The quintessential form of diastolic heart failure in older adults: Wild type transthyretin cardiac amyloidosis

Wild-type transthyretin cardiac amyloidosis (ATTRwt) is now recognized as a common cause of heart failure with preserved ejection fraction (HFpEF). In this review, we aim to describe the unique epidemiologic, pathophysiologic, and clinical features associated with ATTwt cardiac amyloidosis. Compared to other etiologies of HFpEF, ATTRwt cardiac amyloidosis affects almost exclusively older adults, demonstrating a characteristic age-dependent penetrance that impacts both the diagnosis and treatment of the disease. In addition, ATTR cardiac amyloidosis demonstrates a unique pathophysiology in contrast to other etiologies of HFpEF, which results in a characteristic phenotype that can raise suspicion for ATTRwt cardiac amyloid in the appropriate demographic. With these distinguishing features in mind, we aim to describe the specific signs, symptoms, and imaging characteristics associated with ATTRwt cardiac amyloidosis, including the role of nuclear scintigraphy that has essentially eliminated the need for biopsy in most patients with suspected disease. Finally, we review the evidence behind the available therapeutic agents, as well as those under investigation, which will change the way we manage older patients with ATTRwt cardiac amyloidosis in the coming years.     

Transcatheter valve interventions in heart failure: new answers to old questions

Heart failure (HF) is often associated with different valve diseases, predominantly functional mitral and tricuspid regurgitation. However, the association between HF and aortic stenosis, particularly low-flow low-gradient aortic stenosis, is not infrequent. Severe mitral and tricuspid regurgitations, as well as aortic stenosis, in HF patients worsen prognosis and left ventricular dilatation and induce further reduction in left ventricular ejection fraction. Transcatheter edge-to-edge mitral and tricuspid valve repair and transcatheter aortic valve implantation could be an important therapeutic option with a satisfactory long-term outcome in HF patients with comorbidities and even in patients with severely depressed ejection fraction.     

Sodium–glucose cotransporter 2 inhibitors represent a paradigm shift in the prevention of heart failure in type 2 diabetes patients

Recent major clinical trials of the use of sodium–glucose cotransporter 2 (SGLT2) inhibitors in patients with type 2 diabetes have shown that they reduce three-point major adverse cardiovascular events, cardiovascular death, hospitalization for heart failure (HF) and a composite renal outcome. These beneficial effects of SGLT2 inhibitors are also evident in type 2 diabetes patients with a previous history of atherosclerotic cardiovascular disease or advanced renal disease. HF is a major determinant of the prognosis of diabetes patients. Although HF with low ejection fraction can be effectively treated with antihypertensive drugs, these treatments do not reduce mortality in HF patients with preserved ejection fraction (HFpEF). HFpEF is clinically characterized by left ventricular diastolic dysfunction, perivascular fibrosis and stiffness of cardiomyocytes, defined as “cardiomyopathy”. Therefore, HFpEF is considered to be an entirely separate entity to HF with low ejection fraction. Recent studies have suggested that HFpEF might be treatable using SGLT2 inhibitors, which ameliorate visceral adiposity, insulin resistance, hyperglycemia, hyperlipidemia, volume overload, hypertension and cardiac inflammation. In the final part of the present review, we discuss the biochemical and molecular mechanisms of the effects of SGLT2 inhibitors in type 2 diabetes patients with HFpEF. These involve amelioration of the low nitric oxide production and oxidative stress, a reduction in cardiac inflammatory cytokine signaling, inhibition of Ca²⁺ overload, and an improvement in cardiac energy metabolism as a result of ketone body production. Investigations of the beneficial effects of SGLT2 inhibitors on cardiorenal outcomes, including hospitalization for HF, are now being carried out in preclinical and clinical studies.     

Clinical Phenotyping of Transthyretin Cardiac Amyloidosis with Bone-Seeking Radiotracers in Heart Failure with Preserved Ejection Fraction

Purpose of Review

The two most common types of cardiac amyloidosis are caused by fibril deposits of immunoglobulin light chains (AL) and transthyretin (TTR), each with distinct prognosis and clinical management. Cardiac amyloidosis is under-recognized among heart failure patients with preserved ejection fraction (HFpEF). Bone-seeking tracers like ^99mTc-PYP and ^99mTc-DPD have long been used to identify cardiac amyloidosis, and more recently, to differentiate TTR from AL cardiac amyloidosis in symptomatic patients. However, results are mainly derived from single-center retrospective studies, with comparable but not standardized imaging protocols and interpretation criteria.

Recent Findings

The clinical scope of cardiac amyloidosis among HFpEF patients and current literature supporting the use of bone-seeking tracers for TTR cardiac amyloidosis are presented. The differences of imaging techniques for cardiac amyloid and bone disease evaluation, bone tracer pharmacodynamics, and imaging interpretation criteria for cardiac amyloidosis diagnosis are discussed. Finally, a diagnostic algorithm to use bone scintigraphy in cardiac amyloidosis diagnosis among HFpEF patients is proposed.

Summary

Bone scintigraphy with ^99mTc-PYP or ^99mTc-DPD can be a useful tool with high sensitivity and specificity for detecting TTR-related cardiac amyloidosis in patients with HFpEF. It is needed to standardize the imaging protocol and interpretation criteria and to perform prospective clinical studies.

     

Heart failure in the patient with diabetes: Epidemiology,aetiology, prognosis,therapy and the effect of glucose-lowering medications

In people with type 2 diabetes the frequency of heart failure (HF) is increased and mortality from HF is higher than with non-diabetic HF. The increased frequency of HF is attributable to the cardiotoxic tetrad of ischaemic heart disease, left ventricular hypertrophy, diabetic cardiomyopathy and an extracellular volume expansion resistant to atrial natriuretic peptides. Activation of the renin-angiotensin-aldosterone system and sympathetic nervous systems results in cardiac remodelling, which worsens cardiac function. Reversal of remodelling can be achieved, and cardiac function improved in people with HF with reduced ejection fraction (HFrEF) by treatment with angiotensin-converting enzyme inhibitors and β-blockers. However, with HF with preserved ejection fraction (HFpEF), only therapy for the underlying risk factors helps. Blockers of mineralocorticoid receptors may be beneficial in both HFrEF and HFpEF. Glucose-lowering drugs can have a negative effect (insulin, sulphonylureas, dipeptidyl peptidase-4 inhibitors and thiazolidinediones), a neutral effect (α-glucosidase inhibitors and glucagon-like peptide-1 receptor agonists) or a positive effect (sodium-glucose co-transporter-2 inhibitors and metformin).     

Epidemiology,Pathophysiology, Diagnosis,and Therapy of Heart Failure With Preserved Ejection Fraction in Japan

Heart failure (HF) with preserved ejection fraction (HFpEF) is a global health care problem, with diagnostic difficulty, limited treatment options and high morbidity and mortality rates. The prevalence of HFpEF is increasing because of the aging population and the increasing burden of cardiac and metabolic comorbidities, such as systemic hypertension, diabetes, chronic kidney disease, and obesity. The knowledge base is derived primarily from the United States and Europe, and data from Asian countries, including Japan, remain limited. Given that phenotypic differences may exist between Japanese and Western patients with HFpEF, careful characterization may hold promise to deliver new therapy specific to the Japanese population. In this review, we summarize the current knowledge regarding the epidemiology, pathophysiology and diagnosis of and the potential therapies for HFpEF in Japan.     

New Drugs and Devices in the Pipeline for Heart Failure with Reduced Ejection Fraction Versus Heart Failure with Preserved Ejection Fraction

Heart failure (HF) is a growing problem in the USA and other industrialized nations. HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF) each make up approximately half of the overall HF burden. Although a variety of medical and surgical therapies exist for the treatment of patients with HFrEF, morbidity and mortality remain high, and cardiac transplantation, considered the current gold standard for patients with HFrEF and severe symptoms, is reserved for relatively few eligible patients. Patients with HFpEF have more limited therapeutic options, because no medical therapy to date has been shown to improve survival in these patients. With the rising prevalence of HF and its increasing role in health care expenditure, there is a substantial need for new drug and device therapies for HFrEF and, in particular, HFpEF. This forms the topic of the current review.     

Current concept in the diagnosis,treatment and rehabilitation of patients with congestive heart failure

Heart failure(HF) is a major public health problem with a prevalence of 1%-2% in developed countries. The underlying pathophysiology of HF is complex and as a clinical syndrome is characterized by various symptoms and signs. HF is classified according to left ventricular ejection fraction(LVEF) and falls into three groups: LVEF ≥ 50%-HF with preserved ejection fraction(HFpEF), LVEF 40%-HF with reduced ejection fraction(HFrEF), LVEF 40%-49%-HF with mid-range ejection fraction. Diagnosing HF is primarily a clinical approach and it is based on anamnesis, physical examination, echocardiogram, radiological findings of the heart and lungs and laboratory tests, including a specific markers of HF-brain natriuretic peptide or N-terminal pro-B-type natriuretic peptide as well as other diagnostic tests in order to elucidate possible etiologies. Updated diagnostic algorithms for HFpEF have been recommended(H2 FPEF, HFA-PEFF). New therapeutic options improve clinical outcomes as well as functional status in patients with HFrEF(e.g., sodium-glucose cotransporter-2-SGLT2 inhibitors) and such progress in treatment of HFrEF patients resulted in new working definition of the term "HF with recovered left ventricular ejection fraction". In line with rapid development of HF treatment, cardiac rehabilitation becomes an increasingly important part of overall approach to patients with chronic HF for it has been proven that exercise training can relieve symptoms, improve exercise capacity and quality of life as well as reduce disability and hospitalization rates. We gave an overview of latest insights in HF diagnosis and treatment with special emphasize on the important role of cardiac rehabilitation in such patients.     

Prevalence,characteristics and prognostic impact of aortic valve disease in patients with heart failure and reduced,mildly reduced,and preserved ejection fraction: An analysis of the ESC Heart Failure Long-Term Registry

Aims

To assess the prevalence, clinical characteristics, and outcomes of patients with heart failure (HF) with or without moderate to severe aortic valve disease (AVD) (aortic stenosis [AS], aortic regurgitation [AR], mixed AVD [MAVD]).

Methods and results

Data from the prospective ESC HFA EORP HF Long-Term Registry including both chronic and acute HF were analysed. Of 15 216 patients with HF (62.5% with reduced ejection fraction, HFrEF; 14.0% with mildly reduced ejection fraction, HFmrEF; 23.5% with preserved ejection fraction, HFpEF), 706 patients (4.6%) had AR, 648 (4.3%) AS and 234 (1.5%) MAVD. The prevalence of AS, AR and MAVD was 6%, 8%, and 3% in HFpEF, 6%, 3%, and 2% in HFmrEF and 4%, 3%, and 1% in HFrEF. The strongest associations were observed for age and HFpEF with AS, and for left ventricular end-diastolic diameter with AR. AS (adjusted hazard ratio [HR] 1.43, 95% confidence interval [CI] 1.23–1.67), and MAVD (adjusted HR 1.37, 95% CI 1.07–1.74) but not AR (adjusted HR 1.13, 95% CI 0.96–1.33) were independently associated with the 12-month composite outcome of cardiovascular death and HF hospitalization. The associations between AS and the composite outcome were observed regardless of ejection fraction category.

Conclusions

In the ESC HFA EORP HF Long-Term Registry, one in 10 patients with HF had AVD, with AS and MAVD being especially common in HFpEF and AR being similarly distributed across all ejection fraction categories. AS and MAVD, but not AR, were independently associated with increased risk of in-hospital mortality and 12-month composite outcome, regardless of ejection fraction category.     

Role of Cardiac Contractility Modulation in Heart Failure With a Higher Ejection Fraction

Cardiac contractility modulation (also known as CCM) is a novel device therapy that delivers nonexcitatory electric stimulation to cardiac myocytes during the absolute refractory period, and it has been shown to improve functional status and clinical outcomes in patients with heart failure (HF) with reduced ejection fraction (HFrEF). CCM therapy is currently recommended for a subset of patients with advanced HFrEF who are not candidates for cardiac resynchronization therapy. A growing body of evidence demonstrates the benefit of CCM therapy in patients with HFrEF and with ejection fraction at the upper end of the spectrum and in patients with HF and with mildly reduced ejection fraction (HFmrEF). Experimental studies have also observed reversal of pathological biomolecular intracellular changes with CCM therapy in HF with preserved ejection fraction (HFpEF), indicating the potential for clinically meaningful benefits of CCM therapy in these patients. In this review, we sought to discuss the basis of CCM therapy and its potential for management of patients with HF with higher ejection fractions.     

Outcomes and Predictors of Mortality Among Cardiac Intensive Care Unit Patients With Heart Failure

BackgroundLittle is known regarding the causes of critical illness and determinants of prognosis of patients with heart failure (HF) admitted to the modern cardiac intensive care unit (CICU). We sought to describe the epidemiology and outcomes of patients with HF admitted to the contemporary CICU.Methods and ResultsRetrospective cohort analysis of Mayo Clinic CICU patients admitted with HF from 2007 to 2018 who had left ventricular ejection fraction (LVEF) data. HF with reduced LVEF (HFrEF) was defined as a LVEF of less than 50%, and HF with preserved LVEF (HFpEF) as a LVEF of 50% or greater. In-hospital mortality was analyzed using multivariable logistic regression. Survival to 1 year was analyzed using a Kaplan–Meier analysis. We included 4012 patients, including 67.8% with HFrEF and 32.2% with HFpEF. Patients with HFrEF and HFpEF were comparable and had equivalent severity of illness. Critical care therapies were used in 59.4%, with a slight preponderance in patients with HFrEF. In-hospital mortality occurred in 12.5% of patients and was similar in HFrEF vs HFpEF. Shock and cardiac arrest were the strongest predictors of adjusted in-hospital mortality, followed by Braden skin score and serum chloride level; patients with HFrEF and HFpEF had similar adjusted mortality rates. The 1-year survival after hospital discharge was 74.5% and was slightly lower for patients with HFpEF. All-cause rehospitalization occurred in 36.6%, and 52.8% of hospital survivors died or were readmitted within 1 year.ConclusionsCICU patients with HF have a substantial burden of critical illness, high use of critical care therapies, and poor outcomes regardless of LVEF. This finding emphasizes the potential unmet care needs in this cohort.Lay summaryPatients with heart failure who require admission to the cardiac intensive care unit have high severity of illness and are at significant risk of death during and after hospitalization. These patients often require specialized critical care therapies to treat manifestations of critical illness. Patients who are admitted with cardiac arrest or shock, including those who require mechanical ventilation or vasopressors, are at particularly high risk of death. Patients’ left ventricular ejection fraction is not strongly associated with the risk of death when accounting for other major predictors including frailty and laboratory abnormalities.     

Cardiac amyloidosis: An underdiagnosed/underappreciated disease

Cardiac amyloidosis or amyloid cardiomyopathy (ACM), commonly resulting from extracellular deposition of amyloid fibrils consisted of misfolded immunoglobulin light chain (AL) or transthyretin (TTR) protein, is an underestimated cause of heart failure and cardiac arrhythmias. Among the three types of cardiac amyloidosis (wild-type or familial TTR and light-chain), the wild-type (Wt) TTR-related amyloidosis (ATTR) is an increasingly recognized cause of heart failure with preserved ejection fraction (HFpEF), and amyloidosis should be considered in the differential diagnosis of this heart failure group of patients. Recent advances in the diagnosis and drug treatment of ACM have ushered in a new era in early disease detection and better management of these patients. Certain clues in cardiac and extracardiac manifestations of ACM may heighten clinical suspicion and guide further confirmatory testing. Newer noninvasive imaging methods (strain echocardiography, cardiac magnetic resonance and bone scintigraphy) may obviate the need for endomyocardial biopsy in ATTR patients, while newer targeted therapies may alter the adverse prognosis in these patients. Early recognition of ACM is crucial in halting the disease process before irreversible organ damage occurs. Chemotherapy and stem-cell transplantation combined with immunomodulatory therapy may also favorably affect the course and prognosis of light chain ACM. Finally, in select patients with end-stage disease, heart transplantation may render results comparable to non-ACM patients. All these issues are herein reviewed.     

Epidemiology and clinical characteristics of hospitalized elderly patients for heart failure with reduced,mid-range and preserved ejection fraction

Introduction: Elderly patients hospitalized with heart failure (HF) have high mortality rates and requires specific evidence based theraphy, however there are few studies which have focused on patients older than 80 years hospitalized with HF. The aim of the present study is to evaluate the overall clinical characteristics, management, and in-hospital outcomes of elderly patients hospitalized with HF.Methods: Journey-HF study was conducted in 37 different centers in Turkey and recruited 1606 patients who were hospitalized with HF between September 2015 and September 2016. In this study, clinical profile of patients ≥ 80 years old and 65-79 years old hospitalized with HF were described and compared based on EF-related classification: HFrEF (HF with reduced ejection fraction), HFmrEF (HF with mid-range ejection fraction) and HFpEF (HF with preserved ejection fraction).Results: A total of 1034 elder patients (71.6% 65–79 years old and 28.4% ≥80 years old) were recruited. Of the 65–79 years old patients 67.4% had HFrEF, 16.2% had HFmrEF and 16.3% had HFpEF. Among patients ≥80 years old 61.6% had HFrEF, 15.6% had HmrEF and 22.8% had HFpEF.When compared with patients with HFrEF and HFmrEF, patients ≥80 years old with HFpEF were more likely to be older, have atrial fibrilation (AF), and less likely to have diabetes mellitus (DM), coronary artery disease (CAD) or to be recieving an angiotensin-converting enzyme inhibitor (ACEi) or beta blocker theraphy. When compared to patients 65–79 years old with HFpEF, patients ≥80 years with HFpEF had a higher rate of AF and less likely DM. Acute coronary syndrome was the most common precipitant factor for hospitalization in both age groups with HFrEF group. Arrhythmia was a major precipitant factor for hospitalization of patients ≥80 years old with HFpEF. Non-compliance with theraphy was a major problem of patients ≥80 years old with HFrEF.Conclusion: Elderly patients with HFrEF, HFmrEF and HFpEF each had characterized unique patient profiles and the guideline recommended medications were less likely to be used in these patient populations. In hospital mortality rate is worrisome and reflects a need for more specific tretment strategy.     

Características e Tendências na Mortalidade em Diferentes Fenótipos de Insuficiência Cardíaca na Atenção Primária

Background:The classification of heart failure (HF) by phenotypes has a great relevance in clinical practice.Objective:The study aimed to analyze the prevalence, clinical characteristics, and outcomes between HF phenotypes in the primary care setting.Methods:This is an analysis of a cohort study including 560 individuals, aged ≥ 45 years, who were randomly selected in a primary care program. All participants underwent clinical evaluations, b-type natriuretic peptide (BNP) measurements, electrocardiogram, and echocardiography in a single day. HF with left ventricular ejection fraction (LVEF) < 40% was classified as HF with reduced ejection fraction (HFrEF), LVEF 40% to 49% as HF with mid-range ejection fraction (HFmrEF) and LVEF ≥ 50% as HF with preserved ejection fraction (HFpEF). After 5 years, the patients were reassessed as to the occurrence of the composite outcome of death from any cause or hospitalization for cardiovascular disease.Results:Of the 560 patients included, 51 patients had HF (9.1%), 11 of whom had HFrEF (21.6%), 10 had HFmrEF (19.6%) and 30 had HFpEF (58.8%). HFmrEF was similar to HFpEF in BNP levels (p < 0.001), left ventricular mass index (p = 0.037), and left atrial volume index (p < 0.001). The HFmrEF phenotype was similar to HFrEF regarding coronary artery disease (p = 0.009). After 5 years, patients with HFmrEF had a better prognosis when compared to patients with HFpEF and HFrEF (p < 0.001).Conclusion:The prevalence of ICFEI was similar to that observed in previous studies. ICFEI presented characteristics similar to ICFEP in this study. Our data show that ICFEi had a better prognosis compared to the other two phenotypes.     

Noninvasive Identification of ATTRwt Cardiac Amyloid: The Re-emergence of Nuclear Cardiology

More than half of all subjects with chronic heart failure are older adults with preserved ejection fraction (HFpEF). Effective therapy for this condition is yet to be delineated by clinical trials, suggesting that a greater understanding of underlying biologic mechanisms is needed, especially for the purpose of clinical intervention and future clinical trials. Amyloid infiltration of the myocardium is an underappreciated contributing factor to HFpEF that is often caused by misfolded monomers or oligomers of the protein transthyretin. While previously called senile cardiac amyloidosis and traditionally requiring endomyocardial biopsy for diagnosis, advances in our pathophysiologic understanding of this condition, coupled with nuclear imaging techniques using bone isotopes that can diagnose this condition noninvasively and the development of potential therapies, have resulted in a renewed interest in this previously considered “rare” condition. This reviewer focuses on the re-emergence of nuclear cardiology using pyrophosphate agents that hold promise for early, noninvasive identification of affected individuals.     

Trends in Heart Failure Hospitalizations in the US from 2008 to 2018

BackgroundHeart failure (HF) is a major driver of health care costs in the United States and is increasing in prevalence. There is a paucity of contemporary data examining trends among hospitalizations for HF that specifically compare HF with reduced or preserved ejection fraction (HFrEF or HFpEF, respectively).Methods and ResultsUsing the National Inpatient Sample, we identified 11,692,995 hospitalizations due to HF. Hospitalizations increased from 1,060,540 in 2008 to 1,270,360 in 2018. Over time, the median age of patients hospitalized because of HF decreased from 76.0 to 73.0 years (P < 0.001). There were increases in the proportions of Black patients (18.4% in 2008 to 21.2% in 2018) and of Hispanic patients (7.1% in 2008 to 9.0% in 2018; P < 0.001, all). Over the study period, we saw an increase in comorbid diabetes, sleep apnea and obesity (P < 0.001, all) in the entire cohort with HF as well as in the HFrEF and HFpEF subgroups. Persons admitted because of HFpEF were more likely to be white and older compared to admissions because of HFrEF and also had lower costs. Inpatient mortality decreased from 2008 to 2018 for overall HF (3.3% to 2.6%) and HFpEF (2.4% to 2.1%; P < 0.001, all) but was stable for HFrEF (2.8%, both years). Hospital costs, adjusted for inflation, decreased in all 3 groups across the study period, whereas length of stay was relatively stable over time for all groups.ConclusionsThe volume of patients hospitalized due to HF has increased over time and across subgroups of ejection fraction. The demographics of HF, HFrEF and HFpEF have become more diverse over time, and hospital inpatient costs have decreased, regardless of HF type. Inpatient mortality rates improved for overall HF and HFpEF admissions but remained stable for HFrEF admissions.     

Reframing the association and significance of co‐morbidities in heart failure

Several co‐existing diseases and/or conditions (co‐morbidities) are present in patients with heart failure (HF), with diverse clinical relevance. Multiple mechanisms may underlie the co‐existence of HF and co‐morbidities, including direct causation, associated risk factors, heterogeneity, and independence. The complex inter‐relationship of co‐morbidities and their impact on the cardiovascular system contribute to the features of HF, both with reduced (HFrEF) and preserved ejection fraction (HFpEF). The purpose of this work is to provide an overview of the contribution of major cardiac and non‐cardiac co‐morbidities to HF development and outcomes, in the context of both HFpEF and HFrEF. Accordingly, epidemiological evidence linking co‐morbidities to HF and the effect of prevalent and incident co‐morbidities on HF outcome will be reviewed.     

Heart failure in people with type 2 diabetes vs. those without diabetes: A retrospective observational study from South India

Background and aimDespite diabetes being an independent risk for HF, only some DM patients develop HF and hence our aim was to compare the clinical features of DM with and without HF and non-DM with and without HF.MethodsA retrospective observational study was conducted among 397 individuals who visited two tertiary care centres. They were classified into 4 groups – DM with HF(DM-HF), DM without HF, non-DM with HF(non-DM-HF) and non-DM without HF. We assessed and compared the clinical profile of DM with HF vs. DM without HF and non-DM with HF groups respectively.ResultsThe parameters such as age, BMI, BP, eGFR showed significant difference between the groups. People with DM-HF were older compared to DM without HF group(58.9 ± 9.2vs.49.5 ± 9.3; p < 0.001). An increasing trend was observed in HF prevalence with increasing duration of DM among the DM-HF group. DM-HF showed a higher prevalence of hypertension and coronary artery disease(CAD) by history than DM without HF group. DM-HF group(91.2%) had HF with preserved left ventricular ejection fraction(HFpEF) whereas a high proportion(43.5%) of non-DM-HF group had HF with reduced LV ejection fraction(HFrEF).ConclusionsThe DM-HF group differed from other groups significantly in age, diabetes duration, HbA1c level, prevalence of hypertension, CAD and HFpEF.     

The Relationship Between Atrial Fibrillation,Mitral Regurgitation,and Heart Failure Subtype: The ARIC Study

BackgroundAtrial fibrillation (AF) and mitral regurgitation (MR) are closely interrelated in the setting of heart failure (HF). Here we investigate the prevalence and prognostic significance of AF in patients with acute decompensated HF (ADHF) stratified by MR severity.Methods and ResultsThe Atherosclerosis Risk in Communities Study investigated ADHF hospitalizations in residents greater than or equal to 55 years of age in 4 US communities. ADHF cases were stratified by MR severity (none/mild or moderate/severe) and HF subtype (HF with reduced [HFrEF] or preserved [HFpEF] ejection fraction). The odds of AF in patients with increasing MR severity was estimated using multivariable logistic regression, adjusting for age, race, sex, diabetes, hypertension, coronary artery disease, hemodialysis, stroke, and anemia. Cox regression models were used to assess the association of AF with 1-year mortality in patients with HFpEF and HFrEF, stratified by MR severity and adjusted as described, also adjusting for the year of hospitalization. From 2005 to 2014, there were 3,878 ADHF hospitalizations (17,931 weighted). AF was more likely in those with higher MR severity regardless of HF subtype; more so in HFpEF (odds ratio [OR] 1.38, 95% confidence interval [CI], 1.31–1.45) than in HFrEF (OR, 1.19, 95% CI, 1.13–1.25) (interaction P [by HF subtype] < .01). When stratified by HF type, association between AF and 1-year mortality was noted in patients with HFpEF (OR, 1.28, 95% CI 1.04–1.56) but not HFrEF (OR 0.96, 95% CI 0.79–1.16) (interaction by EF subtype, P = .02).ConclusionsIn patients with ADHF, AF prevalence increased with MR severity and this effect was more pronounced in HFpEF compared with HFrEF. AF was associated with an increased 1-year mortality only in patients with HFpEF and concomitant moderate/severe MR.RegistrationNCT00005131, https://clinicaltrials.gov/ct2/show/NCT00005131     

Use of sodium–glucose co‐transporter‐2 inhibitors in patients with and without type 2 diabetes: implications for incident and prevalent heart failure

Type 2 diabetes (T2D) is associated with an increased risk of heart failure (HF), with recent reports indicating that HF with preserved ejection fraction (HFpEF) may be more common than HF with reduced ejection fraction (HFrEF) in patients with T2D. T2D and HF result in worse outcomes than either disease alone. Sodium–glucose co‐transporter‐2 inhibitors (SGLT‐2is) have significantly improved HF outcomes in patients with T2D and may represent a new therapeutic alternative for patients with T2D at risk for or with HF. Current guidelines recommend prevention of HF through risk factor management. Once developed, treatment of HFrEF should include neurohormonal and haemodynamic modulations; however, there are no specific treatments available for HFpEF. SGLT‐2is are the first class of glucose‐lowering therapy to prevent HF in clinical trials and real‐world studies in patients with T2D (with or without established cardiovascular disease and with or without baseline HF). Mechanistic studies suggest that SGLT‐2is have beneficial effects on both systolic and diastolic function and additional systemic effects that could benefit HF outcomes. In patients with HFrEF, SGLT‐2i treatment as add‐on to standard HF therapy has had beneficial effects on HF outcomes, irrespective of T2D status. These results and those of ongoing outcomes trials with SGLT‐2is may help establish this drug class as a treatment for HF in patients with HFrEF and HFpEF, as well as HF in patients without T2D.