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Heart failure (HF) is the leading cause of mortality in patients with acute myocardial infarction (AMI), with incidence ranging from 14% to 36% in patients admitted due to AMI. HF post-MI develops due to complex inter-play between macrovascular obstruction, microvascular dysfunction, myocardial stunning and remodeling, inflammation, and neuro-hormonal activation. Cardiogenic shock is an extreme presentation of HF post-MI and is associated with a high mortality. Early revascularization is the only therapy shown to improve survival in patients with cardiogenic shock. Treatment of HF post-MI requires prompt recognition and timely introduction of guideline-directed therapies to improve mortality and morbidity. This article aims to provide an up-to-date review on the incidence and pathogenesis of HF post-MI, current strategies to prevent and treat onset of HF post-MI, promising therapeutic strategies, and knowledge gaps in the field. [ABSTRACT FROM AUTHOR]

Despite robust scientific evidence and strong guideline recommendations, there remain significant gaps in initiation and dose titration of guideline-directed medical therapy (GDMT) for heart failure (HF) among eligible patients. Reasons surrounding these gaps are multifactorial, and largely attributed to patient, healthcare professionals, and institutional challenges. Concurrently, HF remains a predominant cause of mortality and hospitalization, emphasizing the critical need for improved delivery of therapy to patients in routine clinical practice. To optimize GDMT, various implementation strategies have emerged in the recent decade such as in-hospital rapid initiation of GDMT, improving patient adherence, addressing clinical inertia, improving affordability, engagement in quality improvement registries, multidisciplinary clinics, and EHR-integrated interventions. This review highlights the current use and barriers to optimal utilization of GDMT, and proposes novel strategies aimed at improving GDMT in HF. [ABSTRACT FROM AUTHOR]

• In patients with HFrEF, the extent of vascular disease is associated with the risk for adverse cardiovascular outcomes. • The benefits of empagliflozin in cardiovascular and renal outcomes were seen in patients across the spectrum of baseline vascular disease but were attenuated in those with polyvascular disease. • Adverse events were more numerous in those with polyvascular disease, but no major differences were noted between empagliflozin and placebo assignment according to baseline vascular disease. The presence of ischemic heart disease impacts prognosis in patients affected by heart failure and reduced ejection fraction (HFrEF). It is not well known how the extent of vascular disease impacts prognoses and responses to therapy in this setting. In this post hoc analysis of the EMPEROR-Reduced trial, outcomes and the effects of empagliflozin, were assessed in study participants according to the extent (none vs mono 1 vs poly [≥ 2] vascular bed) of vascular disease. Vascular disease was defined as investigator-reported coronary artery disease (CAD), peripheral artery disease (PAD) and cerebrovascular disease at baseline. Cox proportional-hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Incidence rates are presented per 100 person-years (py) of follow-up. Of the 3730 study participants enrolled, 1324 (35.5%) had no vascular disease, 1879 (50.4%) had monovascular disease, and 527 (14.1%) had polyvascular disease. Participants with polyvascular disease tended to be older and male and to have had histories of hypertension, diabetes and smoking. In the placebo arm, a significantly higher risk for cardiovascular death existed in those with polyvascular disease (HR 1.57, 95% CI1.02, 2.44, compared to those with no vascular disease). In adjusted analysis, the benefit of empagliflozin in cardiovascular death or hospitalization due to HF, HF hospitalization, cardiovascular death, renal composite endpoint, estimated glomerular filtration slope changes, and health status scores were seen across the 3 groups (interaction P > 0.05 for all) but were attenuated in those with polyvascular disease. Adverse events were higher in those with polyvascular disease, but no major differences were noted between empagliflozin or placebo assignment in the 3 groups. In patients with HFrEF, the extent of vascular disease is associated with the risk for adverse cardiovascular outcomes. Empagliflozin offers cardiovascular and renal benefits in HFrEF across the extent of vascular disease, but this benefit is attenuated in those with polyvascular disease. [Display omitted] [ABSTRACT FROM AUTHOR]

Whether the timing of hospital presentation impacts care delivery and clinical outcomes for patients hospitalized for heart failure (HF) remains a matter of debate. In this study, we examined all-cause and HF-specific 30-day readmission rates for patients who were admitted for HF on a weekend vs admitted for HF on a weekday. We conducted a retrospective analysis using the 2010–2019 Nationwide Readmission Database to compare 30-day readmission rates among patients who were admitted for HF on a weekday (Monday to Friday) vs patients who were admitted for HF on a weekend (Saturday or Sunday). We also compared in-hospital cardiac procedures and temporal trends in 30-day readmission by day of index hospital admission. Among 8,270,717 index HF hospitalizations, 6,302,775 were admitted on a weekday and 1,967,942 admitted on a weekend. For weekday and weekend admissions, the 30-day all-cause readmission rates were 19.8% vs 20.3%, and HF-specific readmission rates were 8.1% vs 8.4%, respectively. Weekend admissions were independently associated with higher risk of all-cause (adjusted odds ratio [aOR] 1.04, 95% confidence interval [CI] 1.03–1.05, P <.001) and HF-specific readmission (aOR 1.04, 95% CI 1.03–1.05, P <.001). Weekend HF admissions were less likely to undergo echocardiography (aOR 0.95, 95% CI 0.94–0.96, P <.001), right heart catheterization (aOR 0.80, 95% CI 0.79–0.81, P <.001), electrical cardioversion (aOR 0.90, 95% CI 0.88–0.93, P <.001), or receive temporary mechanical support devices (aOR 0.84, 95% CI 0.79–0.89, P <.001). The mean length of stay was shorter for weekend HF admissions (5.1 days vs 5.4 days, P <.001). Between 2010 and 2019, 30-day all-cause (18.5% to 18.2%, trend P <.001) and HF-specific (8.4% to 8.3%, trend P <.001) readmission rates decreased among weekday HF admissions. Among weekend HF admissions, the HF-specific 30-day readmission rate decreased (8.8% to 8.7%, trend P <.001), but the all-cause 30-day readmission rate remained stable (trend P =.280). Among patients hospitalized for HF, weekend admissions were independently associated with excess risk of 30-day all-cause and HF-specific readmission and a lower likelihood of undergoing in-hospital cardiovascular testing and procedures. The 30-day all-cause readmission rate has decreased modestly over time among patients admitted on weekdays, but has remained stable among patients admitted on weekends. [Display omitted] [ABSTRACT FROM AUTHOR]

Despite the availability of lifesaving guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF), there remain major gaps in utilization of these therapies among eligible patients. Simultaneous with these gaps in quality of care, HFrEF continues as a leading cause of death and hospitalization with associated clinical risk far exceeding most other cardiovascular and noncardiovascular conditions. In the context of this urgent need to improve provision of appropriate therapy, multiple lines of evidence support various implementation strategies. Such strategies include in-hospital initiation of GDMT, simultaneous or rapid sequence initiation of GDMT, participation in quality improvement registries to assess site performance and provide feedback, multidisciplinary titration clinics, virtual consult teams, reduction of cost-sharing, remote algorithm-based medication optimization, electronic health record-based interventions, and direct-to-patient educational initiatives. This review describes and contextualizes the evidence surrounding each of these potential avenues for improving use of foundational GDMTs for patients with HFrEF. [Display omitted] • There are wide gaps in use of guideline-recommended medications for patients with HFrEF. • Several strategies are available to improve utilization of GDMT for HFrEF. • Wider adoption of these strategies could enhance quality of care and clinical outcomes for a large number of patients. [ABSTRACT FROM AUTHOR]

Background: The six-minute walk test (6MWT) is widely used to measure exercise capacity; however, the magnitude of change that is clinically meaningful for individuals is not well established in heart failure with reduced ejection fraction (HFrEF).Objective: To calculate the minimal clinically important difference (MCID) for change in exercise capacity on the 6MWT in iron-deficient HFrEF populations.Methods: In this pooled secondary analysis of FAIR-HF and CONFIRM-HF trials, mean changes in 6MWT from baseline to weeks 12 and 24 were calculated and calibrated against the Patient Global Assessment (PGA) tool [clinical anchor] to derive MCIDs for improvement and deterioration.Results: Of 760 patients included in the two trials, 6MWT and PGA data were available for 680 (89%) and 656 (86%) patients at weeks 12 and 24, respectively. The mean 6MWT distance at baseline was 281±103m. There was a modest correlation between changes in 6MWT and PGA from baseline to week 12 (r=0.31, p<0.0001) and week 24 (r=0.43, p<0.0001). Respective estimates (95% confidence intervals) for MCID in 6MWT at weeks 12 and 24 were 14m (5;23) and 15m (3;27) for a "little improvement" (vs no change), 20m (10;30) and 24m (12;36) for "moderate improvement" vs a "little improvement", -11m (-32;9.2) and -31m (-53;-8) for a "little deterioration" (vs no change), and -84m (-144;-24) and -69m (-118;-20) for "moderate deterioration" vs a "little deterioration".Conclusions: The MCID for improvement in exercise capacity on the 6MWT was 14-15m in patients with HFrEF and iron deficiency. These MCIDs can aid clinical interpretation of study data. [ABSTRACT FROM AUTHOR]

• More than 1 in 10 trials reported outcomes inconsistent with those prespecified. • The majority of the inconsistencies favored statistically significant findings. • Single-center recruitment was associated with inconsistent outcome reporting. Randomized controlled trials (RCTs) may report outcomes different from those prespecified on trial-registration websites, protocols and statistical analysis plans (SAPs). This study sought to investigate the prevalence and characteristics of heart failure (HF) RCTs that report outcomes different from those prespecified. MEDLINE via PubMed was searched to include phase II–IV HF RCTs in 9 high-impact journals from 2010 to 2020. Outcomes reported in trial publications were compared with prespecified outcomes in protocols, registration websites and SAPs. We used the χ2 or Fisher exact test to analyze correlations between trial characteristics and inconsistencies. Among 216 trials, 32 inconsistencies were observed in 28 trials (13.0%). Among 32 inconsistencies, 2 (6.3%) pertained to omission of prespecified primary outcomes, 4 (12.5%) to omission of prespecified secondary outcomes, 2 (6.3%) to changing prespecified primary outcomes to secondary outcomes, and 2 (6.3%) to changing prespecified secondary outcomes to primary outcomes. Of the inconsistencies, 3 (9.4%) pertained to addition of new primary outcomes, 17 (53.1%) to addition of new secondary outcomes, and 2 (6.3%,) to changes in the timing of assessment of primary outcomes. The majority of the inconsistencies favored statistically significant findings; 78 (36.1%) were registered retrospectively. Single-center recruitment was associated with outcome inconsistencies (β = -0.14; 95% CI, -0.22 – -0.01; P = 0.035). More than 1 in 10 trials reported outcomes inconsistent with those specified in trial registration websites, SAPs and protocols. An action plan is warranted to minimize selective reporting and improve transparency. [Display omitted] [ABSTRACT FROM AUTHOR]

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Although chronic kidney disease is characterized by low glomerular filtration rate (GFR) or albuminuria, estimated GFR (eGFR) is more widely utilized as a marker of risk profile in cardiovascular diseases, including heart failure (HF). The presence and magnitude of albuminuria confers a strong prognostic association in forecasting risk of incident HF as well as its progression, irrespective of eGFR. Despite the high prevalence of albuminuria in HF, whether it adds incremental prognostic information in clinical practice and serves as an independent risk marker, and whether there are any therapeutic implications of assessing albuminuria in patients with HF is less well-established. In this narrative review, we assess the potential role of albuminuria in risk profiling for development and progression of HF, strengths and limitations of utilizing albuminuria as a risk marker, its ability to serve in HF risk prediction models, and the implications of adopting albuminuria as an effective parameter in cardiovascular trials and practice. [Display omitted] • Albuminuria is prevalent in patients with heart failure and confers a strong, consistent and independent association with risk. • The causes of albuminuria in patients with heart failure are incompletely understood, as are the mechanisms linking it to disease progression and adverse outcomes. • Interventions that reduce albuminuria may potentially lower the risk of incident heart failure or prevent progression of existing heart failure. [ABSTRACT FROM AUTHOR]

Heart failure (HF) and end-stage kidney disease (ESKD) frequently coexist; 1 comorbidity worsens the prognosis of the other. HF is responsible for almost half the deaths of patients on dialysis. Despite patients' with ESKD composing an extremely high-risk population, they have been largely excluded from landmark clinical trials of HF, and there is, thus, a paucity of data regarding the management of HF in patients on dialysis, and most of the available evidence is observational. Likewise, in clinical practice, guideline-directed medical therapy for HF is often down-titrated or discontinued in patients with ESKD who are undergoing dialysis; this is due to concerns about safety and tolerability. In this state-of-the-art review, we discuss the available evidence for each of the foundational HF therapies in ESKD, review current challenges and barriers to managing patients with HF on dialysis, and outline future directions to optimize the management of HF in these high-risk patients. [ABSTRACT FROM AUTHOR]

Background: Heart failure (HF) poses a substantial economic burden on the United States (US) health care system. In contrast, little is known about the financial challenges faced by patients with HF. In this study, we examined the scope and sociodemographic predictors of subjective financial hardship due to medical bills incurred by patients with HF.Methods: In the Medical Expenditure Panel Survey (MEPS; years 2014--2018), a US nationally representative database, we identified all patients who reported having HF. Any subjective financial hardship due to medical bills was assessed based on patients' reporting either themselves or their families (1) having difficulties paying medical bills in the past 12 months, (2) paying bills late or (3) being unable to pay bills at all. Logistic regression was used to evaluate independent predictors of financial hardship among patients with HF. All analyses took into consideration the survey's complex design.Results: A total of 116,563 MEPS participants were included in the analysis, of whom 858 (0.7%) had diagnoses of HF, representing 1.8 million (95% CI 1.6-2.0) patients annually. Overall, 33% (95% CI 29%-38%) reported any financial hardship due to medical bills, and 13.2% were not able to pay bills at all. Age ≤ 65 years and lower educational attainment were independently associated with higher odds of subjective financial hardship due to medical bills.Conclusion: Subjective financial hardship is a prevalent issue for patients with HF in the US, particularly those who are younger and have lower educational attainment. There is a need for policies that reduce out-of-pocket costs for the care of HF, an enhanced identification of this phenomenon in the clinical setting, and approaches to help minimize financial toxicity in patients with HF while ensuring optimal quality of care. [ABSTRACT FROM AUTHOR]

Prior studies have reported improvements in population-level risk factor burden and cardiovascular disease (CVD) outcomes using polypills for CVD risk reduction. However, a comprehensive assessment of the impact of polypills on CVD outcomes, mortality, adherence, and side effects across different settings has not previously been reported. We performed a systematic review and meta-analysis of randomized controlled trials examining the association between polypill therapy and CVD outcomes published before February 2021. The primary outcome of interest was the risk of major adverse CVD events (MACE). Risk ratios for dichotomous outcomes were converted to log RR and pooled using a generic inverse variance weighted random-effects model. Data for continuous outcomes were pooled using random-effects modeling and presented as mean differences with 95% CIs. Eight studies representing 25,584 patients were included for analysis. In the overall pooled analysis, the use of polypills was associated with a non-significant reduction in the risk of MACE (RR: 0.85; 95% CI: 0.70-1.02) and significant reductions in the risk of all-cause mortality (RR: 0.90; 95% CI: 0.81-1.00). The reductions in the risk of MACE with polypill use varied by baseline risk and nature of the study population (primary prevention vs. secondary prevention), with the most significant risk reduction among lower-risk cohorts, including within primary prevention populations [RR 0.70 (0.62, 0.79)]. Among measures of CVD risk factors, modest but significant reductions were observed for systolic and diastolic blood pressure [systolic: mean difference 1.99 mmHg (95% CI: -3.07 to -0.91); diastolic: mean difference 1.30 mmHg (95% CI: -2.42 to -0.19), but not for levels of total or low-density lipoprotein-cholesterol. Use of the polypill strategy significantly improved drug adherence (RR: 1.31; 95% CI: 1.11-1.55) with no association between polypill use and rates of adverse events or drug discontinuation. The use of polypill formulations is associated with significant reductions in CVD risk factors and the risk of all-cause mortality and MACE, particularly in the low-risk and primary prevention population. [ABSTRACT FROM AUTHOR]

Bariatric surgery may play a role in the management of morbidly obese patients with end-stage heart failure through increasing eligibility and improving the outcomes of destination therapies. We conducted a nationally representative, retrospective cohort study of patients with previous bariatric surgery undergoing either heart transplantation or left ventricular assist device implantation. Of 200 patients, < 6% experienced in-hospital mortality after destination therapy, comparable to that reported in the general population of heart recipients. Risk-adjusted outcomes differed minimally from those of obese patients undergoing destination therapy without previous bariatric surgery. This study provides important safety benchmarking data and demonstrates the feasibility of bariatric surgery as a potential bridge to left ventricular assist device implantation or heart transplantation in obese patients with end-stage heart failure. [ABSTRACT FROM AUTHOR]

Aim: To determine the trends in hospitalizations for heart failure (HF), acute myocardial infarction (AMI), and stroke in the United States (US).Method and Results: A retrospective analysis of the National Inpatient Sample weighted data between January 1, 2004 and December 31, 2018 which included hospitalized adults ≥18 years with a primary discharge diagnosis of HF, AMI, or stroke using International Classification of Diseases-9/10 administrative codes. Main outcomes were hospitalization for HF, AMI, and stroke per 1000 United States adults, length of stay, and in-hospital mortality. There were 33.4 million hospitalizations for HF, AMI, and stroke, with most being for HF (48%). After the initial decline in HF hospitalizations (5.3 hospitalizations/1000 US adults in 2004 to 4 hospitalizations/1000 US adults in 2013, P < .001), there was a progressive increase in HF hospitalizations between 2013 and 2018 (4.0 hospitalizations/1000 US adults in 2013 to 4.9 hospitalizations/1000 US adults in 2018; P < .001). Hospitalization for AMI decreased (3.1 hospitalizations/1000 US adults in 2004 to 2.5 hospitalizations/1000 US adults in 2010, P < .001) and remained stable between 2010 and 2018. There was no significant change for hospitalization for stroke between 2004 and 2011 (2.3 hospitalizations/1000 US adults in 2004 vs 2.3 hospitalizations per 1000 US adults in 2011, P = .614); however, there was a small but significant increase in hospitalization for stroke after 2011 that reached 2.5 hospitalizations/1000 US adults in 2018. Adjusted length of stay and in-hospital mortality decreased for HF, AMI, and stroke hospitalizations.Conclusions: In contrast to the trend of AMI and stroke hospitalizations, a progressive increase in hospitalizations for HF has occurred since 2013. From 2004 to 2018, in-hospital mortality has decreased for HF, AMI, and stroke hospitalizations. [ABSTRACT FROM AUTHOR]

This study examines the feasibility of using fast pyrolysis bio-oil (FPBO) made from non-food woody biomass in a micro-gas turbine with a unique burner design, motivated by the recent surge in the development of renewable carbon-neutral biomass-derived liquids in energy applications. The study is comprehensive and covers FPBO production and applications, physicochemical properties and spray characteristics, and combustion performance. The effects of fuel spray formation and preparation on the combustion of FPBO, ethanol (EtOH) and diesel fuel were investigated using two twin-fluid nozzles with distinct atomization mechanisms, externally- and internally-mixed, and a premixer tube. In contrast to diesel fuel and EtOH, reaching a stable flame using 100% FPBO was impossible because of the fuel polymerization (or coking) when impinging on the high-temperature inner wall of the premixer tube. EtOH addition was, therefore, used to address the problem by improving the FPBO's volatility. The FPBO spray flame generated by the internally-mixed nozzle exhibited less gas- and solid-phase emissions than the externally-mixed one and required less EtOH addition for stabilization. While this study shows the feasibility for deployment of FPBO in the present micro-gas turbine design, injector modification or fuel upgrading are necessary prior to it being used to replace fossil oils. • Spray combustion and emissions of FPBO in a micro gas turbine burner were studied. • Two twin-fluid nozzles with distinct atomization mechanisms were compared. • EtOH addition reduced the FPBO coking propensity consistent with its TGA residue. • FPBO gas- and solid-phase emissions were reduced using an internally-mixed nozzle. • Suggestions for the future deployment of biomass-derived liquids are presented. [ABSTRACT FROM AUTHOR]

Background: Diabetes is associated with abnormalities in cardiac remodeling and high risk of heart failure (HF).Objectives: The purpose of this study was to evaluate the prevalence and prognostic implications of diabetes with cardiomyopathy (DbCM) among community-dwelling individuals.Methods: Adults without prevalent cardiovascular disease or HF were pooled from 3 cohort studies (ARIC [Atherosclerosis Risk In Communities], CHS [Cardiovascular Health Study], CRIC [Chronic Renal Insufficiency Cohort]). Among participants with diabetes, DbCM was defined using different definitions: 1) least restrictive: ≥1 echocardiographic abnormality (left atrial enlargement, left ventricle hypertrophy, diastolic dysfunction); 2) intermediate restrictive: ≥2 echocardiographic abnormalities; and 3) most restrictive: elevated N-terminal pro-B-type natriuretic peptide levels (>125 in normal/overweight or >100 pg/mL in obese) plus ≥2 echocardiographic abnormalities. Adjusted Fine-Gray models were used to evaluate the risk of HF.Results: Among individuals with diabetes (2,900 of 10,208 included), the prevalence of DbCM ranged from 67.0% to 11.7% in the least and most restrictive criteria, respectively. Higher fasting glucose, body mass index, and age as well as worse kidney function were associated with higher risk of DbCM. The 5-year incidence of HF among participants with DbCM ranged from 8.4%-12.8% in the least and most restrictive definitions, respectively. Compared with euglycemia, DbCM was significantly associated with higher risk of incident HF with the highest risk observed for the most restrictive definition of DbCM (HR: 2.55 [95% CI: 1.69-3.86]; least restrictive criteria HR: 1.99 [95% CI: 1.50-2.65]). A similar pattern of results was observed across cohort studies, across sex and race subgroups, and among participants without hypertension or obesity.Conclusions: Regardless of the criteria used to define cardiomyopathy, DbCM identifies a high-risk subgroup for developing HF. [ABSTRACT FROM AUTHOR]

Context: Palliative care (PC) improves outcomes in noncancer illness. We hypothesized the benefit is driven by studies of heart failure (HF) patients exclusively versus studies of other noncancer illnesses.Objectives: To assess difference in outcomes in trials with HF patients exclusively vs studies of other noncancer chronic illness.Methods: We performed a meta-analysis of studies that assessed association of PC with hospital admissions, emergency department (ED) visits and advance care planning in noncancer chronic illness and compared studies of HF patients versus those with other noncancer chronic illness.Results: Our analysis included 10 HF studies (n = 4,057) and 16 non-HF studies (11 mixed conditions, 3 dementia, 2 COPD, n = 10,235). PC led to reduction in hospital admissions in HF studies (OR = 0.67 [95% CI = 0.48-0.95]) but not in other noncancer illness studies (OR = 0.86 [95% CI = 0.62-1.21]). PC intervention was nonsignificant for change in ED visits in either HF (OR = 0.70 [95% CI = 0.38-1.28]) or other noncancer studies (OR = 0.86 [95% CI = 0.69-1.07]). Increase in advance care planning was noted in both HF (OR = 4.29 [95% CI = 1.44-12.76]) and other studies (OR = 2.67 [95% CI = 1.29-5.52]). Nonsignificant reductions in symptom burden were noted for both HF-studies and non-HF studies, though overall there was a significant improvement in symptom burden (weighted mean difference -1.15 [95% CI = -1.65, -0.65]). Similar results were noted when studies of mixed populations were excluded from the non-HF studies.Conclusion: PC is particularly effective at reducing potentially unwanted hospital admissions for patients with HF compared to other noncancer illnesses. Our findings should further encourage efforts to increase PC access to HF patients. [ABSTRACT FROM AUTHOR]

Background: N-terminal pro-B-type natriuretic peptide (NT-proBNP) plasma concentrations are independent prognostic markers in patients with heart failure and reduced ejection fraction (HFrEF). Whether a differential risk association between NT-proBNP plasma concentrations and risk of cardiovascular (CV) vs non-CV adverse events exists is not well known.Objective: To assess if there is a differential proportional risk of CV vs non-CV adverse events by NT-proBNP plasma concentrations.Methods: In this post hoc combined analysis of PARADIGM-HF and ATMOSPHERE trials, proportion of CV vs non-CV mortality and hospitalizations were assessed by NT-proBNP levels (<400, 400-999, 1000-1999, 2000-2999, and >3000 pg/mL) at baseline using Cox regression adjusting for traditional risk factors.Results: A total of 14,737 patients with mean age of 62 ± 8 years (24% history of atrial fibrillation [AF]) were studied. For CV deaths, the event rates per 1000 patient-years steeply increased from 33.8 in the ≤400 pg/mL group to 142.3 in the ≥3000 pg/mL group, while the non-CV death event rates modestly increased from 9.0 to 22.7, respectively. Proportion of non-CV deaths decreased across the 5 NT-proBNP groups (21.1%, 18.4%, 17.9%, 17.4%, and 13.7% respectively). Similar trend was observed for non-CV hospitalizations (46.4%, 42.6%, 42.9%, 42.0%, and 36.9% respectively). These results remained similar when stratified according to the presence of AF at baseline and prior HF hospitalization within last 12 months.Conclusions: The absolute CV event rates per patient years of follow-up were greater and had higher stepwise increases than non-CV event rates across a broad range of NT-proBNP plasma concentrations indicating a differential risk of CV events at varying baseline NT-proBNP values. These results have implications for future design of clinical trials. [ABSTRACT FROM AUTHOR]

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In this report, we aim to provide an updated meta-analysis of the sodium-glucose cotransporter 2 (SGLT2) inhibitors trial data with the new trial data on sotagliflozin, a first-in-class dual SGLT1 and SGLT2 inhibitor. We searched Medline, Cochrane library, and Embase databases for randomized clinical trials comparing cardiovascular and kidney outcomes between SGLT2 and dual SGLT1/2 inhibitors and placebo. Nine randomized clinical trials with a total of 60,914 patients with type 2 diabetes were included. In patients with type 2 diabetes, the use of SGLT2 and dual SGLT1/2 inhibitors improves the cardiovascular and kidney outcome. [ABSTRACT FROM AUTHOR]

Sodium-glucose cotransporter 2 inhibitor (SGLT2i) use is associated with improved cardiovascular and kidney outcomes. However, the magnitude and potential heterogeneity of effect across patients with varying types of cardiometabolic and kidney disease is unclear. To examine the effect of SGLT2i on cardiovascular and kidney outcomes among patients with type 2 diabetes mellitus (T2DM), and independent of T2DM status, among patients with heart failure (HF), and chronic kidney disease.Method: Medline, Embase, Cochrane library and scientific conferences were searched from inception till September 24, 2020 for randomized controlled trials comparing cardiovascular and kidney outcomes between SGLT2i and placebo. Random effects hazard ratios (HR) with 95% confidence intervals (CIs) were calculated.Results: Eight trials with a combined 59,747 patients were included. In the overall population, SGLT2i reduced the risk of all-cause mortality (HR 0.84; 95% CI [0.78-0.91]), cardiovascular mortality (HR 0.84; 95% CI [0.76-0.93]) hospitalization for HF (HR 0.69; 95% CI [0.64-0.74]), myocardial infarction (HR 0.91; 95% CI [0.84-0.99]), and composite kidney outcome (HR 0.62; 95% CI [0.56-0.70]). There was no significant effect on the risk of stroke (HR 0.98; 95% CI [0.86-1.11]). Results were consistent across subgroups stratified by diabetes and HF status. SGLT2i use was not associated with a greater risk of hypoglycemia (OR 0.92; 95% CI [0.84-1.01]) or amputation (OR 1.25; 95% CI [0.97-1.62]). There were 64 diabetic ketoacidosis events with SGLT2i use and 18 with placebo (OR 2.86; 95% CI [1.39-5.86]).Conclusions: In patients with cardiometabolic and kidney disease, SGLT2i improved cardiovascular and kidney outcomes, regardless of T2DM, HF, and/or CKD status. The magnitude of risk reduction was largest for hospitalization for HF and progression of kidney disease, more modest for mortality and MI and absent for stroke. [ABSTRACT FROM AUTHOR]

Cardiovascular randomized controlled trials (RCTs) typically set composite end points as the primary outcome to enhance statistical power. However, influence of individual component end points on overall composite outcomes remains understudied.Methods: We searched MEDLINE for RCTs published in 6 high-impact journals (The Lancet, the New England Journal of Medicine, Journal of the American Medical Association, Circulation, Journal of the American College of Cardiology and the European Heart Journal) from 2011 to 2017. Two-armed, parallel-design cardiovascular RCTs which reported composite outcomes were included. All-cause or cardiovascular mortality, myocardial infarction, heart failure, and stroke were deemed "hard" end points, whereas hospitalization, angina, and revascularization were identified as "soft" end points. Type of outcome (primary or secondary), event rates in treatment and control groups for the composite outcome and of its components according to predefined criteria.Results: Of the 45.8% (316/689) cardiovascular RCTs which used a composite outcome, 79.4% set the composite as the primary outcome. Death was the most common component (89.8%) followed by myocardial infarction (66.1%). About 80% of the trials reported complete data for each component. One hundred forty-seven trials (46.5%) incorporated a "soft" end point as part of their composite. Death contributed the least to the estimate of effects (R2 change = 0.005) of the composite, whereas revascularization contributed the most (R2 change = 0.423).Conclusions: Cardiovascular RCTs frequently use composite end points, which include "soft" end points, as components in nearly 50% of studies. Higher event rates in composite end points may create a misleading interpretation of treatment impact due to large contributions from end points with less clinical significance. [ABSTRACT FROM AUTHOR]

Background: Elamipretide, a novel mitochondrial modulating agent, improves myocardial energetics; however, it is unknown whether this mechanistic benefit translates into improved cardiac structure and function in heart failure (HF) with reduced ejection fraction (HFrEF). The objective of this study was to evaluate the effects of multiple subcutaneous doses of elamipretide on left ventricular end systolic volume (LVESV) as assessed by cardiac magnetic resonance imaging.Methods: We randomized 71 patients with HFrEF (LVEF ≤ 40%) in a double-blind, placebo-controlled trial in a 1:1:1 ratio to receive placebo, 4 mg or 40 mg elamipretide once daily for 28 consecutive days.Results: The mean age (standard deviation) of the study population was 65 ± 10 years, 24% were females, and the mean EF was 31% ± 7%. The change in LVESV from baseline to week 4 was not significantly different between elamipretide 4 mg (89.4 mL to 85 mL; difference, -4.4 mL) or 40 mg (77.9 mL to 76.6 mL; difference, -1.2 mL) compared with placebo (77.7 mL to 74.6 mL; difference, -3.8 mL) (4 mg vs placebo: difference of means, -0.3; 95% CI, -4.6 to 4.0; P  =  0.90; and 40 mg vs placebo: difference of means, 2.3; 95% CI, -1.9 to 6.5; P  =  0.28). Also, no significant differences in change in LVESV and LVEF were observed between placebo and either of the elamipretide groups. Rates of any study drug-related adverse events were similar in the 3 groups.Conclusions: Elamipretide was well tolerated but did not improve LVESV at 4 weeks in patients with stable HFrEF compared with placebo. [ABSTRACT FROM AUTHOR]

Current guidelines give balloon pulmonary angioplasty (BPA) a Class IIb recommendation for use in inoperable chronic thromboembolic pulmonary hypertension (CTEPH), as its safety and efficacy remain poorly defined. We conducted a systematic review and meta-analysis to evaluate BPA effectiveness. Medline, Cochrane Library and Scopus were searched for original studies from database inception dates until 24th May 2018. Prospective studies reporting outcomes before and after BPA in inoperable CTEPH patients were included. Studies with <20 patients were excluded. Data were pooled using a random effects model represented as weighted mean differences with 95% confidence intervals (CIs). Seventeen noncomparative studies comprising 670 CTEPH patients (mean age 62 years; 68% women) were included. Meta-analysis showed significantly decreased mean pulmonary artery pressure (−14.2 mm Hg [95% CI −18.9, −9.5]), pulmonary vascular resistance (−303.5 dyn·s/cm5 [95% CI −377.6, −229.4]) and mean right atrial pressure (−2.7 mm Hg [95% CI −4.1, −1.3]) after BPA. Six-minute walk distance (67.3 m [95% CI 53.8, 80.8]) and cardiac output (0.2 l/min [95% CI 0.0, 0.3]) were significantly increased following BPA. From 12 studies reporting mortality with median follow-up of 9 months after BPA (range, 1–51 months), pooled incidence of short (≤1 month) and long-term mortality (>1 month) was 1.9% and 5.7%, respectively. This systematic review and meta-analysis suggests mildly improved hemodynamics and overall low mortality rates following BPA in inoperable CTEPH patients. This non-comparative evidence can be used to facilitate decision making until the results of larger, controlled studies become available. • Balloon pulmonary angioplasty (BPA) is a relatively safe procedure. • Significant hemodynamic improvements observed after BPA. • Reperfusion lung injury and reperfusion edema are common complications after BPA. [ABSTRACT FROM AUTHOR]

Background: Role of statins in prevention of contrast-induced acute kidney injury (CI-AKI) in patients undergoing coronary angiography remains controversial. We studied the use of statins in decreasing CI-AKI following coronary angiography.Methods: We reviewed all patients who underwent coronary angiography with or without PCI and had a follow-up creatinine from January 2012 to December 2016 at a single tertiary care center in the United States. CI-AKI was defined as 0.3 mg/dL absolute rise in creatinine. Patients who were on moderate to high-intensity statins or received moderate to high-intensity statins prior to coronary angiography were included in the statin group. Crude and adjusted odds ratios (AOR) were calculated using univariate multiple logistic regression analysis.Results: Out of 2055 patients (females = 30.7%, mean age 58.0 ± 12.5 years, statin group = 886, non-statin group = 1169), 293 (14.3%) developed CI-AKI. Mean estimated glomerular filtration rate (eGFR) was not significantly different between the statin and the non-statin group (86.5 mL/min/1.73 m2 vs 87.1 mL/min/1.73 m2, p = 0.65). There was no significant difference in the incidence of CI-AKI between statin and non-statin group (14.4% vs 14.1%, p = 0.83). When adjusted for other risk factors, statin use was not significantly associated with decreased risk of CI-AKI (AOR) = 0.8, [95% confidence interval (CI) = 0.6-1.1, p = 0.19]. Results remained statistically non-significant on subgroup analysis of patients with acute coronary syndrome (ACS) (OR = 0.8, 95% CI = 0.6-1.2, p = 0.27), patients who had percutaneous coronary intervention (PCI) (OR = 1.1, 95% CI = 0.6-1.7, p = 0.81) and patients with eGFR < 60 mL/min/1.73 m2 (OR = 0.9, 95% CI = 0.6-1.5, p = 0.9).Conclusion: Statin use prior to coronary angiography is not associated with decreased incidence of CI-AKI. [ABSTRACT FROM AUTHOR]

Background Limited data exist studying the outcomes of the 2 minimally invasive aortic valve replacement (AVR) strategies—mini-sternotomy (AVR-st) and right anterior thoracotomy (AVR-th). We conducted an indirect meta-analysis to compare the outcomes of these minimally invasive approaches with each other and with conventional AVR (cAVR). Methods We Searched Medline, PubMed, Embase, and Web of Science in December 2017 for studies comparing AVR-st, AVR-th, and cAVR. Clinical outcomes were compared between cohorts with inverse weighted random effects modeling. Endpoints studied included hospital mortality, stroke, atrial fibrillation, cardiopulmonary bypass (CPB) time, and length of stay. Results A total of 19 studies (>10,000 pooled patients) met the inclusion criteria. Mortality (p = 0.06) and stroke (p = 0.15) were comparable between minimally invasive and conventional AVR. CPB times were longer with AVR-th versus cAVR (12.4 minutes [range, 5 to 19]; p < 0.01). In the AVR-th cohort, CPB duration was weakly inversely related to study size (p = 0.06). Atrial fibrillation was much less after AVR-th (odds ratio 0.47 [0.35 to 0.63]; p < 0.001). Hospital stay was significantly lower after minimally invasive surgery (0.8 [0.4 to 1.3] days; p < 0.01). AVR-th patients were dismissed 2.1 (1.6 to 2.7) days earlier than cAVR patients. Conclusions Minimally invasive approaches to AVR yield excellent outcomes in high-volume centers. They reduce hospital stay and incidence of postoperative atrial fibrillation, and therefore should be considered in patients undergoing AVR. The operative approach should be selected according to surgeon's technical expertise and what is best for specific patient profile, however. [ABSTRACT FROM AUTHOR]

Recent studies focusing on the prevalence, characteristics, and outcomes of primary heart failure (HF) with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF) in non-alcoholic fatty liver disease (NAFLD) are sparse. We sought to assess these using a nationally-representative population. We used the 2016-2018 National Inpatient Sample database to study the prevalence, characteristics, clinical risk profiles, morbidity, mortality, cost, and resource utilization among primary HFpEF and HFrEF hospitalizations with and without NAFLD. In the period from January 1, 2016, to December 31, 2018, there were 3,522,459 admissions of patients aged ≥18 years with a diagnosis of primary HF. Of these, 82,585 (2.3%) hospitalizations had secondary diagnosis of NAFLD. Admissions with NAFLD and HFrEF were associated with higher rates of in-hospital mortality (aOR 1.84, CI 1.66-2.04, P < 0.001) compared to admissions of HFrEF without NAFLD. Similarly, hospitalizations with HFpEF-NAFLD were associated with higher rates of in hospital mortality (aOR 1.65 CI 1.43-1.9, P < 0.001) compared to HFpEF admissions without NAFLD. Pressors use, cardiogenic shock, AKI with or without dialysis use, cardiac arrest, LOS and hospitalization cost were higher in admissions of HFrEF and HFpEF with NAFLD compared to those without NAFLD. In-hospital mortality, was higher in primary HFrEF and HFpEF admissions with NAFLD compared to without NAFLD. Physicians must be aware of the worse clinical outcomes of HFrEF and HFpEF in patients with NAFLD. Further clinical research is needed to address the knowledge gap and treatment options available for the patients with HF and NAFLD. [ABSTRACT FROM AUTHOR]

Background: Transcatheter closure of patent foramen ovale (PFO) after cryptogenic stroke has long been a contentious issue. Herein, we pool aggregate data examining safety and efficacy of transcatheter closure of PFO compared with medical therapy following initial cryptogenic stroke.Methods: We searched for randomized clinical trials (RCT) that compared device closure with medical management and reported on subsequent stroke and adverse events. Stroke was considered as the primary efficacy endpoint, whereas bleeding and atrial fibrillation were considered primary safety endpoints. Data were pooled by the random effects model and I2 was used to assess heterogeneity.Results: A total of 5 RCT investigating 3630 patients met inclusion criteria. Pooled analysis revealed that device closure compared to medical management was associated with a significant reduction in stroke (RR=0.3, 95% CI=0.02-0.57). There was, however, a significant increase in atrial arrhythmias with device therapy (RR=4.8, 95% CI=2.2-10.7). We found no increase in bleeding (RR=0.80, 95% CI=0.5-1.4), death (RR=0.76, 95% CI=0.3-1.99) or "any adverse events" (RR=1.02, 95% CI=0.85-1.23) with device therapy. Sub-group analysis revealed that device closure significantly reduced the incidence of the composite primary endpoint among patients who had moderate to large shunt sizes (RR=0.22, 95% CI=0.02-0.42).Conclusions: Transcatheter closure is associated with a significant reduction in the risk of stroke compared to medical management at the expense of an increased risk of atrial arrhythmias. [ABSTRACT FROM AUTHOR]

Heart failure with reduced ejection fraction (HFrEF) is a complex and progressive clinical condition characterized by dyspnea and functional impairment. HFrEF has a high burden of mortality and readmission rate making it one of the most significant public health challenges. Basic treatment strategies include diuretics for symptom relief and use of quadruple therapy (Angiotensin receptor blocker/neprilysin inhibitors, evidence-based beta-blockers, mineralocorticoid receptor antagonists, and sodium–glucose co-transporter 2 inhibitors) for reduction in hospitalizations, all-cause mortality, and cardiovascular mortality. Despite compelling evidence of clinical benefit, guideline directed medical therapy is vastly underutilized in the real-world clinical practice. Other medications such as intravenous iron, ivabradine, hydralazine/nitrates and vericiguat may also have a role in certain subgroup of HFrEF patients. Specific groups of patients with HFrEF may also be candidates for various device therapies such as implanted cardioverter defibrillators, cardiac resynchronization therapy and trans catheter mitral valve repair. This review provides a comprehensive overview of drug and device management approaches for patients with HFrEF, recommendations for initiation and titrations of therapies, and challenges associated with guideline directed medical therapy in the management of patients with HFrEF (Graphical abstract). [Display omitted] [ABSTRACT FROM AUTHOR]

Heart failure (HF), diabetes, and chronic kidney disease (CKD) frequently coexist, with one comorbidity worsening the prognosis of another. β-blockers, angiotensin-receptor–neprilysin inhibitors, renin-angiotensin-aldosterone system inhibitors, mineralocorticoid-receptor antagonists, and sodium-glucose cotransporter-2 inhibitors all have been shown to reduce mortality in patients with HF with reduced ejection fraction. However, their uptake in real-world clinical practice remains low, especially among patients who have multiple other comorbidities such as CKD and diabetes. The management of HF in patients with diabetes and CKD can be especially challenging because these patients typically are older, frail, and have multiple other comorbidities, and guideline-directed medical therapy used in HF potentially can affect renal function acutely and chronically. In this article, we discuss the available evidence for each of the foundational HF therapies in patients with diabetes and CKD, emphasizing the current challenges and outlining future directions to optimize the management of HF among these high-risk patients. [ABSTRACT FROM AUTHOR]

Although the prevalence of HF in young adults (age <50 years) is increasing, there are limited data on the trajectory of decongestion and short-term outcomes in young adults with acute heart failure (AHF). We pooled patients from 3 randomized trials of AHF conducted within the Heart Failure Network (the Diuretic Optimization Strategies trial, the Renal Optimization Strategies Trial, and the Cardiorenal Rescue Study in Acute Decompensated Heart Failure). The association between young age (<50 years and >50 years) and in-hospital changes in various measures of decongestion as well as short-term outcomes including risk for rehospitalization, and all-cause mortality was evaluated. Of 762 patients, 72 (10.3%) patients were young. Young adults were more likely to be African American (53.8% vs 19.3%), to have a lower rate of ischemic HF etiology (25.6% vs 60.4%, P <0.001), and a lower burden of hypertension, chronic kidney disease and atrial fibrillation. Young adults had a lower left ventricular ejection fraction (median 20% vs 33%, P < 0.001); they had a higher admission weight (median 242.7 lbs vs 201.5 lbs, P < 0.001), but lower NT-pro BNP levels (median 3622 pg/mL vs 4676 pg/mL, P = 0.003). After covariate adjustment, there was no difference in the change in NT-pro BNP (P = 0.25), net fluid loss (P = 0.42), or renal function (P = 0.56) between young and older adults by 72 or 96 hours of randomization. There was no difference in orthodema congestion score or the composite clinical endpoint during the follow-up (all-cause mortality or any rehospitalization) (adjusted odds ratios (95% confidence intervals): 2.51 (0.78-8.01), P = 0.12). In this pooled analysis of 3 clinical trial cohorts, compared with older adults, younger adults had a unique demographic and clinical profile. Despite these differences, there was no difference by age group in in-hospital decongestion or post-discharge readmission or mortality. [ABSTRACT FROM AUTHOR]

Background: With limited health care resources, bibliometric studies can help guide researchers and research funding agencies towards areas where reallocation or increase in research activity is warranted. Bibliometric analyses have been published in many specialties and sub-specialties but our literature search did not reveal a bibliometric analysis on Cardiovascular Magnetic Resonance (CMR). The main objective of the study was to identify the trends of the top 100 cited articles on CMR research. Methods: Web of Science (WOS) search was used to create a database of all English language scientific journals. This search was then cross-referenced with a similar search term query of Scopus® to identify articles that may have been missed on the initial search. Articles were ranked by citation count and screened by two independent reviewers. Results: Citations for the top 100 articles ranged from 178 to 1925 with a median of 319.5. Only 17 articles were cited more than 500 times, and the vast majority (n= 72) were cited between 200-499 times. More than half of the articles (n= 52) were from the United States of America, and more than one quarter (n= 21) from the United Kingdom. More than four fifth (n= 86) of the articles were published between the time period 2000-2014 with only 1 article published before 1990. Circulation and Journal of the American College of Cardiology made up more than half (n= 62) of the list. We found 10 authors who had greater than 5 publications in the list. Conclusion: Our study provides an insight on the characteristics and quality of the most highly cited CMR literature, and a list of the most influential references related to CMR. [ABSTRACT FROM AUTHOR]

Current kidney death definitions across heart failure (HF) trials are ambiguous and lack standardization. The interlinked shared pathways of HF and kidney failure makes it difficult to adjudicate the cause versus effect relationship of worsening HF and kidney failure events and raises concerns whether 'kidney death' is an affirmative or exclusionary diagnosis. Universally standardized definition of kidney death is therefore of utmost importance to accurately ascertain if kidney death is due to kidney failure itself or due to complications associated with it. Conceptually comprehensive and applicable definition(s) would be beneficial for clinicians and investigators in comparing data across trials and for shared decision making. Herein, we review the current definitions of kidney death, the frequency of reporting it across HF trials and the limitations associated with it. Additionally, we propose clinically relevant and comprehensive definitions pertaining kidney organ death which may aid clinicians and researchers alike in accurately distinguishing kidney death from a non-kidney death event. [ABSTRACT FROM AUTHOR]