Eric J. Velazquez

Comparison of coronary artery bypass grafting versus medical therapy on long-term outcome in patients with ischemic cardiomyopathy (a 25-year experience from the Duke Cardiovascular Disease Databank)

In this observational treatment comparison in a single center over 25 years, we sought to assess long-term outcomes of coronary artery bypass surgery (CABG) or medical therapy in patients with heart failure, coronary artery disease, and left ventricular systolic dysfunction. The benefit of CABG compared with medical therapy alone in these patients is a source of continuing clinical debate. This analysis considered all patients with New York Heart Association class II or greater symptoms, 1 or more epicardial coronary vessels with a > or = 75% stenosis, and a left ventricular ejection fraction <40% who underwent an initial cardiac catheterization at Duke University Medical Center from 1969 to 1994. Patients were classified into the medical therapy group (n = 1,052) or CABG group (n = 339) depending on which therapy they received within 30 days of catheterization. Cardiovascular event and mortality follow-up commenced on the day of CABG, or at catheterization plus 8 days (the mean time to CABG) for the medical therapy arm. A Cox proportional-hazards model was employed to adjust for differences in baseline characteristics. In the first 30 days from baseline, there was an interaction between treatment strategy and number of diseased vessels. Unadjusted, event-free, and adjusted survival strongly favored CABG over medical therapy after 30 days to >10 years regardless of the extent of coronary disease (p <0.001). Thus, regardless of the severity of coronary disease, heart failure symptoms, or ventricular dysfunction, CABG provides extended event-free and survival advantage over medical therapy alone in patients with an ischemic cardiomyopathy.

Evaluation of mechanical dyssynchrony and myocardial perfusion using phase analysis of gated SPECT imaging in patients with left ventricular dysfunction

AbstractBackground. Using phase analysis of gated single photon emission computed tomography (SPECT) imaging, we examined the relation between myocardial perfusion, degree of electrical dyssynchrony, and degree of SPECT-derived mechanical dyssynchrony in patients with left ventricular (LV) dysfunction. Methods and Results. We retrospectively examined 125 patients with LV dysfunction and ejection fraction of 35% or lower. Fourier analysis converts regional myocardial counts into a continuous thickening function, allowing resolution of phase of onset of myocardial thickening. The SD of LV phase distribution (phase SD) and histogram bandwidth describe LV phase dispersion as a measure of dyssynchrony. Heart failure (HF) patients with perfusion abnormalities have higher degrees of dyssynchrony measured by median phase SD (45.5° vs 27.7°, P<.0001) and bandwidth (117.0° vs 73.0°, P=.0006). HF patients with prolonged QRS durations have higher degrees of dyssynchrony measured by median phase SD (54.1° vs 34.7°, P<.0001) and bandwidth (136.5° vs 99.0°, P=.0005). Mild to moderate correlations exist between QRS duration and phase analysis indices of phase SD (r=0.50) and bandwidth (r=0.40). Mechanical dyssynchrony (phase SD >43°) was 43.2%. Conclusions. HF patients with perfusion abnormalities or prolonged QRS durations have higher degrees of mechanical dyssynchrony. Gated SPECT myocardial perfusion imaging can quantify myocardial function, perfusion, and dyssynchrony and may help in evaluating patients for cardiac resynchronization therapy. (J Nucl Cardiol 2008;15:663-70.)

Acute heart failure complicating acute coronary syndromes: a deadly intersection.

Patients manifesting symptomatic pulmonary congestion during an acute myocardial infarction have long been recognized to be at heightened risk of both short- and long-term mortality.1–3 Acute heart failure (AHF) complicates acute myocardial infarction as a result of a complex interaction of structural, hemodynamic, neurohormonal, and genetic maladaptations. Abrupt myocyte loss leading to contractile dysfunction and AHF is an obvious mechanism, and the extent of biomarker elevation correlates with prognosis and the range of functional recovery.4 In those without extensive myocyte necrosis, postischemic left ventricular systolic dysfunction (LVSD) leading to AHF can result from transient myocardial stunning or hibernation depending on the extent of coronary reperfusion.5 Ventricular remodeling can increase wall stress to viable regions that may be relatively underperfused, furthering ischemia and adding to this cycle. Ischemia-induced impairment in myocardial relaxation can increase left ventricular filling pressures irrespective of global systolic function and lead to AHF. Furthermore, ischemia can also precipitate acute mitral regurgitation in some patients, contributing to the risk of pulmonary congestion. Recent data also suggest that AHF potentiates apoptosis in and outside the infarct zone,6 which focuses attention beyond mechanics, hemodynamics, and perfusion to alterations in signaling pathways and genetic expression. Regardless of which processes dominate in individual patients, it is clear that the intersection of AHF and myocardial infarction remains deadly even in the current era of acute reperfusion.7 See p 494 In this issue of Circulation , the Global Registry of Acute Coronary Events (GRACE) investigators8 expand on our understanding of the interrelation between AHF and acute coronary syndrome (ACS), clarify the impact for patients across the spectrum of ACS presentations, and provide disturbing revelations on …

Extent of coronary and myocardial disease and benefit from surgical revascularization in ischemic LV dysfunction [Corrected].

BACKGROUND Patients with ischemic left ventricular dysfunction have higher operative risk with coronary artery bypass graft surgery (CABG). However, those whose early risk is surpassed by subsequent survival benefit have not been identified. OBJECTIVES This study sought to examine the impact of anatomic variables associated with poor prognosis on the effect of CABG in ischemic cardiomyopathy. METHODS All 1,212 patients in the STICH (Surgical Treatment of IsChemic Heart failure) surgical revascularization trial were included. Patients had coronary artery disease (CAD) and ejection fraction (EF) of ≤35% and were randomized to receive CABG plus medical therapy or optimal medical therapy (OMT) alone. This study focused on 3 prognostic factors: presence of 3-vessel CAD, EF below the median (27%), and end-systolic volume index (ESVI) above the median (79 ml/m(2)). Patients were categorized as having 0 to 1 or 2 to 3 of these factors. RESULTS Patients with 2 to 3 prognostic factors (n = 636) had reduced mortality with CABG compared with those who received OMT (hazard ratio [HR]: 0.71; 95% confidence interval [CI]: 0.56 to 0.89; p = 0.004); CABG had no such effect in patients with 0 to 1 factor (HR: 1.08; 95% CI: 0.81 to 1.44; p = 0.591). There was a significant interaction between the number of factors and the effect of CABG on mortality (p = 0.022). Although 30-day risk with CABG was higher, a net beneficial effect of CABG relative to OMT was observed at >2 years in patients with 2 to 3 factors (HR: 0.53; 95% CI: 0.37 to 0.75; p<0.001) but not in those with 0 to 1 factor (HR: 0.88; 95% CI: 0.59 to 1.31; p = 0.535). CONCLUSIONS Patients with more advanced ischemic cardiomyopathy receive greater benefit from CABG. This supports the indication for surgical revascularization in patients with more extensive CAD and worse myocardial dysfunction and remodeling. (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease [STICH]; NCT00023595).

Exercise Capacity and Mortality in Patients With Ischemic Left Ventricular Dysfunction Randomized to Coronary Artery Bypass Graft Surgery or Medical Therapy: An Analysis From the STICH Trial (Surgical Treatment for Ischemic Heart Failure)

OBJECTIVES The objective of this study was to assess the prognostic significance of exercise capacity in patients with ischemic left ventricular (LV) dysfunction eligible for coronary artery bypass graft surgery (CABG). BACKGROUND Poor exercise capacity is associated with mortality, but it is not known how this influences the benefits and risks of CABG compared with medical therapy. METHODS In an exploratory analysis, physical activity was assessed by questionnaire and 6-min walk test in 1,212 patients before randomization to CABG (n = 610) or medical management (n = 602) in the STICH (Surgical Treatment for Ischemic Heart Failure) trial. Mortality (n = 462) was compared by treatment allocation during 56 months (interquartile range: 48 to 68 months) of follow-up for subjects able (n = 682) and unable (n = 530) to walk 300 m in 6 min and with less (Physical Ability Score [PAS] >55, n = 749) and more (PAS ≤55, n = 433) limitation by dyspnea or fatigue. RESULTS Compared with medical therapy, mortality was lower for patients randomized to CABG who walked ≥300 m (hazard ratio [HR]: 0.77; 95% confidence interval [CI]: 0.59 to 0.99; p = 0.038) and those with a PAS >55 (HR: 0.79; 95% CI: 0.62 to 1.01; p = 0.061). Patients unable to walk 300 m or with a PAS ≤55 had higher mortality during the first 60 days with CABG (HR: 3.24; 95% CI: 1.64 to 6.83; p = 0.002) and no significant benefit from CABG during total follow-up (HR: 0.95; 95% CI: 0.75 to 1.19; p = 0.626; interaction p = 0.167). CONCLUSIONS These observations suggest that patients with ischemic left ventricular dysfunction and poor exercise capacity have increased early risk and similar 5-year mortality with CABG compared with medical therapy, whereas those with better exercise capacity have improved survival with CABG. (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease [STICH]; NCT00023595).

Prognostic Significance of Biomarkers in Predicting Outcome in Patients With Coronary Artery Disease and Left Ventricular Dysfunction Results of the Biomarker Substudy of the Surgical Treatment for Ischemic Heart Failure Trials

Background—Patients with heart failure and coronary artery disease often undergo coronary artery bypass grafting, but assessment of the risk of an adverse outcome in these patients is difficult. To evaluate the ability of biomarkers to contribute independent prognostic information in these patients, we measured levels in patients enrolled in the biomarker substudies of the Surgical Treatment for Ischemic Heart Failure (STICH) trials. Patients in STICH Hypothesis 1 were randomized to medical therapy or coronary artery bypass grafting, whereas those in STICH Hypothesis 2 were randomized to coronary artery bypass grafting or coronary artery bypass grafting with left ventricular reconstruction. Methods and Results—In substudy patients assigned to STICH Hypothesis 1 (n=606), plasma levels of soluble tumor necrosis factor-&agr; receptor-1 (sTNFR-1) and brain natriuretic peptide (BNP) were highly predictive of the primary outcome variable of mortality by univariate analysis (BNP: &khgr;2=40.6; P<0.0001 and sTNFR-1: &khgr;2=38.9; P<0.0001). When considered in the context of multivariable analysis, both BNP and sTNFR-1 contributed independent prognostic information beyond the information provided by a large array of clinical factors independent of treatment assignment. Consistent results were seen when assessing the predictive value of BNP and sTNFR-1 in patients assigned to STICH Hypothesis 2 (n=626). Both plasma levels of BNP (&khgr;2=30.3) and sTNFR-1 (&khgr;2=45.5) were highly predictive in univariate analysis (P<0.0001) and in multivariable analysis for the primary end point of death or cardiac hospitalization. In multivariable analysis, the prognostic information contributed by BNP (&khgr;2=6.0; P=0.049) and sTNFR-1 (&khgr;2=8.8; P=0.003) remained statistically significant even after accounting for other clinical information. Although the biomarkers added little discriminatory improvement to the clinical factors (increase in c-index ⩽0.1), net reclassification improvement for the primary end points was 0.29 for BNP and 0.21 for sTNFR-1 in the Hypothesis 1 cohort, and 0.15 for BNP and 0.30 for sTNFR-1 in the Hypothesis 2 cohort, reflecting important predictive improvement. Conclusions—Elevated levels of sTNFR-1 and BNP are strongly associated with outcomes, independent of therapy, in 2 large and independent studies, thus providing important cross-validation for the prognostic importance of these 2 biomarkers.

Usefulness of Beta Blockers in High-Risk Patients After Myocardial Infarction in Conjunction With Captopril and/or Valsartan (from the VALsartan In Acute Myocardial Infarction [VALIANT] Trial)

Concern has been raised about combining beta blockers with angiotensin-receptor blockers in patients with heart failure. The VALsartan In Acute myocardial infarction (VALIANT) trial enrolled 14,703 patients with myocardial infarction complicated by heart failure or documented left ventricular systolic dysfunction. These patients were randomly allocated to treatment with valsartan, captopril, or both. Physicians were also encouraged to prescribe beta blockers because of previous evidence of benefit. The baseline characteristics, treatments, and outcomes were compared among 4 groups: patients taking beta blockers at admission only, at discharge only, at both admission and discharge, and neither. Patients treated with beta blockers were at lower risk than those not treated at any period. Those treated with beta blockers at both intervals had a lower 3-year mortality rate (17.7%) than those treated only at randomization (30.7%) or only at discharge (25.9%). The greatest mortality (35.1%) occurred in patients not treated at either point. No statistically significant interaction with prognosis was observed between beta-blocker use and treatment with valsartan or valsartan plus captopril. Patients discharged with a beta blocker had a significant survival advantage after adjustment for differences in baseline characteristics and intervening complications (hazard ratio 0.89, 95% confidence interval 0.81 to 0.98, p = 0.02). This association was most pronounced in patients prescribed consistent beta blockers at randomization and discharge and was present in both patients with impaired and those with preserved systolic left ventricular function. These results have further confirmed that beta blockers reduce the risk of death and nonfatal cardiovascular events in patients with heart failure or systolic left ventricular dysfunction after myocardial infarction. In conclusion, no evidence was found of adverse interactions between the angiotensin-receptor blocker valsartan and beta blockers or of a negative effect of the combination of valsartan, captopril, and beta blockers.

Variability in Ejection Fraction Measured By Echocardiography, Gated Single-Photon Emission Computed Tomography, and Cardiac Magnetic Resonance in Patients With Coronary Artery Disease and Left Ventricular Dysfunction

Key Points Question What is the variability in left ventricular ejection fraction (LVEF) as measured by different cardiac imaging modalities? Findings In this multicenter diagnostic study of 2032 patients with coronary artery disease and LVEF of 35% or less with imaging interpreted by core laboratories, correlation of LVEF between modalities ranged from r = 0.493 (for biplane echocardiography and cardiovascular magnetic resonance) to r = 0.660 (for cardiovascular magnetic resonance and gated single-photon emission computed tomography). There was no systematic overestimation or underestimation of LVEF for any modality. Meaning There is substantial variability in LVEF assessment between modalities, which should be considered in trial design and clinical management.

IMPAIRED LEFT VENTRICULAR GLOBAL LONGITUDINAL STRAIN IN PATIENTS WITH HEART FAILURE WITH PRESERVED EJECTION FRACTION: INSIGHTS FROM THE RELAX TRIAL

While abnormal resting left ventricular (LV) global longitudinal strain (GLS) has been described in patients with heart failure with preserved ejection fraction (HFpEF), its prevalence and clinical significance are poorly understood. Patients enrolled in the RELAX trial of sildenafil in HFpEF (EF