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This article discusses the role of anti-obesity drugs in heart failure, specifically focusing on heart failure with preserved ejection fraction (HFpEF). Obesity is a significant risk factor for cardiovascular diseases, including HFpEF, and is associated with unfavorable clinical characteristics and worse symptoms. The pathophysiology of obesity-related HFpEF involves impaired left ventricular function, oxidative stress, inflammation, and adipose tissue dysfunction. The article also explores the potential benefits of anti-obesity drugs in improving outcomes for patients with HFpEF. However, the use of these drugs in heart failure with reduced ejection fraction (HFrEF) is less clear, and further research is needed to determine their efficacy and safety in this population. [Extracted from the article]

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]

Summary: Obesity is a worsening public health epidemic that remains challenging to manage. Obesity substantially increases the risk of cardiovascular diseases and presents a significant financial burden on the healthcare system. Digital health interventions, specifically telemedicine, may offer an attractive and viable solution for managing obesity. During the COVID‐19 pandemic, the need for a safer alternative to in‐person visits led to the increased popularity of telemedicine. Multiple studies have tested the efficacy of telemedicine modalities, including digital coaching via videoconferencing sessions, e‐health monitoring using wearable devices, and asynchronous forms of communication such as online chatrooms with counselors. In this review, we discuss the available evidence for telemedicine interventions in managing obesity, review current challenges and barriers to using telemedicine, and outline future directions to optimize the management of patients with obesity using telemedicine. [ABSTRACT FROM AUTHOR]

This article discusses the challenges and effectiveness of early post-discharge follow-up for patients hospitalized with heart failure (HF). While guidelines recommend early follow-up visits after discharge, the evidence supporting their effectiveness is limited. A study from France found that combined follow-up with a general practitioner and cardiologist was associated with a lower risk of death or rehospitalization, but a higher risk of HF readmission. The article emphasizes the importance of optimizing guideline-directed medical therapy (GDMT) during these visits and initiating GDMT prior to discharge to improve outcomes for HF patients. However, the article acknowledges the limitations of the study and the need for further research in this area. [Extracted from the article]

The article discusses the underutilization of guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF). It highlights the findings of the CHAMP-HF registry, which revealed that many eligible patients did not receive GDMT. The article explores various reasons for this, including patient out-of-pocket costs, poor tolerability, patient preference, and clinical inertia. The authors present the results of the HELP-HF registry, which examined the reasons for non-prescription or non-titration of GDMT. However, the study faced limitations due to missing data and the subjective nature of reasons provided. The article emphasizes the need for definitive data to understand the barriers to GDMT utilization and improve patient care. [Extracted from the article]

Aims: The therapeutic mechanism of sodium–glucose cotransporter 2 inhibitors (SGLT2i) on left cardiac remodelling in patients with heart failure with reduced ejection fraction (HFrEF) is not well‐established. This study meta‐analysed the impact of SGLT2i on left cardiac structure and function in patients with HFrEF. Methods and results: Online databases were queried up to April 2023 for trials reporting indicators of left cardiac structure and function in patients with HFrEF treated with SGLT2i. Data from studies were pooled using a random‐effects model to derive weighted mean differences (WMDs) and 95% confidence intervals (CIs). Six trials were included (n = 555). Compared with control, SGLT2i significantly improved left ventricular end‐diastolic volume (LVEDV; WMD: −17.07 ml [−23.84, −10.31]; p < 0.001), LVEDV index (WMD: −5.62 ml/m2 [−10.28, −0.97]; p = 0.02), left ventricular end‐systolic volume (LVESV; WMD: −15.63 ml [−26.15, −5.12]; p = 0.004), LVESV index (WMD: −6.90 ml/m2 [−10.68, −3.11]; p = 0.001), left ventricular ejection fraction (WMD: 2.71% [0.70, 4.72]; p = 0.008), and left atrial volume index (WMD: −2.19 ml/m2 [−4.26, −0.11]; p = 0.04) in patients with HFrEF. SGLT2i use was associated with a non‐significant trend towards a reduction in left ventricular mass index (WMD: −6.25 g/m2 [−12.79, 0.28]; p = 0.06). No significant impact on left ventricular global longitudinal strain was noted (WMD: 0.21% [−0.25, 0.67]; p = 0.38). Conclusions: Sodium–glucose cotransporter 2 inhibitors improve cardiac structure and function in patients with HFrEF. [ABSTRACT FROM AUTHOR]

Aims: The relationship between accelerometry data and changes in Kansas City Cardiomyopathy Questionnaire‐Physical Limitation Score (KCCQ‐PLS) or 6 min walk test (6MWT) is not well understood. Methods and results: VITALITY‐HFpEF accelerometry substudy (n = 69) data were assessed at baseline and 24 weeks. Ordinal logistic regression models were used to assess the association between accelerometry activity and deterioration, improved, or unchanged KCCQ‐PLS (≥8.33 and ≤ −4.17 points) and 6MWT (≥32 vs. ≤ −32 m). KCCQ‐PLS score deteriorated in 16 patients, improved in 34, and was unchanged in 19. 6MWT deteriorated in 8 patients, improved in 21, and was unchanged in 19. Mean accelerometer wear was 21.4 (±2.1) h/day. Changes in hours active from baseline to 24 weeks were not significantly different among patients who exhibited deterioration, improvement, or no change in KCCQ‐PLS [odds ratio (OR) 0.91, 95% confidence interval (CI) 0.71–1.18; P = 0.48] or 6MWT (OR 1.21, 95% CI 0.91–1.60; P = 0.18). Similar lack of association was observed for other accelerometry metrics and change in KCCQ and 6MWT. These findings were unaffected when KCCQ and 6MWT were examined as continuous variables. Conclusions: Accelerometer‐based activity measures did not correlate with subjective or objective standard measures of health status and functional capacity in heart failure with preserved ejection fraction. Further investigation of their relationships to clinical outcomes is required. [ABSTRACT FROM AUTHOR]

A study published in the European Journal of Heart Failure examined the association between a diabetes-specific heart failure risk score (WATCH-DM) and the presence of subclinical cardiomyopathy in individuals with diabetes. The study included 150 adults with diabetes and found that those with high WATCH-DM scores had a significantly greater prevalence of diabetic cardiomyopathy (DbCM) compared to those with low scores. The study suggests that the WATCH-DM risk score may be a useful tool for identifying individuals with diabetes who are at high risk of developing heart failure. However, the study has limitations, such as a small sample size and the inability to establish causality. The study was supported by a research grant and the authors have disclosed potential conflicts of interest. [Extracted from the article]

Heart failure (HF) is a heterogeneous syndrome affecting more than 60 million individuals globally. Despite recent advancements in understanding of the pathophysiology of HF, many issues remain including residual risk despite therapy, understanding the pathophysiology and phenotypes of patients with HF and preserved ejection fraction, and the challenges related to integrating a large amount of disparate information available for risk stratification and management of these patients. Risk prediction algorithms based on artificial intelligence (AI) may have superior predictive ability compared to traditional methods in certain instances. AI algorithms can play a pivotal role in the evolution of HF care by facilitating clinical decision making to overcome various challenges such as allocation of treatment to patients who are at highest risk or are more likely to benefit from therapies, prediction of adverse outcomes, and early identification of patients with subclinical disease or worsening HF. With the ability to integrate and synthesize large amounts of data with multidimensional interactions, AI algorithms can supply information with which physicians can improve their ability to make timely and better decisions. In this review, we provide an overview of the AI algorithms that have been developed for establishing early diagnosis of HF, phenotyping HF with preserved ejection fraction, and stratifying HF disease severity. This review also discusses the challenges in clinical deployment of AI algorithms in HF, and the potential path forward for developing future novel learning‐based algorithms to improve HF care. [ABSTRACT FROM AUTHOR]

This article discusses the prevalence and implications of albuminuria in transthyretin cardiac amyloidosis (ATTR-CA), a condition that is often under-recognized as a cause of heart failure. The study found that almost half of the patients with ATTR-CA had albuminuria, which is associated with an increased risk of mortality. The findings suggest that albuminuria can be a useful risk marker in patients with ATTR-CA and should be considered in clinical practice and trials. Further research is needed to understand the mechanisms behind kidney involvement in ATTR-CA and to explore potential treatments for albuminuria in these patients. [Extracted from the article]

Aims: Iron deficiency is common in patients with heart failure (HF) and reduced ejection fraction (HFrEF) and is associated with a poor prognosis. Whether intravenous iron replacement improves recurrent HF hospitalizations and cardiovascular mortality of these patients is uncertain although several trials were conducted. Moreover, none of the trials were powered to assess the effect of intravenous iron in clinically important subgroups. Therefore, we conducted a Bayesian analysis to derive precise estimates of the effect of intravenous iron replacement on recurrent HF hospitalizations and cardiovascular mortality in iron‐deficient HFrEF patients using consistent subgroup definitions across trials. Methods and results: Individual participant data were used from the FAIR‐HF (n = 459), CONFIRM‐HF (n = 304) and AFFIRM‐AHF (n = 1108) trials. These data were re‐analysed following as closely as possible the approach taken in the analyses of IRONMAN (n = 1137), for which study level data were used. Definitions of outcomes and subgroups from the FAIR‐HF, CONFIRM‐HF and AFFIRM‐AHF were matched with those used in IRONMAN. The primary endpoint was recurrent HF hospitalizations and cardiovascular mortality. The analysis of recurrent events was based on rate ratios (RR) derived from the Lin‐Wei‐Yang‐Ying model, and the data were pooled using Bayesian random‐effects meta‐analysis. Compared with placebo, intravenous iron significantly reduced the rates of recurrent HF hospitalizations and cardiovascular mortality (RR 0.73, 95% credible interval [CI] 0.48–0.99; between‐trial heterogeneity tau = 0.16). The pooled treatment effects did not provide evidence for any differential effects for subgroups based on sex (ratio of rate ratios [RRR] 1.49 [95% CI 0.95–2.37], age <69.4 vs. ≥69.4 years) (RRR 0.68 [0.40–1.15]), ischaemic versus non‐ischaemic aetiology of HF (RRR 0.73 [0.42–1.33]), transferrin saturation <20% vs. ≥20% (RRR 0.75 [0.40–1.34]), estimated glomerular filtration rate ≤60 versus >60 ml/min/1.73 m2 (RRR 0.97 [0.56–1.68]), haemoglobin <11.8 versus ≥11.8 (RRR 0.95 [0.53–1.60]), ferritin <35 versus ≥35 μg/L (RRR 1.26 [0.72–2.48]) and New York Heart Association class II versus III/IV (RRR 0.91 [0.54–1.56]). Conclusions: Treatment of iron‐deficient HFrEF patients with intravenous iron – namely with ferric carboxymaltose or ferric derisomaltose – results in significant reduction in recurrent HF hospitalizations and cardiovascular mortality. Results were nominally consistent across the subgroups studied, but for several of these subgroups uncertainty remains present. [ABSTRACT FROM AUTHOR]

Pulmonary arterial pressures are often used as surrogates for intravascular blood volume. However, the relationship between pressure and volume remains controversial. To contextualize and provide concrete examples and impact on clinical management, we report two cases of heart failure (one in heart failure with reduced ejection fraction and one in heart failure with preserved ejection fraction) where pressure‐based measurements did not accurately represent the intravascular status and affected clinical management. [ABSTRACT FROM AUTHOR]

Aims: Baseline body mass index (BMI) and weight loss promoted by sodium–glucose cotransporter 2 inhibitors may impact outcomes in patients with heart failure with reduced ejection fraction (HFrEF). We assessed in the EMPEROR‐Reduced population treated with empagliflozin versus placebo the relationship between baseline BMI, weight loss and effects on the primary (time to first hospitalization for heart failure [HHF] or cardiovascular death) and key secondary outcomes. Methods and results: We categorized patients according to their baseline BMI: <20 kg/m2 (n = 180); 20 to <25 kg/m2 (n = 1038); 25 to <30 kg/m2 (n = 1345); 30 to <35 kg/m2 (n = 774) and ≥35 kg/m2 (n = 393). The treatment effect of empagliflozin on the primary outcome was consistent across all BMI categories (hazard ratios in subgroups 0.66–0.88, interaction trend p = 0.32), as was the effect on total (first plus recurrent) HHF (interaction trend p = 0.31). Empagliflozin reduced the rate of estimated glomerular filtration rate decline consistently across the BMI categories (interaction trend p = 0.67). Overall, incidence rates of any or serious adverse events were comparable between the treatment groups across all BMI categories. A total of 313 (17.4%) patients treated with empagliflozin experienced a weight loss of more than 5% at week 52 versus 230 (12.8%) in placebo. When analysed separately within each treatment group, presence of weight loss was similarly associated with an increased risk of all‐cause mortality. Conclusion: The benefits of empagliflozin versus placebo were consistently present across all BMI categories in HFrEF patients. Weight loss was associated with higher risk of all‐cause mortality, regardless of treatment group. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the contribution of baseline and longitudinal changes in cardiometabolic health (CMH) towards heart failure (HF) risk among adults with type 2 diabetes (T2D). Methods and results: Participants of the Look AHEAD trial with T2D and without prevalent HF were included. Adjusted Cox models were used to create a CMH score incorporating target levels of parameters weighted based on relative risk for HF. The associations of baseline and changes in the CMH score with risk of overall HF, HF with preserved (HFpEF) and reduced ejection fraction (HFrEF) were assessed using Cox models. Among the 5080 participants, 257 incident HF events occurred over 12.4 years of follow‐up. The CMH score included 2 points each for target levels of waist circumference, glomerular filtration rate, urine albumin‐to‐creatinine ratio, and 1 point each for blood pressure and glycated haemoglobin at target. High baseline CMH score (6–8) was significantly associated with lower overall HF risk (adjusted hazard ratio [HR], ref = low score (0–3): 0.31, 95% confidence interval [CI] 0.21–0.47) with similar associations observed for HFpEF and HFrEF. Improvement in CMH was significantly associated with lower risk of overall HF (adjusted HR per 1‐unit increase in score at 4 years: 0.80, 95% CI 0.70–0.91). In the ACCORD validation cohort, the baseline CMH score performed well for predicting HF risk with adequate discrimination (C‐index 0.70), calibration (chi‐square 5.53, p = 0.70), and risk stratification (adjusted HR [high (6–8) vs. low score (0–3)]: 0.35, 95% CI 0.26–0.46). In the Look AHEAD subgroup with available biomarker data, incorporating N‐terminal pro‐B‐type natriuretic peptide to the baseline CMH score improved model discrimination (C‐index 0.79) and risk stratification (adjusted HR [high (8–10) vs. low score (0–4)]: 0.18, 95% CI 0.09–0.35). Conclusions: Achieving target levels of more CMH parameters at baseline and sustained improvements were associated with lower HF risk in T2D. [ABSTRACT FROM AUTHOR]

Aim: Intravenous ferric carboxymaltose (FCM) has been shown to improve overall quality of life in iron‐deficient heart failure with reduced ejection fraction (HFrEF) patients at a trial population level. This FAIR‐HF and CONFIRM‐HF pooled analysis explored the likelihood of individual improvement or deterioration in Kansas City Cardiomyopathy Questionnaire (KCCQ) domains with FCM versus placebo and evaluated the stability of this response over time. Methods and results: Changes versus baseline in KCCQ overall summary score (OSS), clinical summary score (CSS) and total symptom score (TSS) were assessed at weeks 12 and 24 in FCM and placebo groups. Mean between‐group differences were estimated and individual responder analyses and analyses of response stability were performed. Overall, 760 (FCM, n = 454) patients were studied. At week 12, the mean improvement in KCCQ OSS was 10.6 points with FCM versus 4.8 points with placebo (least‐square mean difference [95% confidence interval, CI] 4.36 [2.14; 6.59] points). A higher proportion of patients on FCM versus placebo experienced a KCCQ OSS improvement of ≥5 (58.3% vs. 43.5%; odds ratio [95% CI] 1.81 [1.30; 2.51]), ≥10 (42.4% vs. 29.3%; 1.73 [1.23; 2.43]) or ≥15 (32.1% vs. 22.6%; 1.46 [1.02; 2.11]) points. Differences were similar at week 24 and for CSS and TSS domains. Of FCM patients with a ≥5‐, ≥10‐ or ≥15‐point improvement in KCCQ OSS at week 12, >75% sustained this improvement at week 24. Conclusion: Treatment of iron‐deficient HFrEF patients with intravenous FCM conveyed clinically relevant improvements in health status at an individual‐patient level; benefits were sustained over time in most patients. [ABSTRACT FROM AUTHOR]

Aims: Clinically important thresholds in patient‐reported outcomes measures like the Kansas City Cardiomyopathy Questionnaire (KCCQ) have not been defined for patients with heart failure and preserved ejection fraction (HFpEF). The aim of this study was to estimate meaningful thresholds for improvement or worsening in the KCCQ physical limitation score (PLS) in patients with HFpEF. Methods and results: In this pre‐specified analysis from VITALITY‐HFpEF, anchor‐ and distribution‐based approaches were used to estimate thresholds for improvement or worsening in the KCCQ‐PLS using Patient Global Impression of Change (PGIC) as an anchor. The KCCQ‐PLS contains six elements, with each increment in response resulting in a change of 4.17 points when converted to a 0–100 scale. The mean change in KCCQ‐PLS from baseline to week 12 was calculated for each PGIC group to estimate a meaningful within‐patient change. Of 789 patients enrolled, 698 had complete KCCQ‐PLS and PGIC data at week 12. The mean (± standard deviation) changes in KCCQ‐PLS corresponding to PGIC changes of 'a little better', 'better', and 'much better' were 5.7 ± 18.6, 11.6 ± 19.3, and 18.4 ± 25.3 points, respectively. The scores of patients who responded 'a little better' (n = 177) overlapped substantially with those who reported 'no change' (n = 193; mean change 2.8 ± 18.9). The mean change in KCCQ‐PLS for patients responding 'a little worse' (n = 32) was −2.6 ± 18.0 points. The threshold for meaningful within‐patient change in KCCQ‐PLS based on distribution‐based analyses was 12.3 points. Using area under the curve (AUC) analyses of KCCQ‐PLS, the sensitivity and specificity of a 4.17‐point change were 0.61 and 0.57, for an 8.33‐point change they were 0.49 and 0.64, and for a 12.5‐point change they were 0.44 and 0.72 for being at least a little better on the PGIC (AUC = 0.54). Conclusion: In the VITALITY‐HFpEF trial, a change in KCCQ‐PLS of ≥8.33 points (corresponding to an improvement in ≥2 response categories of KCCQ‐PLS) may represent the minimal clinically important difference for improvement and a change of ≤ −4.17 points (corresponding to a worsening in ≥1 response category of KCCQ‐PLS) may suggest deterioration in patients with HFpEF. [ABSTRACT FROM AUTHOR]

Aim: Improving functional capacity is a key goal in heart failure (HF). This pooled analysis of FAIR‐HF and CONFIRM‐HF assessed the likelihood of improvement or deterioration in 6‐min walk test (6MWT) among iron‐deficient patients with chronic HF with reduced ejection fraction (HFrEF) receiving ferric carboxymaltose (FCM). Methods and results: Data for 760 patients (FCM: n = 454; placebo: n = 306) were analysed. The proportions of patients receiving FCM or placebo who had ≥20, ≥30, and ≥40 m improvements or ≥10 m deterioration in 6MWT at 12 and 24 weeks were assessed. Patients receiving FCM experienced a mean (standard deviation) 31.1 (62.3) m improvement in 6MWT versus 0.1 (77.1) m improvement for placebo at week 12 (difference in mean changes 26.8 [16.6–37.0]). At week 12, the odds [95% confidence interval] of 6MWT improvements of ≥20 m (odds ratio 2.16 [1.57–2.96]; p < 0.0001), ≥30 m (2.00 [1.44–2.78]; p < 0.0001), and ≥40 m (2.29 [1.60–3.27]; p < 0.0001) were greater with FCM versus placebo, while the odds of a deterioration ≥10 m were reduced with FCM versus placebo (0.55 [0.38–0.80]; p = 0.0019). Among patients who experienced 6MWT improvements of ≥20, ≥30, or ≥40 m with FCM at week 12, more than 80% sustained this improvement at week 24. Conclusion: Ferric carboxymaltose resulted in a significantly higher likelihood of improvement and a reduced likelihood of deterioration in 6MWT versus placebo among iron‐deficient patients with HF. Of the patients experiencing clinically significant improvements at week 12, the majority sustained this improvement at week 24. These results are supportive of FCM to improve exercise capacity in HF. [ABSTRACT FROM AUTHOR]

Aims: Hospitalization for heart failure (HF) constitutes a major healthcare and economic burden. Trends and characteristics of hospitalizations for HF for the recent years are not clear. We sought to determine the trends and characteristics of hospitalization for HF in the United States. Method and results: A retrospective analysis of the National Inpatient Sample weighted data between 1 January 2004 and 31 December 2018, which included hospitalized adults ≥ 18 years with primary discharge diagnosis of HF using International Classification of Diseases‐9/10 administrative codes. Main outcomes were trends in hospitalizations for HF (per 1000 person) and inpatient mortality (%) between 2004 and 2018. Conclusions: Hospitalizations for HF have been increasing across both sexes and age groups since 2013, whereas inpatient mortality has been decreasing over the study period. Blacks have the highest risk of hospitalization for HF, and Whites have the highest in‐hospital mortality. There are significant racial and geographic disparities related to hospitalizations for HF. [ABSTRACT FROM AUTHOR]

Aims: Recent trials have evaluated sodium–glucose co‐transporter 2 inhibitors in patients with heart failure (HF). We sought to assess the robustness of findings from these trials using the fragility index (FI). Methods and results: Fragility index is defined as the minimum number of patients that must be moved from the 'non‐event' to the 'event' group to turn a statistically significant result to non‐significant. In addition to FI, fragility quotient [(FQ); FI divided by the sample size] was calculated to assess the proportion of events that must be moved to change the significance. For statistically non‐significant outcomes, reverse fragility index (RFI) and reverse fragility quotient (RFQ) were calculated. Robustness of findings after pooling data from all three trials was also assessed. A robust reduction in first HF hospitalization or cardiovascular mortality was seen with dapagliflozin (FI = 62 and FQ = 0.013), empagliflozin (FI = 50 and FQ = 0.013), and sotagliflozin (FI = 60 and FQ = 0.049). Dapagliflozin nominally improved all‐cause and cardiovascular mortality, with modest FI (n = 8 and 5) and FQ (0.002 and 0.001). Empagliflozin and sotagliflozin did not demonstrate statistically significant reductions in all‐cause mortality, with modest RFI (empagliflozin: RFI = 26 and RFQ = 0.007; sotagliflozin: RFI = 6 and RFQ = 0.005). A similar trend was seen with cardiovascular mortality (empagliflozin: RFI = 24 and RFQ = 0.006; sotagliflozin: RFI = 7 and RFQ = 0.006). Upon meta‐analysis, the result for first HF hospitalization or cardiovascular mortality was robust (FI = 95 and FQ = 0.010). The reductions in all‐cause (FI = 12 and FQ = 0.001) and cardiovascular mortality (FI = 9 and FQ = 0.001), while statistically significant, were fragile. Conclusion: Improvement in the composite outcome of first HF hospitalization or cardiovascular death was highly concordant and robust across sodium–glucose co‐transporter 2 inhibitor trials. In contrast, secondary endpoints of all‐cause and cardiovascular mortality were statistically fragile, underscoring the need to power trials for mortality to fully understand the benefit of therapies on fatal events. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the performance of the WATCH‐DM risk score, a clinical risk score for heart failure (HF), in patients with dysglycaemia and in combination with natriuretic peptides (NPs). Methods and results: Adults with diabetes/pre‐diabetes free of HF at baseline from four cohort studies (ARIC, CHS, FHS, and MESA) were included. The machine learning‐ [WATCH‐DM(ml)] and integer‐based [WATCH‐DM(i)] scores were used to estimate the 5‐year risk of incident HF. Discrimination was assessed by Harrell's concordance index (C‐index) and calibration by the Greenwood–Nam–D'Agostino (GND) statistic. Improvement in model performance with the addition of NP levels was assessed by C‐index and continuous net reclassification improvement (NRI). Of the 8938 participants included, 3554 (39.8%) had diabetes and 432 (4.8%) developed HF within 5 years. The WATCH‐DM(ml) and WATCH‐DM(i) scores demonstrated high discrimination for predicting HF risk among individuals with dysglycaemia (C‐indices = 0.80 and 0.71, respectively), with no evidence of miscalibration (GND P ≥0.10). The C‐index of elevated NP levels alone for predicting incident HF among individuals with dysglycaemia was significantly higher among participants with low/intermediate (<13) vs. high (≥13) WATCH‐DM(i) scores [0.71 (95% confidence interval 0.68–0.74) vs. 0.64 (95% confidence interval 0.61–0.66)]. When NP levels were combined with the WATCH‐DM(i) score, HF risk discrimination improvement and NRI varied across the spectrum of risk with greater improvement observed at low/intermediate risk [WATCH‐DM(i) <13] vs. high risk [WATCH‐DM(i) ≥13] (C‐index = 0.73 vs. 0.71; NRI = 0.45 vs. 0.17). Conclusion: The WATCH‐DM risk score can accurately predict incident HF risk in community‐based individuals with dysglycaemia. The addition of NP levels is associated with greater improvement in the HF risk prediction performance among individuals with low/intermediate risk than those with high risk. [ABSTRACT FROM AUTHOR]

Also, for patients not receiving medication at baseline, it is often unclear from registries if patients with chronic HF may have previously been trialed on medications before enrollment but proven to be intolerant. Outcomes were medication dose titration and discontinuation within each medication class, as well time-to-first HF hospitalization and all-cause mortality endpoints. This issue may be particularly relevant when interpreting rates of drug discontinuation, as thresholds to discontinue these medications may be lower among patients with mid-range or preserved ejection fraction. [Extracted from the article]

Aims: To appraise meta‐analytically determined effect of dietary interventions and nutritional supplements on heart failure (HF)‐related outcomes, and create an evidence map to visualize the findings and certainty of evidence. Methods and results: Online databases were systematically searched for meta‐analyses of randomized controlled trials (RCTs) evaluating the effect of dietary interventions and nutritional supplements on HF outcomes and incidence. These were then updated if new RCTs were available. Estimates were pooled using a random‐effects model and reported as risk ratios (RRs) or mean differences with 95% confidence intervals. We identified 14 relevant meta‐analyses, to which 21 new RCTs were added. The total evidence base reviewed included 122 RCTs (n = 176 097 participants) assessing 14 interventions. We found that coenzyme Q10 was associated with lower all‐cause mortality [RR 0.69 (0.50–0.96); I2 = 0%; low certainty of evidence] in HF patients. Incident HF risk was reduced with Mediterranean diet [RR 0.45 (0.26–0.79); I2 = 0%; low certainty of evidence]. Vitamin E supplementation was associated with a small but significant increase in the risk of HF hospitalization [RR 1.21 (1.04–1.40); I2 = 0%; moderate certainty of evidence]. There was moderate certainty of evidence that thiamine, vitamin D, iron, and L‐carnitine supplementation had a beneficial effect on left ventricular ejection fraction. Conclusion: Coenzyme Q10 may reduce all‐cause mortality in HF patients, while a Mediterranean diet may reduce the risk of incident HF; however, the low certainty of evidence warrants the need for further RCTs to confirm a definite clinical role. RCT data were lacking for several common interventions including intermittent fasting, caffeine, DASH diet, and ketogenic diet. More research is needed to fill the knowledge gap. [ABSTRACT FROM AUTHOR]

This can be substantiated by inferring event rates of HF hospitalization in trials such as EMPEROR-Reduced (155 per 1000 patient-years), DAPA-HF (98 per 1000 patient-years), CHARM-Alternative (Candesartan in Patients with Chronic Heart Failure and Reduced Systolic Function Intolerant to Angiotensin-Converting Enzyme Inhibitors) (128 per 1000 patient-years), CHARM-Added (Candesartan in Patients with Chronic Heart Failure and Reduced Systolic Function Taking Angiotensin-Converting Enzyme Inhibitors) (110 per 1000 patient-years) and PARADIGM-HF (Angiotensin-Neprilysin Inhibition vs. This is hypothesized as the HF hospitalization event rates observed in the placebo arm were similar to event rates observed in other HFpEF trials such as PEP-CHF (Perindopril in Elderly People with Chronic Heart Failure) (74 per 1000 patient-years), CHARM-Preserved (Candesartan in Patients with Chronic Heart Failure and Preserved Ejection Fraction) (69 per 1000 patient-years), PARAGON-HF (Angiotensin-Neprilysin Inhibition in Heart Failure with Preserved Ejection Fraction) (50 per 1000 patient-years), TOPCAT (Spironolactone for Heart Failure with Preserved Ejection Fraction) (46 per 1000 patient-years), and I-PRESERVE (Irbesartan in Patients with Heart Failure and Preserved Ejection Fraction) (43 per 1000 patient-years) ( I Figure i 2A).22-26 In contrast, HFrEF trials have had higher event rates for HF hospitalization in the placebo arm. Over the last three decades, several lifesaving therapies for the treatment of heart failure with reduced ejection fraction (HFrEF) have emerged; however, this is not the case for heart failure with preserved ejection fraction (HFpEF). While trials in this patient population are ongoing, the current models of HFpEF pathophysiology, the pharmacodynamic profile of SGLT2 inhibitors, and secondary analyses of previous trials, all provide hope that these drugs may indeed benefit patients with HFpEF. [Extracted from the article]

Introduction: To evaluate the safety of uninterrupted versus interrupted direct oral anticoagulation (DOAC) for patients undergoing catheter ablation (CA) of atrial fibrillation (AF). Methods: We conducted a systematic search of MEDLINE and EMBASE for randomized controlled trials (RCT) and observational studies comparing uninterrupted versus interrupted DOAC for patients undergoing CA of AF. Primary outcome was major bleeding. Secondary outcomes included minor bleeding, stroke or transient ischemic attack (TIA) or thromboembolism (TE), silent cerebral ischemic events, and cardiac tamponade. Meta‐analysis was stratified by study design. Risk ratios (RR) with 95% confidence intervals were calculated using random effects model and Mantel–Haenszel method was used to pool RR. Results: A total of 13 studies (7 randomized, 6 observational) comprising 3595 patients were included. The RCT restricted analysis did not show any difference in terms of major bleeding (risk ratio [RR] = 0.79; [0.35–1.79]), minor bleeding (RR = 0.99 [0.68–1.43]), stroke or TIA or TE (RR = 0.80 [0.19–3.32]), silent cerebral ischemic events (RR = 0.64 [0.32–1.28]), and cardiac tamponade (RR = 0.61 [0.20–1.92]). Observational study restricted analysis showed a protective effect of uninterrupted DOAC on silent cerebral ischemic events (RR = 0.45 [0.31–0.67]) and no difference in other outcomes. Conclusions: There is no difference in bleeding and thromboembolic outcomes with uninterrupted versus interrupted DOAC for CA of AF and observational data suggests that uninterrupted DOACs are protective against silent cerebral ischemic lesions. [ABSTRACT FROM AUTHOR]

Aims: The Carillon Mitral Contour System has been shown to reduce mitral regurgitation and left ventricular volumes in symptomatic heart failure patients with functional mitral regurgitation. We sought to evaluate the effects of the Carillon device on quality of life and functional capacity in these patients. Methods and results: An individual participant data meta‐analysis was conducted utilizing data from REDUCE‐FMR, TITAN, and TITAN II studies. The main outcomes assessed were changes from baseline in Kansas City Cardiomyopathy Questionnaire overall summary scores (KCCQ‐OSS), 6 min walk test (6MWT) distance, and New York Heart Association (NYHA) classification at Months 1 and 12 after device implantation. Subgroup analyses were conducted for patients with severe functional mitral regurgitation (Grade 3 or 4). Pooled estimates were calculated using a random‐effects model and are presented as weighted proportions or weighted mean differences along with 95% confidence intervals (CIs). Among 139 patients included in the analysis, Carillon device significantly improved the 6MWT distance (63.0 m; 95% CI 18.8–107.2, P = 0.0056) and KCCQ‐OSS score (15.1; 95% CI 5.6–24.7, P = 0.0022) at 1 month from baseline. These benefits were sustained at 12 months (64.1 m; 95% CI 13.2–115.0, P = 0.0141, for 6MWT distance, and 12.3; 95% CI 4.7–19.8, P = 0.0019, for KCCQ‐OSS score). More than 50% of the patients had improvements in KCCQ‐OSS by ≥5 (60.4%; 95% CI 47.4–72.1) and 10 points (50.5%; 95% CI 34.9–66.0) at 12 months. Almost half of the patients experienced a ≥1 class improvement in NYHA class after implantation of the device at 1 month (67.9%; 95% CI 37.3–88.3) and at 12 months (48.8%; 95% CI 31.8–66.2). Results remained similar for KCCQ‐OSS, 6MWT distance, and NYHA classification when only patients with Grade 3 or 4 mitral regurgitation were analysed. The pooled estimates of 30 day and 1 year all‐cause mortality were 2.2% (95% CI 0.7–6.5) and 17.3% (95% CI 11.8–24.5), respectively. Conclusions: The Carillon Mitral Contour System significantly improved patient‐reported quality‐of‐life outcomes in heart failure patients with functional mitral regurgitation. [ABSTRACT FROM AUTHOR]

Aims: The objective of this study was to compare functional outcomes through 1 year in patients with core‐lab verified moderate to severe (Grades 2+ to 4+) functional mitral regurgitation (FMR) treated with the Carillon device or control in the blinded sham‐controlled REDUCE‐FMR (Carillon Mitral Contour System for Reducing Functional Mitral Regurgitation) study. Methods and results: The main outcomes of this analysis were the change in 6 min walk test (6MWT) distance, incidence of heart failure hospitalization or death, change in New York Heart Association (NYHA) class, and change in Kansas City Cardiomyopathy Questionnaire (KCCQ) score through 1 year of follow‐up. The minimum clinically important difference (MCID) was defined as a ≥30 m increase in 6MWT distance, an NYHA decrease in ≥1 class, and a ≥3 point increase in KCCQ score. The proportion of patients achieving the MCID in each treatment group was compared using Fisher's exact test, and the number needed to treat (NNT) with the Carillon device was calculated. Among 83 patients (62 Carillon and 21 sham), no statistically significant group differences were observed in the baseline characteristics. All outcomes at 1 year numerically favoured the Carillon group, including MCID for the 6MWT distance (59% vs. 23%, P = 0.029; NNT = 2.8), NYHA class (48% vs. 33%, P = 0.38; NNT = 6.9), KCCQ score (69% vs. 47%, P = 0.14; NNT = 4.5), and freedom from heart failure hospitalization or death (60% vs. 48%, P = 0.45; NNT = 8.3). Conclusions: REDUCE‐FMR was the first blinded sham‐controlled trial to report outcomes with percutaneous therapy for the treatment of FMR. Trends towards improvement in mean 6MWT distance, KCCQ score, and NYHA class were observed with the Carillon device. A substantially higher number of patients achieved MCID for all patient‐centred outcomes with the Carillon device compared with the sham procedure. [ABSTRACT FROM AUTHOR]

Background: Representation trends of women, older adults, and ethnic/racial minorities in randomized controlled trials (RCTs) of atrial fibrillation (AF) are uncertain. Methods: We systematically reviewed 134 AF related RCTs (phase II and III) encompassing 149,162 participants using Medline and ClinicalTrials.gov through April 2019 to determine representation trends of women, older patients (≥75 years), and ethnic/racial minorities. Weighted data on the prevalence of AF from epidemiological studies were used to compare the representation of the studied groups of interest in AF RCTs to their expected burden of the disease. Results: Only 18.7% of the RCTs reported proportion of older patients, and 12.7% RCTs reported ethnic/racial minorities. The proportions of women in RCTs versus general population were 35.2% and 35.1%, of Hispanics were 11.9% and 5.2%, of Blacks were 1.2% and 5.7%, of American Indian/Alaskans were 0.2% and 0.2%, of Asians were 14.2% and 2.4%, of native Hawaiian/Pacific Islanders were 0.05% and 0.1% and of non‐Whites were 19.5% and 22.5%, respectively. The weighted mean age (SD) across the trials was 65.3 (3.2) years which was less than the corresponding weighted mean age of 71.1 (4.5) years in the comparative epidemiological data. Conclusion: The reporting of older patients and ethnic/racial minorities was poor in RCTs of AF. The representation of women and American Indian/Alaskan natives matched their expected population share of disease burden. Hispanics and Asians were over‐represented and Blacks, native Hawaiian/Pacific Islanders and non‐Whites were under‐represented in RCTs of AF. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to investigate the reporting of subgroup analyses in heart failure (HF) randomized controlled trials (RCTs) and to determine the strength and credibility of subgroup claims. Methods and results: All primary HF RCTs published in nine high‐impact journals from 1 January 2008 to 31 December 2017 were included. Multivariable regression analysis was used to identify factors that may favour the reporting of results in specific subgroups. Strength of the subgroup effect claimed was classified into (i) strong, (ii) likely, or (iii) suggestive. Credibility of subgroup claim was scored using a pre‐specified 10 pointer criteria. Of the 261 HF RCTs studied, 107 (41%) reported subgroup analyses. Twenty‐five (23%) RCTs claimed a subgroup effect for the primary outcome of which six (24%) made a strong claim, eight (32%) claimed a likely effect, and 11 (44%) suggested a possible subgroup effect. Seven of the 25 RCTs did not employ interaction testing for subgroup claims of the primary outcome. Three out of 10 pre‐specified credibility criteria were satisfied by half of the trials. Fourteen trials justified the choice of subgroups, and 10 explicitly stated they were underpowered to detect differences within subgroups. Source of funding did not influence the frequency of reporting subgroup analyses (OR 0.53, 95% CI 0.78–3.62, P = 0.52). Conclusions: Appropriate credibility criteria were rarely met even by HF RCTs that held strong subgroup claims. Subgroup analyses should be pre‐specified, be adequately powered, present interaction terms, and be replicated in independent data before being integrated into clinical decision making. [ABSTRACT FROM AUTHOR]

Aims: Discontinuation or non‐publication of trials may hinder scientific progress and violates the commitment made to research participants. We sought to identify the prevalence of discontinuation and non‐publication of heart failure (HF) clinical trials. Methods and results: We conducted a cross‐sectional search of ClinicalTrials.gov to identify all completed and discontinued HF clinical trials. We limited our search to only include trials that were completed by 31 December 2017. Trials were investigated to identify reasons for discontinuation. Informative termination was defined as trial termination due to safety or efficacy concerns. Data pertaining to the trial phase, funding, intervention, enrolment, and trial completion date were extracted for each trial. A total of 572 trials were included. Of these, 21% (n = 118) were discontinued before completion. Patient accrual was the most frequently cited reason (n = 42; 36%) for trial discontinuation, followed by informative termination (n = 16; 14%) and funding (n = 14; 12%). Overall, 24 780 patients were enrolled in trials that were terminated. Of trials that were completed and not terminated, nearly one‐third (n = 131/454; 29%) were not published. Seventy‐nine (24%) trials were published within 12 months, 192 (59%) within 24 months, and 252 (78%) trials within 36 months. Conclusions: Discontinuation and non‐publication of HF trials is common. This raises ethical concerns towards participants who volunteer for research and are exposed to potential risks, inconvenience, and discomfort without furthering scientific progress. [ABSTRACT FROM AUTHOR]

Aims: We sought to conduct a meta‐analysis regarding the safety and efficacy of sodium‐glucose co‐transporter 2 (SGLT2) inhibitors in patients with heart failure (HF). Methods and results: MEDLINE, Scopus, Cochrane CENTRAL, and ClinicalTrials.gov were searched from their inception to November 2020 for placebo‐controlled randomized controlled trials of SGLT2 inhibitors. Randomized controlled trials were selected if they reported at least one of the prespecified outcomes in patients with HF. Hazard ratios (HRs) or risk ratios and their corresponding 95% confidence intervals were pooled using a random‐effects model. A total of seven trials including 16 820 HF patients (N = 8884 in the SGLT2 inhibitor arms; N = 7936 in the placebo arms) were included. In the overall HF cohort, SGLT2 inhibitors compared with placebo significantly reduced the risk of the composite endpoint of first HF hospitalization or cardiovascular death [HR: 0.77 (0.72–0.83); P < 0.001; I2 = 0%], time to first HF hospitalization [HR: 0.71 (0.64–0.78); P < 0.001; I2 = 0], cardiovascular mortality [HR: 0.87 (0.79–0.96); P = 0.005; I2 = 0%], and all‐cause mortality [HR: 0.89 (0.82–0.96); P = 0.004; I2 = 0%]. Results remained consistent across HF‐specific trials and according to diabetes mellitus status. A trend towards benefit was observed in patients with HF with preserved ejection fraction for the composite of HF hospitalization and cardiovascular death [HR: 0.80 (0.63–1.00); P = 0.05; I2 = 29%]. No increased risk of hypovolaemia, hyperkalaemia, and hypotension was seen with SGLT2 inhibitors compared with placebo. Conclusions: SGLT2 inhibitors significantly improve cardiovascular outcomes including cardiovascular and all‐cause mortality in patients with HF without an increased risk of serious adverse events. A trend towards benefit was observed in patients with HF with preserved ejection fraction. [ABSTRACT FROM AUTHOR]

Aims: Intravenous ferric carboxymaltose (FCM) has been shown to improve functional capacity and quality of life in iron deficient heart failure patients. However, FCM's effect on hospitalizations and mortality remains unclear as previous randomized controlled trials (RCTs) and their meta‐analyses have been underpowered to detect significant differences. We sought to conduct an updated meta‐analysis using recently published RCT data. Methods and results: Online databases were searched from inception until November 2020 for RCTs evaluating the effects of FCM on clinical outcomes in iron‐deficient heart failure patients. Outcomes of interest included heart failure hospitalizations, all‐cause mortality, and cardiovascular mortality. Meta‐analysis was performed using a fixed‐effect model and estimates were reported as odds ratios (ORs), hazard ratios, or rate ratios (RRs) along with corresponding 95% confidence intervals (CIs). A total of 1947 patients (n = 1062 in the FCM group; n = 885 in the placebo group) were included. FCM, compared with placebo, significantly reduced the risk of the composite endpoint of time to first heart failure hospitalization or cardiovascular death (hazard ratio = 0.76; 95% CI = 0.63–0.90; I2 = 55%). FCM also significantly reduced the risk of recurrent heart failure hospitalizations (RR = 0.68; 95% CI = 0.54–0.85; I2 = 71%) and recurrent cardiovascular hospitalizations (RR = 0.71; 95% CI = 0.59–0.86; I2 = 56%). However, FCM had no significant effect on the risk of all‐cause (OR = 0.97; 95% CI = 0.73–1.28; I2 = 0%) or cardiovascular mortality (OR = 0.93; 95% CI = 0.69–1.27; I2 = 0%). Conclusions: Ferric carboxymaltose reduces heart failure hospitalizations and cardiovascular hospitalizations with no beneficial effect on all‐cause and cardiovascular mortality in iron‐deficient heart failure patients. These findings reinforce the role of FCM as a therapeutic option in heart failure patients. [ABSTRACT FROM AUTHOR]

Aims: The primary objective of this systematic review was to estimate the prevalence and temporal changes in chronic comorbid conditions reported in heart failure (HF) clinical trials.Methods and Results: We searched MEDLINE for HF trials enrolling more than 400 patients published between 2001 and 2016.Trials were divided into HF with reduced ejection fraction (HFrEF), HF with preserved ejection fraction (HFpEF), or trials enrolling regardless of ejection fraction. The prevalence of baseline chronic comorbid conditions was categorized according to the algorithm proposed by the Chronic Conditions Data Warehouse, which is used to analyse Medicare data. To test for a trend in the prevalence of comorbid conditions, linear regression models were used to evaluate temporal trends in prevalence of comorbidities. Overall, 118 clinical trials enrolling a cumulative total of 215 508 patients were included. Across all comorbidities examined, data were reported in a mean of 35% of trials, without significant improvement during the study period. Reporting of comorbidities was more common in HFrEF trials (51%) compared with HFpEF trials (27%). Among trials reporting data, hypertension (63%), ischaemic heart disease (44%), hyperlipidaemia (48%), diabetes (33%), chronic kidney disease (25%) and atrial fibrillation (25%) were the major comorbidities. The prevalence of comorbidities including hypertension, atrial fibrillation and chronic kidney disease increased over time while the prevalence of smoking decreased in HFrEF trials.Conclusion: Many HF trials do not report baseline comorbidities. A more rigorous, systematic, and standardized framework needs to be adopted for future clinical trials to ensure adequate comorbidity reporting and improve recruitment of multi-morbid HF patients. [ABSTRACT FROM AUTHOR]

Aims: While the associations of health-related quality of life scores in heart failure (HF) [e.g. the Kansas City Cardiomyopathy Questionnaire (KCCQ)] with clinical outcomes are well established, their interpretation in the context of what magnitudes of change are clinically important to patients is less clear. The main objective of this study was to correlate the changes in the KCCQ and Patient Global Assessment (PGA) in patients with HF with reduced ejection fraction (HFrEF) to determine minimal clinically important difference (MCID).Methods and Results: We analysed data from 459 patients of the FAIR-HF trial. Both KCCQ and PGA were assessed at 4 and 24 weeks after enrolment. An anchor-based approach was used to calculate MCID at week 4 and 24. PGA was chosen as the clinical anchor against which changes in the KCCQ scores were calibrated. For each category of change in PGA, the corresponding differences were calculated by the mean scores of various domains of KCCQ along with 95% confidence intervals (CIs). There was fair correlation between PGA and changes in overall summary scores (OSS) (r = 0.31; P < 0.001), clinical summary scores (CSS) (r = 0.36; P < 0.001) and physical limitation scores (PLS) (r = 0.31; P < 0.001) from baseline to week 4. KCCQ OSS, CSS and PLS MCID for 'little improvement' at week 4 were 3.6 (1.0-6.2), 4.5 (1.8-7.2) and 4.7 (1.4-8.0) points, respectively. OSS, CSS and PLS MCID for 'little improvement' at week 24 were 4.3 (0.2-8.4), 4.5 (0.5-8.5) and 4.0 (-0.9-9.0) points, respectively.Conclusion: The MCID threshold for KCCQ score was generally consistent and numerically lower than the threshold of 5-point change considered for clinical outcome prognosis and were stable between 4 and 24 weeks. This suggests that even changes smaller than the traditional 5-point improvements in KCCQ may be clinically meaningful. Also, these results can aid in the clinical interpretation of patient-reported outcomes, and better endpoint selection in future studies. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is causing considerable morbidity and mortality worldwide. Multiple reports have suggested that patients with heart failure (HF) are at a higher risk of severe disease and mortality with COVID-19. Moreover, evaluating and treating HF patients with comorbid COVID-19 represents a formidable clinical challenge as symptoms of both conditions may overlap and they may potentiate each other. Limited data exist regarding comprehensive management of HF patients with concomitant COVID-19. Since these issues pose serious new challenges for clinicians worldwide, HF specialists must develop a structured approach to the care of patients with COVID-19 and be included early in the care of these patients. Therefore, the Heart Failure Association of the European Society of Cardiology and the Chinese Heart Failure Association & National Heart Failure Committee conducted web-based meetings to discuss these unique clinical challenges and reach a consensus opinion to help providers worldwide deliver better patient care. The main objective of this position paper is to outline the management of HF patients with concomitant COVID-19 based on the available data and personal experiences of physicians from Asia, Europe and the United States. [ABSTRACT FROM AUTHOR]

Aims: Left atrial (LA) mechanical function may play a significant role in the development and progression of heart failure with preserved ejection fraction (HFpEF). We performed a systematic review and meta-analysis to evaluate association of impaired LA function with outcomes in HFpEF.Methods and Results: Multiple databases were searched for original studies measuring different phases of LA function in HFpEF patients. Comparative LA function between HFpEF patients and healthy controls was assessed by pooling weighted mean differences (WMD). Adjusted hazard ratios (HRs) with 95% confidence intervals were pooled to evaluate the prognostic utility of LA function. Twenty-two studies (2 trials, 20 observational) comprising 1974 HFpEF patients and 751 healthy controls were included. HFpEF patients had decreased LA reservoir [WMD = -12.21% (-15.47, -8.95); P < 0.001], LA conduit [WMD = -5.68% (-8.56, -2.79); P < 0.001], and pump [WMD = -11.07% (-14.81, -7.34); P < 0.001] emptying fractions compared with controls. LA reservoir [WMD = -13.38% (-16.07, -10.68); P < 0.001], conduit [WMD = -4.09% (-6.77, -1.42); P = 0.003], and pump [WMD = -3.53% (-4.47, -2.59); P < 0.001] strains were also significantly lower in HFpEF patients. Decreased LA reservoir strain [HR 1.24 (1.02, 1.50); P = 0.03] was significantly associated with risk of composite all-cause mortality or heart failure hospitalization.Conclusions: Impaired LA function appears to have diagnostic and prognostic value in HFpEF, but whether indices of LA function truly refine discrimination for diagnosis or prognosis remains to be fully determined. Larger studies are needed to better evaluate associations between LA function and clinical outcomes and the role of LA function as a target for novel HFpEF therapies. [ABSTRACT FROM AUTHOR]