Modified design of stimulation of the left ventricular endocardium for cardiac resynchronization therapy in nonresponders, previously untreatable and high-risk upgrade patients (SOLVE-CRT) trial.

The WiSE system is a novel, leadless endocardial system that can provide cardiac resynchronization therapy in patients who cannot be treated with a conventional epicardial left ventricular lead. Safety and efficacy were being evaluated in the pivotal, randomized, double-blind SOLVE-CRT Trial (Stimulation of the Left Ventricular Endocardium for Cardiac Resynchronization Therapy.) The trial was initiated in 2018; however, patient enrollment was significantly impacted by the COVID-19 pandemic necessitating a change in design. This article describes the revised trial and the scientific rationale for the specific changes in the protocol.

Transcatheter Aortic Valve Replacement With the HLT Meridian Valve.

BACKGROUND: While most self-expanding transcatheter valves are repositionable, only one fully retrievable valve is currently available. The Meridian valve is a new self-expanding valve with full retrievability properties. The objective of our study was to evaluate the early feasibility, preliminary safety, and efficacy of transcatheter aortic valve replacement with the HLT Meridian valve (HLT, Inc). METHODS: This was a multicenter early feasibility study including patients with severe aortic stenosis at high surgical risk undergoing transfemoral transcatheter aortic valve replacement with the 25-mm Meridian valve. All serious adverse events were adjudicated by an independent clinical events committee according to Valve Academic Research Consortium-2 criteria. Echocardiography data were assessed by an independent echocardiography core laboratory. RESULTS: A total of 25 patients (mean age, 85±6 years; 80% of men) were included. The valve was successfully implanted in 22 (88%) patients (annulus too large and extreme horizontal aorta in 2 and 1 unsuccessful cases, respectively). Valve retrieval because of an initial nonadequate positioning was attempted and successfully performed in 10 (40%) patients. Echocardiography post-transcatheter aortic valve replacement showed a low mean residual gradient (10±4 mm Hg) and the absence of moderate-severe aortic regurgitation (none-trace and mild aortic regurgitation in 76% and 24% of patients, respectively). Mortality at 30 days was 8%, with no cases of disabling stroke, valve embolization, or major/life-threatening bleeding complications. At 6-month follow-up, the cumulative mortality rate was 12%, with no changes in echocardiographic parameters and no cases of valve dysfunction. The majority of patients (89%) were in New York Heart Association class I-II at 6 months. CONCLUSIONS: Transcatheter aortic valve replacement with the Meridian valve was feasible and associated with acceptable early and 6-month clinical results. Valve retrieval after full valve deployment was successfully performed in all attempted cases, and valve performance was excellent, with low residual gradients, no cases of moderate-severe aortic regurgitation, and none-trace residual aortic regurgitation in the majority of patients. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02838680 (RADIANT-Canada); NCT02799823 (RADIANT-US).

Transcatheter Interatrial Shunt Device for the Treatment of Heart Failure: Rationale and Design of the Randomized Trial to REDUCE Elevated Left Atrial Pressure in Heart Failure (REDUCE LAP-HF I).

UNLABELLED: Heart failure with preserved ejection fraction (HFpEF), a major public health problem with high morbidity and mortality rates, remains difficult to manage because of a lack of effective treatment options. Although HFpEF is a heterogeneous clinical syndrome, elevated left atrial pressure-either at rest or with exertion-is a common factor among all forms of HFpEF and one of the primary reasons for dyspnea and exercise intolerance in these patients. On the basis of clinical experience with congenital interatrial shunts in mitral stenosis, it has been hypothesized that the creation of a left-to-right interatrial shunt to decompress the left atrium (without compromising left ventricular filling or forward cardiac output) is a rational, nonpharmacological strategy for alleviating symptoms in patients with HFpEF. A novel transcatheter interatrial shunt device has been developed and evaluated in patients with HFpEF in single-arm, nonblinded clinical trials. These studies have demonstrated the safety and potential efficacy of the device. However, a randomized, placebo-controlled evaluation of the device is required to further evaluate its safety and efficacy in patients with HFpEF. In this article, we give the rationale for a therapeutic transcatheter interatrial shunt device in HFpEF, and we describe the design of REDUCE Elevated Left Atrial Pressure in Heart Failure (REDUCE LAP-HF I), the first randomized controlled trial of a device-based therapy to reduce left atrial pressure in HFpEF. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02600234.

Vagus Nerve Stimulation for the Treatment of Heart Failure: The INOVATE-HF Trial.

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: The INOVATE-HF (Increase of Vagal Tone in Heart Failure) trial assessed the safety and efficacy of vagal nerve stimulation (VNS) among patients with HF and a reduced ejection fraction. METHODS: INOVATE-HF was a multinational, randomized trial involving 85 centers including patients with chronic HF, New York Heart Association functional class 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 composite of death from any cause or first event for worsening HF. RESULTS: Patients (n = 707) were randomized and followed up for a mean of 16 months. The primary efficacy outcome occurred in 132 of 436 patients in the VNS group, compared to 70 of 271 in the control group (30.3% vs. 25.8%; hazard ratio: 1.14; 95% confidence interval: 0.86 to 1.53; p = 0.37). During the trial, the estimated annual mortality rates were 9.3% and 7.1%, respectively (p = 0.19). Quality of life, New York Heart Association functional class, and 6-min walking distance were favorably affected by VNS (p < 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. (INcrease Of VAgal TonE in CHF [INOVATE-HF]; NCT01303718).

Comparison of cardiac resynchronization therapy outcomes in patients with New York Heart Association functional class I/II versus III/IV heart failure.

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.

Pacemaker optimization in nonresponders to cardiac resynchronization therapy: left ventricular pacing as an available option.

BACKGROUND: Echocardiographic (ECHO)-guided pacemaker optimization (PMO) in cardiac resynchronization therapy (CRT) nonresponders acutely improves left ventricular (LV) function. However, the chronic results of LV pacing in this group are less understood. METHODS: We retrospectively studied 28 CRT nonresponders optimized based on ECHO to LV pacing and compared them to 28 age- and gender-matched patients optimized to biventricular (BiV) pacing. ECHOs with tissue Doppler imaging assessed LV hemodynamics before, immediately after, and 29 ± 16 months after PMO. Also, 56 age- and gender-matched CRT responders were included for comparison of clinical outcomes. RESULTS: PMO resulted in acute improvements in longitudinal LV systolic function and several measures of dyssynchrony, with greater improvements in the LV paced group. Chronic improvements in ejection fraction (EF) (3.2 ± 7.7%), and left ventricle end-systolic volume (LVESV) (-11 ± 36 mL) and one dyssynchrony measure were seen in the combined group. Chronically, both LV and BiV paced patients improved some measures of systolic function and dyssynchrony although response varied between the groups. Survival at 3.5 years was similar (P = 0.973) between the PMO (58%) and nonoptimized groups (58%) but survival free of cardiovascular hospitalization was significantly (P = 0.037) better in the nonoptimized group. CONCLUSIONS: CRT nonresponders undergoing PMO to either LV or BiV pacing have acute improvements in longitudinal systolic function and some measures of dyssynchrony. Some benefits are sustained chronically, with improvements in EF, LVESV, and dyssynchrony. A strategy of ECHO-guided PMO results in survival for CRT nonresponders similar to that of CRT patients not referred for PMO.

Cardiac resynchronization therapy in the real world: comparison with the COMPANION study.

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.

Beneficial effects of the CorCap cardiac support device: five-year results from the Acorn Trial.

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.

Mitral valve repair in heart failure: five-year follow-up from the mitral valve replacement stratum of the Acorn randomized trial.

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.

Mechanisms of recurrent functional mitral regurgitation after mitral valve repair in nonischemic dilated cardiomyopathy: importance of distal anterior leaflet tethering.

BACKGROUND: Recurrent functional mitral regurgitation (MR) has been reported after mitral valve repair with annuloplasty in patients with dilated cardiomyopathy, but the mechanism is not understood completely. The authors sought to identify abnormalities of the mitral valve and left ventricle that are associated with recurrent MR after mitral annuloplasty. METHOD AND RESULTS: In 104 patients with idiopathic dilated cardiomyopathy who underwent annuloplasty for functional MR, basal mitral anterior leaflet angle, distal mitral anterior leaflet angle (ALAtip), posterior leaflet angle, coaptation depth, tenting area, mitral annular dimensions, left ventricular volumes, and MR severity were quantified by echocardiography before surgery and at 6-month intervals after it. Compared with patients without MR recurrence (n=79), patients with recurrent MR (defined as > or =2+) (n=25) had greater ALAtip (P<0.001) and basal mitral anterior leaflet angle (P<0.001), greater coaptation depth and tenting area (P<0.001), larger left ventricular volumes (P<0.001), and worse left ventricular ejection fraction (P<0.05) but similar mitral annular dimensions and postoperative exaggeration in posterior leaflet angle. Multivariable analysis identified postoperative ALAtip as the major determinant of postoperative MR. Receiver operator characteristic curves identified preoperative ALAtip as the best predictor of MR recurrence (area under curve, 0.98). For ALA(tip) >25 degrees, the sensitivity, specificity, and positive and negative predictive values in predicting recurrent MR were 88%, 94%, 82%, and 93%, respectively. Three distinct patterns of anterior leaflet tethering (minimal, basal, and distal) with an increasing risk of recurrent MR were identified. CONCLUSIONS: Posterior leaflet tethering is invariable after mitral annuloplasty, rendering postoperative mitral competence highly dependent on distal anterior leaflet mobility.

Diastolic dysfunction and left atrial enlargement as contributing factors to functional mitral regurgitation in dilated cardiomyopathy: data from the Acorn trial.

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 > or =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.

Clinical evaluation of the CorCap Cardiac Support Device in patients with dilated cardiomyopathy.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Sustained benefits of the CorCap Cardiac Support Device on left ventricular remodeling: three year follow-up results from the Acorn clinical trial.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Mitral valve surgery in heart failure: insights from the Acorn Clinical Trial.

OBJECTIVE: The study objective was to evaluate in a prospective, randomized, multicenter trial the safety and efficacy of mitral valve surgery with and without the CorCap cardiac support device (Acorn Cardiovascular, St Paul, Minn) in patients with New York Heart Association Class II to IV heart failure. BACKGROUND: Although mitral valve surgery has been performed successfully in patients with heart failure, the safety and long-term efficacy have not been established in a multicenter prospective trial. Cardiac support devices that reduce ventricular wall stress and promote beneficial reverse remodeling have been proposed as a new treatment option as a stand-alone procedure and as an adjunct to mitral valve surgery. METHODS: A subgroup of 193 patients were enrolled in the mitral valve repair or replacement stratum of the Acorn Clinical Trial; 102 patients were randomized to the mitral valve surgery alone group (control) and 91 patients were randomized to mitral valve surgery with implantation of the CorCap cardiac support device. Patients were followed for a median duration of 22.9 months. RESULTS: For the entire mitral valve surgery group, the 30-day operative mortality rate was only 1.6% at 30 days. Mitral surgery was associated with progressive reductions in left ventricle end-diastolic volume, left ventricle end-systolic volume, and left ventricular mass, and increases in left ventricle ejection fraction and sphericity index, all consistent with reverse remodeling. Recurrence of clinically significant mitral regurgitation was uncommon. Quality of life, exercise performance, and New York Heart Association functional class were all improved. Finally, the addition of the CorCap cardiac support device led to greater decreases in left ventricular end-diastolic volume and left ventricular end-systolic volume, a more elliptical shape, and a trend for a reduction in major cardiac procedures and improvement in quality of life compared with mitral surgery alone. CONCLUSIONS: These findings suggest that there is clear benefit to the surgical elimination of mitral regurgitation and that there is additional benefit with the CorCap cardiac support device. Given the improvement in left ventricle structure and function, along with a low mortality rate, physicians should strongly consider offering mitral valve surgery in combination with the CorCap cardiac support device to patients with heart failure who are on an optimal medical regimen.

One-year clinical experience with the Acorn CorCap cardiac support device: results of a limited market release safety study in Italy and Sweden.

BACKGROUND: The Acorn CorCap cardiac support device (CSD) is a mesh-like device intended to provide end-diastolic support and reduce ventricular wall stress. Animal studies with the CorCap CSD have demonstrated beneficial reverse remodeling, and preliminary safety studies in patients with heart failure have shown that the device is safe and associated with improved left ventricular (LV) structure and function. The objective of the current study was to further evaluate the safety and efficacy of the CorCap CSD in patients with advanced heart failure. METHODS: Twenty-four patients with dilated cardiomyopathy, severe LV dysfunction, and advanced heart failure (NYHA class II-IV) were enrolled at four centers in Italy and Sweden. All patients underwent CorCap CSD implantation either alone (n = 3) or in combination with mitral valve repair/replacement (n = 13), coronary artery bypass surgery (n = 6), combined mitral valve repair/coronary artery bypass surgery (n = 1) or aneurysmectomy (n = 1). RESULTS: The LV end-diastolic diameter decreased from 69.3 +/- 7.2 to 60.1 +/- 9.0 mm at 3 months, 60.9 +/- 9.6 mm at 6 months, and 58.9 +/- 8.0 mm at 12 months (all p < 0.05). A trend toward an improved LV ejection fraction (28.8 +/- 10.5% at baseline and 32.4 +/- 12.7, 33.1 +/- 10.8, and 33.8 +/- 13.9% at 3, 6 and 12 months respectively) was also noted. The NYHA functional class, 6-min walking distance, and quality of life as measured using Uniscale were all improved. There were no differences in response among the patients submitted to the different types of concomitant surgery. CONCLUSIONS: In agreement with earlier safety studies, even the present investigation demonstrated improvements in cardiac structure and function as well as in patient functional status after Cor Cap CSD implantation. Randomized controlled trials are in progress.

Statin use and risks of death or fatal rejection in the Heart Transplant Lipid Registry.

Although small, randomized trials have shown that statin use is associated with decreased risks of mortality and severe rejection, no study has examined statin therapy as used in actual practice in large numbers of heart transplant recipients. We analyzed data from the Heart Transplant Lipid Registry (n = 12 centers). Patients were included if they underwent transplantation between 1995 and 1999, survived >/=30 days after transplantation, and had >/=30 days of Registry follow-up. Multivariable Cox regression models, with propensity scoring performed to adjust for nonrandom allocation of statin therapy, were performed to determine the association of statin therapy with death and fatal rejection. The study included 1,186 patients, with a mean follow-up of 580 +/- 469 days; 937 patients (79%) received statin therapy. Overall, 71 patients (6%) died and 40 (3.4%) had fatal rejection. The statin group had a lower frequency of death (4% vs 13.7%, p <0.0001) and fatal rejection (2.4% vs 7.2%, p = 0.0001). Using multivariable Cox regression, with propensity scoring included to adjust for likelihood of receiving statin therapy, statin use was the only factor associated with lower risk of death (hazard ratio 0.29, 95% confidence interval 0.13 to 0.67) and fatal rejection (hazard ratio 0.27, 95% confidence interval 0.09 to 0.78). This study represents the largest population of heart transplant recipients analyzed for the relation between statin therapy and clinical outcomes in actual practice. Statin therapy was significantly associated with lower risk of death and fatal rejection, benefits that were independent of lipid values.

Rationale, design, and methods for a pivotal randomized clinical trial for the assessment of a cardiac support device in patients with New York health association class III-IV heart failure.

BACKGROUND: Heart failure remains a progressive disease with incremental morbidity and mortality despite optimal medical therapy. A growing body of evidence suggests that progressive left ventricular (LV) remodeling is directly related to a deterioration in LV performance and untoward clinical outcomes for heart failure patients. Preclinical and early phase I clinical studies with the CorCap Cardiac Support Device (CSD), a passive cardiac support device that prevents cardiac remodeling, have shown that it is safe and is associated with improvements in LV structure and function, as well as patient symptomatology. METHODS AND RESULTS: The Acorn Pivotal Trial is a pivotal prospective, randomized, evaluation of the CorCap CSD in patients with New York Heart Association class III-IV heart failure. Patients will be enrolled into one of two different strata. Patients who require a mitral valve repair/replacement (MVR) will fall into the "MVR stratum" and will be randomized to either treatment (MVR surgery plus the CSD) or control (MVR surgery alone). Patients who do not have a clinical indication for MVR surgery will fall into the "no-MVR stratum" and will also be randomized to either treatment (CSD implant plus optimal medical therapy) or control (optimal medical therapy alone). A total of 300 patients (150 treatment and 150 control) will be enrolled. The primary endpoint of the trial is the change in clinical status from baseline to the end of the efficacy phase (1 year), as determined by a clinical composite score. Patients will be classified as improved, worsened, or unchanged based upon patient vital status, the occurrence of a major cardiac procedure indicative of heart failure progression, and a change in the assessment of New York Heart Association functional class. CONCLUSIONS: The Acorn Pivotal Trial will formally test the hypothesis that preventing LV remodeling using a passive cardiac support device will favorably impact the untoward natural history of heart failure and thus represents an important departure from all previous medical and device studies that have been reported to date.

Development and validation of a patient questionnaire to determine New York Heart Association classification.

BACKGROUND: New York Heart Association (NYHA) classification correlates with quality of life and is useful in tracking changes in status in clinical trials. We explored methods to determine NYHA class in multicenter trials where double-blind conditions could not be maintained. METHODS AND RESULTS: A questionnaire was developed containing 7 major questions based on the standard definitions of NYHA classes. The questionnaire was administered to 116 patients with varying degrees of heart failure. When comparing NYHA determined by physicians at the site to NYHA assigned by 3 independent physician graders, there was an approximate 60% concordance. Concordance between independent reviewers was approximately 75%. Results of repeat grading of 30 randomly selected questionnaires indicated that graders provided the same score 90% of the time. Thus, although there were some differences from the site determination of NYHA class, the questionnaire had good inter- and intragrader reproducibility. In a second group of 103 patients enrolled in an ongoing device-intervention trial, we demonstrated that it is feasible to employ the questionnaire in a multicenter trial. Finally, NYHA class was correlated with quality of life and peak exercise oxygen consumption. CONCLUSIONS: A standardized questionnaire provided an approximate 60% concordance in assigning NYHA classification compared to the site assessment with approximately 90% reproducibility. This approach may be useful to determine NYHA classification within the context of clinical trials where blinded conditions are not possible.