María Ángeles Castel

Chronic vagal stimulation for the treatment of low ejection fraction heart failure: results of the NEural Cardiac TherApy foR Heart Failure (NECTAR-HF) randomized controlled trial

Aim The neural cardiac therapy for heart failure (NECTAR-HF) was a randomized sham-controlled trial designed to evaluate whether a single dose of vagal nerve stimulation (VNS) would attenuate cardiac remodelling, improve cardiac function and increase exercise capacity in symptomatic heart failure patients with severe left ventricular (LV) systolic dysfunction despite guideline recommended medical therapy. Methods Patients were randomized in a 2 : 1 ratio to receive therapy (VNS ON) or control (VNS OFF) for a 6-month period. The primary endpoint was the change in LV end systolic diameter (LVESD) at 6 months for control vs. therapy, with secondary endpoints of other echocardiography measurements, exercise capacity, quality-of-life assessments, 24-h Holter, and circulating biomarkers. Results Of the 96 implanted patients, 87 had paired datasets for the primary endpoint. Change in LVESD from baseline to 6 months was −0.04 ± 0.25 cm in the therapy group compared with −0.08 ± 0.32 cm in the control group (P = 0.60). Additional echocardiographic parameters of LV end diastolic dimension, LV end systolic volume, left ventricular end diastolic volume, LV ejection fraction, peak V02, and N-terminal pro-hormone brain natriuretic peptide failed to show superiority compared to the control group. However, there were statistically significant improvements in quality of life for the Minnesota Living with Heart Failure Questionnaire (P = 0.049), New York Heart Association class (P = 0.032), and the SF-36 Physical Component (P = 0.016) in the therapy group. Conclusion Vagal nerve stimulation as delivered in the NECTAR-HF trial failed to demonstrate a significant effect on primary and secondary endpoint measures of cardiac remodelling and functional capacity in symptomatic heart failure patients, but quality-of-life measures showed significant improvement.

Decreased likelihood of response to cardiac resynchronization in patients with severe heart failure

We hypothesized that a very advanced stage of dilated cardiomyopathy is associated with lower response to cardiac resynchronization therapy (CRT).

Survival in New York Heart Association class IV heart failure patients treated with cardiac resynchronization therapy compared with patients on optimal pharmacological treatment

AIMS Although the benefit of cardiac resynchronization therapy (CRT) in selected patients with heart failure is well established, its effect on mortality in New York Heart Association (NYHA) class IV patients remains unclear. Our study evaluated the effect of CRT on urgent transplant-free survival in NYHA class IV patients treated with CRT, compared with medication-only treatment. METHODS AND RESULTS Forty NYHA class IV patients treated with CRT (80% men, 62.5% ischaemic, mean age of 65) were matched 1:1 by age, gender and aetiology of cardiomyopathy with patients treated with optimal medical therapy (OPT group). No significant differences were found between the groups in left ventricular diastolic diameter (71 +/- 6 vs. 73 +/- 9 mm), left ventricular systolic diameter (58 +/- 7 vs. 61 +/- 11 mm), and left ventricular ejection fraction (23 +/- 5 vs. 22 +/- 6%). Mean follow-up was 13.2 +/- 9.5 months for the CRT group and 17.3 +/- 11.6 months for the OPT group. Time to all-cause death or urgent transplantation [hazard ratios (HR), 1.29; 95% CI: 0.59-2.83; P = 0.52] or to cardiovascular death or urgent transplantation (HR, 1.53; 95% CI: 0.64-3.67; P = 0.34) was not reduced significantly in patients treated with CRT. CONCLUSION In this study, CRT did not significantly improve survival of NYHA class IV heart failure patients compared with pharmacological therapy.

Six-minute walking test predicts long-term cardiac death in patients who received cardiac resynchronization therapy

AIMS Cardiac resynchronization therapy (CRT) has been proven to be effective in patients suffering from chronic heart failure (CHF) associated with electrical dyssynchrony. However, long-term predictors of mortality in that subset have not been extensively investigated. The aim of this study was to establish baseline long-term predictors of cardiovascular mortality in CHF patients treated with CRT. METHODS AND RESULTS A total of 188 consecutive patients with moderate to severe CHF who had undergone a successful CRT implant were evaluated. Baseline measurements included clinical history, a 6-min walking test (6MWT), and echocardiographic parameters. Patients with cardiac or non-cardiac diseases limiting their ability to perform a 6MWT were excluded, with the final count totalling 155 patients [82% men, mean age 69 +/- 8 years, New York Heart Association (NYHA) functional class: II 22%, III 73.5%, IV 4.5%]. A total of 24 patients (15.5%) died of cardiovascular causes and one patient underwent heart transplantation during a mean follow-up of 24.4 +/- 18.1 months. Univariate analysis showed that NYHA class, distance walked in the 6MWT, left atrial diameter, digoxine and left ventricle (LV) ejection fraction were all significantly related to rates of mortality. Multivariate Cox regression after adjustment for the presence of a defibrillator showed that the LV ejection fraction [HR 0.91 (95% CI: 0.84-0.98) P = 0.008] and 6MWT distance <225 m [HR 5.6 (95% CI: 1.2-25.3) P = 0.026] were independent predictors of cardiovascular mortality. CONCLUSION Baseline functional capacity, measured by the 6MWT distance, and LV ejection fraction are independent predictors of mortality in moderate to severe CHF patients, despite CRT. A 6MWT distance walked of <225 m identifies patients at high risk of cardiovascular death at mid-long term.

Long-term prognostic value of elevated heart rate one year after heart transplantation.

BACKGROUND Elevated heart rate (HR) is associated with adverse cardiovascular outcome in the general population and in patients with cardiovascular disease. Elevated HR due to graft denervation is often found in heart transplantation (HTx) patients; the effect on graft survival and vasculopathy is unclear. Thus, the aim of this study was to evaluate the role of elevated HR at 12 months post-HTx and its power to predict HTx long-term outcome. METHODS We evaluated retrospectively a prospective database of 312 patients undergoing HTx at two centers. HR was registered at 12 months post-HTx. The median HR was used as a cutoff point. Cox regression analysis was performed with variables known to be clinically relevant to mortality and those selected from the univariate analysis. RESULTS During a mean follow-up of 5.5 ± 2.8 years there were 58 deaths (19%). Patients with a HR ≥ 90 bpm (median HR) at 12 months had an increased risk for all-cause mortality (Hazard Ratio=2.4, 95% CI 1.2 to 4.5, p=0.009) and mortality related to coronary allograft vasculopathy (CAV) (Hazard Ratio=3.0, 95% CI 1.25-7.14, p=0.01). Multivariate analysis showed that a HR ≥ 90 bpm independently predicted mortality (HR 3.2, 95% CI 1.4-7.1, p=0.004). CONCLUSIONS Elevated HR measured at 12 months after HTx is an independent predictor of all-cause mortality in HTx recipients. A HR ≥ 90 bpm identifies a group of patients at high risk of death and CAV-related mortality at mid- to long-term.

Heart transplantation in HIV-infected patients: More cases in Europe

Maria Angeles Castel, MD, PhD, Felix Perez-Villa, MD, PhD, and Jose M. Miro, MD, PhD Heart Failure and Heart Transplantation Program, Thorax Institute, Hospital Clinic, Institut d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS), University of Barcelona; Infectious Disease Service, Clinic Institute of Medicine and Dermatology, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain

Decreased Expression of Thrombospondin-1 in Failing Hearts May Favor Ventricular Remodeling

BACKGROUND Thrombospondin-1 (TSP-1) is a potent inhibitor of angiogenesis and an activator of tissue transforming growth factor-beta1 (TGF-beta1). Analyses using genetically modified mice suggested that TSP-1 may play a protective role to prevent infiltration and tissue remodeling responses after myocardial infarction. The expression levels of TSP-1 and their putative role in ventricular remodeling have not been determined in patients with heart failure (HF). MATERIALS AND METHODS We analyzed the expression of TSP-1 and TGF-beta1 mRNA in myocardial biopsies from 34 subjects with end-stage HF undergoing heart transplantation and 13 healthy controls from heart donors. Among total RNA extracted from the left ventricle, 1 microg was retrotranscribed and mRNA expression levels were quantified by real-time polymerase chain reaction (PCR). RESULTS The mean age of subjects was 54 +/- 2 years; mean ejection fraction, 21 +/- 5%; end-diastolic diameter and end-systolic diameter, 73 +/- 10 and 61 +/- 11 mm, respectively. TSP-1 mRNA expression in ventricular tissue from HF patients was lower (159.04 +/- 14.55 ng-equivalents [ng-equiv]) than in controls (234 +/- 30.66 ng-equiv; P < .05). Tissue from HF subjects also showed lower levels of TGF-beta1 (68.42 +/- 4.36 vs 80.58 +/- 5.26 ng-equiv; P < .05). TSP-1 mRNA levels correlated positively with TGF-beta1 (P = .001; R(2) = .2), and lower TSP-1 mRNA levels were observed with increasing left ventricular diameters. CONCLUSIONS Patients with end-stage HF show decreased TSP-1 mRNA levels, which agrees with published results showing lower circulating TSP-1. Ventricular dilatation observed in these patients may be related to lower expression of TSP-1. Surprisingly, TGF-beta1 mRNA levels were lower in failing hearts, which suggested that fibrogenesis takes place in earlier phases of HF.

Bosentan in heart transplantation candidates with severe pulmonary hypertension: efficacy, safety and outcome after transplantation

Increased pulmonary vascular resistance (PVR) is associated with increased right ventricular failure and mortality after heart transplantation.

Effect of Cardiac Resynchronization Therapy on Left Ventricular Diastolic Function: Implications for Clinical Outcome

BACKGROUND The definition of response to cardiac resynchronization therapy (CRT) remains controversial, with variable rates of response depending on the criteria used. Our aim was to analyze the impact of CRT on diastolic function in different degrees of response, particularly in patients with positive clinical but no echocardiographic response. METHODS AND RESULTS In 250 CRT patients clinical evaluation and echocardiography were performed before and after CRT. Absolute response to CRT was defined as a reduction in left ventricular (LV) end-systolic volume of ≥15% at 1-year follow-up. Additionally, patients were classified into 4 subgroups according to their amount of response: extensive reverse remodeling (RR), slight RR, clinical response without RR, and neither clinical response nor RR. An improvement in estimates of LV filling pressure and a decrease in left atrial dimensions were observed only in responders to CRT. Patients with clinical but no echocardiographic response had significant improvement in E-wave and deceleration time and nonsignificant improvement in other parameters. CONCLUSIONS LV diastolic function improves with CRT. Clinical responders without echocardiographic response show improvement in parameters of diastolic function. That suggests that clinical-only response to CRT is secondary to a real effect of the therapy, rather than a placebo effect.

Rate-responsive pacing in patients with heart failure: long-term results of a randomized study

AIMS Chronotropic incompetence (CI) in patients with congestive heart failure (CHF) develops frequently under beta-blocker and amiodarone therapy. It can be corrected by pacing. We performed a randomized study to test whether pacing is beneficial in CHF patients with CI. METHODS AND RESULTS Congestive heart failure patients under combined beta-blocker and amiodarone therapy (n = 77) were randomly assigned to inhibited pacing (INH; basal rate 40 bpm/hysteresis 30 bpm; n = 38) or to DDDR pacing with optimized atrioventricular delay (OPT; stimulation rate 65-120 bpm, n = 39). Groups showed similar baseline values in NYHA class, heart rate, and ejection fraction (EF) and were followed up to 10 years. The resting and mean 24 h heart rate after 1 year decreased by -2.6/-5 bpm in INH, but increased by +3.6/+6.0 bpm in the OPT group (P < 0.001). The QRS interval after 1 year increased by 12 +/- 23 ms in the INH group, but +32 +/- 36 ms in the OPT group (P < 0.01). Patients with INH developed a greater left ventricular EF (LVEF) when compared with OPT patients (+10.6 +/- 8 vs. +2 +/- 10%, respectively; P = 0.04). Changes in LVEF were negatively correlated with heart rate, but not with QRS width changes. Prognosis and the event rate were better in the INH group. CONCLUSION In the long-term follow-up, single-site ventricular pacing in patients with CHF and low LVEF is associated with significant clinical events and a poor prognosis.