Abstract Background Heart Failure (HF) is increasing in prevalence and is a major cause of morbidity and mortality, despite advances in medical and device therapy. Autonomic imbalance, with excess ...sympathetic activation and decreased vagal tone, is an integral component of the pathophysiology of HF. Objectives INOVATE-HF was designed to assess the safety and efficacy of vagal nerve stimulation (VNS) among patients with heart failure and a reduced ejection fraction. Methods INOVATE-HF was a multinational, randomized trial involving 85 centers in patients with chronic HF, NYHA III symptoms and ejection fraction < 40%. Patients were assigned to device implantation to provide VNS (Active) or continued medical therapy (Control) in a 3:2 ratio. The primary efficacy endpoint was the composite of death from any cause or first event for worsening HF. Results There were 707 patients randomized and followed for a mean of 16 months. The primary efficacy outcome occurred in 132 of 436 patients in the VNS group, as compared with 70 of 271 in the control group (30.3% vs. 25.8%; hazard ratio, 1.14; 95% confidence interval CI, 0.86 to 1.53; P = 0.37). During the trial, the estimated annual mortality rates of 9.3% and 7.1%, respectively (p=0.19). Quality of life, New York Heart Association Class and 6 minute walking distance were favorably affected by VNS (p’s < 0.05), but left ventricular end-systolic volume index was not different (P=0.49). Conclusions VNS does not reduce the rate of death or HF events in chronic HF patients. (Clinical Trials.gov number NCT01303718)
Objective The study objective was to evaluate the long-term (5-year) safety and efficacy of mitral valve surgery with and without the CorCap cardiac support device (Acorn Cardiovascular, St Paul, ...Minn) in patients with dilated cardiomyopathy and New York Heart Association class II–IV heart failure. Background The Acorn trial provided a unique opportunity to assess the long-term safety and efficacy of mitral valve surgery because clinical visits and echocardiograms (read by a core laboratory) were completed for 5 years of follow-up. Further, this study provided follow-up data on the long-term effect of the CorCap cardiac support device as an adjunct to mitral valve surgery. Methods From the original Acorn trial (n = 300 patients), 193 patients were enrolled in the mitral valve repair/replacement stratum. A total of 102 were randomized to mitral valve surgery alone (control group) and 91 were randomized to mitral valve surgery with implantation of the CorCap cardiac support device (treatment group). Patients were followed up for 5 years. Results As previously reported, 30-day operative mortality was only 1.6%. At 5 years, the total mortality was 30% with an average annual mortality rate of approximately 6% per year. The effects of mitral valve surgery led to a progressive decrease in left ventricular end-diastolic and end-systolic volumes, which were highly significant at all time points. At the end of 5 years, there was an average reduction in left ventricular end-diastolic volume of 75 mL, which represents a 28% reduction from baseline. During 5 years of follow-up, 29 patients had recurrent mitral regurgitation and 5 patients underwent repeat mitral valve surgery. The addition of the CorCap device led to greater decreases in left ventricular end-diastolic volume (average difference of 16.5 mL; P = .05), indicating that the CorCap device had an additive effect to the mitral valve operation. Conclusions This study demonstrates long-term improvement in left ventricular structure and function after mitral valve surgery for up to 5 years. These data provide evidence supporting mitral valve repair in combination with the Acorn CorCap device for patients with nonischemic heart failure with severe left ventricular dysfunction who have been medically optimized yet remain symptomatic with significant mitral regurgitation.
Background The CorCap cardiac support device (Acorn Cardiovascular, Inc, St Paul, Minn) is the first device that specifically addresses ventricular remodeling in heart failure by reducing wall ...stress. We previously reported outcomes from the Acorn randomized trial to a common closing date (22.9 months of follow-up). This report summarizes results of extended followup to 5 years. Methods A total of 107 patients were enrolled in the no–mitral valve repair/replacement stratum including 57 in the CorCap treatment group and 50 in the control (optimal medical therapy alone) group. Patients were assessed every year, until completing 5 years of follow-up, for survival, adverse events, major cardiac procedures, New York Heart Association (NYHA) functional status, and echocardiograms, which were read at a core laboratory. Results Overall survivals were similar between the treatment and control groups, demonstrating no late adverse effect on mortality. The treatment group had significant reductions in left ventricular end-diastolic volume ( P = .029) as well as a small increase in sphericity index. More patients in the treatment group improved by at least 1 NYHA functional class ( P = .0005). There was no difference in rates of adverse events. In a subgroup of patients with an intermediate left ventricular end-diastolic dimension, there was a significant reduction in the Kaplan-Meier estimate of the freedom from the composite end point of death and major cardiac procedures ( P = .04). Conclusions These cumulative data demonstrate the sustained reverse remodeling of the left ventricle and the long-term safety and efficacy of the CorCap cardiac support device as an adjunctive therapy for patients with heart failure who remain symptomatic despite optimal medical therapy.
The objective of this study was to assess the long-term effects of the CorCap Cardiac Support Device (CSD; Acorn Cardiovascular, Inc, St. Paul, MN) on left ventricular (LV) structure and function in ...patients with heart failure. Cardiac support devices, which reduce LV wall stress, have been shown to promote reverse remodeling in three different experimental models of heart failure. However, long-term effects in patients with heart failure have not been reported.
We enrolled 300 patients with heart failure in the Acorn Randomized Trial, as previously reported (Ann Thorac Surg 2007;84:1226-35). Echocardiograms were obtained every six months until the last patient was followed for one year, and then annually thereafter. Standard measurements of LV volumes, ejection fraction, and sphericity index were made by a Core laboratory at the Mayo Clinic who were blinded to treatment assignment.
Patients treated with the CorCap Cardiac Support Device had significant reductions in LV end diastolic volume (average difference 18.8 mL; p = 0.005) and LV end systolic volume (average difference 15.6 mL; p = 0.013) compared with the control group. Sphericity index was significantly increased in the treatment group (average difference 0.045 units; p = 0.018). These changes were maintained over three years of follow-up. The improvements in LV size and shape were observed when the CorCap was implanted concomitantly with mitral value surgery or by itself.
These results demonstrate that the CorCap Cardiac Support Device has a long-term beneficial impact on LV size and shape in patients with heart failure.
Left ventricular (LV) remodeling is related to adverse outcomes in heart failure. The CorCap Cardiac Support Device (CSD; Acorn Cardiovascular, Inc, St. Paul, MN) is an implantable device that ...attenuates LV remodeling.
The Acorn trial assessed the safety and efficacy of the CSD in 300 heart failure patients. Patients needing mitral surgery (n = 193) were randomized to mitral surgery alone or mitral surgery plus CSD. Patients who did not need mitral surgery (n = 107) were randomized to medical therapy or medical therapy plus CSD. The primary endpoint was a clinical composite based on changes in patient vital status, the need for major cardiac procedures for worsening heart failure, and a change in New York Heart Association (NYHA) class.
The proportional odds ratio for the primary endpoint favored treatment with the CSD (1.73 confidence interval CI: 1.07 to 2.79; p = 0.024). The CSD-treated patients received significantly (p = 0.01) fewer cardiac procedures indicative of worsening heart failure and had an improvement in New York Heart Association class (p = 0.049). There was no significant difference in survival between groups (p = 0.85). Treatment with the CSD led to a decrease in LV end-diastolic (p = 0.009) and end-systolic volumes (p = 0.017), an increase in the LV sphericity index (p = 0.026), an improvement in the Minnesota Living with Heart Failure score (p = 0.04), and the Short Form-36 Questionnaire (p = 0.015). There was no evidence for a significant difference (p = 0.43) in serious adverse events between the treatment and control groups.
The results of the Acorn trial support the hypothesis that preventing LV remodeling with a CSD favorably impacts the untoward natural history of heart failure.
Background Functional mitral regurgitation (MR) is commonly seen in dilated cardiomyopathy (DCM), which may result from left ventricular (LV) dilatation and alteration in the geometric relationship ...of mitral valve apparatus. However, not all patients with DCM show significant MR and left atrial (LA) enlargement. The aim of this study was to assess responsible factors for developing mitral valve regurgitation. Methods Of 300 patients enrolled in the Acorn trial, baseline echocardiography studies were available in 288, of whom 144 were excluded because of a variety of reasons. Echocardiographic data were examined for the remaining 144 patients in sinus rhythm with DCM, but without organic mitral valve disease and ischemic heart disease. Mitral regurgitation was assessed by color-flow imaging. All echocardiographic parameters were indexed to body surface area. Results Of 144 patients, 87 had MR grade ≥2 (group 1) and 57 had MR grade 0 or +1 (group 2). Group 1 had larger tenting area, tenting height, tethering distance, LA volume index, and mitral annular area than group 2 (all P < .001); LV volume index and ejection fraction were similar between groups. The major determinant of MR severity was tenting area ( r = 0.49, P < .001), and this was best related to mitral annular area ( r = 0.85, P < .001). Mitral annular area was most strongly associated with LA volume ( r = 0.56, P < .001). In addition, LA volume index was highly correlated with LV diastolic dysfunction ( r = 0.58, P < .001), both in total and in group 2 only. Conclusions For patients with DCM in the Acorn trial, MR severity was associated with LA volume and mitral annular area but not with LV volume. Mitral annular area and LA volume were closely related, even in patients without significant MR. These findings suggest that LA enlargement caused by advanced diastolic dysfunction may contribute to causing significant MR by augmenting mitral annular dilatation in DCM.
Abstract Background Several randomized trials have shown that cardiac resynchronization therapy (CRT) benefits New York Heart Association (NYHA) functional class I/II heart failure (HF) patients, but ...it is unknown if similar outcomes occur in the real-world. Methods and Results All patients receiving CRT between 2003 and 2008 with ejection fraction (EF) ≤35% and QRS duration ≥120 ms were included. Outcomes assessed were subjective clinical response, echocardiographic response, and survival free of cardiovascular (CV) hospitalization. Baseline demographics in functional class I/II (n = 155) and functional class III/IV (n = 512) were similar, except for differences in age and several comorbidities. Clinical response was similar in both groups. The functional class I/II group had a greater decrease in left ventricular (LV) end-diastolic dimension ( P = .031), and trended toward greater improvements in LV end-systolic dimension ( P = .056) and EF ( P = .059). The functional class I/II group had a better 5-year survival rate (79 vs 54%; P < .0001) and survival free of CV hospitalization (45% vs 26%; P < .0001). Conclusions In this real-world clinical scenario, NYHA functional class I/II CRT patients improved clinical status, and LV function and size as good as or better than those in NYHA functional class III/IV patients. These observations provide further support for the use of CRT in patients with mild symptoms of HF.
Abstract Background Several clinical trials have confirmed that cardiac resynchronization therapy (CRT) improves outcomes in well defined patient populations. It is uncertain, however, whether ...outcomes are similar in real-world clinical settings. This study compared outcomes after CRT with defibrillator (CRT-D) in a large real-world private-practice cardiology setting with those in the COMPANION multicenter trial. Methods and Results A total of 429 consecutive patients who received CRT-D for standard indications (group 1) were retrospectively compared with the 595 patients (group 3) in the COMPANION CRT-D cohort regarding survival and survival free of cardiovascular (CV) hospitalization. A subgroup of the group 1 patients who met the COMPANION entrance criteria (group 2) was also compared with the COMPANION cohort (group 3) both with and without propensity-matching statistical analysis. Survival and survival free of CV hospitalization was better in group 1 than in group 3. Survival in group 2 with and without propensity matching was similar to group 3. However, survival free of CV hospitalization was better in the real-world patients (group 2) even after adjustment for differences in baseline characteristics. Conclusions Survival and CV hospitalization outcomes in a real-world clinical setting are as good as, or better than, those demonstrated in the COMPANION research trial.
Objectives. This study was conducted to determine the relations among exercise capacity and pulmonary, peripheral vascular, cardiac and neurohormonal factors in patients with chronic heart failure.
...Background. The mechanisms of exercise intolerance in heart failure have not been fully clarified. Previous studies have indicated that peripheral factors such as regional blood flow may be more closely associated with exercise capacity than cardiac function, whereas the role of pulmonary function has received less attention.
Methods. Fifty patients with stable heart failure underwent a comprehensive assessment that included a symptom-limited maximal cardiopulmonary exercise test, right heart catheterization, pulmonary function tests, neurohormonal levels, radionuclide ventriculography and forearm blood flow at rest and alter 5 min of brachial artery occlusion. Univariate and stepwise linear regression analyses were used to relate peak exercise oxygen uptake to indexes of cardiac, peripheral vascular, pulmonary and neurohormonal factors both alone and in combination.
Results. The mean ejection fraction was 19% and peak oxygen uptake was 16.5 ml/min per kg in this group of patients. By univariate analysis, there were no significant correlations between peak oxygen uptake and rest cardiac output, pulmonary wedge pressure, ejection fraction and pulmonary or systemic vascular resistance. In contrast, even in the absence of arterial desaturation during exercise, the forced expiratory volume in 1 s (r = 0.55, p < 0.001), forced vital capacity (r = 0.46, p < 0.01) and diffusing capacity for carbon monoxide (r = 0.47, p < 0.01) were all significantly associated with peak oxygen uptake. Peak postocclusion forearm blood flow (r = 0.45, p < 0.01), the corresponding minimal forearm vascular resistance (r = −0.56; p < 0.01) and plasma norepinephrine level at rest (r = −0.45; p < 0.01) were also significantly correlated with peak oxygen uptake. By multivariate analysis, minimal forearm vascular resistance and forced expiratory volume in 1 s were shown to be independently related to peak oxygen uptake, with a combined R value of 0.71. Other two-variate models included forced expiratory volume and plasma norepinephrine (R = 0.67) and forced expiratory volume and diffusing capacity (R = 0.65). Because forced vital capacity was highly correlated with forced expiratory volume in 1 s, it could be combined with the same variables to yield similar R values. Addition of any third variable did not improve these correlations.
Conclusions. In comparison with rest indexes of cardiac performance, measures of pulmonary function and peripheral vasodilator capacity were more closely associated with peak exercise oxygen uptake in patients with heart failure, Furthermore, the associations were independent of each other and together accounted for 50% of the variance in peak oxygen uptake. These data suggest that pulmonary and peripheral vascular adaptations may be important determinants of exercise intolerance in heart failure.
Patients with heart failure have reduced forearm vasodilator responses when endothelial cell nitric oxide production is stimulated by muscarinic agonists. The aim of this study was to determine if ...activity of the nitric oxide pathway was also abnormal under basal conditions. Forearm blood flow (FBF) was measured with strain-gauge plethysmography in response to the intraarterial infusion of a subsystemic dose range of L-N-monomethylarginine (L-NMMA), a competitive inhibitor of nitric oxide synthase. In 18 normal subjects, the baseline FBF of 3.6 +/- 1.4 was decreased by 0.3 +/- 0.5 (p < 0.01), 1.0 +/- 0.7 (p < 0.01), 1.4 +/- 0.9 (p < 0.01), and 1.3 +/- 1.3 (p < 0.01) ml/min/100 ml forearm volume during infusions of 1, 4, 8, and 16 mumol/min of L-NMMA, respectively. In 10 patients with heart failure, the baseline FBF of 2.6 +/- 0.9 was decreased by 0.4 +/- 0.5 (p < 0.05), 0.4 +/- 0.5 (p < 0.05), 0.9 +/- 0.8 (p < 0.01), and 0.9 +/- 0.7 (p < 0.01) ml/min/100 ml forearm volume with the 4 doses of L-NMMA, respectively. There was no difference in the L-NMMA response between the 2 groups in terms of absolute flow, percent change, or with analysis of covariance to adjust for different baselines. The stable end products of nitric oxide (nitrite and nitrate) were measured in the forearm venous effluent. Nitrite and nitrate levels at baseline were not reduced in patients with heart failure.
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