Download Coronary revascularization strategies in patients with chronic heart

 Review
Coronary revascularization strategies in
patients with chronic heart failure
Chronic heart failure (CHF) is a worldwide public health problem owing to its high prevalence and incidence
(especially in industrialized countries). Although CHF may occur in different physiopathology scenarios,
nowadays, atherosclerotic coronary artery disease represents the most common cause of heart failure.
Data from observational studies suggest that patients with coronary disease and left ventricular dysfunction
may have improved outcomes after both surgical and percutaneous revascularization. However, the
selection of which patients might benefit from revascularization, the time of revascularization and the
choice of treatment strategy in this subset of patients remains under debate. The aim of this article is to
describe the effect revascularization strategy has on outcomes in CHF patients’ and to examine the role
of noninvasive viability testing. It also aims to offer an evidence-based perspective that may differ from
the current standard of practice.
KEYWORDS: coronary artery bypass grafting n chronic heart failure n PCI versus CABG
n percutaneous coronary intervention n viability tests
Chronic heart failure (CHF) is a worldwide public health problem of major and ever-expanding
proportions, affecting approximately 5 million patients in the USA alone [1] . Moreover,
the cost of hospitalization was approximated at
US$2.6 million during the last decade and may
double in the next 40 years [2] . Coronary artery
disease (CAD) is the predominant cause of CHF
and left ventricular dysfunction (LVD). Most
patients with CHF attributable to CAD have
had a prior myocardial infarction (MI) and LVD
can occur as consequence of this.
In Europe, where there are an estimated 15 million patients with CHF, its prevalence is between
2 and 3%, and increases sharply at 75 years of age
with a prevalence in 70–80-year-olds of between
10 and 20%. The overall prevalence of CHF is
increasing owing to an aging population, the
success of prolonging survival in patients suffering coronary events and the spread of secondary
prevention. Almost 60% of the patients in the
Acute Decompensated Heart Failure National
Registry (ADHERE) had a history of CAD [3] .
Similarly, of patients enrolled in CHF clinical trials, the majority (68%) had ischemic heart disease recorded as their heart failure etiology [4] .
Although coronary revascularization by coronary
artery bypass grafting (CABG) and/or percutaneous coronary intervention (PCI) has been studied exhaustively and analyzed in many clinical
contexts, there are a lack of studies specifically
designed to address the role of revascularization
in patients with CAD and CHF. This article
reviews the existing data concerning revascularization as a treatment of CHF in patients
with CAD, exploring noninvasive testing for the
identification of patients who are most likely to
benefit from revascularization therapy.
Rationale for the revascularization of
CHF patients
Revascularization of patients with LVD may
improve their clinical outcome by several
mechanisms. Dysfunctional myocardium can
be related to the presence of necrosis, and/or
with two condition states, including stunning
and hibernating myocardium.
Cell death is categorized pathologically as
either coagulation, contraction band necrosis,
or both, and usually evolves through oncosis,
but it can result to a lesser degree from apoptosis [5] . Careful analysis of histological sections
by an experienced observer is essential for distinguishing these entities. After the onset of
myocardial ischemia, cell death does not occur
immediately but takes a finite period to develop
(as little as 15 min in some animal models, but
even this may be an overestimate). It takes 6 h
before myocardial necrosis can be identified by
standard macroscopic or microscopic postmortem examination [6] . Complete necrosis of all
myocardial cells at risk requires at least 4–6 h or
longer, depending on the presence of collateral
blood flow into the ischemic zone, persistent or
10.2217/ICA.10.97 © 2011 Future Medicine Ltd
Interv. Cardiol. (2011) 3(1), 91–100
Salvatore Davide
Tomasello†,
Luca Costanzo1 &
Alfredo Rugero Galassi1
Department of Internal Medicine &
Systemic Disease, Ferrarotto Hospital,
University of Catania, Catania, Italy
†
Author for correspondence:
Department of Cardiology, MoriggiaPelascini Hospital, Via Pelascini 3,
22015 Gravedona, Como, Italy
[email protected]
1
ISSN 1755-5302
91
Review Tomasello, Costanzo & Galassi
intermittent coronary artery occlusion and the
sensitivity of the myocytes. Infarcts are usually
classified by size – microscopic (focal necrosis),
small (<10% of the left ventricle), medium (10–
30% of the left ventricle) or large (>30% of the
left ventricle) – as well as by location (anterior,
lateral, inferior, posterior or septal, or a combination of locations) [7] . The pathologic identification of myocardial necrosis is made without reference to morphologic changes in the epicardial
coronary artery tree or to the clinical history.
The presence of mononuclear cells and fibroblasts and the absence of polymorpho­nuclear leukocytes characterize a healing infarction [8] . A
healed infarction manifests as scar tissue without
cellular infiltration. The entire process leading to
a healed infarction usually requires 5–6 weeks
or more. Furthermore, reperfusion alters the gross
and microscopic appearance of the necrotic zone
by producing myocytes with contraction bands
and large quantities of extravasated erythrocytes
[9] . Obviously, the extent of necrosis in the myocardium determines the loss of contractile function in the tissue, and although the necrosis may
be confined to a low number of ventricular segments, it may promote an intra-ventricular remodeling phenomenon with a decrease of global left
ventriclular function.
Hibernating myocardium is a chronically
hypocontractile tissue, due to persistently
low flow, with the potential to improve function after restoration of the blood supply [10] .
Hibernating myocardium might represent a
solution to both an impaired coronary flow
reserve and a reduced resting coronary blood
flow [11] . Biopsies of human hibernating myocardium demonstrate histological changes of
cellular dedifferentiation and an embryonic
phenotype [12] . The severity of ultrastructural
changes correlates directly with the time course
of functional recovery, but correction of cellular changes after the restoration of flow or flow
reserve is likely to only be partial [11,12] . These
observations and evidence demonstrating that
apoptosis is important in hibernation, underscore the importance of early revascularization
in this dynamic transition from reversible to
irreversible contractile dysfunction [11] . An
elegant study by Pitt et al. demonstrated that
chronically dysfunctional ischemic myocardium can improve function following revascularization, but waiting for revascularization might cause a decline in viable function
accompanied by pathophysiological changes
indicative of disease progression [13] . Moreover,
such a decline attenuates myocardial function
92
Interv. Cardiol. (2011) 3(1)
recovery. Therefore, in these patients, the therapeutic decision should be made as promptly as
possible following initial assessment.
‘Stunning’ is contractile dysfunction resulting from transient ischemia followed by restoration of perfusion [14] . Its pathogenesis likely
involves oxyradicals and calcium and the associated dysfunction might persist for hours or days,
but generally improves with time. An exception
to this is ‘repetitive stunning’, defined as repeated
episodes of ischemia producing prolonged postischemic contractile dysfunction [11] , which is
similar to hibernation in that revascularization has the potential to improve contractile
function. Hibernation and stunning are often
practically indistinct and they might coexist in
varying degrees in the same patient or myocardial region and represent a continuum of the
same process.
The timing of functional recovery after revascularization appears to differ between both
stunned and hibernating myocardium. In an
echocardiography and radionuclide imaging
study, nearly two-thirds of stunned segments
exhibited early contractile recovery 3 months
after revascularization, and only one tenth
showed late improvement at 14 months [12] . By
contrast, only approximately a third of hibernating segments exhibited early improvement, but
nearly two-thirds showed late recovery. These
observations suggest that many published studies might have assessed contractile recovery too
early and therefore underestimated the degree of
recovery. Recently, Rahimtoola et al. suggested
a unifying concept of hibernation and remodeling, with an emphasis on the importance of
early revascularization [15] .
The interaction between this myocardial
process, cardiovascular disease and several systemic conditions contributes to remodeling,
progression of systolic dysfunction and CHF
(Figure 1) . Of note is post-infarction remodeling,
which involves owing to the replacement of
nonviable myocardium with scar tissue and is
accompanied by secondary pathologic changes
in the shape and size of the left ventricle.
The Open Artery trial (OAT) tested the
‘open artery strategy’ in stable post-MI patients
with late occluded infarct-related arteries [16] .
Analyzing the outcome of 2201 patients, late
routine PCI of infarct-related artery (IR A)
demonstrated no benefit in comparison with
medical therapy in terms of the combined end
point of death, MI and class IV heart failure
[16] . Recently, a nuclear substudy, conducted in
27% of the total OAT population, demonstrated
future science group
Coronary revascularization strategies in patients with chronic heart failure Review
a lack of clinical benefit after late recanalization of IRA in patients with mild-to-moderate
inducible ischemia [17] . However, this evidence
does not allow a definite conclusion to be drawn
because of the post hoc nature of the study and
the absence of patients with severe inducible
ischemia in the main analysis.
In CHF patients, mitral valve regurgitation
is also a factor that might accelerate the remodeling process. Remodeling appears to progress
over time and the ability to reverse the process
may also be time sensitive.
A study by Samady et al. demonstrated an
increased survival in patients with LVD after
revascularization, independently of left ventricular functional improvement [18] . Several
pathophysiological mechanisms may be responsible for this benefit. First, restoration of blood
flow to ischemic myocardium adjacent to the
endocardial scar relieves resting ischemia,
enhances the reparative process of the myocyte
contractile machinery and may protect against
future infarction [19] . Second, revascularization may limit infarct expansion and ventricular dilation, by providing a scaffolding which
supports the surrounding necrotic myocardium
and reduces myocardial compliance [19] . These
mechanisms may also improve diastolic function and may even reduce dynamic mitral regurgitation, culminating in further symptomatic
improvement. Finally, by reducing left ventricular remodeling and the ischemic burden,
revascularization of ischemic myocardium may
reduce the incidence of ventricular arrhythmias
related to the re-entry phenomenon.
Which strategy for
revascularization should be
followed: surgical or percutaneous?
Owing to the paucity of data from contemporary therapies, decision making in CHF patients
requiring revascularization is largely based on
surgical studies performed nearly 20 years
ago. In the two largest retrospective series,
the Coronary Artery Surgery Study registry
(420 medical and 231 surgical patients) [20] and
the Duke University Cardiovascular Database
(409 medical and 301 surgical patients) [21] , a
significant long-term survival advantage was
observed with CABG over medical therapy,
but the surgical survival benefits were greatest
for those patients with the most severe LVDs
(LVEF < 25%), the most extensive CAD and
the most intense angina. Although results from
these and other smaller studies have favored
surgery over medical therapy overall, important
future science group
Myocardial factors:
• Previous infarction
• Hibernating tissue
• Ischemia/stunning
• Cardiac hypertrophy
Cardiovascular nonmyocardial
factors:
• Coronary disease
• Endothelial dysfunction
• Mitral valve diseases
• Arrhythmias
• Diastolic dysfunction
Systemic factors:
• Cytokines
• Sympathetic nervous system
• Renin–angiotensin–
aldosterone system
• Renal and liver disease
• Diabetes
• Age
Left ventricular remodeling
Figure 1. Relationship between factors promoting ventricular remodeling.
limitations have included selection bias for revascularization, inadequate medical therapy in both
medical and surgical groups, the use of outdated
surgical techniques and the small numbers of
patients, particularly those whose symptoms
are predominantly of heart failure. Recently,
an update of more than 18,000 patients entered
into the Duke Databank from 1986 to 2000
confirmed the survival benefit of revascularization in patients with CAD and reduced ejection
fraction (EF) [22] .
It is interesting to note that peri-operative
mortality rates for CABG in patients with left
ventricular systolic dysfunction vary widely,
from approximately 5% among younger adults
to more than 30% among older individuals,
who have more severe left ventricular systolic
dysfunction and comorbidities [23] . There are
many limitations to consider when interpreting
the data from this study, owing to their retrospective nature and the nonstandardized surgical strategy employed. For this reason, several
trials have been specifically designed in order
to address the real value of revascularization in
CHF patients.
www.futuremedicine.com
93
Review Tomasello, Costanzo & Galassi
The aim of the Heart Failure Revascularization
(HEART) trial was to evaluate whether revascularization could improve the prognosis in
CHF patients [24] . Patients with LVEF under
35% requiring chronic diuretic therapy, with
evidence of at least five segments being affected
by ischemia and/or hibernation were included.
The study aimed to enroll 800 patients, but
owing to problems with recruitment and funding, the study was stopped early. Of the 139
patients enrolled, 69 were randomized to PCI
and 45 underwent CABG. There were no differences in the incidence of all-cause mortality
and in quality of life [25] .
The Surgical Treatment for Ischemic Heart
Failure (STICH) trial was designed to define
the role of cardiac surgery in the treatment of
patients with heart failure and CAD [26] . The
study had two major hypotheses: the first was
to compare the optimal medical therapy with
surgical revascularization and the second was
that surgical ventricular reconstruction, when
added to CABG, would decrease the rate of
death or hospitalization owing to a cardiac
event when compared with CABG alone.
After a randomization of 1000 patients (499
assigned to CABG and 501 to CABG plus surgical ventricular reconstruction) in the arm of
the second hypothesis this study did not show
any clinical benefit of adding surgical ventricular reconstruction to CABG [27] . However, no
data have yet been reported concerning the
first hypothesis. Therefore, the results of this
randomized trial are underway to evaluate
the effect of CABG on revascularization in
CHF patients.
The Alberta Provincial Project for Outcomes
Assessment in Coronary Artery Disease
(APPROACH) trial used data obtained from
a prospective data collection initiative [28] .
In this study, a total of 4228 patients were
enrolled; a total of 2538 patients received
revascularization and a total of 1690 did not
receive revascularization. Mortality rates at
1 year were 11.8% in those who underwent
revascularization and 21.6% in those who did
not (hazard ratio: 0.52; 95% CI: 0.47–0.58).
The benefit of revascularization continued
up to the 7-year follow-up (hazard ratio:
0.50; 95% CI: 0.44–0.57). After propensity
score adjusting, patients undergoing CABG
appeared to have slightly better survival than
those who received PCI.
Much data supporting the benefit of PCI for
treating acute heart failure, presumably related
to myocardial stunning, have been reported.
94
Interv. Cardiol. (2011) 3(1)
Percutaneous revascularization with stenting
can be safely performed in patients with low EF
with acceptable late major adverse cardiac event
rates [29] .
Gioia and colleagues demonstrated for the
first time, that drug-eluting stent (DES) implantation in patients with severe LVD improves
mortality compared with the use of a bare-metal
stent alone [30] . The use of DESs in this study
decreased cardiovascular mortality by 78% and
was the only predictor of survival.
Conversely, a recent substudy of the Clinical
Outcomes Utilizing Revascularization and
Aggressive Drug Evaluation (COURAGE) trial
investigated the outcome of high-risk patients
(those with low EF or stabilized acute coronary
syndrome) [31] . Therefore, an initial strategy of
optimal medical therapy alone for these highrisk patients did not result in increased death or
MI at 4.6 years or worse angina at 1 year, but
it was associated with a high rate of crossover
to revascularization.
In a recent large registry of 55,709 patients,
Wallace et al. demonstrated that the severity
of LV systolic dysfunction was directly related
to hospital mortality and major adverse cardiac
events (MACE), in patients who underwent
elective PCI [32] . On the basis of this study’s
data, patients with EFs of 25% or less and
26–35% had fourfold and twofold increased
risks, respectively, of hospital mortality, independent of multiple other clinical and procedural risk factors. These findings were consistent across multiple subgroups, including gender,
heart failure, kidney disease, diabetes and multivessel CAD, and, therefore, we maintain that the
extent of systolic dysfunction is independently
important in risk assessment.
A single small randomized trial comparing
PCI with CABG in a low-EF population concluded that outcomes were similar with the two
revascularization methods [33] .
By contrast, a large registry report from
the State University of New York (USA) suggested that better outcomes were obtained
for patients with impaired LV function who
underwent CABG compared with those who
underwent stenting. They compared a total of
37,212 patients with multivessel disease who
underwent CABG (26% with EF <40%) and
a total of 22,102 patients who underwent PCI
(18.5% with EF <40%) from January 1997 to
December 2000 [34] . For the patients with an
EF less than 40% and with two- or three-vessel
disease with involvement of the proximal left
anterior descending coronary artery, the hazard
future science group
Coronary revascularization strategies in patients with chronic heart failure Review
ratios strongly favored CABG over stenting. The
hazard ratios were not significantly different for
other patients with two-vessel disease.
These results were confirmed by propensity
analysis of long-term outcomes after surgical
or percutaneous revascularization in patients
with multivessel disease and a high-risk profile, in which CABG was associated with better survival than PCI after adjustment for risk
profile [35] .
However, another small retrospective registry
did not show any clinical difference in terms
of mortality and major adverse cardio- and
cerebro-­vascular events rate in a selected highrisk patients cohort with severe LVD treated
with DES implantation or CABG [36] .
The recent Synergy Between Percutaneous
Coronary Intervention with Taxus and Cardiac
Surgery (SYNTAX) trial demonstrated lower
rates of MACE and/or major adverse cerebro­
vascular events at 1 year after CABG in comparison with PCI (12.4 vs 17.8%; p = 0.002)
in patients affected by three-vessel or left main
CAD, in large part guided by lower repeat revascularization (5.9 vs 13.5%; p < 0.001). Notably,
the rates of death and MI were similar between
the two groups and stroke was significantly more
likely to occur with CABG (2.2 vs 0.6% with
PCI; p = 0.003) [37] .
In practice, a careful revision of a patient’s
clinical history is needed to choose the most
appropriate revascularization approach. A history of previous bypass surgery is a common reason for prefering PCI over CABG, whereas the
need for concomitant mitral valve repair makes
a surgical approach more appealing. The ability
to achieve complete revascularization is often an
important topic when choosing between PCI
and surgical revascularization, with some believing that late outcome is influenced more by completeness of revascularization than by method.
It especially seems reasonable to try to achieve
revascularization of all viable arterial segments.
Finally, PCI is often the procedure of last resort
for patients who have been denied surgery. Table 1
highlights the factors that might influence the
selection of revascularization strategy.
Test for the assessment of viability
Viability testing may be useful to identify a
subset of patients with ischemic LVD who are
likely to benefit from cardiac revascularization
procedures. Viability may be evaluated by an
assortment of techniques, including single photon emission computed tomography (SPECT),
PET, dobutamine echocardiography and, most
recently, MRI.
„„ Nuclear imaging techniques
Single photon emission computed tomography
and PET rely predominantly on the demonstration of cellular integrity (intact cell membrane
and mitochondria) and metabolic functions
(preserved glucose utilization), respectively, to
identify viable myocardium. With SPECT, both
stress-induced perfusion abnormalities and resting isotope uptake of approximately 50–60%
predict functional recovery [38] . Compared with
PET, SPECT underestimates viability [39,40] ;
SPECT is widely available, but its lower-energy
tracers, lower spatial resolution and lack of builtin attenuation correction limit its diagnostic
accuracy. The most established PET technique
for assessing viability is the combined examination of myocardial perfusion (with either N-13
ammonia or rubidium-82) and myocardial
Table 1. Factors that may guide the selection of revascularization strategy.
Multiple comorbidities
PCI favored for
Focal lesions
Small vessel
Diffuse disease
Complex lesions
Proximal lesions
Multivessel disease
+
CABG favored for
+
+
+
+
+
Clinical factors
Previous CABG
COPD
Advanced age
Need for concomitant valve surgery
Multiple comorbidities
+
+
+
+
+
CABG: Coronary artery bypass grafting; COPD: Chronic obstructive pulmonary disease; PCI: Percutaneous
coronary intervention.
future science group
www.futuremedicine.com
95
Review Tomasello, Costanzo & Galassi
glucose metabolism (with F-18 fluorodeoxyglucose [FDG]). The most specific pattern for
functional recovery is the mismatch between
reduced perfusion and preserved metabolism [41] .
Hypocontractile regions with more than 50%
FDG uptake (compared with normal or remote
regions) might also recover contractile function
after revascularization, but at a lower frequency,
likely because of subendocardial scarring [38] .
With its built-in attenuation correction, greater
temporal and spatial resolution, and higherenergy tracers, PET has superior image quality
and high diagnostic accuracy. Its disadvantages
include limited availability, cost, complexity
and dependence of FDG uptake on the patient’s
metabolic state. Moreover, a recent randomized
trial did not demonstrate a significant reduction
in cardiac events in patients with LVD and suspected coronary disease for FDG PET-assisted
management versus standard care [42] .
„„ Dobutamine echocardiography
The most commonly used echocardiographic
technique for assessing viability relies on demonstrating contractile reserve with dobutamine
administration. Dobutamine increases heart rate,
blood pressure and contractility, and, therefore,
myocardial oxygen demand and coronary blood
flow. Functional improvement in hypocontractile
segments, with or without subsequent contractile
deterioration (biphasic response), indicates viability and ischemia and predicts functional recovery [43] . When conventional echocardiographic
imaging does not provide adequate images, both
harmonic imaging [44] and intravenous blood pool
contrast [45] can improve endocardial definition.
Although widely available and less technically
complex in comparison with other functional
testes, echocardiography is limited by its qualitative assessment, with high interobserver and intercenter variation and inadequate acoustic windows
in a substantial number of patients, even when
combined with harmonic imaging and contrast.
„„ MRI
MRI has enormous potential thanks to its major
attributes of high image quality and resolution
combined with nonionizing radiation and versatility. It can provide high-quality diagnostic
information about cardiac and valvular function, coronary anatomy, coronary flow reserve,
myocardial perfusion, myocardial viability,
contractile reserve and cardiac metabolism. It
allows the assessment of even subtle wall motion
disturbances resulting from the consistently
high endocardial border definition, and the
96
Interv. Cardiol. (2011) 3(1)
measurement of myocardial perfusion can be
integrated into the same examination, with the
high spatial resolution of the scans facilitating
the determination of the transmural extent of a
regional perfusion deficit.
Recently, the technique of late enhancement with gadolinium contrast agent has been
described. The gadolinium concentrates in the
necrotic area (in acute infarction) or scar tissue
(in chronic infarction) because of an increased
partition coefficient, and the infarct area becomes
bright [46] . There is a very close correlation
between the volume of signal enhancement and
infarct size in animal experiments of acute infarction. The technique has high resolution and
can define the transmural extent of necrosis and
scar, for the first time, in vivo. Although the technique has been recently developed, it has obvious
applications in defining whether infarction has
actually occurred in borderline cases.
The technique of late enhancement also has a
relevant clinical application in the assessment of
viability and it is an excellent technique for the
detection and quantification of MI, as reported
by many studies [47,48] . First-pass perfusion is the
most widely used MRI technique for the detection of reduced myocardial blood flow and yields
superior results compared with those of SPECT
[49] . Recently, the US FDA reported a warning
on the use of gadolinium contrast in patients
with impaired renal function (glomerular filtration rate <30 ml/min/1.73 m2) owing to an
increased risk of nephrogenic system fibrosis [101] .
In recent studies, the simple morphological
measure of the percentage of transmural replacement of normal myocardium by scar tissue, has
been demonstrated to be a powerful predictor of
post-revascularization contraction recovery [50] .
Segments with less than 50% transmural replacement had improved function, while those with
higher grades of transmural replacement failed
to improve [49] . This technique has many clinical advantages, including being morphologically
based, making analysis straightforward and that
there is no radiation burden. It is anticipated that
the late-enhancement technique will make a substantial clinical impact in the management of
infarction and its sequelae.
A recent meta-analysis has described the relative merits of dobutamine echocardiography,
tallium-201 and technetium-99m scintigraphy,
PET and MRI for the diagnosis of hibernating myocardium and the prediction of patients’
outcome. This study demonstrated a lower
sensitivity of dobutamine echocardiography
in comparison with other imaging techniques
future science group
Coronary revascularization strategies in patients with chronic heart failure Review
and a similar sensitivity compared with nuclear
tests. On the other hand, no significant changes
were observed in the specificity of these imaging
techniques [51] .
Nowadays, the viability tests do not play a
pivotal role in clinical decision making regarding patients with CHF; instead, their use is more
common to refine the therapeutical strategy in
those patients suitable for revascularization. In a
study similar to the OAT, but in which the decision to revascularize the infarct-related artery
was made considering the presence of myocardium viability assessed by a nuclear stress
test, PCI resulted in a better outcome in terms
of a lower rate of MACEs in comparison with
medical therapy. Moreover, LVEF remained
preserved in PCI patients, which underlines the
importance of viability for myocardial recovery
recovery [54] .
An updated guideline for CABG incorporated viability in its class IIa recommendation,
stating that a revascularization decision might
be undertaken in patients with poor LV function with significant viable noncontracting
myocardium, and recognized that a subgroup of
patients might experience benefit [55] . However,
there are no strict criteria to determine which
patients are too sick to be considered for revascularization. On the basis of the available literature, performing revascularization might be
a reasonable strategy when non­invasive testing
„„ Clinical implication
Nowadays, the decisions regarding revascularization in patients with ischemic severe LVD
are a challenge for clinicians. The benefits of
pharmacologic management are strongly evidence based and all patients should receive optimal medical management with recommended
agents according to current CHF guidelines
[52,102] . In addition, device therapy with defibrillators and possibly cardiac resynchronization therapy should be considered in many of
these patients [53] .
Routine coronary angiography in these
patients is not suggested in the American
College of Cardiology (ACC)/American Heart
Association (AHA) and the European Society of
Cardiology (ESC) guidelines, but in the case of
angina symptoms, both guidelines recommend,
as class I, the invasive assessment of CAD and
revascularization. Moreover, the guidelines also
recommend coronary angiography in patients
without symptoms but with a high risk of CAD.
Patient with CHF without
angina symptoms
High probability of LV
dysfunction by ischemic origin
Yes
No
Ischemia/viability
noninvasive test
Positive
Viability of
dysfunctional
myocardium >25%
Negative
Viability of
dysfunctional
myocardium <25%
Coronary angiography
Revascularization
PCI/CABG
Medical therapy/
transplant/IDC-CRT
Figure 2. Practical algorithm for the management of a chronic heart failure patient without
angina symptoms.
CABG: Coronary artery bypass graft; CHF: Chronic heart failure; IDC-CRT: Implanted defibrillator
cardioverter–cardiac resynchronization therapy; LV: Left ventricle; PCI: Percutaneous
coronary intervention.
future science group
www.futuremedicine.com
97
Review Tomasello, Costanzo & Galassi
shows at least 25–30% LV viability of dysfunctional myocardium. However, it should be
underlined that in patients with advanced age
or who have compelling comorbidities, such
as multi­organ failure, a conservative management is obviously required. Figur e 2 shows a
possible algorithm for the treatment of patients
with CHF by ischemic origin in the absence of
angina symptoms.
For these reasons, viability testing might
have a potential role in patient selection and in
predicting response to therapy [56] . The choice
of viability techniques depends on many factors, including availability, expertise and cost.
Although reported diagnostic accuracies differ
among techniques for predicting functional
recovery, there are no data to meaningfully
compare individual techniques with respect to
patient outcome.
Conclusion & future perspective
The outcomes of several multiple observational
studies support the benefit of revascularization
in patients with CHF. Viability testing can identify those patients who may have hibernating or
stunned myocardium and may play a supportive role in clinical decision making. The choice
of revascularization technique, either surgical
or percutaneous, should be made on the basis
of anatomical and clinical characteristics. The
first hypothesis of the STICH randomized trial
should better define the role of revascularization in this subset of patients, clarifying how
the revascularization strategy should be chosen. However, other large randomized trials are
needed to assess the role of viability testing, which
will allow the development of more comprehensive clinical guidelines for the management of
CHF patients.
Financial & competing interests disclosure
The authors have no relevant affiliations or financial
involvement with any organization or entity with a financial interest in or financial conflict with the subject matter
or materials discussed in the manuscript. This includes
employment, consultancies, honoraria, stock ownership or
options, expert testimony, grants or patents received or
pending, or royalties.
No writing assistance was utilized in the production of
this manuscript.
Executive summary
Epidemiology
ƒƒ Chronic heart failure (CHF) is a worldwide public health problem of major and ever-expanding proportions. In Europe, there are at least
15 million patients with CHF and its prevalence in 70–80-year-olds is between 10 and 20%.
Rationale for the revascularization of CHF patients
ƒƒ Revascularization of patients with CHF may improve patient outcomes by several mechanisms:
- Chronically dysfunctional ischemic myocardium can improve function following revascularization.
- Revascularization reduces repeated episodes of ischemia, which determines prolonged post-ischemic contractile dysfunction.
- Restoration of blood flow to ischemic myocardium adjacent to endocardial scar tissue relieves resting ischemia and enhances the
reparative process of the myocyte contractile machinery influencing the post-infarct ventricular remodeling.
- Revascularization may improve diastolic function and may even reduce dynamic mitral regurgitation, culminating in further
symptomatic improvement.
- Revascularization can reduce the incidence of ventricular arrhythmias related to the re-entry phenomenon.
Selection of revascularization strategy
ƒƒ Data reported in the literature showed that both surgical and percutaneous revascularization can reduce the mortality of CHF patients.
Although there is a lack a conclusive evidence regarding the best revascularization modality, it is reasonable to select a surgical
approach in case of multivessel or complex coronary disease, concomitant valve disease and the absence of co-morbidities. Conversely,
percutaneous coronary intervention is preferably selected in case of single-vessel coronary disease and high-risk-profile patients.
Test for the assessment of myocardium viability
ƒƒ Viability testing may be useful to identify a subset of patients with ischemic left ventricular dysfunction who are likely to benefit from
cardiac revascularization procedures. Viability may be evaluated by an assortment of techniques including nuclear imaging, dobutamine
echocardiography and, most recently, MRI.
Clinical implication
ƒƒ On the basis of the available literature, performing revascularization might be a reasonable strategy when noninvasive testing reveals at
least 25–30% left ventricular viability of a dysfunctional myocardium. However, it should be underlined that in patients with advanced
age or who have compelling comorbidities; such as multiorgan failure, conservative management is obviously required.
Conclusion & future perspective
ƒƒ The selection method of revascularization strategy in patients affected by CHF remains debatable. The first hypothesis of the Surgical
Treatment for Ischemic Heart Failure randomized trial should better define the role of revascularization in patients affected by CHF
clarifying how a revascularization strategy should be chosen.
98
Interv. Cardiol. (2011) 3(1)
future science group
Coronary revascularization strategies in patients with chronic heart failure Review
Bibliography
11
Papers of special note have been highlighted as:
nn of considerable interest
1
2
3
4
5
6
Thom T, Haase N, Rosamond W et al.; for
the American Heart Association Statistics
Committee and Stroke Statistics
Subcommittee: heart disease and stroke
statistics – 2006 update: a report from the
American Heart Association Statistics
Committee and Stroke Statistics
Subcommittee. Circulation 113, e85–e151
(2006).
Hunt SA, Baker DW, Chin MH et al.:
ACC/AHA guidelines for the evaluation and
management of chronic heart failure in the
adult: a report of the American College of
Cardiology/American Heart Association
Task Force on Practice Guidelines
(Committee to Revise the 1995 Guidelines
for the Evaluation and Management of Heart
Failure). Circulation 104, 2996 –3007
(2001).
Adams KF Jr, Fonarow GC, Emerman CL
et al.: Characteristics and outcomes of
patients hospitalized for heart failure in the
United States: rationale, design, and
preliminary observations from the first
100,000 cases in the Acute Decompensated
Heart Failure National Registry
(ADHERE). Am. Heart J. 149, 209–216
(2005).
Gheorghiade M, Bonow RO: Chronic heart
failure in the United States: a manifestation
of coronary artery disease. Circulation 97,
282–289 (1998).
Myocardial Infarction Redefined. A
consensus document of The Joint European
Society of Cardiology/American College of
Cardiology Committee for the Redefinition of
Myocardial Infarction and The Joint
European Society of Cardiology/American
College of Cardiology Committee. J. Am.
Coll. Cardiol. 3, 959–969 (2000).
Buja LM: Modulation of the myocardial
response to injury. Lab. Invest. 78, 1345–1373
(1998).
7
Kajstura J, Cheng W, Reiss K et al.: Apoptotic
and necrotic myocyte cell deaths are
independent contributing variables of infarct
size in rats. Lab. Invest. 74, 86–107 (1996).
8
Fishbein MC, Maclean D, Maroko PR: The
histopathologic evolution of myocardial
infarction. Chest 73, 743–749 (1978).
9
Mallory GK, White PD, Salcedo-Salga J: The
speed of healing of myocardial infarction: a
study of the pathologic anatomy in 72 cases.
Am. Heart J. 18, 647–671 (1939).
10
Rahimtoola SH: The hibernating
myocardium. Am. Heart J. 117, 211–221
(1989).
future science group
Dispersyn GD, Borgers M, Flameng W:
Apoptosis in chronic hibernating
myocardium: sleeping to death? Cardiovasc.
Res. 45, 696–703 (2000).
with moderate or severe left ventricular
systolic dysfunction. JAMA 272, 1528–1534
(1994).
24 Cleland JG, Freemantle N, Ball SG et al. The
heart failure revascularization trial
(HEART): rationale, design and
methodology. Eur. J. Heart Fail. 5, 295–303
(2003).
12 Bax JJ, Visser FC, Poldermans D et al.: Time
course of functional recovery of stunned and
hibernating segments after surgical
revascularization. Circulation 104(Suppl. 1),
I314–I318 (2001).
25 Coletta AP, Cleland JG, Cullington D,
Clark AL: Clinical trials update from Heart
Rhytm 2008 and Heart Failure 2008:
ATHENA, URGENT, INH study, HEART
and CK-1827452. Eur. J. Heart Fail. 10,
917–920 (2008).
13 Pitt M, Dutka D, Pagano D, Camici P,
Bonser R: The naural history of myocardium
awating revascularization in patients with
impaired left ventricular function. Eur. Heart
J. 25, 500–507 (2004).
14
15
16
17
18
19
Kim SJ, Depre C, Vatner SF: Novel
mechanisms mediating stunned myocardium.
Heart Fail. Rev. 8, 143–153 (2003).
Rahimtoola SH, La Canna G, Ferrari R et al.:
Hibernating myocardium another piece of the
puzzle falls into place. J. Am. Coll. Cardiol.
47, 978–980 (2006).
Menon V, Pearte CA, Buller CE et al.: Lack
of benefit from percutaneous intervention of
persistently occluded infarct arteries after the
acute phase of myocardial infarction is time
independent: insights from Occluded Artery
Trial. Eur. Heart J. 30, 183–191 (2009).
Cantor WJ, Baptista SB, Srinivas VS et al.:
Impact of stress testing before percutaneous
coronary intervention or medical
management on outcomes of patients with
persistent total occlusion after myocardial
infarction: analysis from the occluded artery
trial. Am. Heart J. 157, 666–672 (2009).
Samady H, Elefteriades JA, Abbott BG et al.:
Failure to improve left ventricular function
after coronary revascularization for ischemic
cardiomyopathy is not associated with worse
outcome. Circulation 100, 1298–1304
(1999).
Braunwald E: Myocardial reperfusion,
limitations of infarct size, reduction of left
ventricular dysfunction and improved
survival: should the paradigm be expanded?
Circulation 79, 441–444 (1989).
26 Velazquez EJ, Lee KL, O’Connor CM et al.:
The rationale and design of the Surgical
Treatment for Ischemic Heart Failure
(STICH) trial. J. Thorac. Cardiovasc. Surg.
134, 1540–1547 (2007).
nn
27 Jones RH, Valazquez EJ, Michler RE et al.:
Coronary bypass surgery with or without
surgical ventricular reconstruction. N. Engl. J.
Med. 17, 1705–1717 (2009).
nn
Knudtson ML, Graham MM: for the
APPROACH Investigators: revascularization
in patients with heart failure. CMAJ 175,
361–365 (2006).
29 Di Sciascio G, Patti G, D’Ambrosio A et al.:
Coronary stenting in patients with depressed
left ventricular function: acute and long-term
results in a selected population. Catheter
Cardiovasc. Interv. 59, 429–433 (2003).
30 Gioia G, Matthai W, Benassi A, Rana H,
Levite HA, Ewing LG: Improved survival
with drug-eluting stent implantation in
comparison with bare metal stent in patients
with severe left ventricular dysfunction.
Catheter Cardiovasc. Interv. 68, 392–398
(2006).
Results of coronary artery surgery in patients
with poor left ventricular dysfunction
(CASS). Circulation 68, 785–795 (1983).
Bounous EP, Mark DB, Pollock BG et al.:
Surgical survival benefits for coronary disease
patients with left ventricular dysfunction.
Circulation 78, 1151–1157 (1988).
31
22 Smith PK, Califf RM, Tuttle RH et al.:
Selection of surgical or percutaneous coronary
intervention provides differential longevity
benefit. Ann. Thorac. Surg. 82, 1420–1428
(2006).
23 Baker DW, Jones R, Hodges J et al.:
Management of heart failure. III. The role of
revascularization in the treatment of patients
www.futuremedicine.com
The largest randomized trial that analyzed
the outcome of patients with CHF who
underwent CABG with or without
ventricular surgical reconstruction.
28 Tsuyuki RT, Shrive FM, Galbraith PD,
20 Alderman E, Fisher LD, Litwin P et al.:
21
Design of the first randomized trial in
patients with chronic heart failure (CHF)
treated by medical therapy, coronary artery
bypass grafting (CABG) or percutaneous
coronary intervention.
nn
Maron DJ, Spertus JA, Mancini GB et al.:
Impact of an initial strategy of medical
therapy without percutaneous coronary
intervention in high-risk patients from the
Clinical Outcomes Utilizing
Revascularization and Aggressive DruG
Evaluation (COURAGE) trial. Am. J.
Cardiol. 104, 1055–1062 (2009).
Provided important information regarding
the therapeutic strategy for ischemic
non-high-risk patients.
99
Review Tomasello, Costanzo & Galassi
32 Wallace TW, Berger JS, Wang A,
41 Knuuti J, Schelbert HR, Bax JJ: The need for
Velazquez EJ, Brown DL: Impact of left
ventricular dysfunction on hospital mortality
among patients undergoing elective
percutaneous coronary intervention. Am. J.
Cardiol. 103, 355–360 (2009).
33 Sedlis SP, Ramanathan KB, Morrison DA
et al.: Outcome of percutaneous coronary
intervention versus coronary bypass grafting
for patients with low left ventricular ejection
fractions, unstable angina pectoris, and risk
factors for adverse outcome with bypass (the
AWESOME randomized trial and registry).
Am. J. Cardiol. 94, 118–120 (2004).
42 Beanlands RS, Nichol G, Huszti E et al.:
F-18-fluorodeoxyglucose positron emission
tomography imaging-assisted management of
patients with severe left ventricular
dysfunction and suspected coronary disease.
A randomized, controlled trial (PARR-2).
J. Am. Coll. Cardiol. 50, 2002–2012 (2007).
Zoghbi WA, Marwick TH: Myocardial
viability during dobutamine
echocardiography predicts survival in patients
with coronary artery disease and severe left
ventricular systolic dysfunction. J. Am. Coll.
Cardiol. 32, 921–926 (1998).
Long-term outcomes of coronary-artery
bypass grafting versus stent implantation.
N. Engl. J. Med. 352, 2174–2183 (2005).
35
Large retrospective study on long-term
outcomes on the basis of the
revascularization strategy.
Brener SJ, Lytle BW, Casserly IP et al.:
Propensity analysis of long-term survival after
surgical or percutaneous revascularization in
patients with multivessel coronary artery
disease and high-risk features. Circulation
109, 2290–2295 (2004).
new tune for an old fiddle? Heart 83, 131–132
(2000).
45
Colombo A, Holmes DR et al.: Percutaneous
coronary intervention versus coronary artery
bypass grafting for severe coronary artery
disease. N. Engl. J. Med. 360, 961–972
(2009).
nn
First randomized trial that compared the
long-term outcome of patients treated with
percutaneous coronary intervention with
drug-eluting stent versus CABG.
Relationship of MRI delayed contrast
enhancement to irreversible injury, infarct
age, and contractile function. Circulation 100,
1992–2002 (1999).
40 Sawada SG, Allman KC, Muzik O et al.:
Positron emission tomography detects
evidence of viability in rest technetium-99m
sestamibi defects. J. Am. Coll. Cardiol. 23,
92–98 (1994).
55
nn
MRIMPACT: comparison of perfusioncardiac magnetic resonance with singlephoton emission computed tomography for
the detection of coronary artery disease in a
multicentre, multivendor, randomized trial.
Eur. Heart J. 29, 480–489 (2008).
50 Kim RJ, Wu E, Rafael A et al.: The use of
„„ Websites
101 Information on gadolinium-containing
contrast agents
www.fda.gov/drugs/drugsafety/
postmarketdrugsafetyinformation­
forpatientsandproviders/ucm142882.htm
102 Hunt SA, Abraham WT, Chin MH et al.
ACC/AHA 2005 guideline update for the
diagnosis and management of chronic heart
failure in the adult: a report of the American
College of Cardiology/American Heart
Association Task Force on Practice Guidelines
(Writing Committee to update the 2001
guidelines for the evaluation and management
of heart failure). American College of
Cardiology Web Site 2005
www.acc.org/clinical/guidelines/failure//
index.pdf.
contrast-enhanced magnetic resonance
imaging to identify reversible myocardial
dysfunction. N. Engl. J. Med. 343, 1445–1453
(2000).
51
Schinkel AF, Bax JJ, Poldermans D,
Elhendy A, Ferrari R, Rahimtoola SH.
Hibernating myocardium: diagnosis and
patient outcomes. Curr. Probl. Cardiol. 32,
375–410 (2007).
nn
100
Interv. Cardiol. (2011) 3(1)
American guideline update for
CABG surgery.
Horton R, Camici PG, Bonser RS: Coronary
artery bypass surgery as treatment for
ischemic heart failure: the predictive value of
viability assessment with quantitative positron
emission tomography for symptomatic and
functional outcome. J. Thorac. Cardiovasc.
Surg. 115, 791–779 (1998).
Judd RM: Myocardial magnetic resonance
imaging contrast agent concentrations after
reversible and irreversible ischemic injury.
Circulation 105, 224–229 (2002).
49 Schwitter J, Wacker C, van Rossum A et al.:
Eagle KA, Guyton RA, Davidoff R et al.:
ACC/AHA 2004 guideline update for
coronary artery bypass graft surgery:
summary article: a report of the American
College of Cardiology/American Heart
Association Task Force on Practice Guidelines
(Committee to Update the 1999 Guidelines
for Coronary Artery Bypass Graft Surgery).
Circulation 110, 1168–1176 (2004).
56 Pagano D, Townend JN, Littler WA,
48 Rehwald WG, Fieno DS, Chen EL, Kim RJ,
Radionuclide techniques for the assessment of
myocardial viability and hibernation. Heart
90(Suppl. 5), V26–V33 (2004).
Nienaber C, Phelps ME, Schelbert HR:
Positron emission tomography detects
metabolic viability in myocardium with
persistent 24-hour single-photon emission
computed tomography 201Tl defects.
Circulation 86, 1357–1369 (1992).
et al.: Effects of percutaneous coronary
interventions in silent ischemia after
myocardial infarction: the SWISSI II
randomized controlled trial. JAMA 297,
1985–1991 (2007).
47 Kim RJ, Fieno DS, Parrish TB et al.:
38 Bax JJ, van der Wall EE, Harbinson M:
39 Brunken RC, Mody FV, Hawkins RA,
54 Erne P, Schoenenberger AW, Burckhardt D
46 Kim RJ, Fieno DS, Parrish RB et al.:
37 Serruys PW, Morice MC, Kappetein AP,
European guidelines on CHF.
heart failure: when and for whom? Am. J.
Cardiovasc. Drugs 8, 147–153 (2008).
Zoghbi WA: Evaluation of myocardial
viability with contrast echocardiography. Am.
J. Cardiol. 90, 65J–71J (2002).
Relationship of MRI delayed contrast
enhancement to irreversible injury, infarct
age, and contractile function. Circulation 100,
185–192 (1999).
Dickstein K, Cohen-Solal A, Filippatos G
et al: ESC guidelines for the diagnosis and
treatment of acute and chronic heart failure
2008: the Task Force for the Diagnosis and
Treatment of Acute and Chronic Heart
Failure 2008 of the European Society of
Cardiology. Developed in collaboration with
the Heart Failure Association of the ESC
(HFA) and endorsed by the European Society
of Intensive Care Medicine (ESICM). Eur. J.
Heart Fail. 10, 933–989 (2008).
53 Shams OF, Ventura HO: Device therapy for
44 Monaghan MJ: Second harmonic imaging: a
36 Gioia G, Matthai W, Gillin K et al.:
Revascularization in severe left ventricular
dysfunction: outcome comparison of
drug-eluting stent implantation versus
coronary artery by-pass grafting. Catheter
Cardiovasc. Interv. 70, 26–33 (2007).
nn
43 Afridi I, Grayburn PA, Panza JA, Oh JK,
34 Hannan EL, Racz MJ, Walford G et al.:
nn
52
standardisation of cardiac FDG PET imaging
in the evaluation of myocardial viability in
patients with chronic ischaemic left
ventricular dysfunction. Eur. J. Nucl. Med.
29, 1257–1266 (2002).
US guidelines on CHF.
future science group