Abstract Background Whether myocardial recovery occurs more frequently in peripartum cardiomyopathy (PPCM) than in recent onset cardiomyopathies in men and nonperipartum women has not been ...prospectively evaluated. This was examined through an analysis of outcomes in the Intervention in Myocarditis and Acute Cardiomyopathy 2 (IMAC2) registry. Methods and Results IMAC2 enrolled 373 subjects with recent onset nonischemic dilated cardiomyopathy. Left ventricular ejection fraction (LVEF) was assessed at entry and 6 months, and subjects followed for up to 4 years. Myocardial recovery was compared between men (group 1), nonperipartum women (group 2) and subjects with PPCM (group 3). The cohort included 230 subjects in group 1, 104 in group 2, and 39 in group 3. The mean LVEF at baseline in groups 1, 2, and 3 was 0.23 ± 0.08, 0.24 ± 0.08, and 0.27 ± 0.07 ( P = .04), and at 6 months was 0.39 ± 0.12, 0.42 ± 0.11, and 0.45 ± 0.14 ( P = .007). Subjects in group 3 had a much greater likelihood of achieving an LVEF >0.50 at 6 months than groups 1 or 2 (19 %, 34%, and 48% respectively, P = .002). Conclusions Prospective evaluation confirms myocardial recovery is greatest in women with PPCM, poorest in men, and intermediate in nonperipartum women. On contemporary therapy, nearly half of women with PPCM normalize cardiac function by 6 months.
Objectives A pre-planned substudy of a larger multicenter randomized trial was undertaken to compare the efficacy of everolimus with reduced-dose cyclosporine in the prevention of cardiac allograft ...vasculopathy (CAV) after heart transplantation to that of mycophenolate mofetil (MMF) with standard-dose cyclosporine. Background CAV is a major cause of long-term mortality following heart transplantation. Everolimus has been shown to reduce the severity and incidence of CAV as measured by first year intravascular ultrasound (IVUS). MMF, in combination with cyclosporine, has also been shown to have a beneficial effect in slowing the progression of CAV. Methods Study patients were a pre-specified subgroup of the 553 - patient Everolimus versus mycophenolate mofetil in heart transplantation: a randomized, multicenter trial who underwent heart transplantation and were randomized to everolimus 1.5 mg or MMF 3 g/day. IVUS was performed at baseline and at 12 months. Evaluable IVUS data were available in 189 patients (34.6%). Results Increase in average maximal intimal thickness (MIT) from baseline to month 12 was significantly smaller in the everolimus 1.5 mg group compared with the MMF group (0.03 mm vs. 0.07 mm, p < 0.001). The incidence of CAV, defined as an increase in MIT from baseline to month 12 of greater than 0.5 mm, was 12.5% with everolimus versus 26.7% with MMF (p = 0.018). These findings remained irrespective of sex, age, diabetic status, donor disease, and across lipid categories. Conclusions Everolimus was significantly more efficacious than MMF in preventing CAV as measured by IVUS among heart-transplant recipients after 1 year, a finding, which was maintained in a range of patient subpopulations. CV surgery: transplantation, ventricular assistance, cardiomyopathy
Background We investigated the role of the renin-angiotensin system in women with signs and symptoms of ischemia without obstructive coronary artery disease (CAD). Although microvascular dysfunction ...has been suggested to explain this syndrome and recently was found to predict adverse outcomes, the mechanisms and treatments remain unclear. Methods In a substudy within the WISE, 78 women with microvascular dysfunction (coronary flow reserve CFR <3.0 following adenosine) and no obstructive CAD were randomly assigned to either an angiotensin-converting enzyme inhibition (ACE-I) with quinapril or a placebo treatment group. The primary efficacy parameter was CFR at 16 weeks adjusted for baseline characteristics and clinical site. The secondary response variable was freedom from angina symptoms assessed using the Seattle Angina Questionnaire. Results A total of 61 women completed the 16-week treatment period with repeat CFR measurements, and treatment was well tolerated. For the primary outcome, at 16 weeks, CFR improved more with ACE-I than placebo ( P < .02). For the secondary outcome of symptom improvement, ACE-I treatment ( P = .037) and CFR increase ( P = .008) both contributed. Conclusions Microvascular function improves with ACE-I therapy in women with signs and symptoms of ischemia without obstructive CAD. This improvement is associated with reduction in angina. The beneficial response of the coronary microvasculature was limited to women with lower baseline CFR values, suggesting that the renin-angiotensin system may be more involved among women with more severe microvascular defects.
Abstract Background SERCA2a deficiency is commonly seen in advanced heart failure (HF). This study is designed to investigate safety and biological effects of enzyme replacement using gene transfer ...in patients with advanced HF. Methods and Results A total of 9 patients with advanced HF (New York Heart Association NYHA Class III/IV, ejection fraction EF ≤30%, maximal oxygen uptake VO2 max <16 mL·kg·min, with maximal pharmacological and device therapy) received a single intracoronary infusion of AAV1/SERCA2a in the open-label portion of this ongoing study. Doses administered ranged from 1.4 × 1011 to 3 × 1012 DNase resistant particles per patient. We present 6- to 12-month follow-up data for these patients. AAV1/SERCA2a demonstrated an acceptable safety profile in this advanced HF population. Of the 9 patients treated, several demonstrated improvements from baseline to month 6 across a number of parameters important in HF, including symptomatic (NYHA and Minnesota Living with Heart Failure Questionnaire, 5 patients), functional (6-minute walk test and VO2 max, 4 patients), biomarker (NT-ProBNP, 2 patients), and LV function/remodeling (EF and end-systolic volume, 5 patients). Of note, 2 patients who failed to improve had preexisting anti-AAV1 neutralizing antibodies. Conclusions Quantitative evidence of biological activity across a number of parameters important for assessing HF status could be detected in several patients without preexisting neutralizing antibodies in this open-label study, although the number of patients in each cohort is too small to conduct statistical analyses. These findings support the initiation of the Phase 2 double-blind, placebo-controlled portion of this study.
Cardiorenal Interactions Nohria, Anju, MD; Hasselblad, Vic, PhD; Stebbins, Amanda, PhD ...
Journal of the American College of Cardiology,
04/2008, Letnik:
51, Številka:
13
Journal Article
Recenzirano
Odprti dostop
Cardiorenal Interactions: Insights From the ESCAPE Trial Anju Nohria, Vic Hasselblad, Amanda Stebbins, Daniel F. Pauly, Gregg C. Fonarow, Monica Shah, Clyde W. Yancy, Robert M. Califf, Lynne W. ...Stevenson, James A. Hill Examination of the ESCAPE (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness) database shows that baseline renal insufficiency impacts outcomes more than worsening renal function (WRF) in patients with advanced decompensated heart failure. Neither baseline renal function nor WRF were explained by measured cardiac hemodynamics. These results suggest that poor forward flow alone does not explain the renal perturbations seen in advanced heart failure. In-hospital hemodynamic optimization using a pulmonary artery catheter–guided treatment strategy does not prevent WRF or improve renal function and short- and long-term outcomes compared with a strategy based on clinical assessment alone.
Right ventricular (RV) failure after left ventricular assist device (LVAD) implantation is associated with a high rate of morbidity and mortality. We sought to determine pre-operative right heart ...echocardiographic predictors of post-LVAD severe RV failure.
RV failure, defined as the need for inotropic support or pulmonary vasodilators for >or=14 days post-operatively, was evaluated in 33 patients (age 54 +/- 13 years) with LVADs. Preoperative RV systolic and diastolic echocardiographic parameters, including RV fractional area change, tricuspid annular motion, right atrial volume index, RV index of myocardial performance, hepatic vein Doppler velocities, tricuspid regurgitation severity, and RV systolic pressures (RVSPs) in patients with and without RV failure were compared.
Of the 33 patients evaluated, 11 (33%) had post-LVAD RV failure (2 needed RVAD support). Patients with post-LVAD RV failure had significantly lower pre-operative tricuspid annular motion (8 +/- 4 vs 15 +/- 6 mm, p < 0.01) and higher RVSPs (60 +/- 14 vs 46 +/- 11 mm Hg, p = 0.02). In 13 patients (39%) with moderate tricuspid regurgitation, pre-operative tricuspid annular motion remained significantly reduced (6.0 +/- 0.5 vs 13.5 +/- 5.0 mm, p = 0.045). Other echocardiographic parameters were not significantly different between patients. Tricuspid annular motion of <7.5 mm provides 91% specificity and 46% sensitivity in predicting post-LVAD RV failure.
Tricuspid annular motion is a predictor of post-LVAD RV failure. Using tricuspid annular motion in addition to conventional criteria may aid in early identification of patients with prolonged inotropic support or severe RV failure and allow for better pre-operative planning.
Abstract Background Among various cardiac autoantibodies (AAbs), those recognizing the β1 -adrenergic receptor (β1 AR) demonstrate agonist-like effects and induce myocardial damage that can be ...reversed by β-blockers and immunoglobulin G3 (IgG3) immunoadsorption. Objectives The goal of this study was to investigate the role of β1 AR-AAbs belonging to the IgG3 subclass in patients with recent-onset cardiomyopathy. Methods Peripheral blood samples were drawn at enrollment in patients with recent-onset cardiomyopathy (left ventricular ejection fraction LVEF ≤0.40; <6 months). The presence of IgG and IgG3-β1 AR-AAb was determined, and echocardiograms were assessed, at baseline and 6 months. Patients were followed up for ≤48 months. Results Among the 353 patients who had blood samples adequate for the analysis, 62 (18%) were positive for IgG3-β1 AR-AAbs (IgG3 group), 58 (16%) were positive for IgG but not IgG3 (non-IgG3 group), and the remaining were negative. There were no significant differences in baseline systolic blood pressure, heart rate, or LVEF among the groups at baseline. Left ventricular end-diastolic and end-systolic diameters were significantly larger in the non-IgG3 group compared with the other groups (left ventricular end-diastolic diameter, p < 0.01; left ventricular end-systolic diameter, p = 0.03). At 6 months, LVEF was significantly higher in the IgG3 group (p = 0.007). Multiple regression analysis showed that IgG3-β1 AR-AAb was an independent predictor of LVEF at 6 months and change in LVEF over 6 months, even after multivariable adjustment (LVEF at 6 months, β = 0.20, p = 0.01; change in LVEF, β = 0.20, p = 0.008). In patients with high New York Heart Association functional class (III or IV) at baseline, the IgG3 group had a lower incidence of the composite endpoint of all-cause death, cardiac transplantation, and hospitalization due to heart failure, whereas the non-IgG3 group had the highest incidence of the composite endpoint. Conclusions IgG3-β1 AR-AAbs were associated with more favorable myocardial recovery in patients with recent-onset cardiomyopathy.
Abstract Background Given the potential for recovery in recent onset nonischemic cardiomyopathy (ROCM), the timing and need for implantable cardioverter-defibrillator (ICDs) remains controversial. We ...examined the utilization of ICDs and the impact on survival for subjects with ROCM. Methods and Results An National Heart, Lung, and Blood Institute sponsored registry enrolled 373 subjects with ROCM, all with a left ventricular ejection fraction (LVEF) ≤0.40 and ≤6 months of symptoms. The mean age was 45 ± 14 years, 38% were female, 21% black, 75% New York Heart Association II/III, and the mean LVEF was 0.24 ± 0.08. Survival was comparable for subjects with an ICD within 1 month of entry (n = 43, 1/2/3 year % survival = 97/97/92) and those with no ICD at 1 month (n = 330, % survival = 98/97/95, P = .30) and between those with and without an ICD at 6 months (ICD, n = 73, 1/2/3 year % survival = 98/98/95; no ICD, n = 300, % survival = 98/96/95, P = .95). There were only 6 sudden cardiac deaths (SCD) noted (% survival free from SCD = 99/98/97) and these occurred in 1.9% of subjects without ICD and 0.9% of those with a device ( P = .50). Conclusions In a multicenter cohort of ROCM the risk of SCD was low at 1% per year. Early ICD placement did not impact survival and can be deferred while assessing potential for myocardial recovery.
Heart failure (HF) is characterized by neurohormonal activation of the sympathetic nervous and renin-angiotensin systems. Genetic polymorphisms in these systems could alter the prognosis in HF. We ...hypothesized the genetic polymorphisms in the sympathetic nervous and renin-angiotensin systems are associated with adverse outcomes, defined as death or heart transplantation in patients with HF. A total of 227 patients with HF were enrolled from a tertiary care clinic and followed for outcomes for ≤4 years. Eight polymorphisms in 6 genes were genotyped: β1 -adrenergic receptor (ADRB1, S49G, R389G), β2 -adrenergic receptor (ADRB2, G16R, Q27E), α2c -adrenergic receptor (ADRA2C, insertion/deletion 322-325), angiotensinogen (AGT, M235T), angiotensin receptor type 1 (AGTR1, 1166A>C), and angiotensin-converting enzyme (ACE, insertion/deletion in intron 16). Most patients were treated according to consensus guidelines. Male gender (hazard ratio 2.24, 95% confidence interval 1.27 to 3.94), higher New York Heart Association functional class (hazard ratio 2.54, 95% confidence interval 1.84 to 3.52), and 2 copies of ADRB2 Arg16Gln27 haplotype (hazard ratio 1.91, 95% confidence interval 1.09 to 3.36) increased the risk of adverse outcomes. In contrast, a higher serum sodium level (hazard ratio 0.91, 95% confidence interval 0.86 to 0.97) and higher creatinine clearance (hazard ratio 0.99, 95% confidence interval 0.98 to 0.99) decreased the risk of adverse outcomes. None of the other genotypes/haplotypes were associated with adverse outcomes. In conclusion, ADRB2 Arg16Gln27 haplotype may significantly increase the risk of adverse outcomes in patients with HF receiving contemporary HF pharmacotherapy.
Acute decompensated heart failure may occur de novo, but it most often occurs as an exacerbation of underlying chronic heart failure. Hospitalization for heart failure is usually a harbinger of a ...chronic disease that will require long-term, ongoing medical management. Leaders in the field generally agree that repeated inpatient admissions for treatment reflect a failure of the health care delivery system to manage the disease optimally. Newer management strategies focus on ameliorating symptoms by optimizing the hemodynamics, restoring neurohormonal balance, and making frequent outpatient adjustments when needed.
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