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Among patients with heart failure who have mitral regurgitation due to left ventricular dysfunction, the prognosis is poor. Transcatheter mitral-valve repair may improve their clinical outcomes.At 78 sites in the United States and Canada, we enrolled patients with heart failure and moderate-to-severe or severe secondary mitral regurgitation who remained symptomatic despite the use of maximal doses of guideline-directed medical therapy. Patients were randomly assigned to transcatheter mitral-valve repair plus medical therapy (device group) or medical therapy alone (control group). The primary effectiveness end point was all hospitalizations for heart failure within 24 months of follow-up. The primary safety end point was freedom from device-related complications at 12 months; the rate for this end point was compared with a prespecified objective performance goal of 88.0%.Of the 614 patients who were enrolled in the trial, 302 were assigned to the device group and 312 to the control group. The annualized rate of all hospitalizations for heart failure within 24 months was 35.8% per patient-year in the device group as compared with 67.9% per patient-year in the control group (hazard ratio, 0.53; 95% confidence interval [CI], 0.40 to 0.70; P0.001). The rate of freedom from device-related complications at 12 months was 96.6% (lower 95% confidence limit, 94.8%; P0.001 for comparison with the performance goal). Death from any cause within 24 months occurred in 29.1% of the patients in the device group as compared with 46.1% in the control group (hazard ratio, 0.62; 95% CI, 0.46 to 0.82; P0.001).Among patients with heart failure and moderate-to-severe or severe secondary mitral regurgitation who remained symptomatic despite the use of maximal doses of guideline-directed medical therapy, transcatheter mitral-valve repair resulted in a lower rate of hospitalization for heart failure and lower all-cause mortality within 24 months of follow-up than medical therapy alone. The rate of freedom from device-related complications exceeded a prespecified safety threshold. (Funded by Abbott; COAPT ClinicalTrials.gov number, NCT01626079 .).

This study examined the relationship between income inequality and heart failure outcomes.The income inequality hypothesis postulates that population health is influenced by income distribution within a society, with greater inequality associated with worse outcomes.This study analyzed heart failure outcomes in 2 large trials conducted in 54 countries. Countries were divided by tertiles of Gini coefficients (where 0% represented absolute income equality and 100% represented absolute income inequality), and heart failure outcomes were adjusted for standard prognostic variables, country per capita income, education index, hospital bed density, and health worker density.Of the 15,126 patients studied, 5,320 patients lived in Gini coefficient tertile 1 countries (coefficient: 33%), 6,124 patients lived in tertile 2 countries (33% to 41%), and 3,772 patients lived in tertile 3 countries (41%). Patients in tertile 3 were younger than tertile 1 patients, were more often women, and had less comorbidity and several indicators of less severe heart failure, yet the tertile 3-to-1 hazard ratios (HRs) for the primary composite outcome of cardiovascular death or heart failure hospitalization were 1.57 (95% confidence interval [CI]: 1.38 to 1.79) and 1.48 for all-cause death (95% CI: 1.29 to 1.71) after adjustment for recognized prognostic variables. After additional adjustments were made for per capita income, education index, hospital bed density, and health worker density, these HRs were 1.46 (95% CI: 1.25 to 1.70) and 1.30 (95% CI: 1.10 to 1.53), respectively.Greater income inequality was associated with worse heart failure outcomes, with an impact similar to those of major comorbidities. Better understanding of the societal and personal bases of these findings may suggest approaches to improve heart failure outcomes.

The V-LAP™ measures left atrial pressure (LAP) and enables bi-directional communications with an external unit, designed to monitor heart failure patients. We hereby describe the pre-clinical experience. Following an ex vivo phase, the system was implanted at the interatrial septum of 10 ovine subjects. LAP readouts were compared with pulmonary capillary wedge pressure (PCWP) at index procedure and 1, 2 and 3–6 months after the implantation, at rest and after volume loading. Histopathology assessment (n = 8) was performed up to 50 weeks post procedure. Procedural success was 100%. Measurements showed a mean difference of 0.19 ± 2.51 mmHg. During this period, correlation of V-LAP™ with PCWP was excellent (R2 = 0.95, for 119 total measurements). There were no major adverse events related to the V-LAP™ system. In an animal model, the implantation of the novel wireless left atrial pressure sensor V-LAP™ was feasible, safe, and showed good accuracy and precision.

Background In heart failure (HF) with reduced ejection fraction, 2 clinical trials, the BEST (β-Blocker Evaluation of Survival Trial) and HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training), have reported an effectiveness interaction between the ADRB1 (β-1 adrenergic receptor) Arg389Gly polymorphism and β-blockers (BBs). HF-ACTION additionally reported a dose-related interaction of unclear origin. If confirmed and pharmacogenetically resolved, these findings may have important implications for HF with reduced ejection fraction precision therapy. We used uniform methodology to investigate BB dose-ADRB1 Arg389Gly polymorphism interaction with major clinical end points in BEST/bucindolol and HF-ACTION/other BB databases. Methods This was a retrospective analysis of prospectively designed DNA substudies from BEST (N=1040) and HF-ACTION (N=957). Subjects were genotyped for ADRB1 Arg389Gly and ADRA2C (α2C adrenergic receptor) Ins322-325Del. BB dose was defined as either no/low dose or high dose, according to total daily dose of either bucindolol (BEST subjects) or other BB (HF-ACTION subjects) standardized to carvedilol equivalents. The main outcome of interest was all-cause mortality, and CV mortality/HF hospitalization was a secondary outcome. Results Subjects in each trial had less all-cause mortality with high- versus no/low-dose BB if they had ADRB1 Arg389Arg (BEST: hazard ratio [HR]=0.40, P=0.002; HF-ACTION: HR=0.45, P=0.005) but not Arg389Gly genotype (both P>0.2). Among gene-dose groups, there was a differential favorable treatment effect of 46% for high-dose bucindolol with ADRB1 Arg389Arg versus Gly carrier genotype (HR, 0.54; P=0.018), but not for no/low-dose bucindolol. In contrast, HF-ACTION Arg389Arg genotype subjects taking no/low-dose BB had greater all-cause mortality compared with 389Gly carriers (HR, 1.83; P=0.015), whereas all-cause mortality did not vary by genotype among subjects taking high-dose BB (HR, 0.84; P=0.55). Conclusions The enhanced HF with reduced ejection fraction efficacy of bucindolol in the ADRB1 Arg389Arg versus 389Gly carrier genotypes occurs at high dose. Other BBs taken at low dose have reduced efficacy for Arg389Arg genotype subjects compared with 389Gly carriers, suggesting a greater relative treatment effect at high dose. These data support guideline recommendations to use high, clinical trial target doses of all BBs to treat HF with reduced ejection fraction.

Aims Nearly 60% of the world's population lives in Asia but little is known about the characteristics and outcomes of Asian patients with heart failure with reduced ejection fraction (HFrEF) compared to other areas of the world. Methods and results We pooled two, large, global trials, with similar design, in 13 174 patients with HFrEF (patient distribution: China 833, India 1390, Japan 209, Korea 223, Philippines 223, Taiwan 199 and Thailand 95, Western Europe 3521, Eastern Europe 4758, North America 613, and Latin America 1110). Asian patients were younger (55.0–63.9 years) than in Western Europe (67.9 years) and North America (66.6 years). Diuretics and devices were used less, and digoxin used more, in Asia. Mineralocorticoid receptor antagonist use was higher in China (66.3%), the Philippines (64.1%) and Latin America (62.8%) compared to Europe and North America (range 32.8% to 49.6%). The rate of cardiovascular death/heart failure hospitalization was higher in Asia (e.g. Taiwan 17.2, China 14.9 per 100 patient‐years) than in Western Europe (10.4) and North America (12.8). However, the adjusted risk of cardiovascular death was higher in many Asian countries than in Western Europe (except Japan) and the risk of heart failure hospitalization was lower in India and in the Philippines than in Western Europe, but significantly higher in China, Japan, and Taiwan. Conclusion Patient characteristics and outcomes vary between Asia and other regions and between Asian countries. These variations may reflect several factors, including geography, climate and environment, diet and lifestyle, health care systems, genetics and socioeconomic influences.

Background Few therapies are available for the safe and effective treatment of atrial fibrillation (AF) in patients with heart failure. Bucindolol is a non-selective beta-blocker with mild vasodilator activity previously found to have accentuated antiarrhythmic effects and increased efficacy for preventing heart failure events in patients homozygous for the major allele of the ADRB1 Arg389Gly polymorphism (ADRB1 Arg389Arg genotype). The safety and efficacy of bucindolol for the prevention of AF or atrial flutter (AFL) in these patients has not been proven in randomized trials. Methods/design The Genotype-Directed Comparative Effectiveness Trial of Bucindolol and Metoprolol Succinate for Prevention of Symptomatic Atrial Fibrillation/Atrial Flutter in Patients with Heart Failure (GENETIC-AF) trial is a multicenter, randomized, double-blinded “seamless” phase 2B/3 trial of bucindolol hydrochloride versus metoprolol succinate, for the prevention of symptomatic AF/AFL in patients with reduced ejection fraction heart failure (HFrEF). Patients with pre-existing HFrEF and recent history of symptomatic AF are eligible for enrollment and genotype screening, and if they are ADRB1 Arg389Arg, eligible for randomization. A total of approximately 200 patients will comprise the phase 2B component and if pre-trial assumptions are met, 620 patients will be randomized at approximately 135 sites to form the Phase 3 population. The primary endpoint is the time to recurrence of symptomatic AF/AFL or mortality over a 24-week follow-up period, and the trial will continue until 330 primary endpoints have occurred. Conclusions GENETIC-AF is the first randomized trial of pharmacogenetic guided rhythm control, and will test the safety and efficacy of bucindolol compared with metoprolol succinate for the prevention of recurrent symptomatic AF/AFL in patients with HFrEF and an ADRB1 Arg389Arg genotype. ( ClinicalTrials.gov NCT01970501 ).

Objectives This study sought to confirm a subgroup analysis of the prior FIX-HF-5 (Evaluate Safety and Efficacy of the OPTIMIZER System in Subjects With Moderate-to-Severe Heart Failure) study showing that cardiac contractility modulation (CCM) improved exercise tolerance (ET) and quality of life in patients with ejection fractions between 25% and 45%. Background CCM therapy for New York Heart Association (NYHA) functional class III and IV heart failure (HF) patients consists of nonexcitatory electrical signals delivered to the heart during the absolute refractory period. Methods A total of 160 patients with NYHA functional class III or IV symptoms, QRS duration Results The difference in peak Vo2 between groups was 0.84 (95% Bayesian credible interval: 0.123 to 1.552) ml O2/kg/min, satisfying the primary endpoint. Minnesota Living With Heart Failure questionnaire (p Conclusions CCM is safe, improves exercise tolerance and quality of life in the specified group of HF patients, and leads to fewer HF hospitalizations. (Evaluate Safety and Efficacy of the OPTIMIZER System in Subjects With Moderate-to-Severe Heart Failure; NCT01381172)

Despite advancements in diagnostic and therapeutic modalities, the rate of HF hospitalizations (HFH) has not changed substantially in recent years. While non-invasive monitoring approaches have generally failed to reduce the risk of HFH, management guided by intracardiac or pulmonary artery pressure has. Purpose: To present the initial experience with a novel battery-less and wireless left-sided pressure system, directly assessing left-atrial pressure (LAP) in ambulatory HF patients, from the V-LAP monitoring systEm for patients with Chronic sysTOlic and diastolic congestive heart failuRe first-in-human (VECTOR) study. Methods: The V-LAP™ sensor is able to directly measure absolute pressures in the LA in high resolution, compensate for pressure drift, transmit daily hemodynamic feedback, and detect common comorbidities such as Afib and MR. It is implanted using a TS approach, under angiographic and echocardiographic guidance. The V-LAP™ system includes an external unit, which powers the implant remotely and collects data via RF communication on a daily basis. The system is undergoing initial clinical evaluation in the VECTOR-HF Trial, in order to assess the safety, performance and usability of the system in patients with HF. Results: In pre-clinical studies, the device was shown to enable accurate and safe LAP measurement. Currently, two patients have been successfully implanted with the device. In the first case the patient has great variability in LAP on a daily basis, likely due to rapid changes in preload due to variability in venous capacitance and possibly volume status, accompanied by preload-dependent changes in the severity of functional MR, which was well observed during both TTE and LAP waveform morphology. This patient might be at high-risk for HFH. In the second case the LAP is well-controlled with little variability. During the conference we will describe and discuss the first 8 cases, and discuss the potential role of the V-LAP™ wireless sensor in the management of patients with HF in the future. Conclusions: The VECTOR-HF trial currently enrolled the first two patients, who were safely implanted with the V-LAP™ wireless sensor. Clinical trials will demonstrate whether the system enables optimal therapy for HF patients, reduces readmissions and detects co-morbidities in a personalized manner. Daily hemodynamic feedback from the heart opens a new era in the management of HF patients and scientific outcomes based on LAP data.

Central sleep apnea (CSA) is one of the most common comorbidities in patients with heart failure with reduced ejection fraction and is associated with negative consequences. Despite several recent advances, there are currently no widely accepted therapies for CSA. In this review we will discuss available therapies for CSA and review the published trials addressing treatment of CSA in HFrEF patients.

Summary Background In the CHAMPION trial, significant reductions in admissions to hospital for heart failure were seen after 6 months of pulmonary artery pressure guided management compared with usual care. We examine the extended efficacy of this strategy over 18 months of randomised follow-up and the clinical effect of open access to pressure information for an additional 13 months in patients formerly in the control group. Methods The CHAMPION trial was a prospective, parallel, single-blinded, multicentre study that enrolled participants with New York Heart Association (NYHA) Class III heart failure symptoms and a previous admission to hospital. Patients were randomly assigned (1:1) by centre in block sizes of four by a secure validated computerised randomisation system to either the treatment group, in which daily uploaded pulmonary artery pressures were used to guide medical therapy, or to the control group, in which daily uploaded pressures were not made available to investigators. Patients in the control group received all standard medical, device, and disease management strategies available. Patients then remained masked in their randomised study group until the last patient enrolled completed at least 6 months of study follow-up (randomised access period) for an average of 18 months. During the randomised access period, patients in the treatment group were managed with pulmonary artery pressure and patients in the control group had usual care only. At the conclusion of randomised access, investigators had access to pulmonary artery pressure for all patients (open access period) averaging 13 months of follow-up. The primary outcome was the rate of hospital admissions between the treatment group and control group in both the randomised access and open access periods. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00531661. Findings Between Sept 6, 2007, and Oct 7, 2009, 550 patients were randomly assigned to either the treatment group (n=270) or to the control group (n=280). 347 patients (177 in the former treatment group and 170 in the former control group) completed the randomised access period in August, 2010, and transitioned to the open access period which ended April 30, 2012. Over the randomised access period, rates of admissions to hospital for heart failure were reduced in the treatment group by 33% (hazard ratio [HR] 0·67 [95% CI 0·55–0·80]; p Interpretation Management of NYHA Class III heart failure based on home transmission of pulmonary artery pressure with an implanted pressure sensor has significant long-term benefit in lowering hospital admission rates for heart failure. Funding St Jude Medical Inc.

Objectives The aim of current study is to assess the near term impact of percutaneous ventricular restoration therapy (PVR), Parachute® on mitral valve (MV) geometry by cardiac computed tomography (CCT). Background Recent data demonstrates the feasibility of PVR for treatment of post anterior myocardial infarction (MI) heart failure. Little is known, however, about the interaction of the device and left ventricular structures, particularly the MV apparatus. Methods This is a retrospective Core Laboratory analysis of Parachute Trials’ CCT data. Patients with paired (before and after Parachute implant) CCT acquisitions were included into analysis. MV geometric parameters were measured. Results Thirty-three patients were included in the analysis. The mean time of follow-up CCT post procedure was 188 ± 52 days. There were significant reduction in tenting height (A1P1: −1.70 ± 1.89 mm, −17.40 ± 20.20%; A2P2: −1.43 ± 1.89 mm, −12.10 ± 15.00%; A3P3: −1.54 ± 1.58 mm, −15.50 ± 15.20%, P

Aims and methods: To: (i) describe the baseline characteristics of patients in ATMOSPHERE and the changes in the planned analysis of ATMOSPHERE resulting from the mandated discontinuation of study treatment in patients with diabetes; (ii) compare the baseline characteristics of patients in ATMOSPHERE with those in the Prospective comparison of Angiotensin Receptor neprilysin inhibitors with Angiotensin converting enzyme inhibitors to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF); and (iii) compare the characteristics of patients with and without diabetes at baseline in ATMOSPHERE. Results: A total of 7063 patients were randomized into ATMOSPHERE April 2009–April 2014 at 755 sites in 43 countries. Their average age was 63 years and 78% were men. ATMOSPHERE patients were generally similar to those in PARADIGM-HF although fewer had diabetes, renal dysfunction, and were treated with a mineralocorticoid receptor antagonist. In ATMOSPHERE, patients with diabetes differed in numerous ways from those without. Patients with diabetes were older and had worse heart failure status but a similar left ventricular ejection fraction (mean 28%); they had a higher body mass index and more co-morbidity, especially hypertension and coronary heart disease. Mean estimated glomerular filtration rate was slightly lower in those with diabetes compared with those without. Conclusion: ATMOSPHERE will determine whether patients with HF and reduced ejection fraction (particularly those without diabetes) benefit from the addition of a direct renin inhibitor to standard background therapy, including an angiotensin-converting enzyme inhibitor, beta-blocker, and a mineralocorticoid receptor antagonist. ATMOSPHERE will also determine whether aliskiren alone is superior to, or at least non-inferior to, enalapril.

Objectives This study sought to assess the lifelong extrapolated patient outcomes with cardiac resynchronization therapy (CRT) in mild heart failure (HF), beyond the follow-up of randomized clinical trials (RCTs). Background RCTs have demonstrated short-term survival and HF hospitalization benefits of CRT in mild HF. We used data from the 5-year follow-up of the REVERSE (REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction) study to extrapolate survival and HF hospitalizations. We compared CRT-ON versus CRT-OFF and CRT defibrillators (CRT-D) versus CRT pacemakers (CRT-P). Methods Multivariate regression models were used to estimate treatment-specific all-cause mortality, disease progression, and HF-related hospitalization rates. Rank-preserving structural failure time (RPSFT) models were used to adjust for protocol-mandated crossover in the survival analysis. Results CRT-ON was predicted to increase survival by 22.8% (CRT-ON 52.5% vs. CRT-OFF 29.7%; hazard ratio [HR]: 0.45; p = 0.21), leading to an expected survival of 9.76 years (CRT-ON) versus 7.5 years (CRT-OFF). CRT-D showed a significant improvement in survival compared with CRT-P (HR: 0.47; 95% confidence interval [CI]: 0.25 to 0.88; p = 0.02) and were predicted to offer 2.77 additional life-years. New York Heart Association (NYHA) functional class II patients had a 30.6% higher HF hospitalization risk than class I (I vs. II incident rate ratio [IRR]: 0.69; 95% CI: 0.57 to 0.85; p Conclusions RPSFT estimates yielded results demonstrating clinically important long-term benefit of CRT in mild HF. CRT was predicted to reduce mortality, with CRT-D prolonging life more than CRT-P. NYHA functional class I/II patients were shown to have a significantly reduced risk of HF hospitalization compared with class III, leading to CRT reducing HF hospitalization rates.

Mitral regurgitation (MR) is one of the most prevalent valve disorders and has numerous etiologies, including primary (organic) MR, due to underlying degenerative/structural mitral valve (MV) pathology, and secondary (functional) MR, which is principally caused by global or regional left ventricular remodeling and/or severe left atrial dilation. Diagnosis and optimal management of MR requires integration of valve disease and heart failure specialists, MV cardiac surgeons, interventional cardiologists with expertise in structural heart disease, and imaging experts. The introduction of transcatheter MV therapies has highlighted the need for a consensus approach to pragmatic clinical trial design and uniform endpoint definitions to evaluate outcomes in patients with MR. The Mitral Valve Academic Research Consortium is a collaboration between leading academic research organizations and physician-scientists specializing in MV disease from the United States and Europe. Three in-person meetings were held in Virginia and New York during which 44 heart failure, valve, and imaging experts, MV surgeons and interventional cardiologists, clinical trial specialists and statisticians, and representatives from the U.S. Food and Drug Administration considered all aspects of MV pathophysiology, prognosis, and therapies, culminating in a 2-part document describing consensus recommendations for clinical trial design (Part 1) and endpoint definitions (Part 2) to guide evaluation of transcatheter and surgical therapies for MR. The adoption of these recommendations will afford robustness and consistency in the comparative effectiveness evaluation of new devices and approaches to treat MR. These principles may be useful for regulatory assessment of new transcatheter MV devices, as well as for monitoring local and regional outcomes to guide quality improvement initiatives. (C) 2015 by the American College of Cardiology Foundation.

Objectives: The objective of this clinical trial was to assess the safety and efficacy of carotid BAT in advanced HF. Background: Increased sympathetic and decreased parasympathetic activity contribute to heart failure (HF) symptoms and disease progression. Baroreflex activation therapy (BAT) results in centrally mediated reduction of sympathetic outflow and increased parasympathetic activity. Methods: Patients with New York Heart Association (NYHA) functional class III HF and ejection fractions≤35% on chronic stable guideline-directed medical therapy (GDMT) were enrolled at 45 centers in the United States, Canada, and Europe. They were randomly assigned to receive ongoing GDMT alone (control group) or ongoing GDMT plus BAT (treatment group) for 6 months. The primary safety end point was system- and procedure-related major adverse neurological and cardiovascular events. The primary efficacy end points were changes in NYHA functional class, quality-of-life score, and 6-minute hall walk distance. Results: One hundred forty-six patients were randomized, 70 to control and 76 to treatment. The major adverse neurological and cardiovascular event-free rate was 97.2% (lower 95% confidence bound 91.4%). Patients assigned to BAT, compared with control group patients, experienced improvements in the distance walked in 6 min (59.6 ± 14 m vs. 1.5± 13.2 m; p= 0.004), quality-of-life score (-17.4 ± 2.8 points vs. 2.1 ± 3.1 points; p< 0.001), and NYHA functional class ranking (p=0.002 for change in distribution). BAT significantly reduced N-terminal pro-brain natriuretic peptide (p= 0.02) and was associated with a trend toward fewer days hospitalized for HF (p= 0.08). Conclusions: BAT is safe and improves functional status, quality of life, exercise capacity, N-terminal pro-brain natriuretic peptide, and possibly the burden of heart failure hospitalizations in patients with GDMT-treated NYHA functional class III HF. (Barostim Neo System in the Treatment of Heart Failure; NCT01471860; Barostim HOPE4HF [Hope for Heart Failure] Study; NCT01720160).

This was a first-in-human study to assess the feasibility, safety, and exploratory efficacy of interatrial shunting for treating high-risk heart failure (HF) in patients with reduced and preserved ejection fraction.A single-arm open-label study of patients with New York Heart Association functional class III or IV HF on optimal therapy was performed at 6 centers. The V-Wave shunt, an hourglass-shaped implant containing a 1-way bioprosthetic valve, was implanted by transseptal catheterization. Clinical, functional, echocardiographic, and hemodynamic evaluations were performed at baseline, 3 and 12 months, and annually (clinical follow-up) thereafter (median follow-up 28 months; interquartile range: 21 to 31 months).A total of 38 patients were enrolled (30 with HF with reduced ejection fraction and 8 with HF with preserved ejection fraction; mean age 66 ± 9 years; 97% and 3% in New York Heart Association functional classes III and IV, respectively), and the shunt device was successfully implanted in all cases without periprocedural mortality. The rate of major device- or procedure-related complications during the first 12 months was 2.6% (periprocedural cardiac tamponade in 1 patient). At 3- and 12-month follow-up, there were improvements in New York Heart Association functional class (classes I and II in 78% and 60% of patients, respectively), quality of life (improvements ≥5 points in 74% and 73% of patients, respectively), and 6-min walk distance (mean increases of 41 ± 63 m and 28 ± 83 m, respectively) (p 0.02 for all, data available for 36 patients), without changes in objective measures of left- or right-sided function. All shunts were patent at 3 months, but 5 of 36 (14%) had occluded, and another 13 of 36 (36%) were stenotic at the valve by 12 months. Patients with widely patent shunts had lower long-term rates of death, left ventricular assist device placement or heart transplantation (p = 0.001), and HF hospitalization (p = 0.008), along with a reduction of pulmonary capillary wedge pressure (from 23.3 ± 5.4 mm Hg at baseline to 18.0 ± 4.0 mm Hg at 12 months; p = 0.011).Interatrial shunting with the V-Wave system was feasible and safe in patients with HF with reduced and preserved ejection fraction. Improvements in clinical and functional status were observed early and at 12 months despite attenuation of shunt patency in one-half of the patients. Patients with preserved shunt patency tended to maintain clinical benefit during longer term follow-up. Device modification that improves the durability of patency is likely worthwhile before confirmation of these findings in a randomized trial.

Background Heart failure education programs are not standardized. The best form of education is unclear. We evaluated whether addition of a novel tablet application to nurse practitioner (NP) education was superior to NP education alone in reducing 30-day readmission after heart failure hospitalization. Methods From February 2015-March 2016, patients admitted to a quaternary academic center with primary diagnosis of heart failure were randomized to 1) treatment – NP education plus tablet application (interactive conditional logic program that flags patient questions to medical staff), or 2) control – NP education. The primary outcome was reduction in 30-day readmission rate. Secondary outcomes included satisfaction and education assessed via survey. Results Randomization included 60 patients to treatment and 66 to control. A total of 13 patients withdrew prior to intervention (treatment n = 4, control n = 1) or were lost to follow-up (treatment n = 3, control n = 5). The 30-day readmission rate trended lower for treatment compared with control, but results were not statistically significant (13.2% [7/53], 26.7% [16/60], respectively, P = .08). Similarly, satisfaction trended higher with treatment than control ( P = .08). Treatment patients rated explanations from their physicians higher than control (Always: 83.7%, 55.8%, respectively, P = .01). Conclusions NP education plus tablet use was not associated with significantly lower 30-day readmission rates in comparison with NP alone, but a positive trend was seen. Patient satisfaction trended higher and heart failure explanations were better with NP education plus tablet. A larger study is needed to determine if NP education plus tablet reduces readmission rates following heart failure admission.

In a randomized trial, baroreflex activation therapy (BAT) improved exercise capacity, quality of life and NT-proBNP in patients with heart failure with reduced ejection fraction (HFrEF). In view of different mechanisms underlying HFrEF, we performed a post-hoc subgroup analysis of efficacy and safety of BAT in patients with and without coronary artery disease (CAD).Patients with left ventricular ejection fraction35% and NYHA Class III were randomized 1:1 to guideline-directed medical and device therapy alone or plus BAT. Patients with a history of CAD, prior myocardial infarction or coronary artery bypass graft were assigned to the CAD group with all others assigned to the no-CAD group. Of 71 BAT treated patients, 52 had CAD and 19 had no CAD. In the control group, 49 of 69 patients had CAD and 20 had no CAD. The system- or procedure-related major adverse neurological or cardiovascular event rate was 3.8% in the CAD group vs. 0% in the no-CAD group (p = 1.0). In the whole cohort, NYHA Class, Minnesota Living with Heart Failure score, 6-minute hall walk distance and NTproBNP were improved in BAT treated patients compared with controls. Statistical analyses revealed no interaction between the presence of CAD and effect of BAT (all p 0.05).No major differences were found in BAT efficacy or safety between patients with and without CAD, indicating that BAT improves exercise capacity, quality of life and NTproBNP in patients with ischemic and non-ischemic cardiomyopathy. CLINICALTRIALS.NCT01471860 and NCT01720160.

Background: The higher risk of heart failure (HF) in African-American and Hispanic women compared with white women is related to the higher burden of risk factors (RFs) in minorities. However, it is unclear if there are differences in the association between the number of RFs for HF and the risk of development of HF and death within racial/ethnic groups. Methods and Results: In the WHI (Women’s Health Initiative; 1993–2010), African-American (n=11 996), white (n=18 479), and Hispanic (n=5096) women with 1, 2, or 3+ baseline RFs were compared with women with 0 RF within their respective racial/ethnic groups to assess risk of developing HF or all-cause mortality before and after HF, using survival analyses. After adjusting for age, socioeconomic status, and hormone therapy, the subdistribution hazard ratio (95% confidence interval) of developing HF increased as number of RFs increased ( P P =0.18)—African-Americans 1 RF: 1.80 (1.01–3.20), 2 RFs: 3.19 (1.84–5.54), 3+ RFs: 7.31 (4.26–12.56); Whites 1 RF: 1.27 (1.04–1.54), 2 RFs: 1.95 (1.60–2.36), 3+ RFs: 4.07 (3.36–4.93); Hispanics 1 RF: 1.72 (0.68–4.34), 2 RFs: 3.87 (1.60–9.37), 3+ RFs: 8.80 (3.62–21.42). Risk of death before developing HF increased with subsequent RFs ( P P =0.001). The number of RFs was not associated with the risk of death after developing HF in any group ( P =0.25; interaction P =0.48). Conclusions: Among diverse racial/ethnic groups, an increase in the number of baseline RFs was associated with higher risk of HF and death before HF but was not associated with death after HF. Early RF prevention may reduce the burden of HF across multiple racial/ethnic groups.

Background We conducted a prospective multicenter study to assess the prognostic value of combined baseline preimplant plasma levels of the biomarkers cardiac troponin T (TnT) and B-type natriuretic peptide (BNP) among cardiac resynchronization therapy (CRT) with or without defibrillator capability (CRT-D) recipients. Methods At CRT-D implant, patients were stratified based on detectable TnT (≥0.01 ng/mL) and elevated BNP (predefined as >440 pg/mL) levels. Patients were classified into three groups: high (both detectable TnT and high BNP), intermediate (either detectable TnT or high BNP), or low (nondetectable TnT and low BNP). Patients were followed for 12 months. Survival curves free from mortality or heart failure hospitalizations (HFH) were assessed. To assess the predictive value of biomarker category, we constructed a multivariate Cox regression model, including the covariates of age, New York Heart Association class, left ventricular ejection fraction (LVEF), and QRS duration. Results A total of 267 patients (age 66 ± 12 years, males 80%, LVEF 25% ± 8%, ischemic cardiomyopathy 52%, QRSd 155 ± 26 ms) were studied. After 1 year, there were 13 deaths and 25 HFH events. A significant difference in event-free survival among the three groups was observed, with high and intermediate categories having worse survival than low (log-rank test, P < 0.001). In the multivariate model, risk category was a significant predictor of outcome: hazard ratios were 7.34 (95% confidence interval [CI]: 2.48–21.69) and 2.50 (95% confidence interval [CI]: 1.04–6.04) for high-risk and intermediate-risk groups, respectively (P < 0.0001). Conclusion Among CRT-D recipients, baseline TnT and BNP values alone or in combination provide significant prognostic value for the outcome of mortality or HFH.

Background Heart failure hospitalizations (HFHs) cost the US health care system ∼$20 billion annually. Identifying patients at risk of HFH to enable timely intervention and prevent expensive hospitalization remains a challenge. Implantable cardioverter defibrillators (ICDs) and cardiac resynchronization devices with defibrillation capability (CRT-Ds) collect a host of diagnostic parameters that change with HF status and collectively have the potential to signal an increasing risk of HFH. These device-collected diagnostic parameters include activity, day and night heart rate, atrial tachycardia/atrial fibrillation (AT/AF) burden, mean rate during AT/AF, percent CRT pacing, number of shocks, and intrathoracic impedance. There are thresholds for these parameters that when crossed trigger a notification, referred to as device observation, which gets noted on the device report. We investigated if these existing device observations can stratify patients at varying risk of HFH. Methods We analyzed data from 775 patients (age: 69 ± 11 year, 68% male) with CRT-D devices followed for 13 ± 5 months with adjudicated HFHs. HFH rate was computed for increasing number of device observations. Data were analyzed by both excluding and including intrathoracic impedance. HFH risk was assessed at the time of a device interrogation session, and all the data between previous and current follow-up sessions were used to determine the HFH risk for the next 30 days. Results 2276 follow-up sessions in 775 patients were evaluated with 42 HFHs in 37 patients. Percentage of evaluations that were followed by an HFH within the next 30 days increased with increasing number of device observations. Patients with 3 or more device observations were at 42× HFH risk compared to patients with no device observation. Even after excluding intrathoracic impedance, the remaining device parameters effectively stratified patients at HFH risk. Conclusion Available device observations could provide an effective method to stratify patients at varying risk of heart failure hospitalization.

Background Hospitalizations for heart failure are associated with a high post-discharge risk for mortality. Identification of modifiable predictors of post-discharge mortality during hospitalization may improve outcome. Sleep disordered breathing (SDB) is the most common co-morbidity in heart failure patients. Design, setting, and participants Prospective cohort study of patients hospitalized with acute heart failure (AHF) in a single academic heart hospital. Between January 2007 and December 2010, all patients hospitalized with AHF who have left ventricular ejection fraction (LVEF) ≤ 45% and were not already diagnosed with SDB were the target population. Main outcomes and measures Patients underwent in-hospital attended polygraphy testing for SDB and were followed for a median of 3 years post-discharge. Mortality was recorded using national and state vital statistics databases. Results During the study period, 1117 hospitalized AHF patients underwent successful sleep testing. Three hundred and forty-four patients (31%) had central sleep apnoea (CSA), 525(47%) patients had obstructive sleep apnoea (OSA), and 248 had no or minimal SDB (nmSDB). Of those, 1096 patients survived to discharge and were included in the mortality analysis. Central sleep apnoea was independently associated with mortality. The multivariable hazard ratio (HR) for time to death for CSA vs. nmSDB was 1.61 (95% CI: 1.1, 2.4, P = 0.02). Obstructive sleep apnoea was also independently associated with mortality with a multivariable HR vs. nmSDB of 1.53 (CI: 1.1, 2.2, P = 0.02). The Cox proportional hazards model adjusted for the following covariates: LVEF, age, BMI, sex, race, creatinine, diabetes, type of cardiomyopathy, coronary artery disease, chronic kidney disease, discharge systolic blood pressure

Central sleep apnea (CSA) is a highly prevalent, though often unrecognized, comorbidity in patients with heart failure (HF). Data from HF population studies suggest that it may present in 30% to 50% of HF patients. CSA is recognized as an important contributor to the progression of HF and to HF-related morbidity and mortality. Over the past 2 decades, an expanding body of research has begun to shed light on the pathophysiologic mechanisms of CSA. Armed with this growing knowledge base, the sleep, respiratory, and cardiovascular research communities have been working to identify ways to treat CSA in HF with the ultimate goal of improving patient quality of life and clinical outcomes. In this paper, we examine the current state of knowledge about the mechanisms of CSA in HF and review emerging therapies for this disorder.

Background Heart failure following myocardial infarction is a common, disabling, and deadly condition. Direct injection of autologous bone marrow mononuclear cells into the myocardium may result in improved functional recovery, relieve symptoms, and improve other cardiovascular outcomes. Methods CardiAMP-HF is a randomized, double-blind, sham-controlled, pivotal trial designed to investigate the safety and efficacy of autologous bone marrow mononuclear cells treatment for patients with medically refractory and symptomatic ischemic cardiomyopathy. The primary end point is change in 6-minute walk distance adjusted for major adverse cardiovascular events at 12 months following treatment. Particularly novel aspects of this trial include a cell potency assay to screen subjects who have bone marrow cell characteristics that suggest a favorable response to treatment, a point-of-care treatment method, a high target dose of 200 million cells, and an efficient transcatheter intramyocardial delivery method that is associated with high cell retention. Conclusions This novel approach may lead to a new treatment for those with ischemic heart disease suffering from medically refractory heart failure.

Background: \ud Cross correlation analysis (CCA) using tissue Doppler imaging has been shown to be associated with outcome after cardiac resynchronization therapy (CRT) in patients with heart failure (HF) with wide QRS. However, its significance in patients with narrow QRS treated with CRT is unknown.\ud \ud Objectives: \ud The aim of the current study was to investigate the association of mechanical activation delay by CCA with study outcome in patients with HF enrolled in the EchoCRT trial.\ud \ud Methods: \ud Baseline CCA could be performed from tissue Doppler imaging in the apical views in 807 of 809 (99.7%) enrolled patients, and 6-month follow-up could be performed in 610 of 635 (96%) patients with available echocardiograms. Patients with a pre-specified maximal activation delay ≥35 ms were considered to have significant delay. The study outcome was HF hospitalization or death.\ud \ud Results: \ud Of 807 patients, 375 (46%) did not have delayed mechanical activation at baseline by CCA. Patients without delayed mechanical activation who were randomized to CRT-On compared with CRT-Off had an increased risk of poor outcome (hazard ratio: 1.70; 95% confidence interval: 1.13 to 2.55; p = 0.01) with a significant interaction term (p = 0.04) between delayed mechanical activation and device randomization for the endpoint. Among patients with paired baseline and follow-up data with no events before 6-month follow-up (n = 541), new-onset delayed mechanical activation in the CRT-On group showed a significant increase in unfavorable events (hazard ratio: 3.73; 95% confidence interval: 1.15 to 12.14; p = 0.03).\ud \ud Conclusions: \ud In the EchoCRT population, absence of delayed mechanical activation by CCA was significantly associated with poor outcomes, possibly due to the onset of new delayed mechanical activation with CRT pacing. (Echocardiography Guided Cardiac Resynchronization Therapy [EchoCRT] Trial; NCT00683696).

Proper timing of left ventricular assist device (LVAD) implantation in advanced heart failure patients is not well established and is an area of intense interest. In addition, optimizing LVAD performance after implantation remains difficult and represents a significant clinical need. Implantable hemodynamic monitoring systems may provide physicians with the physiologic information necessary to improve the timing of LVAD implantation as well as LVAD performance when compared with current methods. The CardioMEMS Heart sensor Allows for Monitoirng of Pressures to Improve Outcomes in NYHA Class III heart failure patients (CHAMPION) Trial enrolled 550 previously hospitalized patients with New York Heart Association (NYHA) class III heart failure. All patients were implanted with a pulmonary artery (PA) pressure monitoring system and randomized to a treatment and control groups. In the treatment group, physicians used the hemodynamic information to make heart failure management decisions. This information was not available to physicians for the control group. During an average of 18 month randomized follow-up, 27 patients required LVAD implantation. At the time of PA pressure sensor implantation, patients ultimately requiring advanced therapy had higher PA pressures, lower systemic pressure, and similar cardiac output measurements. Treatment and control patients in the LVAD subgroup had similar clinical profiles at the time of enrollment. There was a trend toward a shorter length of time to LVAD implantation in the treatment group when hemodynamic information was available. After LVAD implantation, most treatment group patients continued to provide physicians with physiologic information from the hemodynamic monitoring system. As expected PA pressures declined significantly post LVAD implant in all patients, but the magnitude of decline was higher in patients with PA pressure monitoring. Implantable hemodynamic monitoring appeared to improve the timing of LVAD implantation as well as optimize LVAD performance when compared with current methods. Further studies are necessary to evaluate these findings in a prospective manner.

Background: Clinical trials have established the average benefit of cardiac resynchronization therapy (CRT), but estimating benefit for individual patients remains difficult because of the heterogeneity in treatment response. Accordingly, we created a multivariable model to predict changes in quality of life (QoL) with and without CRT. Methods and Results: Patient-level data from 5 randomized trials comparing CRT with no CRT were used to create a prediction model of change in QoL at 3 months using a partial proportional odds model for no change, small, moderate, and large improvement, or deterioration of any magnitude. The C statistics for not worsening or obtaining at least a small, moderate, and large improvement were calculated. Among the 3614 patients, regardless of assigned treatment, 33.3% had a deterioration in QoL, 9.2% had no change, 9.2% had a small improvement, 13.5% had a moderate improvement, and the remaining 34.9% had a large improvement. Patients undergoing CRT were less likely to have a decrement in their QoL (28.2% versus 38.9%; P P Conclusions: There is marked heterogeneity of treatment benefit of CRT that can be predicted based on baseline QoL, age, and QRS duration.

To explore possible associations that may explain the greater benefit from cardiac resynchronization therapy (CRT) reported amongst women.In an individual-patient data meta-analysis of five randomized controlled trials, all-cause mortality and the composite of all-cause mortality or first hospitalization for heart failure (HF) were compared among 794 women and 2702 men assigned to CRT or a control group. Multivariable analyses were performed to assess the impact of sex, QRS duration, HF aetiology, left ventricular end-diastolic diameter (LVEDD), and height on outcome. Women were shorter, had smaller LVEDD, more often left bundle branch block, and less often ischaemic heart disease, but QRS duration was similar between sexes. Women tended to obtain greater benefit from CRT but sex was not an independent predictor of either outcome. For all-cause mortality, QRS duration was the only independent predictor of CRT benefit. For the composite outcome, height and QRS duration, but not sex, were independent predictors of CRT benefit. Further analysis suggested increasing benefit with increasing QRS duration amongst shorter patients, of whom a great proportion were women.In this individual-patient data meta-analysis, CRT benefit was greater in shorter patients, which may explain reports of enhanced CRT benefit among women. Further analyses are required to determine whether recommendations on the QRS threshold for CRT should be adjusted for height. (ClinicalTrials.gov numbers: NCT00170300, NCT00271154, NCT00251251).

The current heart failure clinical trial environment is strained by increasing complexity and cost, regulatory requirements, competing demands on stakeholders, implementation challenges, and decreasing patient and investigator participation. To begin the process of developing potentially effective strategies and tactics, stakeholders including patients; investigators; academic leaders; pharmaceutical and device industry representatives; society representatives; third-party payers; and government representatives from the U.S. Food and Drug Administration, National Institutes of Health, and Centers for Medicare and Medicaid Services convened in March of 2017. This paper summarizes the discussions, outlines current challenges and actionable opportunities, and makes targeted recommendations to achieve the goals of improving efficiency in clinical trials and speeding the development of effective heart failure therapies, including the formation of an organized Heart Failure Collaboratory.

Background Atrial fibrillation (AF) is common in heart failure (HF), but the outcome by type of AF is largely unknown. Objectives This study investigated outcomes related to type of AF (paroxysmal, persistent or permanent, or new onset) in 2 recent large trials in patients with HF with reduced ejection fraction. Methods The study analyzed patients in the PARADIGM-HF (Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure) and ATMOSPHERE (Aliskiren Trial to Minimize Outcomes in Patients with Heart Failure) trials. Multivariable Cox regression models were used to estimate hazard ratios (HRs) for outcomes related to AF type. Results Of 15,415 patients, 5,481 (35.6%) had a history of AF at randomization, and of these, 1,645 (30.0%) had paroxysmal AF. Compared with patients without AF, patients with paroxysmal AF at randomization had a higher risk of the primary composite endpoint of cardiovascular death or HF hospitalization (HR: 1.20; 95% confidence interval [CI]: 1.09 to 1.32; p < 0.001), HF hospitalization (HR: 1.34; 95% CI: 1.19 to 1.51; p < 0.001), and stroke (HR: 1.34; 95% CI: 1.02 to 1.76; p = 0.037), whereas the corresponding risks in patients with persistent or permanent AF were not elevated. Neither type of AF was associated with higher mortality. New onset AF was associated with the greatest risk of adverse outcomes: primary endpoint (HR: 2.21; 95% CI: 1.80 to 2.71), HF hospitalization (HR: 2.11; 95% CI: 1.58 to 2.81), stroke (HR: 2.20; 95% CI: 1.25 to 3.88), and all-cause mortality (HR: 2.26; 95% CI: 1.86 to 2.74), all p values < 0.001, compared with patients without AF. Anticoagulants were used less often in patients with paroxysmal (53%) and new onset (16%) AF than in patients with persistent or permanent AF (71%). Conclusions Among HF patients with a history of AF, those with paroxysmal AF were at greater risk of HF hospitalization and stroke than were patients with persistent or permanent AF, underlining the importance of anticoagulant therapy. New onset AF was associated with increased risk of all outcomes. (Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure [PARADIGM-HF]; NCT01035255) (Aliskiren Trial to Minimize Outcomes in Patients with Heart Failure [ATMOSPHERE]; NCT00853658)

Background: Patients with heart failure and reduced ejection fraction (HFrEF) who are hospitalized for decompensation have a prevalence of obstructive sleep apnea (OSA) that exceeds 50%. We sought to evaluate the effect of in-hospital diagnosis and immediate treatment with auto positive airway pressure (APAP) of OSA in hospitalized HFrEF patients Methods: A single site randomized controlled trial of hospitalized HFrEF patients and in-hospital diagnosed OSA (AHI>15 events/h). All participants (n=150) received guideline directed therapy of heart failure decompensation and were randomized to an intervention arm (APAP) (n=75) or no in-hospital treatment for OSA (n=75). The primary outcome was change in discharge LVEF. Results: LVEF did not change signficantly in the treament vs. control arms (p=0.93). Also, there was no difference in the change in B-type natriuretic peptide. Analysis of patients who used APAP >4 hs/night during the hospitalization showed a significant increase in discharge EF compared to those who used 6 months readmissions decreased in patients who used APAP >4 hours. Rate ratio (RR) = 0.36 (0.14, 0.94), p = 0.04 vs. controls and RR = 0.27 (0.10, 0.76), p = 0.01 vs. Conclusion: In-hospital diagnosis and treatment with APAP did not change discharge LVEF in patients with HFrEF and OSA. Use of APAP was safe and associated with decreased 6 months readmissions when adequately used.

Despite many therapeutic advances, heart failure (HF) remains challenging to treat and continues to be associated with high rates of morbidity and mortality. There is an ongoing need to identify co-morbidities that either contribute to the progression of heart failure or limit the therapeutic response to treatment. One area under active investigation is the treatment of central sleep apnoea (CSA). CSA has consistently been shown to be associated with a worse prognosis in HF patients. Thus, understanding how to diagnose and treat CSA is of paramount importance to the HF clinician. Without treatment, HF patients continue to be at risk for the devastating consequences of CSA. Prognosis is very poor with studies consistently demonstrating poor outcomes among HF patients with CSA. Over the course of the night, each discrete event contributes to increased nor- epinephrine levels and hypoxia which are associated with progressive heart failure and arrhythmias. Initial therapeutic options utilized therapies which were developed for obstructive sleep apnoea with limited success or even harm. ASV is now contraindicated in HF patients with an EF < 45% leaving only 2 potential treatment options: CPAP and transvenous phrenic nerve stimulation. Data from the recently presented (post ESC guidelines) trial on transvenous phrenic nerve stimulation demonstrated efficacy without the need for patient compliance or any safety concerns. It is expected that additional studies in CSA will continue to demonstrate the full impact of treating this important co-morbidity on patients with HF.

Rates of heart failure hospitalization remain unacceptably high. Such hospitalizations are associated with substantial patient, caregiver, and economic costs. Randomized controlled trials of noninvasive telemedical systems have failed to demonstrate reduced rates of hospitalization. The failure of these technologies may be due to the limitations of the signals measured. Intracardiac and pulmonary artery pressure–guided management has become a focus of hospitalization reduction in heart failure. Early studies using implantable hemodynamic monitors demonstrated the potential of pressure-based heart failure management, whereas subsequent studies confirmed the clinical utility of this approach. One large pivotal trial proved the safety and efficacy of pulmonary artery pressure–guided heart failure management, showing a marked reduction in heart failure hospitalizations in patients randomized to active pressure-guided management. “Next-generation” implantable hemodynamic monitors are in development, and novel approaches for the use of this data promise to expand the use of pressure-guided heart failure management.

Despite increased use of guideline-directed medical therapy (GDMT), some patients with heart failure and reduced ejection fraction (HFrEF) remain at high risk for hospitalization and mortality. Remote monitoring of pulmonary artery (PA) pressures provides clinicians with actionable information to help further optimize medications and improve outcomes.CHAMPION (CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Heart Failure Patients trial) analyzed PA pressure-guided heart failure (HF) management in patients with HFrEF based on their ability to tolerate GDMT.CHAMPION enrolled 550 patients with chronic HF regardless of left ventricular ejection fraction. A pre-specified sub-group analysis compared HF hospitalization and mortality rates between treatment and control groups in HFrEF patients (left ventricular ejection fraction ≤40%). Post hoc analyses in patients who tolerated GDMT were also performed. Hospitalizations and mortality were assessed using Andersen-Gill and Cox proportional hazards models.In 456 patients with HFrEF, HF hospitalization rates were 28% lower in the treatment group than in the control group (hazard ratio [HR]: 0.72; 95% confidence interval [CI]: 0.59 to 0.88; p = 0.0013), with a strong trend for 32% lower mortality (HR: 0.68; 95% CI: 0.45 to 1.02; p = 0.06). A 445-patient subset received at least 1 GDMT (angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, or beta-blocker) at baseline; these patients had 33% lower HF hospitalization rates (HR: 0.67; 95% CI: 0.54 to 0.82; p = 0.0002) and 47% lower mortality (HR: 0.63; 95% CI: 0.41 to 0.96, p = 0.0293) than controls. Compared with controls, patients receiving both components of optimal GDMT (n = 337) had 43% lower HF hospitalizations (HR: 0.57; 95% CI: 0.45 to 0.74; p 0.0001) and 57% lower mortality (HR: 0.43; 95% CI: 0.24 to 0.76; p = 0.0026).PA pressure-guided HF management reduces morbidity and mortality in patients with HFrEF on GDMT, underscoring the important synergy of addressing hemodynamic and neurohormonal targets of HF therapy. (CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Heart Failure Patients [CHAMPION]; NCT00531661).

The Dorothy M. Davis Heart and Lung Research Institute (DHLRI) at the Ohio State University (OSU) in Columbus, Ohio, has evolved over the past decade to serve as a platform to translate discovery from the laboratory to new practices in the clinic. Governing concepts for this evolution have been focused mission, leadership and investigator accountability, cross-disciplinary collaboration, and ultimately patient-centered discovery. The DHLRI is one of the largest and most comprehensive Institutes/Centers at the OSU and among the largest freestanding Institutes in the country devoted to cardiovascular, pulmonary, renal, and metabolic disease. The DHLRI was born from the multidisciplinary, programmatic study of heart, lung, and kidney disease at OSU in the late 1990s. In 2000, the DHLRI opened the doors of its new freestanding home—one of the most advanced interdisciplinary facilities on the Ohio State campus (Figure A). In 2001, ≈40 DHLRI investigators published 114 manuscripts. Over the past 16 years, the DHLRI has expanded its scientific scope and research footprint across OSU. Beyond serving as the research arm of OSU Heart and Vascular Center (HVC), the DHLRI now serves >700 faculty, staff, and trainees and generated >600 manuscripts in 2016. In 2017, the DHLRI continues to strive to fulfill its overarching mission to develop innovative strategies to diagnose, prevent, and treat cardiovascular, pulmonary, renal, and metabolic diseases. Numerous core laboratories within the DHLRI offer innovative technologies to support all aspects of basic and clinical research. The clinical care provided nearby at the Richard M. Ross Heart Hospital and OSU Wexner Medical Center offers first-hand perspectives on how research is involved in the prevention, detection, and treatment of disease. Figure. The Dorothy M. Davis Heart and Lung Research Institute. A , Freestanding Institute serves as platform for translational discovery. B , The first demonstration of sinoatrial node exit block during parasympathetic …

Atrial fibrillation (AF), mitral regurgitation (MR) and left ventricular ejection fraction (LVEF) have a complex interplay. We evaluated the role of AF in patients with heart failure (HF) and moderate-to-severe or severe MR enrolled in the COAPT trial and its impact on treatment with the MitraClip

There are limited data on the predictors of death or heart failure (HF) hospitalization in patients with HF and severe functional mitral regurgitation (FMR). In the COAPT trial, 614 symptomatic patients with HF, 3+ or 4+ FMR and left ventricular ejection fraction 20-50% were randomized to maximally

The impact of tricuspid regurgitation (TR) on outcomes after transcatheter mitral valve repair (TMVr) with MitraClip in heart failure (HF) pts with secondary mitral regurgitation (MR) is poorly understood. In the COAPT trial, 614 pts with HF and moderate to severe (3+) or severe (4+) symptomatic

The mechanisms and prognosis of secondary mitral regurgitation (MR) may be different in patients (pts) with ischemic (ICM) and nonischemic cardiomyopathy (NICM). Whether transcatheter mitral valve repair with MitraClip is equally effective in ICM and NICM is unknown. In COAPT, 614 pts with heart

Patients with heart failure (HF) who remain symptomatic despite cardiac resynchronization therapy (CRT) have a poor prognosis. The impact of transcatheter mitral valve repair (TMVr) for secondary mitral regurgitation (MR) in patients with previously implanted CRT is unknown. In the COAPT trial, 614

In the COAPT trial, transcatheter mitral valve repair with the MitraClip plus guideline directed medical therapy (GDMT) improved 2-year clinical outcomes in comparison to GDMT alone in symptomatic patients with heart failure (HF) and 3+ or 4+ secondary mitral regurgitation (SMR) due to LV

In the COAPT trial, transcatheter mitral valve repair with the MitraClip plus guideline directed medical therapy (GDMT) improved clinical outcomes in comparison to GDMT alone in symptomatic patients with heart failure (HF) and 3+ or 4+ secondary mitral regurgitation (SMR) due to LV dysfunction. We

Background Central sleep apnea (CSA) is a neurological breathing disorder, resulting from intermittent disruptions in the neural drive to breath. CSA differs substantially from the more prevalent Obstructive Sleep Apnea (OSA), which occurs as a result of muscles relaxing in the upper airway and preventing the passage of airflow. Sleep apnea is classified as "central" when over 50% of the apnea-hypopnea index (AHI) is driven by central events. CSA is a common and serious comorbidity in patients with heart failure (HF), with a prevalence of 30-50% in patients with a reduced left ventricular ejection fraction LVEF 45%. Patients with HF and untreated CSA suffer from poor outcomes, including increased morbidity and mortality as well as increased hospitalizations. Historically, CSA patients have received the same treatment options as patients suffering from OSA, including positive airway pressure (PAP) devices, nocturnal oxygen, and pharmacological treatments. However, recently published data has highlighted safety and mortality concerns with some forms of PAP therapy on patients with HF, CSA and reduced LVEF. A new FDA-approved implantable device therapy, phrenic nerve stimulation (PNS), has been designed specifically to treat CSA. Unlike positive airway pressure devices that use pressure to overcome obstructions and inflate the lungs, PNS activates the diaphragm to create negative pressure in the chest - mimicking the physiologic mechanism of natural breathing. In our institution we have developed a care pathway with a nurse practitioner designated as care coordinator responsible for initial screening, coordination of testing, and facilitation of treatment plan, whether that be with a sleep physician PAP device or electrophysiologist for implantable treatment. Objectives Describe a methodology and pathway to identify and treat HF patients with CSA. Methodology Guideline directed therapy for patients with HF now recommends sleep testing due to the deleterious effects of untreated sleep disordered breathing. With no clear patient characteristic that is predictive of CSA in patients with HF, clinicians should consider broadly testing patients with HF using polysomnography (PSG) or a home sleep apnea test (HSAT) with the ability to differentiate CSA from OSA. Results Clinical patient information from sleep (e.g. AHI) and cardiology (e.g. LVEF) should be used when determining a treatment plan. Implantable treatment options for CSA necessitate a robust pathway that requires communication across specialties (Figure 1). PNS requires collaboration among three clinical specialties: heart failure, sleep, and electrophysiology. Typically, heart failure identifies patients, sleep diagnoses, and electrophysiology implants the device. Providers also need to make a decision on how to best manage the CSA patient following the implant procedure for therapy titration and long-term patient follow-up. Regardless of which specialty manages the patient's CSA therapy long-term, success in treating patients with heart failure and CSA depends on collaboration and communication among the clinicians. Conclusions Given newly available treatment options for CSA and the risks associated with some forms of PAP therapy for HF patients with reduced LVEF, providers should design a robust treatment pathway across sleep, heart failure, and EP to manage treatment of patients with CSA and HF.