Search

Aims: Interatrial shunts are under evaluation as a treatment for heart failure (HF); however, their in vivo flow performance has not been quantitatively studied. We aimed to investigate the fluid dynamics properties of the 0.51 cm orifice diameter Ventura shunt and assess its lumen integrity with serial transesophageal echocardiography (TEE). Methods and results: Computational fluid dynamics (CFD) and bench flow tests were used to establish the flow‐pressure relationship of the shunt. Open‐label patients from the RELIEVE‐HF trial underwent TEE at shunt implant and at 6 and 12 month follow‐up. Shunt effective diameter (Deff) was derived from the vena contracta, and flow was determined by the continuity equation. CFD and bench studies independently validated that the shunt's discharge coefficient was 0.88 to 0.89. The device was successfully implanted in all 97 enrolled patients; mean age was 70 ± 11 years, 97% were NYHA class III, and 51% had LVEF ≤40%. Patency was confirmed in all instances, except for one stenotic shunt at 6 months. Deff remained unchanged from baseline at 12 months (0.47 ± 0.01 cm, P = 0.376), as did the trans‐shunt mean pressure gradient (5.1 ± 3.9 mmHg, P = 0.316) and flow (1137 ± 463 mL/min, P = 0.384). TEE measured flow versus pressure closely correlated (R2 ≥ 0.98) with a fluid dynamics model. At 12 months, the pulmonary/systemic flow Qp/Qs ratio was 1.22 ± 0.12. Conclusions: When implanted in patients with advanced HF, this small interatrial shunt demonstrated predictable and durable patency and performance. [ABSTRACT FROM AUTHOR]

Aims: Haemodynamic monitoring using implantable pressure sensors reduces the risk of heart failure (HF) hospitalizations. Patient self‐management (PSM) of haemodynamics in HF has the potential to personalize treatment, increase adherence, and reduce the risk of worsening HF, while lowering clinicians' burden. Methods and results: The VECTOR‐HF I and IIa studies are prospective, single‐arm, open‐label clinical trials assessing safety, usability and performance of left atrial pressure (LAP)‐guided HF management using PSM in New York Heart Association class II and III HF patients. Physician‐prescribed LAP thresholds trigger patient self‐adjustment of diuretics. Primary endpoints include the ability to perform LAP measurements and transmit data to the healthcare provider (HCP) interface and the patient guidance application, and safety outcomes. This is an interim analysis of 13 patients using the PSM approach. Over 12 months, no procedure‐ or device‐related major adverse cardiovascular or neurological events were observed, and there were no failures to obtain measurements from the sensor and transmit the data to the HCP interface and the patient guidance application. Patient adherence was 91.4%. Using PSM, annualized HF hospitalization rate significantly decreased compared to a similar period prior to PSM utilization (0 admissions vs. 0.69 admissions over 11.84 months, p = 0.004). At 6 months, 6‐min walk test distance and the Kansas City Cardiomyopathy Questionnaire overall summary score demonstrated significant improvement. Conclusions: Interim findings suggest that PSM using a LAP monitoring system is feasible and safe. PSM is associated with high patient adherence, potentially improving HF patients' functional status, quality of life, and limiting HF hospitalizations. [ABSTRACT FROM AUTHOR]

Aim: The RESHAPE‐HF2 trial is designed to assess the efficacy and safety of the MitraClip device system for the treatment of clinically important functional mitral regurgitation (FMR) in patients with heart failure (HF). This report describes the baseline characteristics of patients enrolled in the RESHAPE‐HF2 trial compared to those enrolled in the COAPT and MITRA‐FR trials. Methods and results: The RESHAPE‐HF2 study is an investigator‐initiated, prospective, randomized, multicentre trial including patients with symptomatic HF, a left ventricular ejection fraction (LVEF) between 20% and 50% with moderate‐to‐severe or severe FMR, for whom isolated mitral valve surgery was not recommended. Patients were randomized 1:1 to a strategy of delivering or withholding MitraClip. Of 506 patients randomized, the mean age of the patients was 70 ± 10 years, and 99 of them (20%) were women. The median EuroSCORE II was 5.3 (2.8–9.0) and median plasma N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) was 2745 (1407–5385) pg/ml. Most patients were prescribed beta‐blockers (96%), diuretics (96%), angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor–neprilysin inhibitors (82%) and mineralocorticoid receptor antagonists (82%). The use of sodium–glucose cotransporter 2 inhibitors was rare (7%). Cardiac resynchronization therapy (CRT) devices had been previously implanted in 29% of patients. Mean LVEF, left ventricular end‐diastolic volume and effective regurgitant orifice area (EROA) were 31 ± 8%, 211 ± 76 ml and 0.25 ± 0.08 cm2, respectively, whereas 44% of patients had mitral regurgitation severity of grade 4+. Compared to patients enrolled in COAPT and MITRA‐FR, those enrolled in RESHAPE‐HF2 were less likely to have mitral regurgitation grade 4+ and, on average, HAD lower EROA, and plasma NT‐proBNP and higher estimated glomerular filtration rate, but otherwise had similar age, comorbidities, CRT therapy and LVEF. Conclusion: Patients enrolled in RESHAPE‐HF2 represent a third distinct population where MitraClip was tested in, that is one mainly comprising of patients with moderate‐to‐severe FMR instead of only severe FMR, as enrolled in the COAPT and MITRA‐FR trials. The results of RESHAPE‐HF2 will provide crucial insights regarding broader application of the transcatheter edge‐to‐edge repair procedure in clinical practice. [ABSTRACT FROM AUTHOR]

Aims: Heart failure (HF) outcomes remain poor despite optimal guideline‐directed medical therapy (GDMT). We assessed safety, effectiveness, and transthoracic echocardiographic (TTE) outcomes during the 12 months after Ventura shunt implantation in the RELIEVE‐HF open‐label roll‐in cohort. Methods and results: Eligibility required symptomatic HF despite optimal GDMT with ≥1 HF hospitalization in the prior year or elevated natriuretic peptides. The safety endpoint was device‐related major adverse cardiovascular or neurological events at 30 days, compared to a prespecified performance goal. Effectiveness evaluations included the Kansas City Cardiomyopathy Questionnaire (KCCQ) at baseline, 1, 3, 6, and 12 months and TTE at baseline and 12 months. Overall, 97 patients were enrolled and implanted at 64 sites. Average age was 70 ± 11 years, 97% were in New York Heart Association class III, and half had left ventricular ejection fraction (LVEF) ≤40%. The safety endpoint was achieved (event rate 0%, p < 0.001). KCCQ overall summary score was improved by 12–16 points at all follow‐up timepoints (all p < 0.004), with similar outcomes in patients with reduced and preserved LVEF. At 12 months, left ventricular end‐systolic and end‐diastolic volumes were reduced (p = 0.020 and p = 0.038, respectively), LVEF improved (p = 0.009), right ventricular end‐systolic and end‐diastolic areas were reduced (p = 0.001 and p = 0.030, respectively), and right ventricular fractional area change (p < 0.001) and tricuspid annular plane systolic excursion (p < 0.001) improved. Conclusion: Interatrial shunting with the Ventura device was safe and resulted in favourable clinical effects in patients with HF, regardless of LVEF. Improvements of left and right ventricular structure and function were consistent with reverse myocardial remodelling. These results would support the potential of this shunt device as a treatment for HF. [ABSTRACT FROM AUTHOR]

Aims: Carotid baroreflex activation therapy (BAT) restores baroreflex sensitivity and modulates the imbalance in cardiac autonomic function in patients with heart failure with reduced ejection fraction (HFrEF). We tested the hypothesis that treatment with BAT significantly reduces cardiovascular mortality and heart failure morbidity and provides long‐term safety and sustainable symptomatic improvement. Methods and results: BeAT‐HF was a prospective, multicentre, randomized, two‐arm, parallel‐group, open‐label, non‐implanted control trial. New York Heart Association (NYHA) class III subjects, ejection fraction ≤35%, previous heart failure hospitalization or N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) >400 pg/ml, no class I indication for cardiac resynchronization therapy and NT‐proBNP <1600 pg/ml were randomized to BAT plus optimal medical management (BAT group) or optimal medical management alone (control). The primary endpoint was cardiovascular mortality and HF morbidity; additional pre‐specified endpoints included durability of safety, quality of life (QOL), exercise capacity (6‐min hall walk distance [6MHWD]), functional status (NYHA class), hierarchical composite win ratio, freedom from all‐cause death, left ventricular assists device (LVAD) implantation, heart transplant. Overall, 323 patients had 332 primary events, median follow‐up was 3.6 years/patient. Both primary endpoint (rate ratio 0.94, 95% confidence interval [CI] 0.57–1.57; p = 0.82) and components of the primary endpoints were not significantly different between BAT and control. The system‐ and procedure‐related major adverse neurological and cardiovascular event‐free rate remained 97% throughout the trial. Symptom improvement (QOL, 6MHWD, NYHA class, all nominal p < 0.001) in the BAT group was durable in time, sustainable in extent. Win ratio (1.26, 95% CI 1.02–1.58) and freedom from all‐cause death, LVAD implantation, heart transplant (hazard ratio 0.66, 95% CI 0.43–1.01) favoured the BAT group but did not reach statistical significance. Conclusion: The BeAT‐HF primary endpoint was neutral; however, BAT provided safe, effective, and sustainable improvements in HFrEF patient's functional status, 6MHWD and QOL. [ABSTRACT FROM AUTHOR]

Aims: Patients with heart failure usually have several other medical conditions that might alter the effects of interventions. We investigated whether the burden of comorbidity modified the clinical response to cardiac resynchronization therapy (CRT). Methods and results: Original patient‐level data from eight randomized trials exploring the effects of CRT versus no CRT were pooled (BLOCK‐HF, MIRACLE, MIRACLE‐ICD, MIRACLE‐ICD II, RAFT, COMPANION, MADIT‐CRT and REVERSE). A prior history of the following comorbidities was considered: episodic or persistent atrial fibrillation (n = 920), coronary artery disease (n = 3732), diabetes (n = 2171), and hypertension (n = 3353). Patients were classified into three groups based on the number of comorbidities: 0, 1–2, or ≥3. The outcomes of interest were time to all‐cause mortality and time to the composite outcome of heart failure hospitalization (HFH) or all‐cause mortality. Outcomes were evaluated within each comorbidity group using a Bayesian hierarchical Weibull survival regression model. Of 6324 patients, 970 (15%) had no comorbidities, 4052 (64%) had 1–2 and 1302 (21%) had ≥3 comorbidities. The adjusted hazard ratio (aHR) for CRT versus no CRT for all‐cause mortality in the overall cohort was 0.79 (95% credible interval [CI] 0.68–0.93) (p = 0.010); for no comorbidities the aHR was 0.54 (95% CI 0.34–0.86), for 1–2 comorbidities was 0.81 (95% CI 0.67–0.97) and for ≥3 comorbidities was 0.83 (95% CI 0.64–1.07) (no significant interaction between CRT and comorbidity burden: p = 0.13). For the endpoint of HFH or all‐cause mortality, the aHR for the overall cohort was 0.74 (95% CI 0.65–0.84) (p = 0.001), for no comorbidities was 0.69 (95% CI 0.50–0.94), for 1–2 comorbidities was 0.77 (95% CI 0.66–0.90) and for ≥3 comorbidities was 0.68 (95% CI 0.55–0.82) (no significant interaction between CRT and comorbidity burden: p = 0.081). Conclusion: In a meta‐analysis of patient‐level data from eight major trials, the totality of evidence suggests that CRT reduces HFH and/or all‐cause mortality even when several comorbid diseases are present. Clinical Trial Registration: NCT00271154, NCT00251251, NCT00267098, NCT00180271. [ABSTRACT FROM AUTHOR]

Despite remarkable improvements in the management of heart failure (HF), HF remains one of the most rapidly growing cardiovascular condition resulting in a substantial burden on healthcare systems worldwide. In clinical practice, however, a relevant proportion of patients are treated with suboptimal combinations and doses lower than those recommended in the current guidelines. Against this background, it remains important to identify new targets and investigate additional therapeutic options to alleviate symptoms and potentially improve prognosis in HF. Therefore, non‐pharmacological interventions targeting autonomic imbalance in HF have been evaluated. This paper aims to review the physiology, available clinical data, and potential therapeutic role of device‐based neuromodulation in HF. [ABSTRACT FROM AUTHOR]

Aim: Although education in self‐management is thought to be an important aspect of the care of patients with heart failure, little is known about whether self‐rated knowledge of self‐management is associated with outcomes. The aim of this study was to assess the relationship between patient‐reported knowledge of self‐management and clinical outcomes in patients with heart failure and reduced ejection fraction (HFrEF). Methods and results: Using individual patient data from three recent clinical trials enrolling participants with HFrEF, we examined patient characteristics and clinical outcomes according to responses to the 'self‐efficacy' questions of the Kansas City Cardiomyopathy Questionnaire. One question quantifies patients' understanding of how to prevent heart failure exacerbations ('prevention' question) and the other how to manage complications when they arise ('response' question). Self‐reported answers from patients were pragmatically divided into: poor (do not understand at all, do not understand very well, somewhat understand), fair (mostly understand), and good (completely understand). Cox‐proportional hazard models were used to evaluate time‐to‐first occurrence of each endpoint, and negative binomial regression analysis was performed to compare the composite of total (first and repeat) heart failure hospitalizations and cardiovascular death across the above‐defined groups. Of patients (n = 17 629) completing the 'prevention' question, 4197 (23.8%), 6897 (39.1%), and 6535 (37.1%) patients had poor, fair, and good self‐rated knowledge, respectively. Of those completing the 'response' question (n = 17 637), 4033 (22.9%), 5463 (31.0%), and 8141 (46.2%) patients had poor, fair, and good self‐rated knowledge, respectively. For both questions, patients with 'poor' knowledge were older, more often female, and had a worse heart failure profile but similar treatment. The rates (95% confidence interval) per 100 person‐years for the primary composite outcome for 'poor', 'moderate' and 'good' self‐rated knowledge in answer to the 'prevention' question were 12.83 (12.11–13.60), 12.08 (11.53–12.65) and 11.55 (11.00–12.12), respectively, and for the 'response' question were 12.88 (12.13–13.67), 12.22 (11.60–12.86) and 11.56 (11.07–12.07), respectively. The lower event rates in patients with 'good' self‐rate knowledge were accounted for by lower rates of cardiovascular (and all‐cause) death and not hospitalization for worsening heart failure. Conclusions: Poor patient‐reported 'self‐efficacy' may be associated with higher rates of mortality. Evaluation of knowledge of 'self‐efficacy' may provide prognostic information and a guide to which patients may benefit from further education about self‐management. [ABSTRACT FROM AUTHOR]

Aims Adjustment of treatment based on remote monitoring of pulmonary artery (PA) pressure may reduce the risk of hospital admission for heart failure (HF). We have conducted a meta-analysis of large randomized trials investigating this question. Methods and results A systematic literature search was performed for randomized clinical trials with PA pressure monitoring devices in patients with HF. The primary outcome of interest was the total number of HF hospitalizations. Other outcomes assessed were urgent visits leading to treatment with intravenous diuretics, all-cause mortality, and composites. Treatment effects are expressed as hazard ratios, and pooled effect estimates were obtained applying random effects meta-analyses. Three eligible randomized clinical trials were identified that included 1898 outpatients in New York Heart Association functional classes II–IV, either hospitalized for HF in the prior 12 months or with elevated plasma NT-proBNP concentrations. The mean follow-up was 14.7 months, 67.8% of the patients were men, and 65.8% had an ejection fraction ≤40%. Compared to patients in the control group, the hazard ratio (95% confidence interval) for total HF hospitalizations in those randomized to PA pressure monitoring was 0.70 (0.58–0.86) (P =.0005). The corresponding hazard ratio for the composite of total HF hospitalizations, urgent visits and all-cause mortality was 0.75 (0.61–0.91; P =.0037) and for all-cause mortality 0.92 (0.73–1.16). Subgroup analyses, including ejection fraction phenotype, revealed no evidence of heterogeneity in the treatment effect. Conclusion The use of remote PA pressure monitoring to guide treatment of patients with HF reduces episodes of worsening HF and subsequent hospitalizations. [ABSTRACT FROM AUTHOR]

Aim: Patients with heart failure (HF) often suffer from a range of comorbidities, which may affect their health status. The aim of this study was to assess the impact of different comorbidities on health status in patients with HF and reduced (HFrEF) and preserved ejection fraction (HFpEF). Methods and results: Using individual patient data from HFrEF (ATMOSPHERE, PARADIGM‐HF, DAPA‐HF) and HFpEF (TOPCAT, PARAGON‐HF) trials, we examined the Kansas City Cardiomyopathy Questionnaire (KCCQ) domain scores and overall summary score (KCCQ‐OSS) across a range of cardiorespiratory (angina, atrial fibrillation [AF], stroke, chronic obstructive pulmonary disease [COPD]) and other comorbidities (obesity, diabetes, chronic kidney disease [CKD], anaemia). Of patients with HFrEF (n = 20 159), 36.2% had AF, 33.9% CKD, 33.9% diabetes, 31.4% obesity, 25.5% angina, 12.2% COPD, 8.4% stroke, and 4.4% anaemia; the corresponding proportions in HFpEF (n = 6563) were: 54.0% AF, 48.7% CKD, 43.4% diabetes, 53.3% obesity, 28.6% angina, 14.7% COPD, 10.2% stroke, and 6.5% anaemia. HFpEF patients had lower KCCQ domain scores and KCCQ‐OSS (67.8 vs. 71.3) than HFrEF patients. Physical limitations, social limitations and quality of life domains were reduced more than symptom frequency and symptom burden domains. In both HFrEF and HFpEF, COPD, angina, anaemia, and obesity were associated with the lowest scores. An increasing number of comorbidities was associated with decreasing scores (e.g. KCCQ‐OSS 0 vs. ≥4 comorbidities: HFrEF 76.8 vs. 66.4; HFpEF 73.7 vs. 65.2). Conclusions: Cardiac and non‐cardiac comorbidities are common in both HFrEF and HFpEF patients and most are associated with reductions in health status although the impact varied among comorbidities, by the number of comorbidities, and by HF phenotype. Treating/correcting comorbidity is a therapeutic approach that may improve the health status of patients with HF. [ABSTRACT FROM AUTHOR]

Aims: To investigate the association of cardiac resynchronization therapy (CRT) on outcomes among participants with and without a history of atrial fibrillation (AF). Methods: Individual‐patient‐data from four randomized trials investigating CRT‐Defibrillators (COMPANION, MADIT‐CRT, REVERSE) or CRT‐Pacemakers (COMPANION, MIRACLE) were analyzed. Outcomes were time to a composite of heart failure hospitalization or all‐cause mortality or to all‐cause mortality alone. The association of CRT on outcomes for patients with and without a history of AF was assessed using a Bayesian‐Weibull survival regression model adjusting for baseline characteristics. Results: Of 3964 patients included, 586 (14.8%) had a history of AF; 2245 (66%) were randomized to CRT. Overall, CRT reduced the risk of the primary composite endpoint (hazard ratio [HR]: 0.69, 95% credible interval [CI]: 0.56–0.81). The effect was similar (posterior probability of no interaction = 0.26) in patients with (HR: 0.78, 95% CI: 0.55–1.10) and without a history of AF (HR: 0.67, 95% CI: 0.55–0.80). In these four trials, CRT did not reduce mortality overall (HR: 0.82, 95% CI: 0.66–1.01) without evidence of interaction (posterior probability of no interaction = 0.14) for patients with (HR: 1.09, 95% CI: 0.70–1.74) or without a history of AF (HR: 0.70, 95% CI: 0.60–0.97). Conclusion: The association of CRT on the composite endpoint or mortality was not statistically different for patients with or without a history of AF, but this could reflect inadequate power. Our results call for trials to confirm the benefit of CRT recipients with a history of AF. [ABSTRACT FROM AUTHOR]

Aims Stroke is an important problem in patients with heart failure (HF), but the intersection between the two conditions is poorly studied across the range of ejection fraction. The prevalence of history of stroke and related outcomes were investigated in patients with HF. Methods and results Individual patient meta-analysis of seven clinical trials enrolling patients with HF with reduced (HFrEF) and preserved ejection fraction (HFpEF). Of the 20 159 patients with HFrEF, 1683 (8.3%) had a history of stroke, and of the 13 252 patients with HFpEF, 1287 (9.7%) had a history of stroke. Regardless of ejection fraction, patients with a history of stroke had more vascular comorbidity and worse HF. Among those with HFrEF, the incidence of the composite of cardiovascular death, HF hospitalization, stroke, or myocardial infarction was 18.23 (16.81–19.77) per 100 person-years in those with prior stroke vs. 13.12 (12.77–13.48) in those without [hazard ratio 1.37 (1.26–1.49), P < 0.001]. The corresponding rates in patients with HFpEF were 14.16 (12.96–15.48) and 9.37 (9.06–9.70) [hazard ratio 1.49 (1.36–1.64), P < 0.001]. Each component of the composite was more frequent in patients with stroke history, and the risk of future stroke was doubled in patients with prior stroke. Among patients with prior stroke, 30% with concomitant atrial fibrillation were not anticoagulated, and 29% with arterial disease were not taking statins; 17% with HFrEF and 38% with HFpEF had uncontrolled systolic blood pressure (≥140 mmHg). Conclusion Heart failure patients with a history of stroke are at high risk of subsequent cardiovascular events, and targeting underutilization of guideline-recommended treatments might be a way to improve outcomes in this high-risk population. [ABSTRACT FROM AUTHOR]

Heart failure with preserved ejection fraction (HFpEF) represents a highly heterogeneous clinical syndrome affected in its development and progression by many comorbidities. The left ventricular diastolic dysfunction may be a manifestation of various combinations of cardiovascular, metabolic, pulmonary, renal, and geriatric conditions. Thus, in addition to treatment with sodium–glucose cotransporter 2 inhibitors in all patients, the most effective method of improving clinical outcomes may be therapy tailored to each patient's clinical profile. To better outline a phenotype‐based approach for the treatment of HFpEF, in this joint position paper, the Heart Failure Association of the European Society of Cardiology, the European Heart Rhythm Association and the European Hypertension Society, have developed an algorithm to identify the most common HFpEF phenotypes and identify the evidence‐based treatment strategy for each, while taking into account the complexities of multiple comorbidities and polypharmacy. [ABSTRACT FROM AUTHOR]

Aims: Multimorbidity, the coexistence of two or more chronic conditions, is synonymous with heart failure (HF). How risk related to comorbidities compares at individual and population levels is unknown. The aim of this study is to examine the risk related to comorbidities, alone and in combination, both at individual and population levels. Methods and results: Using two clinical trials in HF – the Prospective comparison of ARNI (Angiotensin Receptor–Neprilysin Inhibitor) with ACEI (Angiotensin‐Converting Enzyme Inhibitor) to Determine Impact on Global Mortality and morbidity in HF trial (PARADIGM‐HF) and the Aliskiren Trial to Minimize Outcomes in Patients with Heart Failure trials (ATMOSPHERE) – we identified the 10 most common comorbidities and examined 45 possible pairs. We calculated population attributable fractions (PAF) for all‐cause death and relative excess risk due to interaction with Cox proportional hazard models. Of 15 066 patients in the study, 14 133 (93.7%) had at least one and 11 867 (78.8%) had at least two of the 10 most prevalent comorbidities. The greatest individual risk among pairs was associated with peripheral artery disease (PAD) in combination with stroke (hazard ratio [HR] 1.73; 95% confidence interval [CI] 1.28–2.33) and anaemia (HR 1.71; 95% CI 1.39–2.11). The combination of chronic kidney disease (CKD) and hypertension had the highest PAF (5.65%; 95% CI 3.66–7.61). Two pairs demonstrated significant synergistic interaction (atrial fibrillation with CKD and coronary artery disease, respectively) and one an antagonistic interaction (anaemia and obesity). Conclusions: In HF, the impact of multimorbidity differed at the individual patient and population level, depending on the prevalence of and the risk related to each comorbidity, and the interaction between individual comorbidities. Patients with coexistent PAD and stroke were at greatest individual risk whereas, from a population perspective, coexistent CKD and hypertension mattered most. [ABSTRACT FROM AUTHOR]

Aims: Low serum albumin levels are associated with poor prognosis in numerous chronic disease states but the relationship between albumin and outcomes in patients with heart failure (HF) and secondary mitral regurgitation (SMR) has not been described. Methods and results: The randomized COAPT trial evaluated the safety and effectiveness of transcatheter edge‐to‐edge repair (TEER) with the MitraClipTM plus guideline‐directed medical therapy (GDMT) versus GDMT alone in patients with symptomatic HF and moderate‐to‐severe or severe SMR. Baseline serum albumin levels were measured at enrolment. Among 614 patients enrolled in COAPT, 559 (91.0%) had available baseline serum albumin levels (median 4.0 g/dl, interquartile range 3.7–4.2 g/dl). Patients with albumin <4.0 g/dl compared with ≥4.0 g/dl were older and more likely to have ischaemic cardiomyopathy and a hospitalization within the year prior to enrolment. After multivariable adjustment, patients with albumin <4.0 g/dl had higher 4‐year rates of all‐cause death (63.7% vs. 47.6%; adjusted hazard ratio 1.34, 95% confidence interval 1.02–1.74; p = 0.032), but there were no significant differences in HF hospitalizations (HFH) or all‐cause hospitalizations according to baseline serum albumin level. The relative effectiveness of TEER plus GDMT versus GDMT alone was consistent in patients with low and high albumin levels (pinteraction = 0.19 and 0.35 for death and HFH, respectively). Conclusion: Low baseline serum albumin levels were independently associated with reduced 4‐year survival in patients with HF and severe SMR enrolled in the COAPT trial, but not with HFH. Patients treated with TEER derived similarly robust reductions in both death and HFH regardless of baseline albumin level. [ABSTRACT FROM AUTHOR]

Background: Contemporary therapies improve breast cancer (BC) outcomes. Yet, many of these therapies have been increasingly linked with serious cardiotoxicity, including reports of profound hypertension. Yet, the incidence, predictors, and impacts of these events are largely unknown. Methods: Leveraging two large U.S.‐based registries, the National Inpatient Sample (NIS) and the Food and Drug Administration Adverse Event Reporting System (FAERS) databases, we assessed the incidence, factors, and outcomes of hypertensive events among BC patients from 2007 to 2015. Differences in baseline characteristics, hypertension‐related discharges, and complications were examined over time. Further, we performed a disproportionality analysis using reporting‐odds‐ratios (ROR) to determine the association between individual BC drugs and hypertensive events. Utilizing an ROR cutoff of >1.0, we quantified associations by drug‐class, and individual drugs with the likelihood of excess hypertension. Results: Overall, there were 5,464,401 BC‐admissions, of which 46,989 (0.8%) presented with hypertension. Hypertensive BC patients were older, and saw initially increased in‐hospital mortality, which equilibrated over time. The mean incidence of hypertension‐related admissions was 732 per 100,000 among BC patients, versus 96 per 100,000 among non‐cancer patients (RR 7.71, p < 0.001). Moreover, in FAERS, those with hypertension versus other BC‐treatment side‐effects were more frequently hospitalized (40.1% vs. 36.7%, p < 0.001), and were most commonly associated with chemotherapy (45.9%). Outside of Eribulin (ROR 3.36; 95% CI 1.37–8.22), no specific drug was associated with a higher reporting of hypertension; however, collectively BC drugs were associated with a higher odds of hypertension (ROR 1.66; 95% CI 1.09–2.53). Conclusions: BC therapies are associated with a substantial increase in limiting hypertension. [ABSTRACT FROM AUTHOR]

Aims Patients with heart failure with reduced ejection fraction (HFrEF) are at significant risk of stroke. Anticoagulation reduces this risk in patients with and without atrial fibrillation (AF), but the risk-to-benefit balance in the latter group, overall, is not favourable. Identification of patients with HFrEF, without AF, at the highest risk of stroke may allow targeted and safer use of prophylactic anticoagulant therapy. Methods and results In a pooled patient-level cohort of the PARADIGM-HF, ATMOSPHERE, and DAPA-HF trials, a previously derived simple risk model for stroke, consisting of three variables (history of prior stroke, insulin-treated diabetes, and plasma N -terminal pro-B-type natriuretic peptide level), was validated. Of the 20 159 patients included, 12 751 patients did not have AF at baseline. Among patients without AF, 346 (2.7%) experienced a stroke over a median follow up of 2.0 years (rate 11.7 per 1000 patient-years). The risk for stroke increased with increasing risk score: fourth quintile hazard ratio (HR) 2.35 [95% confidence interval (CI) 1.60–3.45]; fifth quintile HR 3.73 (95% CI 2.58–5.38), with the first quintile as reference. For patients in the top quintile, the rate of stroke was 21.2 per 1000 patient-years, similar to participants with AF not receiving anticoagulation (20.1 per 1000 patient-years). Model discrimination was good with a C-index of 0.84 (0.75–0.91). Conclusion It is possible to identify a subset of HFrEF patients without AF with a stroke-risk equivalent to that of patients with AF who are not anticoagulated. In these patients, the risk-to-benefit balance might justify the use of prophylactic anticoagulation, but this hypothesis needs to be tested prospectively. [ABSTRACT FROM AUTHOR]

Aims The impact of mitral valve geometry on outcomes after MitraClip treatment in secondary mitral regurgitation (MR) has not been examined. We therefore sought to evaluate the association between mitral valve geometry and outcomes of patients with heart failure (HF) and secondary MR treated with guideline-directed medical therapy (GDMT) and MitraClip. Methods and results Mitral valve geometry was assessed from the baseline echocardiograms in 614 patients from the COAPT trial. The primary endpoint for the present study was the composite of all-cause mortality or HF hospitalization (HFH) within 2 years. Effect of treatment arm (MitraClip plus maximally tolerated GDMT vs. GDMT alone) on outcomes according to baseline variables was assessed. Among 29 baseline mitral valve echocardiographic parameters, increasing anteroposterior mitral annular diameter was the only independent predictor of the composite endpoint of all-cause mortality or HFH [adjusted hazard ratio (aHR) per cm 1.49; P = 0.04]. The effective regurgitant orifice area (EROA) was independently associated with all-cause mortality alone (aHR per cm2 2.97; P = 0.04) but not with HFH, whereas increasing anteroposterior mitral annular diameter was independently associated with HFH alone (aHR per cm 1.85; P = 0.005) but not all-cause mortality. Other mitral valve morphologic parameters were unrelated to outcomes. MitraClip reduced HFH and mortality independent of anteroposterior mitral annular diameter and EROA (P interaction = 0.77 and 0.27, respectively). Conclusion In patients with HF and severe secondary MR, a large anteroposterior mitral annular diameter and greater EROA were the strongest echocardiographic predictors of HFH and death in patients treated with GDMT alone and with the MitraClip. [ABSTRACT FROM AUTHOR]

Aims: Heart failure with reduced ejection fraction (HFrEF) remains associated with high morbidity and mortality, poor quality of life (QoL) and significant exercise limitation. Sympatho‐vagal imbalance has been shown to predict adverse prognosis and symptoms in HFrEF, yet it has not been specifically targeted by any guideline‐recommended device therapy to date. Barostim™, which directly addresses this imbalance, is the first Food and Drug Administration approved neuromodulation technology for HFrEF. We aimed to analyse all randomized trial evidence to evaluate the effect of baroreflex activation therapy (BAT) on heart failure symptoms, QoL and N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) in HFrEF. Methods and results: An individual patient data (IPD) meta‐analysis was performed on all eligible trials that randomized HFrEF patients to BAT + guideline‐directed medical therapy (GDMT) or GDMT alone (open label). Endpoints included 6‐month changes in 6‐min hall walk (6MHW) distance, Minnesota Living With Heart Failure (MLWHF) QoL score, NT‐proBNP, and New York Heart Association (NYHA) class in all patients and three subgroups. A total of 554 randomized patients were included. In all patients, BAT provided significant improvement in 6MHW distance of 49 m (95% confidence interval [CI] 33, 64), MLWHF QoL of −13 points (95% CI −17, −10), and 3.4 higher odds of improving at least one NYHA class (95% CI 2.3, 4.9) when comparing from baseline to 6 months. These improvements were similar, or better, in patients who had baseline NT‐proBNP <1600 pg/ml, regardless of the cardiac resynchronization therapy indication status. Conclusion: An IPD meta‐analysis suggests that BAT improves exercise capacity, NYHA class, and QoL in HFrEF patients receiving GDMT. These clinically meaningful improvements were consistent across the range of patients studies. BAT was also associated with an improvement in NT‐proBNP in subjects with a lower baseline NT‐proBNP. [ABSTRACT FROM AUTHOR]

Aims Baseline renal dysfunction (RD) adversely impacts outcomes among patients with heart failure (HF) and severe secondary mitral regurgitation (MR). Heart failure and MR, in turn, accelerate progression to end-stage renal disease (ESRD), worsening prognosis. We sought to determine the impact of RD in HF patients with severe MR and the impact of transcatheter mitral valve repair (TMVr) on new-onset ESRD and the need for renal replacement therapy (RRT). Methods and results The COAPT trial randomized 614 patients with HF and severe MR to MitraClip plus guideline-directed medical therapy (GDMT) vs. GDMT alone. Patients were stratified into three RD subgroups based on baseline estimated glomerular filtration rate (eGFR, mL/min/1.73 m2): none (≥60), moderate (30–60), and severe (<30). End-stage renal disease was defined as eGFR <15 mL/min/1.73 m2 or RRT. The 2-year rates of all-cause death or HF hospitalization (HFH), new-onset ESRD, and RRT according to RD and treatment were assessed. Baseline RD was present in 77.0% of patients, including 23.8% severe RD, 6.0% ESRD, and 5.2% RRT. Worse RD was associated with greater 2-year risk of death or HFH (none 45.3%; moderate 53.9%; severe 69.2%; P < 0.0001). MitraClip vs. GDMT alone improved outcomes regardless of RD (P interaction = 0.62) and reduced new-onset ESRD [2.9 vs. 8.1%, hazard ratio (HR) 0.34, 95% confidence interval (CI) 0.15–0.76, P = 0.008] and the need for new RRT (2.5 vs. 7.4%, HR 0.33, 95% CI 0.14–0.78, P = 0.011). Conclusion Baseline RD was common in the HF patients with severe MR enrolled in COAPT and strongly predicted 2-year death and HFH. MitraClip treatment reduced new-onset ESRD and the need for RRT, contributing to the improved prognosis after TMVr. [ABSTRACT FROM AUTHOR]

Despite significant advances in drug-based and device-based therapies, heart failure remains a major and growing public health problem associated with substantial disability, frequent hospitalizations, and high economic costs. Keeping patients well and out of the hospital has become a major focus of heart failure disease management. Achieving and maintaining such stability in heart failure patients requires a holistic approach, which includes at least the management of the underlying heart disease, the management of comorbidities and the social and psychological aspects of the disease, and the management of haemodynamic/fluid status. In this regard, accurate assessment of elevated ventricular filling pressures or volume overload, that is, haemodynamic or pulmonary congestion, respectively, before the onset of worsening heart failure symptoms represents an important management strategy. Unfortunately, conventional methods for assessing congestion, such as physical examination and monitoring of symptoms and daily weights, are insensitive markers of worsening heart failure. Assessment tools that directly measure congestion, accurately and in absolute terms, provide more actionable information that enables the application of treatment algorithms designed to restore patient stability, in a variety of clinical settings. Two such assessment tools, implantable haemodynamic monitors and remote dielectric sensing (ReDS), meet the prerequisites for useful heart failure management tools, by providing accurate, absolute, and actionable measures of congestion, to guide patient management. This review focuses on the use of such technologies, across the spectrum of heart failure treatment settings. Clinical data are presented that support the broad use of pulmonary artery pressure-guided and/or ReDS-guided heart failure management in heart failure patients with reduced and preserved left ventricular ejection fraction. [ABSTRACT FROM AUTHOR]

Background: Sudden death (SD) and pump failure death (PFD) are the two leading causes of death in patients with heart failure and reduced ejection fraction (HFrEF). Objective: Identifying patients at higher risk for mode-specific death would allow better targeting of individual patients for relevant device and other therapies. Methods: We developed models in 7156 patients with HFrEF from the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure (PARADIGM-HF) trial, using Fine-Gray regressions counting other deaths as competing risks. The derived models were externally validated in the Aliskiren Trial to Minimize Outcomes in Patients with Heart Failure (ATMOSPHERE) trial. Results: NYHA class and NT-proBNP were independent predictors for both modes of death. The SD model additionally included male sex, Asian or Black race, prior CABG or PCI, cancer history, MI history, treatment with LCZ696 vs. enalapril, QRS duration and ECG left ventricular hypertrophy. While LVEF, ischemic etiology, systolic blood pressure, HF duration, ECG bundle branch block, and serum albumin, chloride and creatinine were included in the PFD model. Model discrimination was good for SD and excellent for PFD with Harrell's C of 0.67 and 0.78 after correction for optimism, respectively. The observed and predicted incidences were similar in each quartile of risk scores at 3 years in each model. The performance of both models remained robust in ATMOSPHERE. Conclusion: We developed and validated models which separately predict SD and PFD in patients with HFrEF. These models may help clinicians and patients consider therapies targeted at these modes of death. Trial registration number: PARADIGM-HF: ClinicalTrials.gov NCT01035255, ATMOSPHERE: ClinicalTrials.gov NCT00853658. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to assess the ability of a voice analysis application to discriminate between wet and dry states in chronic heart failure (CHF) patients undergoing regular scheduled haemodialysis treatment due to volume overload as a result of their chronic renal failure. Methods and results: In this single‐centre, observational study, five patients with CHF, peripheral oedema of ≥2, and pulmonary congestion‐related dyspnoea, undergoing haemodialysis three times per week, recorded five sentences into a standard smartphone/tablet before and after haemodialysis. Recordings were provided that same noon/early evening and the next morning and evening. Patient weight was measured at the hospital before and after each haemodialysis session. Recordings were analysed by a smartphone application (app) algorithm, to compare speech measures (SMs) of utterances collected over time. On average, patients provided recordings throughout 25.8 ± 3.9 dialysis treatment cycles, resulting in a total of 472 recordings. Weight changes of 1.95 ± 0.64 kg were documented during cycles. Median baseline SM prior to dialysis was 0.87 ± 0.17, and rose to 1.07 ± 0.15 following the end of the dialysis session, at noon (P = 0.0355), and remained at a similar level until the following morning (P = 0.007). By the evening of the day following dialysis, SMs returned to baseline levels (0.88 ± 0.19). Changes in patient weight immediately after dialysis positively correlated with SM changes, with the strongest correlation measured the evening of the dialysis day [slope: −0.40 ± 0.15 (95% confidence interval: −0.71 to −0.10), P = 0.0096]. Conclusions: The fluid‐controlled haemodialysis model demonstrated the ability of the app algorithm to identify cyclic changes in SMs, which reflected bodily fluid levels. The voice analysis platform bears considerable potential as a harbinger of impending fluid overload in a range of clinical scenarios, which will enhance monitoring and triage efforts, ultimately optimizing remote CHF management. [ABSTRACT FROM AUTHOR]

Aims The EMPERIAL (Effect of EMPagliflozin on ExeRcise ability and HF symptoms In patients with chronic heArt faiLure) trials evaluated the effects of empagliflozin on exercise ability and patient-reported outcomes in heart failure (HF) with reduced and preserved ejection fraction (EF), with and without type 2 diabetes (T2D), reporting, for the first time, the effects of sodium-glucose co-transporter-2 inhibition in HF with preserved EF (HFpEF). Methods and results HF patients with reduced EF (HFrEF) (≤40%, N = 312, EMPERIAL-Reduced) or preserved EF (>40%, N = 315, EMPERIAL-Preserved), with and without T2D, were randomized to empagliflozin 10 mg or placebo for 12 weeks. The primary endpoint was 6-minute walk test distance (6MWTD) change to Week 12. Key secondary endpoints included Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS) and Chronic Heart Failure Questionnaire Self-Administered Standardized format (CHQ-SAS) dyspnoea score. 6MWTD median (95% confidence interval) differences, empagliflozin vs. placebo, at Week 12 were −4.0 m (−16.0, 6.0; P = 0.42) and 4.0 m (−5.0, 13.0; P = 0.37) in EMPERIAL-Reduced and EMPERIAL-Preserved, respectively. As the primary endpoint was non-significant, all secondary endpoints were considered exploratory. Changes in KCCQ-TSS and CHQ-SAS dyspnoea score were non-significant. Improvements with empagliflozin in exploratory pre-specified analyses of KCCQ-TSS responder rates, congestion score, and diuretic use in EMPERIAL-Reduced are hypothesis generating. Empagliflozin adverse events were consistent with those previously reported. Conclusion The primary outcome for both trials was neutral. Empagliflozin was well tolerated in HF patients, with and without T2D, with a safety profile consistent with that previously reported in T2D. Hypothesis-generating improvements in exploratory analyses of secondary endpoints with empagliflozin in HFrEF were observed. [ABSTRACT FROM AUTHOR]

Purpose of Review: Wireless hemodynamic monitoring in heart failure patients allows for volume assessment without the need for physical exam. Data obtained from these devices is used to assist patient management and avoid heart failure hospitalizations. In this review, we outline the various devices, mechanisms they utilize, and effects on heart failure patients. Recent Findings: New applications of these devices to specific populations may expand the pool of patients that may benefit. In the COVID-19 pandemic with a growing emphasis on virtual visits, remote monitoring can add vital ancillary data. Summary: Wireless hemodynamic monitoring with a pulmonary artery pressure sensor is a highly effective and safe method to assess for worsening intracardiac pressures that may predict heart failure events, giving lead time that is valuable to keep patients optimized. Implantation of this device has been found to improve outcomes in heart failure patients regardless of preserved or reduced ejection fraction. [ABSTRACT FROM AUTHOR]

Heart failure is a major health and economic challenge in both developing and developed countries. Despite advances in pharmacological and device therapies for patients with a reduced left ventricular ejection fraction (LVEF) and heart failure, their quality of life and exercise capacity are often persistently impaired, morbidity and mortality remain high and the health economic and societal costs are considerable. For patients with heart failure and preserved LVEF, diuretic management has an essential role for controlling congestion and symptoms, even if no intervention has convincingly shown to reduce morbidity or mortality. Remote monitoring might improve care delivery and clinical outcomes for patients regardless of LVEF. A great variety of innovative remote monitoring technologies and algorithms are being introduced, including patient self‐managed testing, wearable devices, technologies either integrated into established clinically indicated therapeutic devices, such as pacemakers and defibrillators, or as stand‐alone are in development providing the promise of further improvements in service delivery and clinical outcomes. In this article, we will discuss unmet needs in the management of patients with heart failure, how remote monitoring might contribute to future solutions, and provide an overview of current and novel remote monitoring technologies. [ABSTRACT FROM AUTHOR]

The Heart Failure Academic Research Consortium is a partnership between the Heart Failure Collaboratory (HFC) and Academic Research Consortium (ARC), comprised of leading heart failure (HF) academic research investigators, patients, United States (US) Food and Drug Administration representatives, and industry members from the US and Europe. A series of meetings were convened to establish definitions and key concepts for the evaluation of HF therapies including optimal medical and device background therapy, clinical trial design elements and statistical concepts, and study endpoints. This manuscript summarizes the expert panel discussions as consensus recommendations focused on populations and endpoint definitions; it is not exhaustive or restrictive, but designed to stimulate HF clinical trial innovation. [ABSTRACT FROM AUTHOR]

Aims: The importance of intra‐ventricular conduction delay (IVCD), the incidence of new IVCD and its relationship to outcomes in heart failure and reduced ejection fraction (HFrEF) are not well studied. We addressed these questions in the PARADIGM‐HF and ATMOSPHERE trials. Methods and results: The risk of the primary composite outcome of cardiovascular death or heart failure hospitalization and all‐cause mortality were estimated by use of Cox regression according to baseline QRS duration and morphology in 11 861 patients without an intracardiac device. At baseline, 1789 (15.1%) patients had left bundle branch block (LBBB), 524 (4.4%) right bundle branch block (RBBB), 454 (3.8%) non‐specific IVCD, 2588 (21.8%) 'mildly abnormal' QRS (110–129 ms) and 6506 (54.9%) QRS <110 ms. During a median follow‐up of 2.5 years, the risk of the primary composite endpoint was higher among those with a wide QRS, irrespective of morphology: hazard ratios (95% confidence interval) LBBB 1.36 (1.23–1.50), RBBB 1.54 (1.31–1.79), non‐specific IVCD 1.65 (1.40–1.94) and QRS 110–129 ms 1.35 (1.23–1.47), compared with QRS duration <110 ms. A total of 1234 (15.6%) patients developed new‐onset QRS widening ≥130 ms (6.1 per 100 patient‐years). Incident LBBB occurred in 495 (6.3%) patients (2.4 per 100 patient‐years) and was associated with a higher risk of the primary composite outcome [hazard ratio 1.42 (1.12–1.82)]. Conclusion: In patients with HFrEF, a wide QRS was associated with worse clinical outcomes irrespective of morphology. The annual incidence of new‐onset LBBB was around 2.5%, and associated with a higher risk of adverse outcomes, highlighting the importance of repeat electrocardiogram review. Trial Registration: ClinicalTrials.gov Identifier NCT0083658 (ATMOSPHERE) and NCT01035255 (PARADIGM‐HF). [ABSTRACT FROM AUTHOR]

Aims: Frailty, characterized by loss of homeostatic reserves and increased vulnerability to physiological decompensation, results from an aggregation of insults across multiple organ systems. Frailty can be quantified by counting the number of 'health deficits' across a range of domains. We assessed the frequency of, and outcomes related to, frailty in patients with heart failure and reduced ejection fraction (HFrEF).Methods and Results: Using a cumulative deficits approach, we constructed a 42-item frailty index (FI) and applied it to identify frail patients enrolled in two HFrEF trials (PARADIGM-HF and ATMOSPHERE). In keeping with previous studies, patients with FI ≤0.210 were classified as non-frail and those with higher scores were divided into two categories using score increments of 0.100. Clinical outcomes were examined, adjusting for prognostic variables. Among 13 625 participants, mean (± standard deviation) FI was 0.250 (0.10) and 8383 patients (63%) were frail (FI >0.210). The frailest patients were older and had more symptoms and signs of heart failure. Women were frailer than men. All outcomes were worse in the frailest, with high rates of all-cause death or all-cause hospitalization: 40.7 (39.1-42.4) vs. 22.1 (21.2-23.0) per 100 person-years in the non-frail; adjusted hazard ratio 1.63 (1.53-1.75) (P < 0.001). The rate of all-cause hospitalizations, taking account of recurrences, was 61.5 (59.8-63.1) vs. 31.2 (30.3-32.2) per 100 person-years (incidence rate ratio 1.76; 1.62-1.90; P < 0.001).Conclusion: Frailty is highly prevalent in HFrEF and associated with greater deterioration in quality of life and higher risk of hospitalization and death. Strategies to prevent and treat frailty are needed in HFrEF. [ABSTRACT FROM AUTHOR]

Aims: More evidence is needed to quantify the association between tricuspid regurgitation (TR) and mortality in patients with heart failure (HF).Methods and Results: Between 2008-2017, using the Optum longitudinal database, a patient-level database that integrates multiple US-based electronic health and claim records from several health care providers, we identified 435 679 patients with new HF diagnosis and both an assessment of the left ventricular ejection fraction and at least 1 year of history. TR was graded as mild, moderate or severe and classified as prevalent (at the time of the initial HF diagnosis) or incident (subsequent new cases thereafter). For prevalent TR, the analysis was performed using a Cox proportional hazards model with adjustment for patient covariates. Incident TR was modelled as a time-updated covariate, as were other non-fatal events during follow-up. Prevalence of mild, moderate and severe TR at baseline was 10.1%, 5.1% and 1.4%, respectively. Over a median follow-up of 1.5 years, 121 273 patients (27.8%) died and prevalent TR was independently associated with survival. Compared to patients with no TR at baseline, the adjusted hazard ratios for mortality were 0.99 [95% confidence interval (CI) 0.97-1.01], 1.17 (95% CI 1.14-1.20) and 1.34 (95% CI 1.28-1.39) for mild, moderate and severe TR, respectively. In the 363 270 patients free from TR at baseline, incident TR (at least mild, at least moderate, or severe) developed during follow-up in 12.1%, 5.1% and 1.1%, respectively. Adjusted mortality hazard ratios for such new cases were 1.48 (95% CI 1.44-1.52), 1.92 (95% CI 1.86-1.99) and 2.44 (95% CI 2.32-2.57), respectively. Findings were consistent across all patient subgroups based on age, gender, rhythm, associated comorbidities, prior cardiac surgery, B-type natriuretic peptide/N-terminal pro-B-type natriuretic peptide, and left ventricular ejection fraction.Conclusions: In this large contemporary patient-level database of almost half-million US patients with HF, TR was associated with a marked increases in mortality risk overall and in all subgroups. Future randomized controlled trials will evaluate the impact of TR correction on clinical outcomes and the causal relationship between TR and mortality. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has important implications for the safety of participants in clinical trials and the research staff caring for them and, consequently, for the trials themselves. Patients with heart failure may be at greater risk of infection with COVID-19 and the consequences might also be more serious, but they are also at risk of adverse outcomes if their clinical care is compromised. As physicians and clinical trialists, it is our responsibility to ensure safe and effective care is delivered to trial participants without affecting the integrity of the trial. The social contract with our patients demands no less. Many regulatory authorities from different world regions have issued guidance statements regarding the conduct of clinical trials during this COVID-19 crisis. However, international trials may benefit from expert guidance from a global panel of experts to supplement local advice and regulations, thereby enhancing the safety of participants and the integrity of the trial. Accordingly, the Heart Failure Association of the European Society of Cardiology on 21 and 22 March 2020 conducted web-based meetings with expert clinical trialists in Europe, North America, South America, Australia, and Asia. The main objectives of this Expert Position Paper are to highlight the challenges that this pandemic poses for the conduct of clinical trials in heart failure and to offer advice on how they might be overcome, with some practical examples. While this panel of experts are focused on heart failure clinical trials, these discussions and recommendations may apply to clinical trials in other therapeutic areas. [ABSTRACT FROM AUTHOR]

Aims: To investigate the relationship between heart rate and outcomes in heart failure and reduced ejection fraction (HFrEF) patients in sinus rhythm (SR) and atrial fibrillation (AF) adjusting for natriuretic peptide concentration, a powerful prognosticator.Methods and Results: Of 13 562 patients from two large HFrEF trials, 10 113 (74.6%) were in SR and 3449 (25.4%) in AF. The primary endpoint was the composite of cardiovascular death or heart failure hospitalization. Heart rate was analysed as a categorical (tertiles, T1-3) and continuous variable (per 10 bpm), separately in patients in SR and AF. Outcomes were adjusted for prognostic variables, including N-terminal prohormone of B-type natriuretic peptide (NT-proBNP), and also examined using change from baseline heart rate to 1 year (≤ -10 bpm, ≥ +10 bpm, < ±10 bpm). SR patients with a higher heart rate had worse symptoms and quality of life, more often had diabetes and higher NT-proBNP concentrations. They had higher risk of the primary endpoint [T3 vs. T1 adjusted hazard ratio (HR) 1.50, 95% confidence interval (CI) 1.35-1.66; P < 0.001; per 10 bpm: 1.12, 95% CI 1.09-1.16; P < 0.001]. In SR, heart rate was associated with a relatively higher risk of pump failure than sudden death (adjusted HR per 10 bpm 1.17, 95% CI 1.09-1.26; P < 0.001 vs. 1.07, 95% CI 1.02-1.13; P = 0.011). Heart rate was not predictive of any outcome in AF.Conclusions: In HFrEF, an elevated heart rate was an independent predictor of adverse cardiovascular outcomes in patients in SR, even after adjustment for NT-proBNP. There was no relationship between heart rate and outcomes in AF.Clinical Trial Registration: ClinicalTrials.gov Identifiers NCT01035255 and NCT00853658. [ABSTRACT FROM AUTHOR]

Sleep-disordered breathing (SDB), including OSA and central sleep apnea, is highly prevalent in patients with heart failure (HF). Multiple studies have reported this high prevalence in asymptomatic as well as symptomatic patients with reduced left ventricular ejection fraction (HFrEF), as well as in those with HF with preserved ejection fraction. The acute pathobiologic consequences of OSA, including exaggerated sympathetic activity, oxidative stress, and inflammation, eventually could lead to progressive left ventricular dysfunction, repeated hospitalization, and excessive mortality. Large numbers of observational studies and a few small randomized controlled trials have shown improvement in various cardiovascular consequences of SDB with treatment. There are no long-term randomized controlled trials to show improved survival of patients with HF and treatment of OSA. One trial of positive airway pressure treatment of OSA included patients with HF and showed no improvement in clinical outcomes. However, any conclusions derived from this trial must take into account several important pitfalls that have been extensively discussed in the literature. With the role of positive airway pressure as the sole therapy for SDB in HF increasingly questioned, a critical examination of long-accepted concepts in this field is needed. The objective of this review was to incorporate recent advances in the field into a phenotype-based approach to the management of OSA in HF. [ABSTRACT FROM AUTHOR]

Cardiac contractility modulation, also referred to as CCM™, by the Optimizer Smart device is an innovative intracardiac device-based therapy that has been recently US FDA-approved for the treatment of patients with chronic heart failure, left ventricular ejection fraction (LVEF) between 25 and 45%, QRS <130 ms who remain symptomatic despite optimal medical therapy. Clinical trials demonstrate that CCM therapy is safe and effective in reducing heart failure hospitalization and improving heart failure symptoms, quality of life and functional performance. This novel device-based therapeutic offers benefits to patients who do not otherwise qualify for cardiac resynchronization therapy. CCM expands the indication beyond the traditional LVEF cutoff of 35% to a newer group including patients who fall in midrange LVEF group, up to 45%. [ABSTRACT FROM AUTHOR]

Purpose of review: Functional mitral regurgitation (MR) in setting of cardiomyopathy causes significant morbidity and worsened survival. Surgical therapies have failed to demonstrate significant overall benefit for functional MR. More recently, major trials utilizing transcatheter therapies for functional MR have been completed and offer new avenues for intervention. This review evaluates and compares 2 major recent trials designed to test the benefit of edge-to-edge repair using the MitraClip system for severe functional MR. Recent findings: The Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (COAPT) and Percutaneous Repair with the MitraClip Device for Severe Functional/Secondary Mitral Regurgitation (MITRA-FR) trials were simultaneous trials evaluating the treatment of effect of MitraClip in the setting of severe functional mitral regurgitation. Results of the trials were quite different with COAPT demonstrating substantial clinical benefit including significantly improved survival compared with MITRA-FR in which no clinical benefit was derived. Summary: Key differences in the patient population between the COAPT and MITRA-FR trials help to explain the contrasting results between the 2 trials designed to test the same hypothesis. Patients in COAPT had higher severity of MR with less dilated ventricles compared with MITRA-FR. These results will help shape patient selection for who will most benefit from MitraClip therapy. Further transcather mitral valve therapies continue to evolve and will likely offer alternative therapies for MR as technology improves. [ABSTRACT FROM AUTHOR]