* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download ppt
Survey
Document related concepts
Transcript
Device Therapy in Heart Failure Teresa M. Menendez Hood, M.D., F.A.C.C. Heart Failure U.S. Annual Incidence Heart Failure Prevalence Annual Mortality 400,000 5.0 million 250,000 Up to 30 % of HF patients have an IVCD (80% with a LBBB) which has been linked to increases in mortality and morbidity. HF is the leading cause of hospitalizations in the US and uses up 5% of the health care costs 2% of the population and 6% of the population >65 Prevalence is on the rise. Heart Failure Background At Risk for Heart Failure Stage A Heart Failure Stage C At high risk of HF but Structural heart without structural heart disease with prior or disease or HF symptoms current HF symptoms Stage B Stage D Structural heart disease Refractory HF but without signs or requiring specialized symptoms of HF interventions NYHA Class-evaluates the disability imposed on the patient who already has structural heart disease Class I Class II Class III Asymptomatic heart failure ejection fraction (EF) <40% Mild symptomatic heart failure with ordinary exertion Moderate symptomatic heart failure with less than ordinary exertion Class IV Symptomatic heart failure at rest Stages of Heart Failure Leading Causes of Death in the U.S. Septicemia You must combine deaths from all cancers to outnumber the deaths from SCA each year. Nephritis Alzheimer’s Disease Influenza/pneumonia Diabetes Accidents/injuries Chronic lower respiratory diseases Cerebrovascular disease Other cardiac causes Sudden cardiac arrest (SCA) All other causes All cancers 0% 5% 10% 15% 20% 25% National Vital Statistics Report. Oct. 12, 2001;49(11). MMWR. State-specific mortality from sudden cardiac death – US 1999. Feb 15, 2002;51:123-126. SCD Rates in CHF Patients with LV Dysfunction Total Mortality Sudden Death Control Group Mortality 30 20 20 19 17 15 11 9 10 7 8 6 4 0 CHF-STAT 45 months GESICA 13 months SOLVD V-HeFT I 41.4 months 27 months SCD accounts for ~50% of the total deaths. MERIT-HF 12 months CIBIS-II 16 months CARVEDILOL-US 6 months SCD in Heart Failure QRS Duration (msec) Cumulative Survival 100% <90 90% 90-120 80% 120-170 170-220 70% >220 60% 0 60 120 180 240 300 360 Days . • QRS duration is an independent predictor of mortality (>140 ms) • Other factors are: age, creatinine, EF, and HR SCD in Heart Failure Degree of SCD risk by class Mortality in NYHA class II is 5 to 15% 50 Mortality in NYHA class III is 20 to 50% Up to 80% of the deaths are Sudden to 50% of the deaths are Sudden Mortality in NYHA class IV is 30 to 70% 5 to 30% of deaths are Sudden (more deaths from pump failure) Right Ventricular Pacing RV apex pacing is harmful in patients with LV dysfunction. Became evident in multiple pacer and ICD trials that it increases HF by producing a “paced” LBBB. Abnormal LV activation Reduced stroke volume Detrimental RV pacing MADIT II (2002) had a survival benefit with the ICD but in a subgroup analysis, there was an increase in heart failure morbidity (more hospitalizations) felt due to forced RV pacing compared to controls in which no pacing was present. MADIT II: Complications New or Worsening HF 19.9% 20.00% 14.9% 10.00% 0.00% (p= 0.09) Conventional Therapy N= 490 ICD Therapy •RV pacing causes ventricular dysynchrony and may lead to worsening HF. • Intrinsic ventricular activation is better for ICD patients with left ventricular dysfunction who do not “need” pacing. •<10% of ICD patients have a Class I pacing indication at the time of implant…they do not NEED pacing. N= 742 •Physicians, when appropriate, should consider programming of ICDs to avoid frequent RV pacing. DAVID — Dual Chamber and VVI Implantable Defibrillator Trial : 2002 ICD indication but no indication for a pacemaker EF < 40% DDDR @ 70BPM versus VVI 40 BPM Search AV Extension and Managed Ventricular Pacing for Promoting Atrioventricular Conduction (SAVE PACe) Trial : 2007 1065 patients with sinus-node disease, intact AV conduction and normal QRS interval Randomized to conventional dual-chamber pacing (n=535) or dual-chamber minimal ventricular pacing (n=530) ― study tests new pacing algorithm that avoids ventricular pacing except during periods of high-grade AV block With dual-chamber pacing, ↓ frequency RV pacing (9.1% vs. 99%; p<0.001) and 40% relative risk ↓ in incidence of persistent AF The Concept In most patients with an IVCD (QRS > 130 ms) , the presence of atrial-biventricular (RV + LV) pacing will provide early stimulation to an otherwise late segment of electrical activation in the LV. This should translate into an increase in the EF, decrease of the LV dimension, improvement in the QOL and NYHA class. This may translate into an decrease in CHF exacerbations , hospitalizations and a decrease in mortality. The Proof 1994 –1997: Mechanistic and both short and longer term observational studies. Studies initially used epicardial leads placed by thoracotomy or thorascope. The first BiV pacer was implanted in 1994 1998 –1999: Randomized, controlled studies to assess exercise capacity, functional status, and quality of life. There was development of transvenous leads via the coronary sinus in to get to the LV. Cohen TJ, Klein J. J Inva2002;14:48-53. The Proof 2000 – 2006: Randomized, controlled trials to assess combined mortality and CHF hospitalization. Also evaluated the combined benefit of ICD’s with CRT. 2006-2008: Trials to identify patients who will benefit from CRT. This uses echocardiographic markers of dyssynchrony and the QRS measurement. 20% of patients do not respond to therapy in clinical trials with a wide QRS and 50% patients with a narrow QRS/CHF have dyssynchrony on echo and may benefit from this therapy. If the QRS is < 150 ms, then the chance of responding to BiVP is ~5%. It will be in this patient group of QRS of 120150 ms where preselection of responders would be most valuable. The Cardiac Resynchronization Clinical Trials PATH-CHF, MUSTIC, MIRACLE, COMPANION, and CARE-HF* *This is not a complete list of all the CRT trials and the dates given are when the trial results were published. Cumulative Patients Cumulative Enrollment in Cardiac Resynchronization Randomized Trials 4000 CARE HF MIRACLE ICD 3000 2000 1000 MIRACLE MUSTIC AF MIRACLE ICD II MUSTIC SR COMPANION PATH CHF PATH CHF II CONTAK CD 0 1999 2000 2001 2002 2003 Results Presented 2004 2005 PATH-CHF: 1999 Pacing Therapy for Congestive Heart Failure This was the first multicenter trial and used the standard endocardial RV lead and an epicardial LV lead via thoracotomy or thorascope Single blinded RCT 53 centers in Europe 41 patients PATH-CHF Primary endpoints Secondary endpoints Peak VO2 Six-minute walk distance Minnesota Living with Heart Failure score (QOL) NYHA class EF Trend towards decrease in Hospitalizations Acute hemodynamic testing revealed that the lateral and posterolateral walls were the best target sites. The best responders were those with QRS>150 , long PR and dP/dt < 700 mm Hg/s MUSTIC: 2001 Multicenter Stimulation in CM European study with 67 patients QRS>150, CHF, EF <35% BiVP versus backup VVI pacing at 40 BPM Increase in 6 minute walk time , QOL and Peak VO2 with BiVP and persisted for up to 12 months 60% decrease in CHF hospitalizations First to use endocardial LV leads via the CS No significant change in mortality, but a trend towards an improvement. Acute hemodynamic studies showed the mid lateral wall to be the best site MIRACLE:2002 Multi-center In Sync Randomized Clinical Evaluation Trial Double blinded RCT First US trial Class 3 or 4, on OPT, QRS >130 ms, EF<35% Enrollment of 453 patients MIRACLE NYHA class III-IV LVEDD > 60 mm QRS > 130 ms Stable 3 month regimen of beta-blocker/ACE inhibitor EF < 35% Randomization CRT on CRT off 1- and 3-month follow-up 1- and 3-month follow-up 6-month follow-up 6-month follow-up CRT on Long-term follow-up MIRACLE Nonresponders: older, ischemic CM, no MR, QRS<150 Responders: had shorter duration on CHF and longer QRS>155 P < 0.001 67% Proportion 60% 40% 39% 34% 27% 20% 17% 16% 0% Improved Control N=225 No Change Worsened CRT N=228 MIRACLE There was a decrease in hospitalizations of 50% at 6 months and a trend towards a decrease in mortality. All other primary and secondary endpoints were met: 6 minute walk time, peak Vo2, QOL, EF , NYHA class, LVEDD Magnitude of improvement not influenced by degree of QRS shortening with BiVP (average in all was –20msec) FDA Approval The first CRT device was approved by the FDA in September 2001 . The first CRT with an ICD was approved by the FDA in May 2002 . The Primary ICD Prevention Trials MADIT 1 1996 required a positive EP study;ischemics MUSTT 1999 required a positive EP study; ischemics; EF<40% MADIT 2 2002 prior MI (ischemic cardiomyopathy) and EF<30% (no EP study required) ;60% had CHF and 50% had QRS > 120 ms; resulted in a 31% decrease risk of death and halted prematurely due to the positive effect of the ICD: resulted in the FDA approving the ICD for primary prevention this patient population, but only those with a QRS > 120 ms. The Primary ICD Prevention Trials SCD-Heft - 2005 The SCD-Heft trial resulted in FDA approval of the ICD January 2005 in patients with CHF and EF<35 % that included both ischemic and nonischemic cardiomyopathy for primary prevention without a positive EP study or ventricular ectopy . No QRS cutoff was required. COMPANION:2004 Comparison of Medical Therapy, Pacing and Defibrillation in Heart Failure • OPT Randomization • OPT • CRT • OPT • CRT-D 1 2 + 2 + COMPANION Enrolled 1520 patients class 3 and 4, QRS >120ms Primary endpoint: death or hospitalization for any cause CRT met the primary endpoints and the CRT +/- ICD significantly reduces mortality This was the first to show mortality benefit from CRT alone Showed that patients with CRT also benefit from ICD therapy OPT had SCD in 36%, 23% in CRT and 3% in CRT+ICD COMPANION • CRT arm had 20% reduction in mortality and hospitalization over OPT arm but it was not statistically significant • Significant reduction in CRT-ICD arm of 40% for mortality over OPT arm (19% in OPT and 11% in CRT-ICD group) • Study was halted prematurely due to its positive benefit. • Mean follow up was 16 months CARE-HFCArdiac REsynchronization in Heart Failure 2005 The effect of cardiac resynchronization on morbidity and mortality in heart failure in 813 patients in Europe ( prospective multicenter RCT) with completed enrollment by 2002 Large patient size and length of trial (average follow up of 29 months) allowed ability to asses effects of CRT Looked at CRT alone (no ICD) Patients with class 3 or 4, EF < 35%, QRS >120 ms There was a 37% reduced mortality or first hospitalization for a cardiac cause compared to OPT CARE-HF All endpoints were met : EF, NYHA, QOL, BNP, Echo and hemodynamic parameters 33% of the deaths in the CRT group were due to SCD For every 9 devices, one death and 3 hospitalizations were prevented Echo criteria in patients with QRS 120-149ms to look for dyssynchrony (had to have 2 of 3)…the “gray area group” Aortic pre-ejection delay of > 140 ms ( onset of QRS to Aortic ejection) Interventricular mechanical delay of >40 ms ( RV-LV) Delayed activation of the postero-lateral LV wall (>50ms) Primary Endpoint (All-cause Mortality or Unplanned Hosp. for Major CVS Event) 1.00 Event-free Survival HR 0.63 (95% CI 0.51 to 0.77) 0.75 CRT : 159 pts (39%) 0.50 P < .0001 Medical : 224 pts Therapy (55 %) 0.25 0.00 Number at risk CRT Medical Therapy 0 409 404 500 323 292 273 232 1000 166 118 68 48 1500 Days 7 3 Conclusions Conclusive results from CARE-HF demonstrate that CRT should be considered as part of routine therapy for patients with moderate to severe HF due to LVSD with evidence (ECG supported by Echo) of cardiac dyssynchrony to*: Improve cardiac function and efficiency Improve symptoms and QoL Reduce morbidity Prolong survival These benefits are in addition to those of optimal pharmacological therapy (OPT) The Resynchronization Therapy in Normal QRS (RethinQ) Study 2007 Background Currently, indications for cardiac resynchronization therapy (CRT) include QRS duration > 120ms, LVEF < 35% and NYHA Class III-IV. 20-30% of patients do not respond to CRT despite application of established selection criteria. Patients with normal conduction or a slightly prolonged QRS duration also exhibit mechanical abnormalities due to intraventricular dyssynchrony. Myocardial Tissue Doppler Imaging (TDI) allows both the velocity and timing of regional longitudinal motion to be measured. LV dyssynchrony may also be useful in predicting the benefit of CRT before implantation of the pulse generator. Hypothesis We hypothesized that patients with NYHA class III, left ventricular ejection fraction less than or equal to 35%, narrow QRS duration < 130 ms, and evidence of mechanical dyssynchrony on echocardiography may benefit from cardiac resynchronization therapy. Echo Criteria for LV Dyssynchrony Mechanical dyssynchrony considered present if either M-Mode - Septal posterior wall mechanical delay (SPWMD) ≥ 130 ms OR Tissue Doppler Imaging (TDI) of the basal ventricular segments in apical 4/2/3 chamber views - Septal to lateral delay ≥ 65ms OR - Antero-septal to posterior delay ≥ 65ms Summary:RethinQ This prospective, multi-center, randomized trial was designed to evaluate the effectiveness of CRT therapy in a HF population with narrow QRS duration and evidence of mechanical dyssynchrony. There was no statistical significant difference in the change in Peak VO2 between the treatment and control group during cardiopulmonary exercise testing. No improvement in other objective parameters including 6-minute walk test, LV reverse remodeling, and secondary endpoint - quality of life score . Conclusion:RethinQ CRT did not improve Peak VO2 during exercise in patients with NYHA Class III heart failure, QRS duration <130ms, EF ≤ 35% and mechanical dyssynchrony as specified in this trial. While there was a statistically significant improvement of NYHA class, a secondary endpoint, there was no improvement in qualityof-life, 6-minute walking test, or echocardiographic measures of reverse LV remodeling A subgroup of patients with QRS duration between 120 ms and 130 ms demonstrated an improvement from CRT, however patients with QRS duration < 120 ms did not demonstrate improvement The subgroup of patients stratified on the basis of cardiomyopathy etiology did not demonstrate an improvement in peak VO2. PROSPECT TRIAL 5/2008 Predictors of response to CRT 53 centers worldwide, 426 patients Patients had standard CRT indications (OMT, EF < 35%, Class III-IV, QRS > 130) 12 ECHO parameters of dyssynchrony 69% of patients clinically improved and 56% showed a decrease in LVESV of >15% No single ECHO measure of dyssynchrony could help select responders to CRT BASE Anterior Posterior APEX RAO is best to distinguish BASE position from APEX ANTERIOR Anterior LAO is best to distinguish LATERAL position from SEPTAL S E P T A L Posterior Lateral INFERIOR L A T E R A L LAO The 3 levels of Dyssynchrony 1. 2. 3. Intraventricular dyssynchrony is best treated by placing the LV lead in the best anatomic location-usually the lateral or posterolateral (proven my multiple studies). Get the LV working. Interventricular dyssynchrony is dealt with by adjusting the V-V interval. Get the RV and the LV to work together. A-V dyssynchrony is dealt with by adjusting the A-V interval. Get the atria and the ventricles working together. Posterolateral or Lateral walls are the best with LBBB where the septum contracts first and then the lateral wall last. Paced at most mechanically delayed LV site Paced at any other LV site 0 10% P=0.04 9% -5 -9.2 Improvement 8% -10 6% -15 4% -20 2% 2% 0% Change in LVEF [%] -25 -30 P=0.04 -28.4 Change in LV End-systolic Volume [ml] CRT and Tissue Doppler Imaging -a measure of intraventricular delay • Measures dyssynchronous (delayed) contraction patterns @ different areas of the ventricle •Measure from the onset of the QRS to the peak systolic shortening of that segment •Defined as a segment with > 50 ms delay: this indicates intraventricular delay or asynchrony by ECHO criteria •Colors: greenyellow-red (the longest delay of >300 ms) V-V Timing: synchronize the RV and the LV The best V-V setting by measuring the RVOT and LVOT via PW Doppler V-V above > 40 ms is considered abnormal In normals, the RV will contract before the LV in the heart by -20 ms LV and RV have different outputs in the newer devices that allow sequential instead of simultaneous delivery of output and thus allow for this to be programmable. AV Delay Optimization Methods 1. Electrocardiographic COMPANION 2. trial method Echocardiographic (combined) Aortic velocity time integral (VTI) methods Mitral velocity Doppler methods:E and A waves Ritter formula 3. Hemodynamic measurements Pulse pressure method dP/dtmax method Cardiac Resynchronization Therapy in Patients With Severe Systolic Heart Failure:2008 Guidelines I IIa IIb IIbIII III I IIa IIb IIbIII III I IIa IIb III For patients who have left ventricular ejection fraction (LVEF) less than or equal to 35%, a QRS duration greater than or equal to 0.12 seconds, and sinus rhythm, cardiac resynchronization therapy (CRT) with or without an ICD is indicated for the treatment of New York Heart Association (NYHA) functional Class III or ambulatory Class IV heart failure symptoms on optimal recommended medical therapy. For patients who have LVEF less than or equal to 35%, a QRS duration greater than or equal to 0.12 seconds, and AF, CRT with or without an ICD is reasonable for the treatment of NYHA functional Class III or ambulatory Class IV heart failure symptoms on optimal recommended medical therapy. For patients with LVEF less than or equal to 35% with NYHA functional Class III or ambulatory Class IV symptoms who are receiving optimal recommended medical therapy and who have frequent dependence on ventricular pacing, CRT is reasonable. Cardiac Resynchronization Therapy in Patients With Severe Systolic Heart Failure : 2008 Guidelines I IIa IIb III I IIa IIb III I IIa IIb III For patients with LVEF less than or equal to 35% with NYHA functional Class I or II symptoms who are receiving optimal recommended medical therapy and who are undergoing implantation of a permanent pacemaker and/or ICD with anticipated frequent ventricular pacing, CRT may be considered. CRT is not indicated for asymptomatic patients with reduced LVEF in the absence of other indications for pacing. CRT is not indicated for patients whose functional status and life expectancy are limited predominantly by chronic noncardiac conditions. Indications for ICD Therapy 2008 Implantable CardioverterDefibrillators I IIa IIb IIbIII III ICD therapy is indicated in patients who are survivors of cardiac arrest due to ventricular fibrillation or hemodynamically unstable sustained VT after evaluation to define the cause of the event and to exclude any completely reversible causes. I IIa IIb III ICD therapy is indicated in patients with structural heart disease and spontaneous sustained VT, whether hemodynamically stable or unstable. I IIa IIb III ICD therapy is indicated in patients with syncope of undetermined origin with clinically relevant, hemodynamically significant sustained VT or VF induced at electrophysiological study. All primary SCD prevention ICD recommendations apply only to patients who are receiving optimal medical therapy and have reasonable expectation of survival with good functional capacity for more than 1 year. Implantable CardioverterDefibrillators I IIa IIb III I IIa IIb III ICD therapy is indicated in patients with LVEF less than or equal to 35% due to prior MI who are at least 40 days post-MI and are in NYHA functional Class II or III. I IIa IIb III ICD therapy is indicated in patients with nonischemic DCM who have an LVEF less than or equal to 35% and who are in NYHA functional Class II or III. I IIa IIb IIbIII III ICD therapy is indicated in patients with LV dysfunction due to prior MI who are at least 40 days post-MI, have an LVEF less than or equal to 30%, and are in NYHA functional Class I. I IIa IIb III ICD therapy is indicated in patients with nonsustained VT due to prior MI, LVEF less than or equal to 40%, and inducible VF or sustained VT at electrophysiological study. All primary SCD prevention ICD recommendations apply only to patients who are receiving optimal medical therapy and have reasonable expectation of survival with good functional capacity for more than 1 year. Implantable CardioverterDefibrillators I IIaIIbIII ICD implantation is reasonable for patients with unexplained syncope, significant LV dysfunction, and nonischemic DCM. I IIaIIbIII ICD implantation is reasonable for patients with sustained VT and normal or near-normal ventricular function. I IIaIIbIII ICD implantation is reasonable for patients with HCM who have 1 or more major† risk factors for SCD. ICD implantation is reasonable for the prevention of SCD in I IIaIIbIII patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) who have 1 or more risk factors for SCD. I IIaIIbIII ICD implantation is reasonable to reduce SCD in patients with longQT syndrome who are experiencing syncope and/or VT while receiving beta blockers. All primary SCD prevention ICD recommendations apply only to patients who are receiving optimal medical therapy and have reasonable expectation of survival with good functional capacity for more than 1 year. † See Section 3.2.4, “Hypertrophic Cardiomyopathy,” in the full-text guidelines for definition of major risk factors. Implantable CardioverterDefibrillators I IIaIIbIII ICD implantation is reasonable for nonhospitalized patients awaiting transplantation. I IIaIIbIII ICD implantation is reasonable for patients with Brugada syndrome who have had syncope. I IIaIIbIII ICD implantation is reasonable for patients with Brugada syndrome who have documented VT that has not resulted in cardiac arrest. I IIaIIbIII ICD implantation is reasonable for patients with catecholaminergic polymorphic VT who have syncope and/or documented sustained VT while receiving beta blockers. I IIaIIbIII ICD implantation is reasonable for patients with cardiac sarcoidosis, giant cell myocarditis, or Chagas disease. All primary SCD prevention ICD recommendations apply only to patients who are receiving optimal medical therapy and have reasonable expectation of survival with good functional capacity for more than 1 year. Implantable CardioverterDefibrillators I IIaIIbIII ICD therapy may be considered in patients with nonischemic heart disease who have an LVEF of less than or equal to 35% and who are in NYHA functional Class I. I IIa IIb IIbIII III ICD therapy may be considered for patients with long-QT syndrome and risk factors for SCD. I IIaIIbIII ICD therapy may be considered in patients with syncope and advanced structural heart disease in whom thorough invasive and noninvasive investigations have failed to define a cause. I IIaIIbIII ICD therapy may be considered in patients with a familial cardiomyopathy associated with sudden death. I IIaIIbIII ICD therapy may be considered in patients with LV noncompaction. All primary SCD prevention ICD recommendations apply only to patients who are receiving optimal medical therapy and have reasonable expectation of survival with good functional capacity for more than 1 year. Implantable CardioverterDefibrillators I IIa IIb III I IIa IIb III ICD therapy is not indicated for patients who do not have a reasonable expectation of survival with an acceptable functional status for at least 1 year, even if they meet ICD implantation criteria specified in the Class I, IIa, and IIb recommendations above. ICD therapy is not indicated for patients with incessant VT or VF. I IIa IIb III ICD therapy is not indicated in patients with significant psychiatric illnesses that may be aggravated by device implantation or that may preclude systematic follow-up. I IIa IIb III ICD therapy is not indicated for NYHA Class IV patients with drug-refractory congestive heart failure who are not candidates for cardiac transplantation or cardiac resynchronization therapy defibrillators (CRT-D). All primary SCD prevention ICD recommendations apply only to patients who are receiving optimal medical therapy and have reasonable expectation of survival with good functional capacity for more than 1 year. Implantable CardioverterDefibrillators I IIa IIb III I IIa IIb III I IIa IIb III ICD therapy is not indicated for syncope of undetermined cause in a patient without inducible ventricular tachyarrhythmias and without structural heart disease. ICD therapy is not indicated when VF or VT is amenable to surgical or catheter ablation (e.g., atrial arrhythmias associated with the Wolff-Parkinson-White syndrome, RV or LV outflow tract VT, idiopathic VT, or fascicular VT in the absence of structural heart disease). ICD therapy is not indicated for patients with ventricular tachyarrhythmias due to a completely reversible disorder in the absence of structural heart disease (e.g., electrolyte imbalance, drugs, or trauma). All primary SCD prevention ICD recommendations apply only to patients who are receiving optimal medical therapy and have reasonable expectation of survival with good functional capacity for more than 1 year. Summary Large number of patients studied in multiple RCTs. CRT improves quality of life, exercise capacity, functional capacity, EF, peak VO2. CRT reduces the risk of mortality, worsening HF, and hospitalizations for CHF. CRT + ICD significantly reduces risk of mortality.