Advanced Systolic Heart Failure Research Articles

Abstract 18454: Novel Extracellular Matrix Biomarkers as Predictors of Adverse Outcome in Chronic Heart Failure

Background: The extracellular matrix (ECM) plays an important role in left ventricular remodeling and changes in expression patterns of ECM proteins may contribute to the progression of heart failure (HF). Endostatin, biglycan and mimecan are ECM proteins that are abundantly expressed in cardiac tissue but have not been evaluated as prognostic markers in HF. We investigated if they were increased in chronic HF and if levels were associated with adverse outcome. Materials and methods: Serum endostatin, biglycan and mimecan were measured in 187 HF patients and 57 matched healthy controls. Associations with adverse outcome were assessed in 1428 patients enrolled in the in the Controlled Rosuvastatin Multinational Trial in HF (CORONA) population, randomly assigned to 10 mg rosuvastatin or placebo, which included patients with HF, aged ≥60 years, in New York Heart Association classes II to IV, who had ischemic heart disease and a reduced left ventricular ejection fraction. Outcome included the primary endpoint (cardiovascular (CV) death, nonfatal myocardial infarction, nonfatal stroke; n=408), all-cause mortality (n=422), CV mortality (n=344), coronary endpoint (n=330) and CV mortality/hospitalization for worsening of HF (n=535). Results: Serum levels of endostatin, biglycan and mimecan were all increased (31-62% p<0.001) in HF patients vs. controls. In univariate analyses and multivariable analysis (adjusting for LVEF, NYHA class, age, BMI, diabetes, sex, intermittent claudication, heart rate, serum creatinine and apoA1 but not CRP and NT-proBNP), endostatin (continuous variable) was associated with all outcomes. However, the predictive value was markedly attenuated and not significant for any outcome after the addition of CRP and NT-proBNP. Biglycan was moderately but significantly associated with all outcome measures (except coronary endpoint) in univariate analysis but not after multivariable adjustment while no associations were observed for mimecan. Conclusions: Serum levels of the ECM proteins endostatin, biglycan and mimecan are all elevated in chronic HF, but add no predictive information beyond NT-proBNP for adverse outcome in older patients with advanced chronic systolic HF of ischemic aetiology.

Abstract 18269: Prognostic Value of Insulin-Like Growth Factor Binding Protein 7 (IGFBP7) in Patients With Heart Failure: Data From CORONA

Background: A recent proteomic analyses of cardiac tissue from a transgenic murine model of heart failure (HF) and clinical myocardial samples identified IGFBP7 as a candidate marker of HF. We investigated if serum levels of IGFBP7 were upregulated in human HF, if IGFBP7 provided independent prognostic information in these patients, and potential interactions with statin therapy. Materials and methods: Serum IGFBP7 was measured in 187 HF patients and 57 matched healthy controls. The associations of serum IGFBP7 with adverse outcome were assessed in a subset of 1428 patients enrolled in the in the Controlled Rosuvastatin Multinational Trial in HF (CORONA) population, randomly assigned to 10 mg rosuvastatin or placebo, which included patients with HF, aged ≥60 years, in New York Heart Association classes II to IV, who had ischemic heart disease and a reduced left ventricular ejection fraction. Outcome included the primary endpoint (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke; n=408), all-cause mortality (n=422), CV mortality (n=344), coronary endpoint (n=330) and CV mortality/hospitalization for worsening of heart failure (n=535). Results: Serum IGFBP-7 levels were markedly elevated (p<0.001) in HF patients compared to controls (median [25th, 75th percentile]: 694 [586,874] ng/mL vs. 458 [425,499] ng/mL, p<0.001) and correlated with clinical severity (i.e. NYHA, p=0.002). In univariate analyses, IGFBP7 (continuous variable) was associated with all outcomes [HR ranging from 1.76 (coronary endpoint, p=0.003) to 3.08 (CV death, p<0.001)]. In multi-variable analyses, IGFBP7 remained significant for most endpoints after step 1 adjustment (adjusting for left ventricular ejection fraction, NYHA class, age, body mass index, diabetes, sex, intermittent claudication, heart rate, serum creatinine and apoA1) but the predictive value was markedly attenuated and not significant for any outcome after the addition of CRP and NT-proBNP. No interaction by treatment effects were observed for any outcome. Conclusions: Serum IGFBP7 levels are elevated in patients with HF but add no predictive information beyond NT-proBNP for adverse outcome in older patients with advanced chronic systolic HF of ischemic aetiology.

Incremental Value of Left Atrium Two-Dimensional Strain in Patients with Heart Failure

Implication for health policy/practice/research/medical education: Left atrium 2D strain is a useful noninvasive method for quantification of regional and global LA deformation. Copyright © 2013, Iran University of Medical Sciences; Published by Kowsar Corp. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Left atrial (LA) size and function is an important determinant of cardiovascular morbidity and mortality. Assessment of LA strain using two-dimensional speckle tracking imaging or velocity vector imaging has been recently introduced for the quantification of regional and global LA deformation. Furthermore, LA strain measurement has been proposed as an alternative method for the estimation of left ventricular (LV) filling pressure (1, 2). Decreased LA strain has been correlated with increased left ventricular end-diastolic pressure (1, 3). Cameli et al. (4) demonstrated that in a group of patients with advanced systolic heart failure, E/Em ratio correlates poorly with invasively obtained LV filling pressures. Nevertheless, LA longitudinal deformation analysis by speckle tracking imaging correlates well with pulmonary capillary wedge pressure, providing a better estimation of LV filling pressure in this particular clinical setting. Recent studies have shown the clinical importance of LA strain in atrial fibrillation, LV systolic and diastolic dysfunction, mitral valve disease, and cardiomyopathies (4, 5). In this issue of the journal, Esmaeilzadeh et al. present interesting data regarding the usefulness of LA 2D strain measurement via velocity vector imaging in LV systolic heart failure patients. They found substantially low 2D LA strain in systolic heart failure patients compared with normal subjects and demonstrated a significant relationship between LA strain and degree of diastolic dysfunction in patients with systolic heart failure. The investigators suggested that a cut-off value of total average LA strain ≥ 23.28% can differentiate between normal and abnormal LA function with sensitivity of 93% and specificity of 100%. The study in question, however, does not mention the effect of other confounding factors such as hypertension and diabetes on LA 2D strain. Mondillo et al. (6) reported reduced peak atrial longitudinal strain in patients with hypertension (29.0 ± 6.5%) and those with diabetes (24.7 ± 6.4%) in comparison with controls (39.6 ± 7.8%). Additionally, they demonstrated that the reduction was more pronounced in patients with both diabetes and hypertension and concluded that LA deformation mechanics are impaired in patients with a normal LA size who have hypertension or diabetes. Dogan et al. (7) confirmed that LA strain has a significant correlation with LV ejection fraction (r = 0.51, P value = 0.001). The authors also reported a significant inverse correlation between LA strain and B-type natriuretic peptide (BNP) level (r = -0.41, P = 0.001) in acute ST-elevation patients. It is, however, worthy of note that different software packages and echocardiography machines are liable to yield different results, rendering the cut-off values incomparable. It seems reasonable to conclude that LA 2D strain is a useful noninvasive tool for the evaluation of LA function in patients with systolic heart failure in as much it correlates well with diastolic dysfunction and LV filling pressure.

The Prognostic Value of Neopterin Concentration in Patients with Advanced Heart Failure

OP-179 Serum levels of neopterin, an immune modulator secreted by activated macrophages. The relationship between neopterin and the risk of HF has yet to be investigated on a large scale. The level of neopterin elevated in patients with advanced systolic heart failure compared with control subjects

Comparison of Right Versus Left Ventricular Strain Analysis as a Predictor of Outcome in Patients With Systolic Heart Failure Referred for Heart Transplantation

The aim of the present study was to explore the relation between right ventricular (RV) and left ventricular (LV) echocardiographic parameters with clinical outcome in patients with advanced heart failure referred for cardiac transplantation. Ninety-eight consecutive patients with advanced systolic heart failure, referred for cardiac transplant evaluation, were enrolled. All patients were prospectively followed for the development of new outcome events, which included hospitalization for acute heart failure, cardiovascular death, heart transplantation, intra-aortic balloon pump implantation, and ventricular assist device implantation. Conventional transthoracic echocardiography was performed in all subjects. RV longitudinal strain (RVLS) by speckle-tracking echocardiography was assessed by averaging all segments in apical 4-chamber view (global RVLS) and by averaging RV free-wall segments (free-wall RVLS). LV global longitudinal and global circumferential strains were also calculated. Of the 98 subjects at baseline, 46 had 67 new events during a mean follow-up of 1.5 ± 0.9years. Free-wall RVLS, global RVLS, N-terminal fragment of the prohormone brain natriuretic peptide, RV fractional area change, and LV end-diastolic volume were independently predictive of combined outcomes (all p <0.0001). The overall performance for the prediction of cardiovascular events was greatest for free-wall RVLS (area under the curve free-wall RVLS: 0.87; global RVLS: 0.67; RV fractional area change: 0.60; N-terminal fragment of the prohormone brain natriuretic peptide, 0.62; global circumferential strain: 0.55; global longitudinal strain: 0.35; and LV ejection fraction: 0.26). Free-wall RVLS showed the highest adjusted hazards ratio. A graded association between the grade of RV dysfunction and the risk of cardiovascular events was only evident for free-wall RVLS and global RVLS. In conclusion, in patients referred for heart transplantation, RVLS is a stronger predictor of outcome than LV longitudinal strain and other conventional parameters, providing a stronger prognostic stratification.

Cardiac contractility modulation therapy in advanced systolic heart failure

Cardiac contractility modulation (CCM) is the application of nonexcitatory electrical signals to the myocardium, during the absolute refractory period of the action potential, to elicit a positive inotropic effect without increasing myocardial oxygen consumption. These effects are independent of QRS duration; consequently, CCM device therapy might benefit symptomatic patients with reduced left ventricular ejection fraction who are not candidates for cardiac resynchronization therapy. Preclinical studies have demonstrated a rapid positive inotropic effect of CCM, which seems to be mediated by modulation of cardiomyocyte Ca(2+) fluxes and alterations in the phosphorylation of cardiac phospholamban. In vivo translational and clinical studies that utilized double biphasic voltage pulses to the right ventricular aspect of the interventricular septum have demonstrated positive global effects on cardiac reverse remodelling and contractility. Long-term application of CCM seems to improve patients' exercise tolerance and quality of life. These benefits are apparently accomplished with an acceptable safety profile; however, to date, no data have demonstrated reductions in hospitalizations for heart failure or mortality. CCM is currently available in Europe and ongoing studies are attempting to identify the ideal target population and accumulate additional outcome data.

Cardiac contractility modulation: first experience in patients with advanced systolic heart failure and permanent atrial fibrillation

Cardiac contractility modulation: first experience in patients with advanced systolic heart failure and permanent atrial fibrillation

Left ventricular assist device implantation improves glycemic control in patients with diabetes and advanced systolic heart failure

Left ventricular assist device implantation improves glycemic control in patients with diabetes and advanced systolic heart failure

Impact of inotropic drugs on the validity of left ventricular filling pressure echocardiographic assessment in end-stage heart failure patients

Purpose: Several studies found that the ratio of early diastolic transmitral flow velocity to tissue Doppler mitral annular early diastolic velocity E/e$'$ correlated well with the mean pulmonary capillary wedge pressure (PCWP). Recently, the validity of E/e' ratio in predicting PCWP was challenged in patients with decompensated end-stage systolic heart failure. In the latter study, influence of inotropic drugs was not taken into consideration. We hypothesize that inotropes modify relaxation properties and may have impaired the validity of E/e' as a surrogate of filling pressure in this setting. Methods and results: Hemodynamic and echocardiographic data were gathered prospectively in 37 patients with decompensated end stage heart failure (EF≤35%, NYHA≥III, LVTDD>31 mm/m2). Those patients (Mean age 56yo, PCWP 22±8 mmHg, septal E/e' 17±5) were admitted for ventricular assist device implantation or heart transplantation. For 11 patients, we had at least two points of evaluation, before and after introduction of inotropes. In the overall study (n=49), E/e' ratio (lateral,septal,mean) was not or poorly correlated to PCWP (r=0,35, p<0,01 for septal E/e'). In examinations performed without inotropic drugs (n=17), correlation between septal E/e' and PCWP was good (r=0,66; p<0,01) while no correlation was found in examinations during inotropes use (n=28). Lateral and mean E/e' were not or poorly correlated to PCWP in both cases. ![Figure][1] PCWP-E/e' correlation-linear regression Conclusions: In decompensated patients with advanced systolic heart failure, the E/e' ratio for assessing left ventricular filling pressure is accurate in the absence of inotropes but unreliable when inotropic drugs are used. [1]: pending:yes

Pulmonary congestion evaluated by lung ultrasound predicts admission in patients with heart failure

Purpose: Lung ultrasound (LUS) assessment of B-lines (also called ultrasound lung comets) has been recently proposed as a reliable and easy evaluation of pulmonary congestion in heart failure (HF) patients. Our aim was to determine the prognostic value of LUS to predict adverse events in a HF outpatient clinic. Methods: Ninety-seven patients admitted to a heart failure clinic due to advanced systolic HF (61% men, mean age 53±13years, 27% post-ischaemic and 54% idiopathic cardiomyopathy) were enrolled. LUS evaluation was independently performed during the outpatient regular visit. B-lines number was obtained by summing the number of B-lines from 28 scanning sites, as previously described. Results: LUS feasibility was 100%. Mean time to perform LUS was 8.7±2min. Significant pulmonary congestion at LUS (total B-lines number>15) was present in 68% patients. Patients were followed-up for a median period of 106±12days (interquartile range: 89-115days). During the follow-up, 21 hospitalization for acute pulmonary oedema occurred. Severity of pulmonary congestion at LUS was related to events (see figure). At multivariate analysis, pulmonary congestion degree assessed by LUS (Hazard Ratio 5.0, 95% Confidence Interval 1.8–13.8) was the strongest predictor of events compared to left ventricular ejection fraction (ns), E/e' (ns), systolic arterial pulmonary pressure (ns), NYHA class (HR 2.5, 95% C.I 1.2–5.3) and NT-proBNP values (ns). No acute pulmonary oedema occurred in patients without significant pulmonary congestion at LUS. ![Figure][1] Kaplan-Meier event-free survival Conclusion: In a HF outpatient setting, B-lines assessment by LUS may help to identify patients most likely to develop acute pulmonary oedema. This simple evaluation could help in identifying decompensated patients, whose treatment should be intensified. [1]: pending:yes

Myocardial Recovery with Optimization of Medical Management in Patients with Advanced Systolic Heart Failure

Myocardial Recovery with Optimization of Medical Management in Patients with Advanced Systolic Heart Failure

Reversing heart failure by CRT: how long do the effects last?

This editorial refers to ‘Long-term impact of cardiac resynchronization therapy in mild heart failure: 5-year results from the REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction (REVERSE) study’[†][1], by C. Linde et al. , on page 2592 Device-based treatment of advanced systolic heart failure by cardiac resynchronization therapy (CRT) is a fairly invasive procedure when compared with conservative pharmacological therapy. Despite all efforts to improve the safety, feasibility, and clinical efficacy of the implantation procedure, a small, but not negligible, perioperative risk and the possibility for long-term complications such as device infection and lead dislocation remain. Furthermore, the upfront costs at the time of implantation are comparatively high. However, the large amount of available evidence which has been accumulated over the last two decades from many well-controlled and randomized trials has proven that the procedure is highly cost-effective and efficient in well selected patients. The stimulus to place an additional pacing lead on the delayed activated left ventricular free wall in patients with left bundle branch block (LBBB) to improve cardiac haemodynamics was based on pathophysiological principles, well-performed animal experiments, and thoughtful clinical observations. However, what initially was meant to be a rescue therapy for end-stage heart failure patients,1,2 has, over time, transformed into a life-saving routine treatment which is now indicated as soon as a patient with depressed systolic function and LBBB develops symptoms of heart failure [e.g. New York Heart Association (NYHA) class ≥II].3 Part of the evidence to support this aggressive therapeutic approach in patients with mild symptoms of heart failure comes from the 12-month results of the REVERSE trial,4 which was the first prospective, randomized trial to include patients with less than NYHA class III–IV. Although the primary endpoint—a composite score of the clinical response of heart failure—failed to reach statistical significance … [1]: #fn-2

Resting Heart Rate and Heart Rate Reserve in Advanced Heart Failure Have Distinct Pathophysiologic Correlates and Prognostic Impact: A Prospective Pilot Study

The purpose of this study was to compare the prognostic impact of clinical and biomarker correlates of resting heart rate (HR) and chronotropic incompetence in heart failure (HF) patients. The mechanisms and underlying pathophysiological influences of HR abnormalities in HF are incompletely understood. In a prospective pilot study, 81 patients with advanced systolic HF (97% were receiving beta-blockers) and 25 age-, sex-, and body-size matched healthy controls underwent maximal cardiopulmonary exercise testing with sampling of neurohormones and biomarkers. Two-thirds of HF patients met criteria for chronotropic incompetence. Resting HR and HR reserve (HRR, a measure of chronotropic response) were not correlated with each other and were associated with distinct biomarker profiles. Resting HR correlated with increased myocardial stress (B-type natriuretic peptide [BNP]: r = 0.26; pro-A-type natriuretic peptide: r = 0.24; N-terminal-proBNP: r = 0.32) and inflammation (leukocyte count: r = 0.28; high-sensitivity C-reactive protein assay: r = 0.25). In contrast, HRR correlated with the neurohumoral response to HF (copeptin: r = -0.33; norepinephrine: r = -0.29) but not with myocyte stress or injury reflected by natriuretic peptides or hs-troponin I. Patients in the lowest chronotropic incompetence quartile (HRR ≤0.38) displayed more advanced HF, reduced exercise capacity, ventilatory inefficiency, and poorer quality of life. Over a median follow-up of 17 months, the combined endpoint of death or urgent transplant/assist device implantation occurred more frequently in patients with higher resting HR (>67 beats/min) or lower HRR, with both markers providing additive prognostic information. Increased resting HR and chronotropic incompetence may reflect different pathophysiological processes, provide incremental prognostic information, and represent distinct therapeutic targets.

Optimizing Cardiac Resynchronization Therapy for Congestive Heart Failure

In patients with advanced systolic heart failure and mechanical dyssynchrony, cardiac resynchronization therapy (CRT) is an effective means of improving symptoms and reducing mortality. There are now several recognized approaches to optimize CRT. Imaging modalities can assist with identifying the myocardium with the latest mechanical activation for targeted left ventricular lead implantation. Device programming can be tailored to maximize biventricular pacing, and thereby is its benefit. Cardiac imaging has shown that atrioventricular and interventricular intervals can be adjusted to further reduce dyssynchrony. We review these various approaches that maximize the benefit derived from CRT.

Right Atrial to Pulmonary Capillary Wedge Pressure Ratio Is Not Associated with Failure of Optimal Medical Management in the INTERMACS 4-5 Population

Purpose Intracardiac filling pressures play an important role in in risk stratification of patients with advanced systolic heart failure (HF) undergoing cardiac transplantation (OHT) and left ventricular assist device (LVAD) placement. The right atrial (RA) pressure to pulmonary capillary wedge pressure (PCWP) ratio has been shown to have important prognostic significance. Less is known about the prognostic impact of cardiac filling pressures in patients with ambulatory advanced HF (INTERMACS profiles 4-5). Methods and Materials We retrospectively evaluated 187 patients referred for consideration of advanced HF therapies at our center from January 2005 to July 2010. The endpoint of failure of optimal medical management (OMM) was defined as death, OHT or LVAD implantation. Tertiles of RA:PCWP ratio were defined as 0.583(tertile 3). Median PCWP in each cohort was 16, 25, and 20 mmHg respectively (p Results Patients in tertile 3 had lower PA oxygen saturation(p= 0.006), RV stroke work index (p 20mmHg, p=0.146). However, when evaluating each RA and PCWP independently, only increasing PCWP was associated with failure of OMM [HR 1.046 (1.020-1.073), p Conclusions In a cohort of patients with advanced ambulatory HF (INTERMACS 4-5), increasing RA:PCWP was associated with worsening RV function and decreased exercise capacity but not with failure of OMM. PCWP varied across tertiles of RA:PCWP ratio and was independently associated with failure of OMM. Our study suggests that left and right-sided filling pressures may need to be interpreted independently in advanced ambulatory heart failure.

Clinical Characteristics and Outcomes in Patients with Mismatched Filling Pressures in Advanced Heart Failure: Looking beyond the JVP

Purpose Right atrial (RA) and pulmonary capillary wedge pressure (PCWP) are concordant in the majority of heart failure (HF) patients, allowing estimation of volume status by jugular venous pressure (JVP). Pts with discordant filling pressures have been identified while undergoing transplant evaluation. However, the incidence and outcomes of discordant filling pressures have not been evaluated in pts with chronic advanced HF. Methods and Materials The MEDAMACS screening pilot was a multicenter, prospective, observational study of pts with advanced systolic HF, including 116 pts who underwent right heart catheterization (RHC) within 6 months of enrollment. Three strata were defined: 1. Matched high (MH, RA≥11mmHg +PCWP≥20mmHg) 2. Matched low (ML, RA≤10 mmHg+PCWP≤19mmHg) or 3. Mismatched (MM i.e. RA≤10 mmHg+PCWP≥20mmHg). Pts were assessed for outcomes of death, initiation of inotropes, mechanical circulatory support, or transplant. Results Of the 116 pts in this analysis, 25%, 47%, and 28% pts were in the ML, MH and MM groups respectively. 49 events were recorded by 6 months. The majority of pts with in the MM group had low RA pressure and high PCWP. There were no differences between the 3 groups in baseline demographics, HF etiology, EF, or NYHA class. The MH and MM groups included fewer pts tolerating ACE-inhibitors (ML 76%, MH 50%, MM 58%, p=0.07), and mean Cr was higher in the MM group (ML 1.3 mmol/L, MH 1.6mmol/L, MM 1.8mmol/L, p= 0.02). Six-month event free survival was 75%, 67% and 55% for the ML, MH and MM groups respectively (p=0.249). Conclusions Discordant filling pressures were found in 28% of advanced HF patients on medical therapy and were associated with impaired renal function and lower tolerance of neurohormonal antagonists. Despite limited evidence of congestion by JVP assessment, event rates are high for pts with discordant filling pressures, affirming a role for selective use of invasive hemodynamic assessment in this population.

The predictive value of galectin-3 for mortality and cardiovascular events in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA)

Galectin-3 is a new biomarker involved in inflammation and fibrogenesis and could therefore contribute to myocardial remodeling. We examined the prognostic value of baseline galectin-3 in a substudy involving approximately 30% of participants in the CORONA study. Patients (n = 1462) aged >60 years with systolic, ischemic heart failure (HF) were randomized to 10 mg/d rosuvastatin or placebo. The primary composite end point was cardiovascular death, nonfatal myocardial infarction, or stroke (n = 408). In the unadjusted analysis, galectin-3 was associated with all end points considered, except hospitalization for worsening of HF. In multivariable analyses, adjusting for other clinical and biochemical predictor variables, galectin-3 was significantly associated with the primary end point (hazard ratio [HR] 1.53 [1.10-2.12], P = .011) as well as all-cause (HR 1.61 [1.20-2.29], P = .002) and cardiovascular mortality (HR 1.70 [1.19-2.42], P = .003), sudden death (HR 1.83 [1.14-2.94], P = .012), and the coronary end point (HR 1.48 [1.03-2.12], P = .035). However, when N-terminal pro-brain natriuretic peptide was added to the model, galectin-3 association with the end points was markedly attenuated and no longer significant. Galectin-3 is not associated with outcome in older patients with advanced chronic systolic HF of ischemic etiology when adjusting for N-terminal pro-brain natriuretic peptide and may therefore have limited use in the prognostication of elderly patients with systolic HF in clinical practice.

The effects of phosphodiesterase 5 inhibition on hemodynamics, functional status and survival in advanced heart failure and pulmonary hypertension: A case–control study

BackgroundThe goal was to examine the hemodynamic and clinical effects of long-term therapy with PDE5 inhibitor sildenafil (SILD) in patients with advanced, pre-transplant heart failure (HF) and severe pulmonary hypertension (PH), in comparison to a similar control group (CON). MethodsIn this non-randomized, retrospective case–control study, 32 middle-aged patients (81% males) with advanced systolic HF (80%≥NYHA III, 56% ischemic) and severe pre-capillary PH (transpulmonary pressure gradient>15mm Hg) were studied before and after initiation of SILD (dose 73±25mg/day) and were compared to 15 CON patients, matched for key clinical characteristics (including PH severity, age and co-morbidities), not exposed to SILD. Changes at 3months and the long-term outcome were compared between groups. ResultsSILD significantly reduced pulmonary vascular resistance (−32% vs. baseline), transpulmonary gradient (−25%) and increased cardiac output (+15%) compared to controls, without affecting systemic or ventricular filling pressures. SILD-treated subjects experienced an improvement in NYHA class and had a steady body weight which contrasted with significant weight loss in the CON group (by −4.8%, absolutely by 4.3±6kg). During follow-up (median 349days from baseline), 60% of patients underwent heart transplantation. Two patients in CON group had severe post-transplant failure of the right ventricle, none in SILD group. Overall pre- and peritransplant survival (censored 30days after transplantation) was significantly better in SILD than CON group (93.7 vs 60%, p=0.0048). ConclusionsIn patients with advanced HF and severe PH, SILD therapy has beneficial effects on hemodynamics, clinical status, cardiac cachexia, and contributes to improved peri-transplant survival.

Randomized controlled trial of ventricular elastic support therapy in the treatment of symptomatic heart failure: Rationale and design

Despite the current drug and device therapies, heart failure remains associated with high rates of disability, morbidity, and mortality. There is a need for newer therapies. One investigational approach is the use of ventricular support devices. These devices reduce ventricular wall stress leading to decreases in left ventricular (LV) volumes, dimensions, and mass. Ventricular support devices have been shown to reverse pathological ventricular remodeling, improve systolic function, and improve symptoms of heart failure. The Prospective Evaluation of Elastic Restraint to LESSen the effects of Heart Failure (PEERLESS-HF) trial was designed to further evaluate the safety and efficacy of one such device, the HeartNet (Paracor Medical, Sunnyvale, CA). The HeartNet is an elastic ventricular restraint device formed from nitinol and covered in silicone, implanted using a minimally invasive approach. The aim of this randomized controlled trial is to compare optimal heart failure drug and device therapy plus the HeartNet (treatment group) to optimal drug and device therapy alone (control group) in patients with advanced systolic heart failure (LV ejection fraction ≤35% and LV end diastolic diameter <85 mm). Primary efficacy end points include the change in peak VO(2), quality of life score, and 6-minute hall walk distance from baseline to 6 months. The primary safety objective is to demonstrate noninferiority for all-cause mortality at 12 months. Planned enrollment is for 272 patients at approximately 35 centers in North America. The PEERLESS-HF trial will evaluate the safety and efficacy of ventricular elastic support in advanced systolic heart failure, advancing our knowledge of this investigational approach to heart failure therapy.

The role of aldosterone receptor antagonists in the management of heart failure: An update

The aldosterone receptor antagonists (ARAs) spironolactone (Aldactone) and eplerenone (Inspra) have become part of standard medical therapy for heart failure, having shown clinical efficacy in randomized trials in patients with advanced symptomatic systolic heart failure, postinfarction heart failure with cardiac dysfunction, and systolic heart failure with mild symptoms. The benefits include a lower rate of death. Yet to be answered is whether the two drugs are clinically equivalent; another question is whether they may benefit everyone with symptomatic heart failure, including diastolic heart failure.