Studies investigating bone marrow stem cell therapy (BMSCT) in patients with chronic ischemic cardiomyopathy have yielded mixed results. A meta-analysis of randomized controlled trials of BMSCT in ...patients with chronic ischemic cardiomyopathy was undertaken to assess its efficacy and the best route of administration. The MEDLINE, Embase, Cumulative Index to Nursing & Allied Health Literature, and Cochrane Library databases were searched through April 2012 for randomized controlled trials that investigated the impact of BMSCT and its route of administration on left ventricular (LV) function in patients with chronic ischemic cardiomyopathy and systolic dysfunction. Of the 226 reports identified, 10 randomized controlled trials including 519 patients (average LV ejection fraction LVEF at baseline 32 ± 7%) were included in the analysis. On the basis of a random-effects model, BMSCT improved the LVEF at 6 months by 4.48% (95% confidence interval CI 2.43% to 6.53%, p = 0.0001). A greater improvement in the LVEF was seen with intramyocardial injection compared with intracoronary infusion (5.13% 95% CI 3.17% to 7.10%, p <0.00001, vs 2.32% 95% CI −2.06% to 6.70%, p = 0.30). Overall, there were reductions in LV end-systolic volume of −20.64 ml (95% CI −33.21 to −8.07, p = 0.001) and LV end-diastolic volume of −16.71 ml (95% CI −31.36 to −2.06, p = 0.03). In conclusion, stem cell therapy may improve LVEF and favorably remodel the heart in patients with chronic ischemic cardiomyopathy. On the basis of current limited data, intramyocardial injection may be superior to intracoronary infusion in patients with LV systolic dysfunction.
Pulmonary vein isolation (PVI) is recognized as a potentially curative treatment for atrial fibrillation (AF). Ablation of complex fractionated atrial electrograms (CFAEs) in addition to PVI has been ...advocated as a means to improve procedural outcomes, but the benefit remains unclear.
This study sought t synthesize the available data testing the incremental benefit of adding CFAE ablation to PVI.
We performed a meta-analysis of controlled studies comparing the effect of PVI with CFAE ablation vs. PVI alone in patients with paroxysmal and nonparoxysmal AF.
Of the 481 reports identified, 8 studies met our inclusion criteria. There was a statistically significant increase in freedom from atrial tachyarrhythmia (AT) with the addition of CFAE ablation (relative risk RR 1.15, P = .03). In the 5 reports of nonparoxysmal AF (3 randomized controlled trials, 1 controlled clinical trial, and 1 trial using matched historical controls), addition of CFAE ablation resulted in a statistically significant increase in freedom from AT (n = 112 of 181 62% for PVI+CFAE vs. n = 84 of 179 47% for PVI alone; RR 1.32, P = .02). In trials of paroxysmal AF (3 randomized controlled trials and 1 trial using matched historical controls), addition of CFAE ablation did not result in a statistically significant increase in freedom from AT (n = 131 of 166 79% for PVI+CFAE vs. n = 122 of 164 74% for PVI alone; RR 1.04, P = .52).
In these studies of patients with nonparoxysmal AF, addition of CFAE ablation to PVI results in greater improvement in freedom from AF. No additional benefit of this combined approach was observed in patients with paroxysmal AF.
Abstract Heart failure (HF) represents a significant and expanding public health burden associated with increasing prevalence and exponential growth in related health care costs. Contemporary ...advances in both pharmacological and nonpharmacological therapies have often been restricted in application and benefit. Given the critical role of the autonomic nervous system (ANS) in maintaining cardiovascular homeostasis in the failing heart, there has been increasing interest in the role of ANS modulation as a therapeutic modality in HF. In this review, we highlight the anatomy of the ANS and its role in the pathophysiology of HF, as well as metrics of its assessment. Given the limitations associated with pharmacological ANS modulation, including lack of specificity and medication intolerance, we focus in this review on contemporary nonpharmacological ANS modulation therapies. For each therapy—vagal nerve stimulation, carotid baroreceptor stimulation, spinal cord stimulation, and renal denervation—we review the rationale for modulation, pre-clinical and clinical assessments, as well as procedural considerations and limitations. We conclude by commenting on novel technologies and strategies for ANS modulation on the horizon.
Implanted devices can provide objective assessment of physical activity over prolonged periods. The purpose of this study was to investigate the prognostic value of device-measured physical activity ...data compared with a six-minute walk test (6MWT) in predicting clinical response to cardiac resynchronization therapy (CRT). This was a single-center study in which patients who underwent CRT for standard indications were evaluated. Daily physical activity and 6MWT were evaluated postimplant at 1, 3, and 6 months. The primary end point was a composite of heart failure hospitalization, transplant, left ventricular (LV) assist device, and all-cause death at 3 years. Echocardiographic response, defined as a ≥10% improvement in LV ejection fraction (LVEF), at 6 months was the secondary end point. About 164 patients were included: average age was 67.3 ± 12.9 years, 77% were men, baseline LVEF was 25% ± 7%. Kaplan-Meier curves showed superior freedom from the composite end point in the highest tertile of both 6MWT and physical activity compared with the lowest tertile (41 vs 23 cases, respectively, p <0.001) for 6MWT and for activity (22 vs 7 cases, respectively, p = 0.001). In an adjusted multivariate model, independent predictors of improved clinical outcome included 1-month physical activity (hazard ratio 0.546, 95% confidence interval CI 0.361 to 0.824, p = 0.004) and 6MWT (hazard ratio 0.581, 95% CI 0.425 to 0.795, p = 0.001). An additional hour of higher activity at 1 month translated to a 1.38 times (95% CI 1.075 to 1.753, p = 0.011) higher likelihood of improved echocardiographic response. In conclusion, device-based measures of physical activity may be useful in predicting echocardiographic reverse remodeling and long-term clinical outcome in patients receiving CRT.
Abstract Background Patients with moderate-to-severe chronic kidney disease (CKD) are poorly represented in clinical trials of cardiac resynchronization therapy (CRT). Objectives This study sought to ...assess the real-world comparative effectiveness of CRT with defibrillator (CRT-D) versus implantable cardioverter-defibrillator (ICD) alone in CRT-eligible patients with moderate-to-severe CKD. Methods We conducted an inverse probability-weighted analysis of 10,946 CRT-eligible patients (ejection fraction <35%, QRS >120 ms, New York Heart Association functional class III/IV) with stage 3 to 5 CKD in the National Cardiovascular Data Registry (NCDR) ICD Registry, comparing outcomes between patients who received CRT-D (n = 9,525) versus ICD only (n = 1,421). Outcomes were obtained via Medicare claims and censored at 3 years. The primary endpoint of heart failure (HF) hospitalization or death and the secondary endpoint of death were assessed with Cox proportional hazards models. HF hospitalization, device explant, and progression to end-stage renal disease were assessed using Fine-Gray models. Results After risk adjustment, CRT-D use was associated with a reduction in HF hospitalization or death (hazard ratio HR: 0.84; 95% confidence interval CI: 0.78 to 0.91; p < 0.0001), death (HR: 0.85; 95% CI: 0.77 to 0.93; p < 0.0004), and HF hospitalization alone (subdistribution HR: 0.84; 95% CI: 0.76 to 0.93; p < 0.009). Subgroup analyses suggested that CRT was associated with a reduced risk of HF hospitalization and death across CKD classes. The incidence of in-hospital, short-term, and mid-term device-related complications did not vary across CKD stages. Conclusions In a nationally representative population of HF and CRT-eligible patients, use of CRT-D was associated with a significantly lower risk of the composite endpoint of HF hospitalization or death among patients with moderate-to-severe CKD in the setting of acceptable complication rates.
A significant minority of patients receiving cardiac resynchronization therapy (CRT) remain nonresponsive to this intervention.
This study aimed to determine whether coronary sinus (CS) or baseline ...peripheral venous (PV) levels of established and emerging heart failure (HF) biomarkers are predictive of CRT outcomes.
In 73 patients (aged 68 ± 12 years; 83% men; ejection fraction 27% ± 7%) with CS and PV blood samples drawn simultaneously at the time of CRT device implantation, we measured amino-terminal pro-B-type natriuretic peptide (NT-proBNP), galectin-3 (gal-3), and soluble ST2 (sST2) levels. NT-proBNP concentrations >2000 pg/mL, gal-3 concentrations >25.9 ng/mL, and sST2 concentrations >35 ng/mL were considered positive on the basis of established PV cut points for identifying "high-risk" individuals with HF. CRT response was adjudicated by the HF Clinical Composite Score. A major adverse cardiovascular event (MACE) was defined as the composite end point of death, cardiac transplant, left ventricular assist device, and HF hospitalization at 2 years.
NT-proBNP concentrations were 20% higher in the CS than in the periphery, while gal-3 and sST2 concentrations were 10% higher in the periphery than in the CS (all P < .001). There were 45% CRT nonresponders at 6 months and 16 (22%) patients with MACE. Triple-positive CS values yielded the highest specificity of 95% for predicting CRT nonresponse. Consistently, CS strategies identified patients at higher risk of developing MACE, with >11-fold adjusted increase for triple-positive CS patients compared to triple-negative patients (all P ≤ .04). PV strategies were not predictive of MACE.
Our findings suggest that CS sampling of HF biomarkers may be better than PV sampling for predicting CRT outcomes. Larger studies are needed to confirm our findings.
Prolongation of the baseline ECG PR interval is frequently encountered among cardiac resynchronization therapy (CRT) recipients. There are conflicting data regarding the association of a prolonged PR ...interval with long-term clinical outcome in this patient group.
The purpose of this study was to compare clinical outcomes and response to CRT in patients with normal (<200 ms) vs prolonged (≥200 ms) baseline PR interval.
In this study, 283 patients (normal PR interval: n = 158; prolonged PR interval: n = 125) with documented baseline intrinsic PR interval were followed for 3 years after CRT implantation. The study population consisted of 24.7% women (mean age 66 ± 13 years, left ventricular ejection fraction 24% ± 7%).
A Cox proportional hazard model identified baseline PR interval as a predictor of the composite end-point (all-cause mortality, heart failure hospitalization, left ventricular assist device implantation, and heart transplantation) in univariate analysis (hazard ratio HR 1.49, 95% confidence interval CI 1.02-2.17, P = .04) but not in multivariate analysis. It also predicted heart failure hospitalization in univariate (HR 1.6, 95% CI 1.1-2.4, P = .02) and multivariate analysis (HR 1.6, 95% CI 1.0-2.3, P = .03). A prolonged PR interval was associated with lower probability of reverse remodeling defined as ≥10% improvement in ejection fraction (64% vs 77%, P = .057), especially in patients with non-left bundle branch block ECG morphology (41% vs 68%, P = .03).
Among patients with CRT, a prolonged baseline PR interval is an independent predictor of worse prognosis and lower probability of reverse remodeling, especially for patients with non-left bundle branch block morphology on ECG.
Abstract Background Cardiac resynchronization therapy (CRT) improves mitral regurgitation (MR) in a subset of patients. We hypothesized that biomarkers (amino-terminal pro-B type natriuretic peptide ...NT-proBNP, high-sensitivity troponin hsTnI, galectin-3 gal-3 and soluble ST-2 sST2) may predict MR response post-CRT. Methods We measured levels of biomarkers during CRT implantation in 132 patients with subsequent 2 years follow-up. MR was graded as no-trace, mild, moderate or severe at baseline and 6 months. Results In patients with baseline at least mild MR, 56% had improvement at 6 months, with lower two-year mortality vs patients without improvement (0% vs 18%, p=0.002). At baseline, patients with MR improvement had lower hsTnI and gal-3 levels compared to those without improvement (19 vs 40 pg/L, p=0.01; 14 vs 18 ng/mL, p=0.007). In multivariable analyses, higher log-transformed gal-3 (OR 0.15, 95% CI 0.04 - 0.65, p=0.01) remained independent predictor for MR non-improvement. Levels of NT-proBNP and sST2 were lower at follow-up in patients with MR improvement (potentially reflecting reduced myocardial stretch and stress) without reaching statistical significance. Conclusion Higher galectin levels at the time of CRT implantation are associated with MR non-response.
Cardiac resynchronization therapy (CRT) nonresponders have poor outcomes. The significance of progressive ventricular dysfunction among nonresponders remains unclear.
We sought to define predictors ...of and clinical outcomes associated with progressive ventricular dysfunction despite CRT.
We conducted an analysis of 328 patients undergoing CRT with defibrillator for standard indications. On the basis of 6-month echocardiograms, we classified patients as responders (those with a ≥5% increase in ejection fraction) and progressors (those with a ≥5% decrease in ejection fraction), and all others were defined as nonprogressors. Coprimary end points were 3-year (1) heart failure, left ventricular assist device (LVAD), transplantation, or death and (2) ventricular tachycardia (VT) or ventricular fibrillation (VF).
Multivariable predictors of progressive ventricular dysfunction were aldosterone antagonist use (hazard ratio HR 0.23; P = .008), prior valve surgery (HR 3.3; P = .005), and QRS duration (HR 0.98; P = .02). More favorable changes in ventricular function were associated with lower incidences of heart failure, LVAD, transplantation, or death (70% vs 54% vs 33%; P < .0001) and VT or VF (66% vs 38% vs 28%; P = .001) for progressors, nonprogressors, and responders, respectively. After multivariable adjustment, progressors remained at increased risk of heart failure, LVAD, transplantation, or death (HR 2.14; P = .0029) and VT or VF (HR 2.03; P = .046) as compared with nonprogressors. Responders were at decreased risk of heart failure, LVAD, transplantation, or death (HR 0.44; P < .0001) and VT or VF (0.51; P = .015) as compared with nonprogressors.
Patients with progressive deterioration in ventricular function despite CRT represent a high-risk group of nonresponders at increased risk of worsened clinical outcomes.
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