1020 reduced both left and right heart filling pressures and systemic vascular resistance, while
increasing cardiac and stroke volume index. Heart rate was unchanged, and arterial pressure declined
modestly.
Conclusions—
These data show the functional efficacy of a novel pure HNO donor to enhance myocardial function and
present first-in-man evidence for its potential usefulness in HF.
Clinical Trial Registration—
URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01096043, NCT01092325.
Nonprescription medication use in patients with heart failure: assessment methods,
utilization patterns, and discrepancies with medical records
30 Nov 2013 08:19 pm
Publication date: Available online 30 October 2013
Source:Journal of Cardiac Failure
Author(s): Matthew Mattila , Lucas Boehm , Stuart Burke , Anita Kashyap , Leah Holschbach , Tim Miller ,
Orly Vardeny
Background The use of over-the-counter products, herbals, and vitamins or supplements (collectively
termed “nonprescription medications”) is common among individuals with cardiovascular disease. We
sought to determine patterns and predictors of nonprescription medication use and assessed whether
different survey methodology may result in variable patient reporting of these products. Methods: We
surveyed 161 patients with heart failure. The first 80 participants were provided a written survey to complete
during their clinic appointment, and the next 80 age-matched participants met with study personnel for
survey administration via a face-to-face interview. Results Over-the-counter product use was reported by
88% of participants, whereas 34.8% took herbal supplements, and 65.2% took vitamins or supplements.
Users of nonprescription medications were older, more likely to have an ischemic etiology, and concomitant
chronic conditions. No differences in reporting were noted for patient versus provider-administered surveys.
Discrepancies between survey and medical record data were common (40.4%), occurring most frequently
with nonprescription aspirin, proton pump inhibitors, magnesium, and acetaminophen. Conclusions The
majority of study participants used nonprescription medications, and often did not report use to health care
providers. Patient education regarding importance of disclosure of nonprescription medications is crucial, as
is consistent querying of use by heart failure providers.
Novel approaches to the post-myocardial infarction/heart failure neural remodeling
30 Nov 2013 12:00 am
Abstract
The review aims to discuss the role of nerve growth factor (NGF) as a potential novel biomarker in postmyocardial infarction (MI) and in heart failure (HF), with a specific focus on neural remodeling and sprouting
processes occurring after tissue damage. Many experimental data show that MI induces nerve sprouting,
leading to increased sympathetic outflow and higher risk of ventricular arrhythmias and sudden cardiac
death. In this framework, cardiac and circulating NGF might be an indicator of the innervation process and
neural remodeling: it dramatically increases after MI, while it declines along with advanced HF and
ventricular dysfunction. The bimodal behavior of NGF in acute and chronic settings leads to the speculation
that NGF modulation may be a pharmacological target for intervention in different stages of the ischemic
heart disease. Specifically, a fascinating possibility is to support or to inhibit NGF receptors, in order to
prevent negative cardiac remodeling after MI and consequent ventricular dysfunction.
Organizing Committee of the 17th Annual Scientific Meeting
30 Nov 2013 08:19 pm
Publication date: October 2013
Source:Journal of Cardiac Failure, Volume 19, Issue 10, Supplement
PRAISE (Prospective Randomized Amlodipine Survival Evaluation) and Criticism∗
01 Dec 2013 07:00 am
Publication date: August 2013
Source:JACC: Heart Failure, Volume 1, Issue 4
Author(s): Marc A. Pfeffer , Hicham Skali
Patterns of Change in Nesiritide Use in Patients With Heart Failure How Hospitals React to
New Information
01 Dec 2013 07:00 am
Publication date: August 2013
Source:JACC: Heart Failure, Volume 1, Issue 4
Author(s): Chohreh Partovian , Shu-Xia Li , Xiao Xu , Haiqun Lin , Kelly M. Strait , John Hwa , Harlan M.
Krumholz
Objectives This study sought to determine hospital patterns of change in use of nesiritide over a 6-year
period after publications of safety concerns in 2005 and to identify hospital characteristics associated with
these patterns. Background The changing nature of medical evidence often requires a change in practice.
Nesiritide was commercialized in 2001 for early relief of dyspnea in patients with decompensated heart
failure. In 2005, concerns about its safety led to recommendations to restrict its use. Little is known about
how hospitals responded to this information. Methods We analyzed data from the Premier database,
including 403 hospitals contributing 813,783 hospitalizations with heart failure from 2005 to 2010. We
applied a growth mixture modeling approach to hospital-level, risk-standardized, quarterly use rates of
nesiritide to distinguish hospital groups on the basis of their patterns of change in use. Results The
proportion of hospitalizations using nesiritide declined from 15.4% in 2005 to 1.2% in 2010. The level and
speed of change varied markedly among hospitals. After adjusting for differences in patient characteristics
across hospitals and years, we identified 3 distinct groups of hospitals: “low users,” “fast de-adopters,” and
“slow de-adopters.” In multivariate regression analysis, these groups did not differ in traditional hospital
characteristics, such as size, urban setting, or teaching status. Conclusions We identified 3 distinct hospital
groups characterized by their patterns of change in nesiritide use. These trajectory curves can provide
hospitals with important feedback on how fast and effectively they react to new information compared with
other hospitals. Uncovering factors that promote organizational learning requires further research.
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