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Heart failure with preserved ejection fraction (HFpEF) is associated with high morbidity and mortality. Important risk factors for the development of HFpEF are similar to risk factors for the progression of tricuspid regurgitation (TR), and both conditions frequently coexist and thus is a distinct phenotype or a marker for advanced HF. Many patients with severe, symptomatic atrial secondary TR have been enrolled in current transcatheter device trials, and may represent patients at an advanced stage of HFpEF. Management of HFpEF thus may affect the pathophysiology of TR, and the physiologic changes that occur following transcatheter treatment of TR, may also impact symptoms and outcomes in patients with HFpEF. This review discusses these issues and suggests possible management strategies for these patients. [ABSTRACT FROM AUTHOR]

Iron deficiency and heart failure frequently co-occur, sparking clinical research into the role of iron repletion in this condition over the last 20 years. Although early nonrandomized studies and subsequent moderate-sized randomized controlled trials showed an improvement in symptoms and functional metrics with the use of intravenous iron, 3 recent larger trials powered to detect a difference in hard cardiovascular outcomes failed to meet their primary endpoints. Additionally, there are potential concerns related to side effects from intravenous iron, both in the short and long term. This review discusses the basics of iron biology and regulation, the diagnostic criteria for iron deficiency and the clinical evidence for intravenous iron in heart failure, safety concerns, and alternative therapies. We also make practical suggestions for the management of patients with iron deficiency and heart failure and outline key areas in need of future research. [Display omitted] • Iron deficiency and heart failure frequently occur concurrently and are associated with adverse cardiovascular outcomes. • Early trials of intravenous iron repletion in patients with heart failure found improvements in symptoms and functional capacity, but subsequent large trials failed to confirm objective consistent benefit. • Side effects of and alternatives to intravenous iron repletion warrant careful consideration. [ABSTRACT FROM AUTHOR]

Empagliflozin reduces the risk of heart failure (HF) hospitalizations but not all-cause mortality when started within 14 days of acute myocardial infarction (AMI). This study sought to evaluate the association of left ventricular ejection fraction (LVEF), congestion, or both, with outcomes and the impact of empagliflozin in reducing HF risk post-AMI. In the EMPACT-MI (Trial to Evaluate the Effect of Empagliflozin on Hospitalization for Heart Failure and Mortality in Patients with Acute Myocardial Infarction) trial, patients were randomized within 14 days of an AMI complicated by either newly reduced LVEF<45%, congestion, or both, to empagliflozin (10 mg daily) or placebo and were followed up for a median of 17.9 months. Among 6,522 patients, the mean baseline LVEF was 41 ± 9%; 2,648 patients (40.6%) presented with LVEF <45% alone, 1,483 (22.7%) presented with congestion alone, and 2,181 (33.4%) presented with both. Among patients in the placebo arm of the trial, multivariable adjusted risk for each 10-point reduction in LVEF included all-cause death or HF hospitalization (HR: 1.49; 95% CI: 1.31-1.69; P < 0.0001), first HF hospitalization (HR: 1.64; 95% CI: 1.37-1.96; P < 0.0001), and total HF hospitalizations (rate ratio [RR]: 1.89; 95% CI: 1.51-2.36; P < 0.0001). The presence of congestion was also associated with a significantly higher risk for each of these outcomes (HR: 1.52, 1.94, and RR: 2.03, respectively). Empagliflozin reduced the risk for first (HR: 0.77; 95% CI: 0.60-0.98) and total (RR: 0.67; 95% CI: 0.50-0.89) HF hospitalizations, irrespective of LVEF or congestion, or both. The safety profile of empagliflozin was consistent across baseline LVEF and irrespective of congestion status. In patients with AMI, the severity of left ventricular dysfunction and the presence of congestion was associated with worse outcomes. Empagliflozin reduced first and total HF hospitalizations across the range of LVEF with and without congestion. (Trial to Evaluate the Effect of Empagliflozin on Hospitalization for Heart Failure and Mortality in Patients with Acute Myocardial Infarction [EMPACT-MI]; NCT04509674) [Display omitted] [ABSTRACT FROM AUTHOR]

The Kidney Disease Improving Global Outcomes (KDIGO) classification integrates both estimated glomerular filtration rate and urine-albumin-creatinine ratio to stratify risk more comprehensively in patients with chronic kidney disease. There are limited data assessing whether this classification system is associated with prognosis and treatment response in heart failure populations. The aim of this study was to evaluate the relative treatment effects of sacubitril/valsartan across the KDIGO risk categories in patients with HFrEF. PARADIGM-HF (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) was a global randomized controlled trial evaluating sacubitril/valsartan vs enalapril in patients with heart failure with reduced ejection fraction (HFrEF). Patients were classified according to low, moderate, and high/very high KDIGO risk. Treatment responses were assessed according to baseline KDIGO risk. The primary outcome was a composite of cardiovascular (CV) death or heart failure hospitalization. A renal composite outcome was defined as sustained decline in estimated glomerular filtration rate by ≥40% or end-stage kidney disease. Among 1,910 (23% of total) participants with available data, 42%, 32%, and 26% were classified as low, moderate, and high/very high KDIGO risk, respectively. Patients in the highest KDIGO risk categories experienced the highest rates of the primary composite outcome (7.6 per 100 person-years [95% CI: 6.5-9.0 per 100 person-years], 9.4 per 100 person-years [95% CI: 7.9-11.2 per 100 person-years], and 14.9 per 100 person-years [95% CI: 12.7-17.6 per 100 person-years]; P < 0.001). Sacubitril/valsartan had a similar safety profile and demonstrated consistent effects on the risk of both the primary outcome (P Interaction = 0.31) and the renal composite outcome (P Interaction = 0.50) across the spectrum of KDIGO risk. One in 4 patients with HFrEF were classified as at least high KDIGO kidney risk; these individuals faced concordantly the highest risks of CV events. Sacubitril/valsartan exhibited consistent CV and kidney protective benefits as well as safety across the spectrum of baseline kidney risk. These data further support initiation of sacubitril/valsartan in HFrEF across a broad range of kidney risk. (This Study Will Evaluate the Efficacy and Safety of LCZ696 Compared to Enalapril on Morbidity and Mortality of Patients With Chronic Heart Failure [PARADIGM-HF]; NCT01035255) [Display omitted] [ABSTRACT FROM AUTHOR]

Sepsis fluid resuscitation is controversial, especially for patients with volume overload risk. The Surviving Sepsis Campaign recommends a 30-mL/kg crystalloid fluid bolus for patients with sepsis-induced hypoperfusion. Criticism of this approach includes excessive fluid resuscitation in certain patients. The aim of this study was to assess the efficacy and safety of guideline-concordant fluid resuscitation in patients with sepsis and heart failure (HF) or end-stage kidney disease (ESKD). A retrospective cohort study was conducted in patients with sepsis who qualified for guideline-directed fluid resuscitation and concomitant HF or ESKD. Those receiving crystalloid fluid boluses of at least 30 mL/kg within 3 h of sepsis diagnosis were placed in the concordant group and all others in the nonconcordant group. The primary outcome was in-hospital mortality. Secondary outcomes included intensive care unit (ICU) and hospital length of stay (LOS); vasoactive medications and net volume over 24 h; new mechanical ventilation, new or increased volume removal, and acute kidney injury within 48 h; and shock-free survival at 7 days. One hundred twenty-five patients were included in each group. In-hospital mortality was 34.4% in the concordant group and 44.8% in the nonconcordant group (p = 0.1205). The concordant group had a shorter ICU LOS (7.6 vs. 10.5 days; p = 0.0214) and hospital LOS (12.9 vs. 18.3 days; p = 0.0163), but increased new mechanical ventilation (37.6 vs. 20.8%; p = 0.0052). No differences in other outcomes were observed. Receipt of a 30-mL/kg fluid bolus did not affect outcomes in a cohort of patients with mixed types of HF and sepsis-induced hypoperfusion. [ABSTRACT FROM AUTHOR]

Conventional time-to-first-event analyses cannot incorporate recurrent hospitalizations and patient well-being in a single outcome. To overcome this limitation, we tested an integrated measure that includes days lost from death and hospitalization, and additional days of full health lost through diminished well-being. The effect of dapagliflozin on this integrated measure was assessed in the DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) trial, which examined the efficacy of dapagliflozin, compared with placebo, in patients with NYHA functional class II to IV heart failure and a left ventricular ejection fraction ≤40%. Over 360 days, patients in the dapagliflozin group (n = 2,127) lost 10.6 ± 1.0 (2.9%) of potential follow-up days through cardiovascular death and heart failure hospitalization, compared with 14.4 ± 1.0 days (4.0%) in the placebo group (n = 2,108), and this component of all measures of days lost accounted for the greatest between-treatment difference (−3.8 days [95% CI: −6.6 to −1.0 days]). Patients receiving dapagliflozin also had fewer days lost to death and hospitalization from all causes vs placebo (15.5 ± 1.1 days [4.3%] vs 20.3 ± 1.1 days [5.6%]). When additional days of full health lost (ie, adjusted for Kansas City Cardiomyopathy Questionnaire–overall summary score) were added, total days lost were 110.6 ± 1.6 days (30.7%) with dapagliflozin vs 116.9 ± 1.6 days (32.5%) with placebo. The difference in all measures between the 2 groups increased over time (ie, days lost by death and hospitalization −0.9 days [−0.7%] at 120 days, −2.3 days [−1.0%] at 240 days, and −4.8 days [−1.3%] at 360 days). Dapagliflozin reduced the total days of potential full health lost due to death, hospitalizations, and impaired well-being, and this benefit increased over time during the first year. (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure; NCT03036124) [Display omitted] [ABSTRACT FROM AUTHOR]

Hypotension is a potential adverse effect of sacubitril/valsartan, but there are limited data regarding the predictors and implications of treatment-related hypotension in heart failure (HF) with mildly reduced and preserved ejection fraction. We investigated predictors of treatment-associated hypotension, clinical outcomes after hypotension, and the relationship between left ventricular ejection fraction (LVEF) and incidence of hypotension in the PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in HF with Preserved Ejection Fraction) trial. PARAGON-HF randomized patients with chronic HF (≥45%) to sacubitril/valsartan or valsartan. Following randomization, hypotension was defined as investigator-reported hypotension with a systolic blood pressure <100 mm Hg. Predictors of hypotension were assessed using multivariable Cox models. Associations between hypotension and clinical outcomes were evaluated in time-updated Cox models. The relationship among treatment, LVEF, and incident rates of hypotension and clinical outcomes was estimated using Poisson regression models. Of 4,796 patients in PARAGON-HF, 637 (13%) experienced hypotension, more frequently in the sacubitril/valsartan arm (P < 0.001). Following documented hypotension, patients had higher risk of cardiovascular death and total HF hospitalizations (adjusted RR: 1.63; 95% CI: 1.27-2.09; P < 0.001) and all-cause death (adjusted HR: 1.62; 95% CI: 1.28-2.05; P < 0.001). LVEF modified the association between sacubitril/valsartan and risk of hypotension (P interaction = 0.019) such that patients with LVEF ≥60% experienced substantially higher treatment-related risks of hypotension. In PARAGON-HF, a higher LVEF was associated with an increased risk of hypotension in patients treated with sacubitril/valsartan compared with valsartan. Because these subjects are also less likely to derive clinical benefit from sacubitril/valsartan, our data reinforce that the benefit/risk ratio favors the use of sacubitril/valsartan in patients with LVEF below normal, but not at higher LVEF. (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711) [Display omitted] [ABSTRACT FROM AUTHOR]

Over the past two decades, several studies have been conducted that have tried to answer questions on management of patients with acute heart failure (AHF) in terms of diagnosis and treatment. Updated international clinical practice guidelines (CPGs) have endorsed the findings of these studies. The aim of this document was to adapt recommendations of existing guidelines to help internists make decisions about specific and complex scenarios related to AHF. The adaptation procedure was to identify firstly unresolved clinical problems in patients with AHF in accordance with the PICO (Population, Intervention, Comparison and Outcomes) process, then conduct a critical assessment of existing CPGs and choose recommendations that are most applicable to these specific scenarios. Seven PICOs were identified and CPGs were assessed. There is no single test that can help clinicians in discriminating patients with acute dyspnoea, congestion or hypoxaemia. Performing of echocardiography and natriuretic peptide evaluation is recommended, and chest X-ray and lung ultrasound may be considered. Treatment strategies to manage arterial hypotension and low cardiac output include short-term continuous intravenous inotropic support, vasopressors, renal replacement therapy, and temporary mechanical circulatory support. The most updated recommendations on how to treat specific patients with AHF and certain comorbidities and for reducing post-discharge rehospitalization and mortality are provided. Overall, 51 recommendations were endorsed and the rationale for the selection is provided in the main text. Through the use of appropriate tailoring process methodology, this document provides a simple and updated guide for internists dealing with AHF patients. [ABSTRACT FROM AUTHOR]

It has been postulated that cancer hampers the delivery of guideline-directed medical therapy (GDMT) for heart failure (HF). However, few data are available in this regard. We performed a retrospective analysis from the HF Outpatient Clinic of the IRCCS Ospedale Policlinico San Martino in Genova, Italy. All HF patients evaluated between 2010 and 2019, with a left ventricular ejection fraction <50% and at least two visits ≥3 months apart with complete information about GDMT were included in the study. We assessed the prescription of GDMT—in particular, beta-blockers (BB), renin-angiotensin system inhibitors (RASi), and mineralocorticoid antagonists (MRA)—at the time of the last HF evaluation and compared it between patients with and without incidental cancer. For those with incidental cancer, we also evaluated modifications of GDMT comparing the HF evaluations before and after cancer diagnosis. Of 464 HF patients, 39 (8%) had incidental cancer. There were no statistical differences in GDMT between patients with and without incidental cancer at last evaluation. In the year following cancer diagnosis, of 33 patients with incidental cancer on BB, none stopped therapy, but two had a down-titration to a dosage <50%; of 27 patients on RASi, two patients stopped therapy and three had a down-titration to a dosage <50%; of 19 patients on MRA, four stopped therapy. Although HF patients with incidental cancer may need to have GDMT down-titrated at the time of cancer diagnosis, this does not appear to significantly hinder the delivery of HF therapies during follow-up. [ABSTRACT FROM AUTHOR]

Central Illustration. Abbreviation: RSV – Respiratory Syncytial Virus. [Display omitted] • Simultaneous vaccination against RSV and Influenza virus among high-risk heart failure patients is safe. • Only small percentage of patients experienced reactions severe enough to prevent daily activities. • Simultaneous vaccination reduces patients contact with healthcare. The safety of simultaneous vaccination for Respiratory Syncytial Virus (RSV) and influenza in vulnerable high-risk heart failure (HF) patients remains unclear. In an open-label, prospective study, 105 patients received concurrent influenza (Vaxigrip Tetra, season 2023/2024, Sanofi) and RSV (Arexvy, GSK) vaccinations from September 15th to November 17th, 2023. Adverse events were collected on the fourth-day post-vaccination. Overall, the vaccination was well tolerated, with the most common reaction being injection site pain (63 %). General symptoms occurred in 33 % of patients, predominantly fatigue (23 %), myalgia (12 %), and headache (9 %). Grade 3 reactions were observed in 6 % of patients, and a few experienced temperature elevation or flu-like symptoms, managing them with antipyretics. Notably, there were no exacerbations of HF, hospitalizations, or deaths within a week post-vaccination. This study indicates the safety of simultaneous influenza and RSV vaccination in high-risk HF patients, with a low incidence of mild adverse events. [ABSTRACT FROM AUTHOR]

To examine the associations between cumulative depressive symptoms and subsequent mortality among patients hospitalized for acute hear failure (AHF). By using data from a prospective cohort study of patients with HF, depressive symptoms were measured by using Patient Health Questionnaire-2 (PHQ-2) at admission, 1-and 12-month after discharge. Cumulative depressive symptoms were interpreted by cumulative PHQ-2 score and cumulative times of depressive symptoms. Outcomes included subsequent 3-year all-cause and cardiovascular mortality. We included 2347 patients with the median follow-up of 4.4 (interquartile range [IQR]: 4.0–5.0) years. Tertile 3 of cumulative PHQ-2 score had the highest risk of all-cause (hazard ratio [HR]: 1.47, 95 % confidence interval [CI]: 1.21–1.78) and cardiovascular mortality (HR: 1.51, 95 % CI: 1.21–1.89) compared with Tertile 1; patients with≥2 times of depressive symptoms had the highest risk of all-cause (HR: 1.62, 95 % CI: 1.31–2.00) and cardiovascular mortality (HR: 1.60, 95 % CI: 1.25–2.05) compared with patients without any depressive symptom. Cumulative PHQ-2 score provided the highest level of incremental prognostic ability in predicting the risk of all-cause (C-statistics: 0.64, 95 % CI: 0.62–0.66) and cardiovascular mortality (C-statistics: 0.65, 95 % CI: 0.62–0.67) on the basis of Get With The Guidelines-Heart Failure score. Cumulative depressive symptoms were associated with the increased risk of subsequent mortality and provided incremental prognostic ability for the outcomes among patients with HF. Repeated depressive symptom measurements could be helpful to monitor long-term depressive symptoms, identify targeted patients and perform psychological interventions and social support to improve clinical outcomes among patients with AHF. • Cumulative depressive symptoms were associated with increased risk of all-cause and cardiovascular mortality among patients with acute heart failure in China. • Cumulative depressive symptoms provided incremental prognostic ability to predict mortality risk compared with GWTG-HF score. • Repeated depressive symptom measurements could be helpful to monitor long-term depressive symptoms in patients with acute heart failure. [ABSTRACT FROM AUTHOR]

Because signs of congestion are associated with adverse outcomes in patients with acute heart failure (AHF), attempts were made to decongest patients as much as possible with diuretic agents (loop diuretic agents, thiazides, acetazolamide) or mechanical devices. Those interventions improved signs of congestion but failed to meaningfully improve patients' symptoms, improve quality of life, or reduce early readmissions or deaths. Recent studies have shown that implementation of guideline-directed medical therapies after an AHF admission led to both more decongestion and improved symptoms, quality of life, and outcomes. Therefore, for most patients with AHF whose symptoms and congestion can be controlled with loop diuretic agents, the main focus should be rapid guideline-directed medical therapy uptitration. Enhanced decongestion, ie, adding a second-line diuretic agent to a loop diuretic agent, should be reserved for those patients who do not respond to loop diuretic agents. [Display omitted] • Congestion in patients with AHF is associated with poor outcomes and frequent hospital readmissions. • Enhanced decongestion leads to minimal improvement in symptoms or outcomes in patients with AHF. • Greater focus on GDMT after discharge can improve outcomes for patients hospitalized with AHF. [ABSTRACT FROM AUTHOR]

• The impact of mitral regurgitation (MR) in patients with advanced heart failure (HF) has not been extensively evaluated, yet. • Among 1079 unselected patients with HF and at least one "I NEED HELP" marker for advanced HF, severe MR was observed in 19.2% of patients and was independently with an increased risk of cardiovascular death and of recurrent HF hospitalizations. • Although our findings may represent a rationale for treating severe MR in advanced HF, randomized trials comparing invasive (i.e., percutaneous intervention) vs. conservative management in this setting are needed to confirm this hypothesis. The impact of mitral regurgitation (MR) in patients with advanced heart failure (HF) is poorly known. We aimed to evaluate the impact of MR on clinical outcomes of a real-world, contemporary, multicentre population with advanced HF. The HELP-HF registry enrolled patients with HF and at least one "I NEED HELP" criterion, at four Italian centres between January 2020 and November 2021. The population was stratified by none/mild MR vs. moderate MR vs. severe MR. Outcomes of interest were all-cause, cardiovascular (CV) death, the composite of all-cause death or first HF hospitalization, first HF hospitalization and recurrent HF hospitalizations. Among 1079 patients, 429 (39.8%) had none/mild MR, 443 (41.1%) had moderate MR and 207 (19.2%) had severe MR. Patients with severe MR were most likely to be inpatients, present with cardiogenic shock, need intravenous loop diuretics and inotropes/vasopressors, have lower ejection fraction and higher natriuretic peptides. Estimated rates of all-cause death, CV death, and the composite of all-cause death or first HF hospitalization at 1 year increased with increasing MR severity. Compared with no/mild MR, severe MR was independently associated with an increased risk of CV death (adjusted HR 1.61, 95% CI 1.04–2.51, p = 0.033) and recurrent HF hospitalizations (adjusted HR 1.49, 95% CI 1.08–2.06, p = 0.015), but not with and increased risk of all-cause death, first HF hospitalization and composite outcome. In unselected patients with advanced HF, severe MR was common and independently associated with an increased risk of CV death and of recurrent HF hospitalizations. [ABSTRACT FROM AUTHOR]

The efficacy and safety of sacubitril/valsartan in patients hospitalized with heart failure (HF) across the spectrum of left ventricular ejection fraction (EF) has not been described. Data from randomized trials of sacubitril/valsartan in HF patients with EF ≤40% (PIONEER-HF [Comparison of Sacubitril/Valsartan Versus Enalapril on Effect of NT-proBNP in Patients Stabilized From an Acute Heart Failure Episode] trial) and >40% (PARAGLIDE-HF [Prospective comparison of ARNI with ARB Given following stabiLization In DEcompensated HFpEF] trial) following recent worsening heart failure (WHF) were pooled to examine treatment effect across the EF spectrum. The PIONEER-HF and PARAGLIDE-HF trials were double-blind, randomized trials of sacubitril/valsartan vs control therapy (enalapril or valsartan, respectively). All participants in the PIONEER-HF trial and 69.5% in the PARAGLIDE-HF trial were enrolled during hospitalization for HF after stabilization. The remainder in the PARAGLIDE-HF trial were enrolled ≤30 days after a WHF event. The primary endpoint of both trials was time-averaged proportional change in N-terminal pro–B-type natriuretic peptide (NT-proBNP) from baseline through weeks 4 and 8. Adjudicated clinical endpoints were analyzed through the end of follow-up, adjusting for trial. The pooled analysis included 1,347 patients (881 from PIONEER-HF, 466 from PARAGLIDE-HF). Baseline characteristics included median age 66 years, 36% women, 31% Black, 34% de novo HF, and median EF 30%. The reduction in NT-proBNP was 24% greater with sacubitril/valsartan vs control therapy (n = 1,130; ratio of change = 0.76; 95% CI: 0.69-0.83; P < 0.0001). Cardiovascular death or hospitalization for HF was reduced by 30% with sacubitril/valsartan vs control therapy (HR: 0.70; 95% CI: 0.54-0.91; P = 0.0077). This effect was consistent across the spectrum of EF ≤60%. Sacubitril/valsartan increased symptomatic hypotension (risk ratio: 1.35; 95% CI: 1.05-1.72). In patients stabilized after WHF, sacubitril/valsartan led to a greater reduction in plasma NT-proBNP and improved clinical outcome compared with control therapy, in particular across the spectrum of EF ≤60%. (Comparison of Sacubitril/Valsartan Versus Enalapril on Effect of NT-proBNP in Patients Stabilized From an Acute Heart Failure Episode [PIONEER-HF]; NCT02554890 ; Changes in NT-proBNP, Safety, and Tolerability in HFpEF Patients With a WHF Event [HFpEF Decompensation] Who Have Been Stabilized and Initiated at the Time of or Within 30 Days Post-decompensation [PARAGLIDE-HF]; NCT03988634) [Display omitted] [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) and heart failure (HF) are common cardiovascular conditions that frequently coexist. Among patients with HF, more than one-half also have AF. Both are associated with significant morbidity and mortality. Moreover, the prevalence of each is increasing globally, and this trend is expected to continue owing to an aging population and increased life expectancy. Diagnosis of AF in a patient with HF is associated with greater symptom burden, more frequent hospitalizations, and a worse prognosis. Guideline-directed medical therapy (GDMT) for HF can affect the incidence of AF. Once present, AF can influence the efficacy of some components of GDMT for HF. In this review, we discuss the effect of GDMT for HF across the spectrum of ejection fraction on prevention of AF as well as the benefit of GDMT in patients with vs without AF. [Display omitted] • AF and HF commonly occur concurrently, and the combination is associated with worse prognosis than either condition alone. • GDMT for HF can reduce the incidence of AF. • Further research is needed to clarify the benefit of GDMT for HF in patients with concomitant AF across the range of left ventricular ejection fractions. [ABSTRACT FROM AUTHOR]

Heart failure (HF) with improved ejection fraction (HFimpEF) is a new category of HF introduced in the newest European Society of Cardiology guidelines. However, clinical characteristics and long-term outcomes of HFimpEF patients remain insufficiently elucidated. We sought to characterize Polish HFimpEF patients and determine their long-term mortality. Of 1186 patients enrolled in the single-center Lesser Poland Cracovian Heart Failure (LECRA-HF) registry between 2009 and 2019 and hospitalized due to HF decompensation, 340 (28.7%) were those with HF with reduced ejection fraction (HFrEF). Based on follow-up echocardiography, 61 (17.9%) of them were classified as HFimpEF and the remaining as HFnon-impEF. HFimpEF patients were more frequently females (P ​< ​0.001), had higher baseline left ventricular ejection fraction (LVEF, P ​< ​0.001), had less often a history of diabetes (P ​= ​0.024), severe chronic kidney disease (P ​= ​0.026) or prior myocardial infarction (P ​= ​0.008) than HFnon-impEF patients. By multivariable analysis the HFimpEF diagnosis was independently predicted by baseline NYHA I/II (odds ratio [OR] 2.347, 95% confidence interval [95%CI] 1.020–5.405), non-ischemic etiology (OR 3.096, 95%CI 1.587–6.024), lack of diabetes mellitus (OR 2.016, 95%CI 1.059–3.846) and higher baseline LVEF (OR 1.084, 95%CI 1.042–1.126, per 1%). Within the median 49 (25–77) months all-cause mortality was lower in HFimpEF than in HFnon-impEF (10.8 vs 16.4%/year, P ​= ​0.004). Our findings indicate that every sixth Polish patient with HFrEF has a chance to improve LVEF during follow-up and to become a HFimpEF patient. Baseline characteristics of HFimpEF patients are different from HFnon-impEF. Simultaneously, the HFimpEF diagnosis is associated with higher long-term survival. [ABSTRACT FROM AUTHOR]

The deleterious consequences of chronically elevated venous pressure in patients with profound right ventricular or biventricular dysfunction are well known, including renal and hepatic dysfunction, and volume overload. The only option for these patients, if they fail optimal medical treatment, is a heart transplant, as they are not candidates for left ventricular assist device therapy. Mean perfusion pressure (MPP) is important in the outcomes of critically ill patients with high venous pressure. The question arises whether MPP is important for the outcomes of heart transplants in patients with elevated pre-transplant venous pressure. Medical management of heart failure patients with reduced ejection fraction involves lowering the systemic afterload with vasodilators while awaiting a transplant. We hypothesised that when venous pressure is elevated prior to transplant, a substantial reduction in systemic arterial elastance (E a) through vasodilation may significantly decrease MPP, resulting in compromised end-organ function and consequent unfavourable outcomes after heart transplantation. This study aims to investigate whether a low MPP serves as a risk factor for adverse outcomes in heart transplant recipients with high venous pressure. A retrospective analysis was conducted on 250 heart transplant recipients undergoing isolated heart transplantation at a single institution from October 2012 to March 2020. Right atrial pressure (RAP) of more than 15 mmHg was considered high. Additionally, E a calculated as the ratio of end-systolic pressure to stroke volume, and MPP calculated as the difference between mean arterial pressure and RAP were considered in our analysis. The outcomes of transplantation were measured in terms of 90-day mortality and survival up to 7 years. High RAP was a significant risk factor for short-term and medium-term survival if E a was low (<2.7 mmHg/mL, the median value). This group had 39.39% in-hospital mortality compared to 14.49% for RAP<15 mmHg (p∼0.005). When E a was high, this difference in survival was not evident: 8% for RAP<15 mmHg vs 4.8% for RAP>15 mmHg (p∼0.550). This effect was mediated through a lower MPP, and the mortality due to lower MPP increased strikingly with higher body surface area (BSA). A negative correlation was observed between MPP indexed to BSA (MPPI) and the Model for End-Stage Liver Disease score (r∼-0.3580, p<0.0001) as well as creatinine (r∼-0.3551, p<0.0001). MPPI less than 40 mmHg/m2 was associated with poorer short-term (23.2% for MPPI<40 mmHg/m2 vs 7.1% for MPPI>40 mmHg/m2, p∼0.001) and medium-term survival. The impact of high RAP and low E a on survival was evident even on medium-term follow-up; only 30% survival at 7 years follow-up for high RAP and low E a vs 75% for RAP<15 mmHg (p∼0.0033). The acceptable blood pressure during vasodilator therapy in patients with high RAP needs to be higher, especially in those with higher BSA. MPPI less than 40 mmHg/m2 is a risk factor for survival, in the short and medium-term, after heart transplantation. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) coexists in up to 50% of heart failure (HF) patients, affecting both those with reduced ejection fraction (HFrEF) and those with preserved ejection fraction (HFpEF). Although the efficacy of several guideline-directed medical therapies (GDMT) has been well established, the treatment recommendations are similar for those patients with HF with and without CKD. We aimed to investigate the efficacy of GDMT in patients with HF with versus those without CKD. This systematic review and meta-analysis included randomised controlled trials that compared the efficacy of GDMT (angiotensin-converting enzyme inhibitor [ACE-I], beta blocker, sodium-glucose cotransporter-2 inhibitor, mineralocorticoid receptor antagonist, angiotensin receptor-neprilysin inhibitor) in patients with HF with and without CKD. The primary outcome was the composite of cardiovascular death and HF hospitalisation. Risk ratios (RR) were pooled using random-effects meta-analysis. A total of 19 trials (15 trials in HFrEF and four trials in HFpEF) enrolling 63,677 (38% had CKD) participants were included. Among HFrEF patients, GDMT reduced the primary endpoint in those with CKD (RR 0.77, 95% confidence interval [CI] 0.72–0.82) and without CKD (RR 0.79, 95% CI 0.74–0.84). Among HFpEF patients, the pooled summary RR for GDMT reducing the primary endpoint was 0.82 (95% CI 0.74–0.91) among those with CKD and 0.88 (95% CI 0.77–0.99) among those without CKD. There was no significant difference in the efficacy of GDMT in head-to-head comparisons between those with and without CKD in HFrEF (ratio of RR 0.97, 95% CI 0.88-1.06) and HFpEF (ratio of RR 0.94, 95% CI 0.80–1.11). Among patients with HF, GDMT had a consistent effect in reducing adverse cardiovascular events in those with and without CKD. Future studies should investigate the best strategy to ensure patients with HF with CKD receive and tolerate GDMT when indicated. [ABSTRACT FROM AUTHOR]

Trials evaluating implantable hemodynamic monitors to manage patients with heart failure (HF) have shown reductions in HF hospitalizations but not mortality. Prior meta-analyses assessing mortality have been limited in construct because of an absence of patient-level data, short-term follow-up duration, and evaluation across the combined spectrum of ejection fractions. The purpose of this meta-analysis was to determine whether management with implantable hemodynamic monitors reduces mortality in patients with heart failure and reduced ejection fraction (HFrEF) and to confirm the effect of hemodynamic-monitoring guided management on HF hospitalization reduction reported in previous studies. The patient-level pooled meta-analysis used 3 randomized studies (GUIDE-HF [Hemodynamic–Guided Management of Heart Failure], CHAMPION [CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Heart Failure Patients], and LAPTOP-HF [Left Atrial Pressure Monitoring to Optimize Heart Failure Therapy]) of implantable hemodynamic monitors (2 measuring pulmonary artery pressures and 1 measuring left atrial pressure) to assess the effect on all-cause mortality and HF hospitalizations. A total of 1,350 patients with HFrEF were included. Hemodynamic-monitoring guided management significantly reduced overall mortality with an HR of 0.75 (95% CI: 0.57-0.99); P = 0.043. HF hospitalizations were significantly reduced with an HR of 0.64 (95% CI: 0.55-0.76); P < 0.0001. Management of patients with HFrEF using an implantable hemodynamic monitor significantly reduces both mortality and HF hospitalizations. The reduction in HF hospitalizations is seen early in the first year of monitoring and mortality benefits occur after the first year. [Display omitted] [ABSTRACT FROM AUTHOR]

Heart failure with preserved ejection fraction (HFpEF) accounts for >50% of heart failure cases and is associated with significant morbidity and health system burden. To date, there have been limited treatment options proven to improve outcomes in these patients, with sodium glucose co-transporter 2 (SGLT2) inhibitors the first class of drug to demonstrate significant clinical benefits, including reductions in heart failure hospitalisation. Obesity is associated with all forms of heart failure and has been linked with worse clinical outcomes. Numerous reviews support the benefits of weight loss in heart failure, more specifically in patients with heart failure with reduced ejection fraction. However, the evidence in HFpEF patients is less clear. With limited pharmacotherapy options and growing support for weight loss in patients with HFpEF, this systematic review and meta-analysis aims to examine the effects of lifestyle interventions on weight loss and other health outcomes in patients with HFpEF. Web of Science, Embase, Scopus, and PubMed databases were searched to identify relevant studies up to February 2023. Included studies were randomised controlled trials (with a duration of four weeks or more) of lifestyle interventions conducted in adults with HFpEF that reported weight loss. Outcomes of interest were body weight, body mass index (BMI), blood pressure (systolic and diastolic), aerobic capacity (6-minute walk distance), New York Heart Association (NYHA) Functional Classification, self-reported health quality of life (Minnesota Living with Heart Failure Questionnaire; MLHFQ), and N-terminal pro B-Type Natriuretic Peptide (NT-proBNP) levels. Review Manager software was used to conduct random effect meta-analyses, forest plots were generated for each outcome, and between-study heterogeneity was estimated using the I2 test statistic. Risk-of-bias assessment used the Cochrane risk-of-bias tool, and the certainty of the evidence was assessed using GRADE. From 2,282 records identified, six studies with a total of 375 participants, between three to six months in duration, were included in this systematic review and meta-analysis. Lifestyle interventions consisted of diet only, exercise only, combination of diet and exercise, and education and exercise. Over a mean follow-up of 4.5 months, pooled effects of the interventions were associated with a reduction in body weight of >5kg (weight mean difference (WMD): −5.30 kg; 95% CI: −8.72 to −1.87; p=0.002), and a reduction in resting systolic (WMD: −2.98 mmHg; 95% CI: −4.20 to −1.76; p<0.001) and diastolic blood pressure (WMD: −4.51 mmHg; 95% CI: −8.39 to −0.64; p=0.02) compared with those who received usual care. Interventions also improved 6-minute walk distance (WMD: 43.63 m; 95% CI: 22.28 to 64.97; p<0.001), NYHA class (WMD: −0.54; 95% CI: −0.75 to −0.33; p<0.001), and MLHFQ score (WMD: −17.77; 95% CL: −19.00 to −16.53; p<0.001). In patients with HFpEF, lifestyle intervention was associated with a significant reduction in body weight and had favourable effects on blood pressure, aerobic capacity, NYHA class, and health-related quality of life. Further research is needed in this population to examine the feasibility and durability of weight loss interventions and to examine the potential impact on hard clinical endpoints. [ABSTRACT FROM AUTHOR]

Mitral valve transcatheter edge-to-edge repair (MTEER) was approved in the United States for treatment of functional mitral regurgitation (FMR) based on results from the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial. The authors sought to analyze outcomes of MTEER in FMR patients who would have been excluded from COAPT. MTEER procedures performed for FMR in the TVT (Transcatheter Valve Therapy) Registry between January 1, 2013, and April 30, 2020, were categorized as "trial-ineligible" if any of the following were present: cardiogenic shock, inotropic support, left ventricular ejection fraction <20%, left ventricular end-systolic dimension >7 cm, home oxygen use, or severe tricuspid regurgitation. Trial-ineligible and trial-eligible groups were compared through 1 year using multivariable models. The primary endpoint was 1-year death or heart failure hospitalization (HFH). Of 6,675 patients who underwent MTEER for FMR, 3,721 (55.7%) were trial-eligible and 2,954 (44.3%) were trial-ineligible. Trial-ineligible patients had lower rates of technical procedural success (86.9% vs 92.6%; P < 0.001) and more frequent in-hospital complications (11.8% vs 5.7%; P < 0.001) compared with trial-eligible patients. A clinically meaningful improvement in health status at 30 days was observed in 78.9% and 77.0% of patients in the trial-ineligible and trial-eligible groups, respectively. There was a higher risk of 1-year death or HFH (HR: 1.73; 95% CI: 1.57-1.91; P < 0.001) in trial-ineligible patients. Among patients who underwent MTEER for FMR in the TVT Registry, nearly one-half would have been ineligible for the COAPT trial. Health status improvement at 30 days was similar in COAPT-ineligible and COAPT-eligible patients, but trial-ineligible patients had higher 1-year rates of death or HFH. [Display omitted] [ABSTRACT FROM AUTHOR]

Sleep-disordered breathing (SDB) is a common comorbidity in patients with heart failure (HF) and is associated with worse prognosis. This study evaluated the effects of adaptive servo-ventilation (ASV) on morbidity and mortality in a large heterogeneous population of HF patients with different etiologies/phenotypes. Consecutive HF patients with predominant central sleep apnea (± obstructive sleep apnea) indicated for ASV were included; the control group included patients who refused or stopped ASV before three months follow-up. Six homogenous clusters were determined using the latent class analysis (LCA) method. The primary endpoint was time to composite first event (all-cause death, lifesaving cardiovascular intervention, or unplanned hospitalization for worsening of chronic HF). Of 503 patients at baseline, 324 underwent 2-year follow-up. Compared to control group, 2-year primary endpoint event-free survival was significantly greater in patients in ASV group only in univariable analysis (1.67, 95% [1.12–2.49]; p = 0.01). Secondary endpoints, event-free of cardiovascular death or heart failure-related hospitalization and all-cause death or all-cause hospitalization were positively impacted by ASV (univariate and multivariable analysis). LCA identified two groups, with preserved and mid-range left ventricular ejection fraction (LVEF) and severe hypoxia, in whom ASV increase prognosis benefit. Patients with HF and SDB are a highly heterogeneous group identified using LCA. Systematic deep phenotyping is essential to ensure that ASV is prescribed to those benefit from therapy, as ASV use in patients with severe hypoxic burden and those with HFpEF was associated with a significant reduction in cardiovascular events and mortality. https://clinicaltrials.gov/ct2/show/NCT01831128. [Display omitted] • Sleep-disordered breathing (SDB) worsens prognosis in heart failure (HF) patients, large RCT have failed to find benefit of treating SDB in HF. • Latent class analysis based on baseline assessment data from the FACE study categorized patients into six clusters with different prognosis. • 2-year follow-up analysis showed that specific phenotypes of patients have a beneficial impact of Adaptive servo ventilation (ASV) on prognosis. • These include HF patients with hypoxic burden, obesity, central and obstructive SDB and either with mid-range and or preserved ejection fraction. • Thus, careful patient selection and phenotyping can be used to ensure that ASV is prescribed to patients most likely to benefit from therapy. [ABSTRACT FROM AUTHOR]

• The impact of asymptomatic atrial fibrillation (AF) in different types of clinical heart failure (HF) is not well established. • We analysed real-world AF patients stratified according to symptomatic status, clinical HF and left ventricular ejection fraction (LVEF). • Asymptomatic AF accounts for a substantial percentage of patients (43-48 %), with similar proportions among the groups stratified for HF status and LVEF. • Asymptomatic AF in patients with HF and reduced LVEF had clear negative implications for outcomes at long-term. The outcome implications of asymptomatic vs. symptomatic atrial fibrillation (AF) in specific groups of patients according to clinical heart failure (HF) and left ventricular ejection fraction (LVEF) need to be clarified. In a prospective observational study, patients were categorized according to overt HF with LVEF≤40 %, or with LVEF>40 %, or without overt HF with LVEF40 %≤ or > 40 %, as well as according to the presence of asymptomatic or symptomatic AF. A total of 8096 patients, divided into 8 groups according to HF and LVEF, were included with similar proportions of asymptomatic AF (ranging from 43 to 48 %). After a median follow-up of 730 [699 -748] days, the composite outcome (all-cause death and MACE) was significantly worse for patients with asymptomatic AF associated with HF and reduced LVEF vs. symptomatic AF patients of the same group (p = 0.004). On adjusted Cox regression analysis, asymptomatic AF patients with HF and reduced LVEF were independently associated with a higher risk for the composite outcome (aHR 1.32, 95 % CI 1.04-1.69) and all-cause death (aHR 1.33, 95 % CI 1.02-1.73) compared to symptomatic AF patients with HF and reduced LVEF. Kaplan-Meier curves showed that HF-LVEF≤40 % asymptomatic patients had the highest cumulative incidence of all-cause death and MACE (p < 0.001 for both). In a large European cohort of AF patients, the risk of the composite outcome at 2 years was not different between asymptomatic and symptomatic AF in the whole cohort but adverse implications for poor outcomes were found for asymptomatic AF in HF with LVEF≤40 %. [ABSTRACT FROM AUTHOR]

The lack of disease-modifying drugs is one of the major unmet needs in patients with heart failure (HF). Peptides are highly selective molecules with the potential to act directly on cardiomyocytes. However, a strategy for effective delivery of therapeutics to the heart is lacking. In this study, the authors sought to assess tolerability and efficacy of an inhalable lung-to-heart nano-in-micro technology (LungToHeartNIM) for cardiac-specific targeting of a mimetic peptide (MP), a first-in-class for modulating impaired L-type calcium channel (LTCC) trafficking, in a clinically relevant porcine model of HF. Heart failure with reduced ejection fraction (HFrEF) was induced in Göttingen minipigs by means of tachypacing over 6 weeks. In a setting of overt HFrEF (left ventricular ejection fraction [LVEF] 30% ± 8%), animals were randomized and treatment was started after 4 weeks of tachypacing. HFrEF animals inhaled either a dry powder composed of mannitol-based microparticles embedding biocompatible MP-loaded calcium phosphate nanoparticles (dpCaP-MP) or the LungToHeartNIM only (dpCaP without MP). Efficacy was evaluated with the use of echocardiography, invasive hemodynamics, and biomarker assessment. DpCaP-MP inhalation restored systolic function, as shown by an absolute LVEF increase over the treatment period of 17% ± 6%, while reversing cardiac remodeling and reducing pulmonary congestion. The effect was recapitulated ex vivo in cardiac myofibrils from treated HF animals. The treatment was well tolerated, and no adverse events occurred. The overall tolerability of LungToHeartNIM along with the beneficial effects of the LTCC modulator point toward a game-changing treatment for HFrEF patients, also demonstrating the effective delivery of a therapeutic peptide to the diseased heart. [Display omitted] [ABSTRACT FROM AUTHOR]

Acute decompensated heart failure involves a high rate of mortality and complications. Management typically involves a multi-day hospital admission. However, patients often lose part of their function with each successive admission, and are at a high risk for hospital-associated complications such as nosocomial infection. This study aims to determine the safety and efficacy of the management of patients presenting with acute decompensated heart failure to clinic-based therapy vs usual inpatient care using a reproducible management pathway. An investigator-initiated, prospective, non-inferiority, 1:1 randomised-controlled trial, stratified by left ventricular ejection fraction including 460 patients with a minimum follow-up of 7 days. This is a multi-centre study to be performed in centres across Victoria, Australia. Participants will be patients with either heart failure with reduced ejection fraction (HFrEF) or heart failure with preserved ejection fraction (HFpEF), admitted for acute decompensation of heart failure. Intervention: Early discharge to an outpatient-based Heart Failure Rapid Access Clinical Review (RACER) in addition to frequent medical/nursing at-home review for patients admitted with decompensated heart failure. The primary endpoint will be a non-inferiority assessment of re-hospitalisation at 30 days. Secondary outcomes include superiority assessment of hospitalisation at 30 days, a composite clinical endpoint of major adverse cardiac and cerebrovascular event (MACCE), hospital re-admission or mortality at 3 months, achievement of guideline-directed medical therapy, patient assessment of symptoms (visual-analogue scale quantified as area under curve and Kansas City Cardiomyopathy Questionnaire-12 [KCCQ-12]), attendance at 3-month outpatient follow-up, number of bed stays/clinics attended, proportion of patients free from congestion, change in serum creatinine level, treatment for electrolyte disturbances, time to transition from intravenous to oral diuretics, and health economics analysis (cost-benefit analysis, cost-utility analysis, incremental cost-effectiveness ratio). The Early Discharge to Clinic-Based Therapy of Patients Presenting with Decompensated Heart Failure (EDICT-HF) trial will help determine whether earlier discharge to out-of-hospital care is non-inferior to the usual practice of inpatient care, in patients with heart failure admitted to hospital for acute decompensation, as an alternative model of care. [ABSTRACT FROM AUTHOR]

• Hyperkalaemia is associated with increased mortality risk in patients with chronic heart failure. • Rapid changes in plasma potassium could be considered both a risk factor or a risk marker for increased mortality in patients with heart faliure. • It is essential to avoid overcorrection of hyperkalaemia and thereby risk patients getting hypokalaemic or borderline hypokalaemic. • The optimal plasma-potassium level is 4.7 mmol/L in patients with chronic HF. There is an increasing prevalence of chronic heart failure (HF). It is well known that patients with HF and disturbances in the potassium level have an increased mortality risk. The aim of this study was to investigate the prognosis of a second plasma-potassium measurement after an episode with hyperkalaemia on short-term mortality in patients with chronic HF. From Danish national registers, 2,339 patients with chronic HF and hyperkalaemia (>4.6 mmol/L) at first potassium measurement within 14–365 days from concomitant treatment were identified. To be included, a second measurement was required within 6–30 days subsequent to the first measurement and the 60-day mortality was observed. Based on the second measurement, the patients were divided into five groups: <3.5 mmol/L (n = 257), 3.5–4.0 mmol/L (n = 709), 4.1–4.6 mmol/L (n = 1,204, reference), 4.7–5.0 mmol/L (n = 89) and >5.0 mmol/L (n = 80). To assess all-cause and cardiovascular mortality, we used the Cox regression model. The multivariable analysis showed that patients with potassium concentrations <3.5 mmol/L (hazard ratio (HR): 3.03; 95% CI: 2.49–3.70) and 3.5–4.0 mmol/L (HR: 1.81; 95% CI: 1.54–2.14) had a worse prognosis compared to the reference. We observed similar results when calculating the risk of cardiovascular mortality. A restricted cubic spline curve showed a U-shaped relationship between plasma-potassium and all-cause mortality. Patients with chronic HF and hyperkalaemia who became hypokalaemic after 6–30 days were associated with a higher 60-day all-cause and cardiovascular mortality compared to the reference. This also applied for patients with low normal potassium concentrations (3.5–4.0 mmol/L). [ABSTRACT FROM AUTHOR]

Acute heart failure (AHF) is a common condition evaluated in the emergency department (ED). Patients may present with a wide range of signs and symptoms, comorbidities, exacerbating factors, and ability to follow-up. Having a decision tool to objectively assess the risk of near-term events would help guide disposition decisions in these patients. What are the data for current tools used to determine the short-term risk of adverse events of patients with AHF in the ED setting? Studies retrieved included six prospective studies and three retrospective cohort studies that evaluated the following five different risk scores that may predict the risk of serious adverse events in those with AHF: Ottawa Heart Failure Risk Score (OHFRS), Emergency Heart Failure Mortality Risk Grade (EHMRG), EHMRG at 30 days with addition of an ST depression variable (EHMRG30-ST), Multiple Estimation of Risk Based on the Emergency Department Spanish 40 Score in Patients with AHF Score (MEESSI-AHF), and the Improving Heart Failure Risk Stratification in the ED (STRATIFY) tool. Based on the available literature, risk scores, including the OHFRS; EHMRG; EHMRG30-ST; MEESSI-AHF; and STRATIFY, can help identify short-term risk of adverse events, but are insufficient in isolation. Clinicians should use these tools in conjunction with other factors, such as the patient's symptom trajectory, hemodynamics, and access to follow-up care. [ABSTRACT FROM AUTHOR]

Many therapies for heart failure (HF) have shown differential impact across the spectrum of left ventricular ejection fraction (LVEF). In this prespecified analysis, the authors assessed the effects of semaglutide across the baseline LVEF strata in patients with the obesity phenotype of HF with preserved ejection fraction (HFpEF) in the STEP-HFpEF (Semaglutide Treatment Effect in People with obesity and HFpEF) trial. STEP-HFpEF randomized 529 patients (263 semaglutide; 266 placebo). For this prespecified analysis, patients were categorized into 3 groups based on LVEF: 45% to 49% (n = 85), 50% to 59% (n = 215), and ≥60% (n = 229). At 52 weeks, semaglutide improved the dual primary endpoints of Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (estimated treatment difference: EF [ejection fraction] 45%-49%: 5.0 points [95% CI: −2.7 to 12.8 points], EF 50%-59%: 9.8 points [95% CI: 5.0 to 14.6 points], and EF ≥60%: 7.4 points [95% CI: 2.8 to 12.0 points]; P interaction = 0.56) and body weight (EF: 45%-49%: −7.6 [95% CI: −10.7 to −4.4], EF 50%-59%: −10.6 [95% CI: −12.6 to −8.6] and EF ≥60%: −11.9 [95% CI: −13.8 to −9.9]; P interaction = 0.08), to a similar extent across LVEF categories. Likewise, LVEF did not influence the benefit of semaglutide on confirmatory secondary endpoints: 6-minute walk distance (P interaction = 0.19), hierarchal composite endpoint (P interaction = 0.43), and high-sensitivity C-reactive protein (P interaction = 0.26); or exploratory endpoint of N-terminal pro-brain natriuretic peptide (P interaction = 0.96). Semaglutide was well-tolerated across LVEF categories. In patients with HFpEF and obesity, semaglutide 2.4 mg improved symptoms, physical limitations, and exercise function, and reduced inflammation and body weight to a similar extent across LVEF categories. These data support treatment with semaglutide in patients with the obesity phenotype of HFpEF regardless of LVEF. (Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity [STEP-HFpEF]; NCT04788511) [Display omitted] [ABSTRACT FROM AUTHOR]

Despite major advances in pharmacological treatment for patients with heart failure, residual mortality remains high. This suggests that important pathways are not yet targeted by current heart failure therapies. We sought integration of genetic, transcriptomic, and proteomic data in a large cohort of patients with heart failure to detect major pathways related to progression of heart failure leading to death. We used machine learning methodology based on stacked generalization framework and gradient boosting algorithms, using 54 clinical phenotypes, 403 circulating plasma proteins, 36,046 transcript expression levels in whole blood, and 6 million genomic markers to model all-cause mortality in 2,516 patients with heart failure from the BIOSTAT-CHF (Systems BIOlogy Study to TAilored Treatment in Chronic Heart Failure) study. Results were validated in an independent cohort of 1,738 patients. The mean age of the patients was 70 years (Q1-Q3: 61-78 years), 27% were female, median N-terminal pro–B-type natriuretic peptide was 4,275 ng/L (Q1-Q3: 2,360-8,486 ng/L), and 7% had heart failure with preserved ejection fraction. During a median follow-up of 21 months, 657 (26%) of patients died. The 4 major pathways with a significant association to all-cause mortality were: 1) the PI3K/Akt pathway; 2) the MAPK pathway; 3) the Ras signaling pathway; and 4) epidermal growth factor receptor tyrosine kinase inhibitor resistance. Results were validated in an independent cohort of 1,738 patients. A systems biology approach integrating genomic, transcriptomic, and proteomic data identified 4 major pathways related to mortality. These pathways are related to decreased activation of the cardioprotective ERBB2 receptor, which can be modified by neuregulin. [Display omitted] [ABSTRACT FROM AUTHOR]

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are guideline recommended in the management of heart failure (HF). Although these therapies can be initiated even in patients with comorbid chronic kidney disease, some patients may face deterioration of kidney function over time. In this study, the authors sought to examine the safety and efficacy of continuing SGLT2 inhibitors in HF when the estimated glomerular filtration rate (eGFR) falls below thresholds for initiation. Associations between a deterioration of eGFR to <25 mL/min/1.73 m2, efficacy, and safety outcomes and treatment with dapagliflozin were evaluated in time-updated Cox proportional hazard models in a participant-level pooled analysis of the DAPA-HF (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure) and DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure) trials. Among 11,007 patients, 347 (3.2%) experienced a deterioration of eGFR to <25 mL/min/1.73 m2 at least once in follow-up. These patients had a higher risk of the primary composite outcome (HR: 1.87; 95% CI: 1.48-2.35; P < 0.001). The risk of the primary outcome was lower with dapagliflozin compared with placebo among patients who did (HR: 0.53; 95% CI: 0.33-0.83) as well as did not (HR: 0.78; 95% CI: 0.72-0.86) experience deterioration of eGFR to <25 mL/min/1.73 m2 (P interaction = 0.17). The risk of safety outcomes, including drug discontinuation, was higher among patients with deterioration of eGFR to <25 mL/min/1.73 m2; however, rates remained similar between treatment groups including among those who remained on study drug. Patients with deterioration of eGFR to <25 mL/min/1.73 m2 had elevated risks of cardiovascular outcomes yet appeared to benefit from continuation of dapagliflozin with no excess in safety outcomes between treatment groups. The benefit-to-risk ratio may favor continuation of dapagliflozin treatment in patients with HF experiencing deterioration of kidney function. Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure [DAPA-HF]; NCT03036124 ; and Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure [DELIVER]; NCT03619213) [Display omitted] [ABSTRACT FROM AUTHOR]

• A discrepancy exists between mitral valve lesion severity and hemodynamic burden of sMR. • For a given EROA or RVol, regurgitant fraction depends on LV stroke volume value. • Aortic stiffness (PWV) is an important determinant of forward LV stroke volume. • An association was observed between PWV and parameters of MR quantification. • Higher PWV was associated with an out of proportion RF for a given value of EROA. By the framework of proportionate/disproportionate secondary mitral regurgitation (sMR), disproportionate sMR is characterized by a low left ventricular stroke volume (SV) and an out of proportion regurgitant fraction (RF) for the same effective regurgitant orifice area (EROA). The degree of aortic stiffness is a determinant of the ventricular forward SV. We aim to analyze the importance of aortic stiffness in influencing the discrepancy between measures of mitral valve lesion severity (EROA) and sMR hemodynamic burden (regurgitant volume [RV] and RF). We enrolled stable patients with heart failure with reduced ejection fraction (HFrEF) and at least mild sMR. Mitral EROA, RV, RF and aortic pulse wave velocity (PWV) were measured by echocardiography. We defined three groups based on the degree of actual RF deviation from RF estimated by the linear regression equation of RF on EROA (concordant, low-discordant [residuals lower-than -5%] and high-discordant RF [residuals higher-than 5%]). 117 patients were analyzed (68±13 years; female 30%; LVEF 33±8%; EROA 16±12mm2; RV 24±15 ml; RF 27±13%; PWV 6.6 ± 3.2 m/s). LVEF, end-diastolic-volume and EROA didn't differ among groups. PWV and RV were higher in patients with high-discordant RF (p ≤ 0.01), whereas total left ventricular-SV and left ventricular outflow tract-SV (LVOT-SV) were lower (p ≤ 0.0004). PWV was associated with LVOT-SV (r =-0.3; p = 0.0008) and RV (r = 0.3; p = 0.0009). High-discordant RF was predicted by PWV (p = 0.001) independently of LVOT-SV and RV. In this HFrEF cohort with sMR, higher PWV was associated with higher-than-expected RF for a given EROA. Aortic stiffness might play a role in the discrepancy between mitral valve lesion severity and sMR hemodynamic burden. [Display omitted] [ABSTRACT FROM AUTHOR]

N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a cardiac biomarker with diagnostic and prognostic utility in patients with heart failure (HF). Whether NT-proBNP can be used to triage inpatient transthoracic echocardiogram (TTE) requirements, and whether this impacts hospital length of stay (LOS), is not clear. Clinical and biochemical data were prospectively recorded on all inpatients at Wollongong Hospital, NSW, Australia, who had a TTE ordered for suspected HF over a 6-month period. NT-proBNP was used to triage TTE priority, where high-priority inpatient TTE, lower-priority inpatient TTE and outpatient (OP) TTE were performed for serum NT-proBNPs of ≥900, 300–899 and <300, respectively. Outcomes were compared with a baseline cohort of HF inpatients in whom TTE requirement was not guided by NT-proBNP. A total of 236 patients were evaluated—31, 31, and 174 in the low, intermediate and high NT-proBNP cohorts, respectively, and 199 patients were in the baseline cohort. Average hospital LOS was significantly reduced in the study cohort compared to baseline (9.97 vs 13.87 days, p<0.001). Of the 31 patients with a very low NT-proBNP who were discharged for OP TTE, seven were readmitted within 30 days, though none were HF-related. There were no deaths at 30 days in the low or intermediate NT-proBNP groups. Using NT-proBNP to triage requirements for inpatient TTE reduces hospital LOS. A very low NT-proBNP may help identify which patients with suspected HF can be safely discharged for OP TTE. • N-terminal pro-B-type natriuretic peptide (NT-proBNP) can be used to triage requirements for inpatient transthoracic echocardiogram. • Triaging patients with NT-proBNP reduces hospital length of stay and costs. • No increased adverse events resulted from a biomarker-based strategy. [ABSTRACT FROM AUTHOR]

Real-world applicability of the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) randomized controlled trial (RCT) has been debated because of careful patient selection and the contrasting results of the MITRA-FR (Multicentre Study of Percutaneous Mitral Valve Repair MitraClip Device in Patients with Severe Secondary Mitral Regurgitation) RCT. The COAPT-PAS (COAPT Post-Approval Study) was initiated to assess the safety and effectiveness of the MitraClip in patients with secondary mitral regurgitation (SMR). COAPT-PAS is a prospective, single-arm, observational study of 5,000 consecutive patients with SMR treated with the MitraClip at 406 U.S. centers participating in the TVT (Transcatheter Valve Therapy) registry from 2019 to 2020. The 1-year outcomes from the COAPT-PAS full cohort and the COAPT-like and MITRA-FR–like subgroups who met RCT inclusion/exclusion criteria are reported. Patients in the COAPT-PAS had more comorbidities, more severe HF and functional limitations, and less guideline-directed medical therapy than those in the COAPT or MITRA-FR RCTs. Patients in the COAPT-PAS full cohort and the COAPT-like (n = 991) and MITRA-FR–like (n = 917) subgroups achieved a 97.7% MitraClip implant rate, a similar and durable reduction of mitral regurgitation to ≤2+ at 1 year (90.7%, 89.7%, and 86.6%, respectively), a large improvement in quality of life at 1 year (Kansas City Cardiomyopathy Questionnaire +29 COAPT-PAS, +27 COAPT-like, and +33 MITRA-FR–like), faster procedure times, similar or lower clinical event rates compared with the RCTs' MitraClip arms, and lower clinical event rates than the RCTs' guideline-directed medical therapy only arms. One-year heart failure hospitalizations was 18.9% in COAPT-PAS, 19.7% in COAPT-like compared with 24.9% in COAPT-RCT, and 28.7% in COAPT-PAS-MITRA-FR–like compared with 47.4% in MITRA-FR-RCT. This large, contemporary, real-world study reinforces the safety and effectiveness of the MitraClip System in patients with SMR, including those who met the COAPT or MITRA-FR RCT inclusion/exclusion criteria and patients excluded from the RCTs. [Display omitted] [ABSTRACT FROM AUTHOR]

Because clinical characteristics and prognosis vary by geographic region in patients with heart failure (HF), the response to treatment may also vary. A previous report suggested that the efficacy of sodium-glucose cotransporter-2 inhibitor efficacy in heart failure with reduced ejection fraction (HFrEF) may be modified by region. The goal of this study was to examine the efficacy and safety of dapagliflozin in patients with HF according to geographic region. We conducted a patient-level pooled analysis of the DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) and DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure) trials, which evaluated the effects of dapagliflozin in HFrEF and heart failure with mildly reduced ejection fraction (HFmrEF)/heart failure with preserved ejection fraction (HFpEF), respectively. The primary outcome was the composite of worsening HF or cardiovascular death. Among 11,007 patients, 5,159 (46.9%) were enrolled in Europe, 1,528 (13.9%) in North America, 1,998 (18.2%) in South America, and 2,322 (21.1%) in Asia. The rate of the primary outcome (per 100 person-years) was higher in North America (13.9 [95% CI: 12.5-15.4]) than in other regions: Europe 10.8 (95% CI: 10.1-11.5), South America 10.0 (95% CI: 9.0-11.1), and Asia 10.5 (95% CI: 9.5-11.5). The benefit of dapagliflozin on the primary outcome was not modified by region: dapagliflozin vs placebo HR: Europe, 0.85 (95% CI: 0.75-0.96); North America, 0.75 (95% CI: 0.61-0.93); South America, 0.72 (95% CI: 0.58-0.89); and Asia, 0.74 (95% CI: 0.61-0.91) (P interaction = 0.40). This was the same when evaluated separately for HFrEF (P interaction = 0.39) and HFmrEF/HFpEF (P interaction = 0.84). Patients in North America discontinued randomized treatment more frequently than did those elsewhere (placebo discontinuation: 21.8% in North America vs 6.4% in South America), but discontinuation rates did not differ between placebo and dapagliflozin by region. The efficacy and safety of dapagliflozin were consistent across global regions despite geographic differences in patient characteristics, background treatment, and event rates. [Display omitted] [ABSTRACT FROM AUTHOR]

• Heart failure (HF) is associated with a substantial risk of hospitalizations and adverse outcomes. • In patients with cardiac implantable electronic devices (CIEDs) there is the possibility of multiparametric remote monitoring of HF. • Several CIEDs parameters may result in multiparametric scores predicting patients' risk of worsening HF. • Patients can be managed days or weeks before overt decompensation, at the time of CIEDs pre-clinical alerts. • Decision making on clinical, laboratory or instrumental checks is needed in order to assess the need for escalating HF medications after a remote monitoring alert. In this review we focus on heart failure (HF) which, as known, is associated with a substantial risk of hospitalizations and adverse cardiovascular outcomes, including death. In recent years, systems to monitor cardiac function and patient parameters have been developed with the aim to detect subclinical pathophysiological changes that precede worsening HF. Several patient-specific parameters can be remotely monitored through cardiac implantable electronic devices (CIED) and can be combined in multiparametric scores predicting patients' risk of worsening HF with good sensitivity and moderate specificity. Early patient management at the time of pre-clinical alerts remotely transmitted by CIEDs to physicians might prevent hospitalizations. However, it is not clear yet which is the best diagnostic pathway for HF patients after a CIED alert, which kind of medications should be changed or escalated, and in which case in-hospital visits or in-hospital admissions are required. Finally, the specific role of healthcare professionals involved in HF patient management under remote monitoring is still matter of definition. We analyzed recent data on multiparametric monitoring of patients with HF through CIEDs. We provided practical insights on how to timely manage CIED alarms with the aim to prevent worsening HF. We also discussed the role of biomarkers and thoracic echo in this context, and potential organizational models including multidisciplinary teams for remote care of HF patients with CIEDs. [ABSTRACT FROM AUTHOR]

Cardiovascular disease remains the leading cause of mortality in human immunodeficiency virus-infected (HIV-positive) patients. Ventricular assist device therapy is rarely offered to these patients and data on outcomes are sparse. We investigated outcomes following ventricular assist device implants for HIV-positive as compared to non-HIV-infected (HIV-negative) patients. We analyzed 22,065 patients from the Interagency Registry for Mechanically Assisted Circulatory Support registry for outcomes by HIV status. A propensity-matched analysis adjusting for 21 preimplant risk factors was also conducted. Compared with 21,980 HIV-negative device recipients, the 85 HIV-positive recipients were younger (median age 58 years vs 59 years, p = 0.02), had lower body mass index (26 kg/m2 vs 29 kg/m2, p = 0.001), and had higher rates of prior stroke (8% vs 4%, p = 0.02). In the matched HIV-positive and HIV-negative cohorts, there was significantly higher mortality in HIV-positive patients in earlier implant years, however, this association was not seen in later implant years (2018-2020). In both unmatched and matched cohorts, no significant differences in postimplantation stroke, major bleeding, or major infection were noted. With recent advancements in mechanical circulatory support and HIV treatment, ventricular assist device therapy is a viable therapeutic option for HIV-positive patients with end-stage heart failure. [ABSTRACT FROM AUTHOR]

The Implantable Cardioverter-Defibrillator (ICD) is a well-established life-saving therapy for heart failure patients, but due to the risk for unnecessary shocks, deactivation of ICD:s is recommended at the end of life. We aimed to identify i) how many people with HF and an ICD who died in Sweden in 2018 received Specialized Palliative Care (SPC), ii) of those dying outside of hospital, the proportion with deactivated ICDs prior to death for the group as a whole and by SPC access. We analyzed data from i) the Swedish ICD and Pacemaker Registry to find all who died with an ICD in Sweden in 2018, ii) the Swedish Register of Palliative Care and, iii) the Swedish Causes of Death Certificate Register to find those who died outside of hospital. Clinical records were obtained to assess if ICDs were deactivated before death. Descriptive statistics, t -tests and chi-squared tests were applied. 46/406 (11%) of those who died with an ICD in Sweden in 2018 had SPC access, of whom 50% also had cancer. 86/164 (52%) ICDs were deactivated prior to death in people dying outside of hospital; higher in those accessing SPC (36/46, (78%) SPC access versus 151/360, (42%) no SPC access; p < 0.05). Half of those with HF and an ICD dying outside of hospital had ICD deactivation prior to death. Those accessing SPC were more likely to have their ICD deactivated but few received SPC, without a comorbid cancer diagnosis. • This is a nationwide, register based study of all who died with heart failure and an ICD in Sweden in 2018. • A study of ICD-deactivation in patients dying outside of hospital and the impact of Specialized Palliative Care (SPC). • Half of those with HF and an ICD dying outside of hospital had ICD deactivation prior to death. • Those in SPC were more likely to have their ICD deactivated but few received SPC, without a comorbid cancer diagnosis. [ABSTRACT FROM AUTHOR]

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome. Diabetes may identify an essential phenotype that significantly affects the prognosis of these patients. The WATCH-DM risk score has been validated for predicting the risk of heart failure in outpatients with type 2 diabetes mellitus (T2DM), but its ability to predict clinical outcomes in HFpEF patients with T2DM is unknown. We aimed to assess whether this risk score could predict the prognosis of diabetic phenotype patients with heart failure and preserved ejection fraction. We enrolled retrospectively 414 patients with HFpEF (70.03 ± 8.654 years, 58.70% female), including 203 (49.03%) type 2 diabetics. Diabetic HFpEF patients were stratified by baseline WATCH-DM risk score. Diabetic HFpEF patients exhibited a trend toward more concentric remodeling/hypertrophy than nondiabetic HFpEF patients. When analyzed as a continuous variable, per 1-point increase in the WATCH-DM risk score was associated with increased risks of all-cause death (HR 1.181), cardiovascular death (HR 1.239), any hospitalization (HR 1.082), and HF hospitalization (HR 1.097). The AUC for the WATCH-DM risk score in predicting incident cardiovascular death (0.7061, 95% CI 0.6329–0.7792) was higher than that of all-cause death, any hospitalization, or HF hospitalization. As a high-risk phenotype for heart failure, diabetic HFpEF necessitates early risk stratification and specific treatment. To the best of our knowledge, the current study is the first to demonstrate that the WATCH-DM score predicts poor outcomes in diabetic HFpEF patients. Its convenience may allow for quick risk assessments in busy clinical settings. • Diabetes may identify an essential phenotype that significantly affects the prognosis of patients with HFpEF. • As a high-risk phenotype for heart failure, diabetic HFpEF necessitates early risk stratification and specific treatment. • Diabetic HFpEF patients exhibited a trend toward more concentric remodeling/hypertrophy than nondiabetic HFpEF patients. • The convenience of the WATCH-DM score may allow for quick risk assessments in busy clinical settings. [ABSTRACT FROM AUTHOR]

Previous studies have shown that arterial stiffness (AS) was a risk factor for heart failure (HF) in nondiabetic patients. We aimed to analyze this impact in a community-based diabetic population. Our study excluded those who had HF before brachial-ankle pulse wave velocity (baPWV) measurement and included 9041 participants finally. Subjects were divided into the normal (<14 m/s), intermediate (14–18 m/s), and elevated baPWV groups (>18 m/s) based on baPWV values. Multivariate Cox proportional hazard model was used to analyze the effect of AS on HF risk. During the median follow-up of 4.19 years, 213 patients had HF. The results of Cox model showed that HF risk in the elevated baPWV group was 2.25 times higher than that in the normal baPWV group (95% confidence interval [CI]: 1.24–4.11). HF risk increased by 18% (95% CI:1.03–1.35) for every 1 additional standard deviation(SD)of baPWV. Restricted cubic spline results showed statistically significant overall and non-linear associations between AS and HF risk (P < 0.05). The subgroup analysis and sensitivity analysis were consistent with that of total population. AS is an independent risk factor for developing HF in the diabetic population, and AS exhibits a dose-response relationship with HF risk. • AS was an independent risk factor for developing HF in the diabetic population. • AS exhibits a dose-response relationship with HF risk. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is a leading cause of death and disability in older adults. Despite decades of high-quality evidence to support their use, guideline-directed medical therapies (GDMTs) that reduce death and disease burden in HF have been suboptimally implemented. Approaches to closing care gaps have focused largely on strategies proven to be ineffective, whilst effective interventions shown to improve GDMT uptake have not been instituted. This review synthesizes implementation interventions that increase the uptake of GDMT, discusses barriers and facilitators of implementation, summarizes conceptual frameworks in implementation science that could improve knowledge uptake, and offers suggestions for trial design that could better facilitate end-of-trial implementation. We propose an evidence-to-care conceptual model that could foster the simultaneous generation of evidence and long-term implementation. By adopting principles of implementation science, policymakers, researchers, and clinicians can help reduce the burden of HF on patients and health care systems worldwide. [Display omitted] • Implementation strategies that are proven-effective in trials are underutilized in clinical settings. • Trials can better facilitate uptake of results by adopting implementation science principles in their designs. • We propose an Evidence-To-Care conceptual framework that is anchored in the health care system and supported by 4 pillars: robust trial design; equitable, sustainable, and scalable intervention; strong stakeholder engagement; and relevant outcomes. [ABSTRACT FROM AUTHOR]

Limited data exist to characterize novel measures of right ventricular (RV) function and the coupling to pulmonary circulation in patients with heart failure and preserved left ventricular ejection fraction (HFpEF). This study sought to assess the clinical implications of RV function, the association with N-terminal pro–B-type natriuretic peptide, and the risk for adverse events among patients with HFpEF. This study analyzed measures of RV function by assessing absolute RV free wall longitudinal strain (RVFWLS) and its ratio to estimated pulmonary artery systolic pressure (PASP) (RVFWLS/PASP ratio) in 528 patients (mean age 74 ± 8 years, 56% female) with adequate echocardiographic images quality enrolled in the PARAGON-HF trial. Associations with baseline N-terminal pro–B-type natriuretic peptide and with total HF hospitalizations and cardiovascular death were assessed, after accounting for confounders. Overall, 311 patients (58%) had evidence of RV dysfunction, defined as absolute RVFWLS <20%, and among the 388 patients (73%) with normal tricuspid annular planar systolic excursion and RV fractional area change, more than one-half showed impaired RV function. Lower values of RVFWLS and RVFWLS/PASP ratios were significantly associated with higher circulating N-terminal pro–B-type natriuretic peptide. With a median follow-up of 2.8 years, there were 277 total HF hospitalizations and cardiovascular deaths. Both absolute RVFWLS (HR: 1.39; 95% CI: 1.05-1.83; P = 0.018) and RVFWLS/PASP ratio (HR: 1.43; 95% CI: 1.13-1.80; P = 0.002) were significantly associated with the composite outcome. Treatment effect of sacubitril/valsartan was not modified by measures of RV function. Worsening RV function and its ratio to pulmonary pressure is common and significantly associated with an increased risk of HF hospitalizations and cardiovascular death in patients with HFpEF. (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711) [Display omitted] [ABSTRACT FROM AUTHOR]

• First, compared with traditional treatment, SGLT2is significantly improved HR, LAVi, LVMi, LVESV, E/e', and LVEF in all populations. • Second, empagliflozin reduced LVMi, LVEDV, LVESV, E/e', LAVi, and improved LVEF. However, other SGLT2is (dapagliflozin or canagliflozin, etc.) compared with control therapy did not exert significant effect on left ventricular diastolic and systolic function. • Third, the anti-remodeling cardiac effects of SGLT2is mainly significant in patients with heart failure. It has been proven that sodium-glucose co-transporter 2 inhibitors (SGLT2is) improve the prognosis of patients with heart failure, independent of the presence of diabetes mellitus. Whether SGLT2 inhibitors affect cardiac structural remodeling and cardiac function is still uncertain. We included published randomized controlled trials (RCTs) to compare the effect of SGLT2is and control therapy in patients with or without heart failure. The meta-analysis was performed using Review Manager 5.3 software. A total of 15 RCTs with a total of 1343 patients were selected for this meta-analysis, 663 of whom were on SGLT2is treatment and 680 of whom were in the control group. SGLT2is significantly improved heart rate (HR) [MD: -2.74, 95% CI (-4.71, -0.77), P = 0.006], left atrium volume index (LAVi) [MD: -1.99, 95% CI (-3.23,-0.75), P = 0.002], E/e' [MD: -1.47, 95% CI (-1.83,-1.10), P <0.00001], left ventricular mass index (LVMi) [MD: -2.38, 95% CI (-4.35, -0.40), P = 0.02], left ventricular end-systolic volume (LVESV) [MD: -6.50, 95% CI (-11.15,-1.84), P = 0.006], and left ventricular ejection fraction (LVEF) [MD: 1.78, 95% CI (0.56,3.01), P = 0.004] in the total population. Subgroup analysis indicated that compared with other SGLT2is, empagliflozin significantly decreased LVEDV, LVESV,LVMi, LAVi, E/e', and increased LVEF (P <0.05). In addition, the cardiac anti-remodeling effects of SGLT2 are particularly significant in patients with heart failure. Our study showed that SGLT2is, particularly empagliflozin, significantly reverse cardiac remodeling in patients with heart failure. Empagliflozin may be a potentially promising agent to reverse cardiac remodeling in clinical practice. [ABSTRACT FROM AUTHOR]

The incidence of heart failure (HF) continues to grow and burden our health care system. Electrophysiological aberrations are common amongst patients with heart failure and can contribute to worsening symptoms and prognosis. Targeting these abnormalities with cardiac and extra-cardiac device therapies and catheter ablation procedures augments cardiac function. Newer technologies aimed to improvement procedural outcomes, address known procedural limitations and target newer anatomical sites have been trialled recently. We review the role and evidence base for conventional cardiac resynchronisation therapy (CRT) and its optimisation, catheter ablation therapies for atrial arrhythmias, cardiac contractility and autonomic modulation therapies. [ABSTRACT FROM AUTHOR]

The 2018 World Symposium on Pulmonary Hypertension (WSPH) changed the definition of pulmonary hypertension (PH) with a new threshold of mean pulmonary artery pressure (mPAP) above 20 mmHg. To evaluate the profile and prognosis of patients with chronic heart failure (HF) considered for heart transplantation with the new definition of PH. Patients with chronic HF considered for heart transplantation were classified as mPAP ≤20mmHg , mPAP 20 – 25 mmHg , and mPAP ≥25mmHg. Using a multivariate Cox model, we compared the mortality of patients with mPAP 20 – 25mmHg , and mPAP ≥25mmHg versus those with mPAP ≤20mmHg. Of 693 patients with chronic HF considered for heart transplantation, 12.7%, 77.5% and 9.8% were classified as mPAP 20 – 25mmHg , mPAP ≥ 25mmHg and mPAP ≤20mmHg. Patients of mPAP ≥ 25mmHg and mPAP 20 – 25 mmHg categories were older than mPAP ≤ 20 mmHg (56 versus 55 and 52 year-old, p = 0.02) with more frequent co-morbidities. Within 2.8 years, the mPAP 20 – 25mmHg category displayed a higher risk of mortality compared with those of the mPAP ≤20mmHg category (aHR 2.75, 95% CI 1.27–5.97, p = 0.01). Overall, the new PH definition using a threshold of mPAP >20 mmHg was associated with a higher risk of death (adj HR 2.71, 95% CI 1.26–5.80) than the previous definition (mPAP >25 mmHg, aHR: 1.35 95% CI 1.00–1.83, p = 0.05). One out of 8 patients with severe HF are reclassified as having PH following the 2018 WSPH. Patients with mPAP 20 – 25 evaluated for heart transplantation displayed significant co-morbidities and high mortality rates. The new definition of pulmonary hypertension in patients with chronic heart failure evaluated for cardiac transplantation. [Display omitted] • In 2018 6th WSPH changed the definition of pulmonary hypertension to mPAP >20 mmHg instead of 25 mmHg. • Using this new definition in 693 patients with chronic heart failure evaluated for heart transplantation, 12.7%, 77.5% and 9.8% were classified as mPAP 20 – 25mmHg , mPAP ≥ 25mmHg and mPAP ≤ 20 mmHg , respectively. • Patients with a mPAP between 20 and 25 mmHg had significant co-morbidities, and a higher risk of mortality compared with patients with mPAP below 20 mmHg. • The new PH definition using mPAP >20 mmHg is associated with a significant risk of mortality. [ABSTRACT FROM AUTHOR]

Exertional oscillatory breathing (EOV) represents an emerging prognostic marker in heart failure (HF) patients, however little is known about EOV meaning with respect to its disappearance/persistence during cardiopulmonary exercise test (CPET). The present single-center study evaluated EOV clinical and prognostic impact in a large cohort of reduced ejection fraction HF patients (HFrEF) and, contextually, if a specific EOV temporal behavior might be an addictive risk predictor. Data from 1.866 HFrEF patients on optimized medical therapy were analysed. The primary cardiovascular (CV) study end-point was cardiovascular death, heart transplantation or LV assistance device (LVAD) implantation at 5-years. For completeness a secondary end-point of total mortality at 5- years was also explored. EOV presence was identified in 251 patients (13%): 142 characterized by EOV early cessation (Group A) and 109 by EOV persistence during the whole CPET (Group B). The entire EOV Group showed worse clinical and functional status than NoEOV Group (n = 1.615) and, within the EOV Group, Group B was characterized by a more severe HF. At CV survival analysis, EOV patients showed a poorer outcome than the NoEOV Group (events 27.1% versus 13.1%, p < 0.001) both unpolished and after matching for main confounders. Instead, no significant differences were found between EOV Group A and B with respect to CV outcome. Conversely the analysis for total mortality failed to be significant. Our analysis, albeit retrospective, supports the inclusion of EOV into a CPET-centered clinical and prognostic evaluation of the HFrEF patients. EOV characterizes per se a more advanced HFrEF stage with an unfavorable CV outcome. However, the EOV persistence, albeit suggestive of a more severe HF, does not emerge as a further prognostic marker. • EOV prevalence stands at 10–15% in a HFrEF population on optimized treatment. • EOV characterizes per se a more advanced HFrEF stage with an unfavorable CV outcome. • EOV identification should be part of the core CPET-variables in HFrEF assessment. • EOV persistence during the entire CPET does not emerge as a reliable prognostic marker. [ABSTRACT FROM AUTHOR]

Acute Kidney Injury (AKI) represents a major complication of acute heart failure and cardiogenic shock (CS). There is a paucity of data on AKI complicating acutely decompensated heart failure patients presenting with CS (ADHF-CS). We aimed to investigate AKI prevalence, risk factors and outcomes in this subgroup of patients. Retrospective observational study on patients admitted for ADHF-CS to our 12-bed Intensive Care Unit (ICU), between January 2010 and December 2019. Demographic, clinical, and biochemical variables were collected at baseline and during hospital stay. Eighty-eight patients were consecutively recruited. The predominant etiologies were idiopathic dilated cardiomyopathy (47%), followed by post-ischemic (24%). AKI was diagnosed in 70 (79.5%) of patients. Forty-three out of 70 patients met the criteria for AKI at ICU admission. On multivariate analysis, a central venous pressure (CVP) higher than 10 mmHg (OR 3.9; 95%CI 1.2–12.6; p = 0.025) and serum lactate higher than 3 mmol/L (OR 4.1; 95%CI 1.01–16.3; p = 0.048) were identified to be independently associated with AKI. Age and AKI stage were independent predictors of 90-day mortality. AKI is a common and early complication of ADHF-CS. Venous congestion and severe hypoperfusion are risk factors for AKI development. Early detection and prevention of AKI could lead to better outcome in this clinical subgroup. • Acute kidney injury is an early complication and has an extremely high prevalence in patients with ADHF-CS. • Venous congestion (CVP >10 mmHg) and hypoperfusion (lactate >3mmol/L) are risk factors for AKI in ADHF-CS patients. • Acute kidney injury in ADHF-CS patients is an independent predictor of 90-day mortality. [ABSTRACT FROM AUTHOR]

Although malnutrition is associated with poor prognosis in several diseases, its prognostic impact in patients with heart failure (HF) and secondary mitral regurgitation (SMR) is not understood. The purpose of this study was to assess the prevalence and impact of malnutrition in HF patients with severe SMR randomized to transcatheter edge-to-edge repair (TEER) with the MitraClip plus guideline-directed medical therapy (GDMT) vs GDMT alone in the COAPT trial. Baseline malnutrition risk was calculated using the validated geriatric nutritional risk index (GNRI) score. Patients were categorized as having "malnutrition" (GNRI ≤98) vs "no malnutrition" (GNRI >98). Outcomes were assessed through 4 years. The primary endpoint of interest was all-cause mortality. Among 552 patients, median baseline GNRI was 109 (IQR: 101-116); 94 (17.0%) had malnutrition. All-cause mortality at 4 years was greater in patients with vs those without malnutrition (68.3% vs 52.8%; P = 0.001). Using multivariable analysis, both baseline malnutrition (adjusted-HR [adj-HR]: 1.37; 95% CI: 1.03-1.82; P = 0.03) and randomization to TEER plus GDMT compared with GDMT alone (adj-HR: 0.65; 95% CI: 0.51-0.82; P = 0.0003) were independent predictors of 4-year mortality. In contrast, GNRI was unrelated to the 4-year rate of heart failure hospitalization (HFH), although TEER treatment reduced HFH (adj-HR: 0.46; 95% CI: 0.36-0.56). The reductions in death (adj- P interaction = 0.46) and HFH (adj- P interaction = 0.67) with TEER were consistent in patients with and without malnutrition. Malnutrition was present in 1 of 6 patients with HF and severe SMR enrolled in COAPT and was independently associated with increased 4-year mortality (but not HFH). TEER reduced mortality and HFH in patients with and without malnutrition. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [The COAPT Trial] and COAPT CAS [COAPT]; NCT01626079) [Display omitted] [ABSTRACT FROM AUTHOR]