Beyond the Initial Insult: Clinical Characteristics and Prognosis of Heart Failure with Improved Ejection Fraction.

INTRODUCTION: Heart Failure with Improved Ejection Fraction (HFimpEF) is a recently defined subtype of HF, characterized by an increase in ejection fraction (EF) after a prior diagnosis of reduced EF. There is limited data on the characteristics and outcome of this patient subset. The study aimed to investigate the clinical profile and prognosis of this patient group. METHODS: HFimpEF patients from a large echocardiography database with comprehensive clinical and outcome data were evaluated for clinical characteristics and outcomes including mortality and cardiovascular hospitalizations. HFimpEF was defined as prior HF diagnosis with EF ≤40% followed by an EF increase of ≥10% to >40%. RESULTS: The study included 2,883 patients with an EF ≤40%. 27% (777) fulfilled criteria of HFimpEF. Non-ischemic cardiomyopathy, female sex, and smaller left ventricular dimensions were associated with EF improvement. Median follow-up duration was 1,346 days. Patients with HFimpEF had a significantly improved prognosis compared to those without EF improvement. Patients with a significant improvement in the EF (≥50%) experienced a 30% lower mortality rate (HR 0.70, 95% CI 0.57-0.86, P<0.001) and a decreased risk of cardiovascular hospitalizations. CONCLUSIONS: HFimpEF is a distinct clinical entity observed in 27% of patients with initially reduced EF and coveys a better prognosis. However, even with improvement, EF in most patients does not fully recover, and clinical events can still occur.

Restrictive cardiomyopathy: definition and diagnosis.

Restrictive cardiomyopathy (RCM) is a heterogeneous group of diseases characterized by restrictive left ventricular pathophysiology, i.e. a rapid rise in ventricular pressure with only small increases in filling volume due to increased myocardial stiffness. More precisely, the defining feature of RCM is the coexistence of persistent restrictive pathophysiology, diastolic dysfunction, non-dilated ventricles, and atrial dilatation, regardless of ventricular wall thickness and systolic function. Beyond this shared haemodynamic hallmark, the phenotypic spectrum of RCM is wide. The disorders manifesting as RCM may be classified according to four main disease mechanisms: (i) interstitial fibrosis and intrinsic myocardial dysfunction, (ii) infiltration of extracellular spaces, (iii) accumulation of storage material within cardiomyocytes, or (iv) endomyocardial fibrosis. Many disorders do not show restrictive pathophysiology throughout their natural history, but only at an initial stage (with an evolution towards a hypokinetic and dilated phenotype) or at a terminal stage (often progressing from a hypertrophic phenotype). Furthermore, elements of both hypertrophic and restrictive phenotypes may coexist in some patients, making the classification challenge. Restrictive pathophysiology can be demonstrated by cardiac catheterization or Doppler echocardiography. The specific conditions may usually be diagnosed based on clinical data, 12-lead electrocardiogram, echocardiography, nuclear medicine, or cardiovascular magnetic resonance, but further investigations may be needed, up to endomyocardial biopsy and genetic evaluation. The spectrum of therapies is also wide and heterogeneous, but disease-modifying treatments are available only for cardiac amyloidosis and, partially, for iron overload cardiomyopathy.

Increased estimated fat-free mass and fat mass associated with improved clinical outcome in heart failure.

BACKGROUND: Increased weight measured by body mass index is associated with better clinical outcomes in heart failure (HF). The effect of specific components of body mass on outcome is limited. We evaluated the impact of fat-free mass and fat mass on mortality and cardiovascular hospitalization in a large real-world cohort of patients with chronic HF. METHODS: Body measurements were assessed in patients with chronic HF. Fat-free mass, fat mass and waist circumference were calculated based on specifically derived formulas. RESULTS: The cohort included 6328 HF patients. Mean follow-up was 744 days. Increased body composition indices including body mass index, fat-free mass index and fat mass index, per cent body fat and waist circumference were associated with better survival. Cox regression analysis after adjustment for other significant parameters demonstrated that these indices were all associated with improved survival. The strongest association was seen with fat-free mass index with a graded increase in survival; lowest death in the highest quartile compared to reference second quartile (hazard ratio 0.79, 95% confidence interval 0.67-0.93, P < .01). There was no interaction with sex or HF type. Analysis of the clinical outcome of death and cardiovascular hospitalization demonstrated that a worse prognosis was in the lowest quartile of all the indices. A sensitivity analysis, analysing these indices as continuous parameters using restricted cubic splines, demonstrated a clear continuous association between these indices and increased survival in both sexes. CONCLUSIONS: Body mass including fat-free mass and fat mass was associated with improved survival in patients with HF.

The effect of intravenous ferric carboxymaltose on health-related quality of life in iron-deficient patients with acute heart failure: the results of the AFFIRM-AHF study.

AIMS: Patients with heart failure (HF) and iron deficiency experience poor health-related quality of life (HRQoL). We evaluated the impact of intravenous (IV) ferric carboxymaltose (FCM) vs. placebo on HRQoL for the AFFIRM-AHF population. METHODS AND RESULTS: The baseline 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12), which was completed for 1058 (535 and 523) patients in the FCM and placebo groups, respectively, was administered prior to randomization and at Weeks 2, 4, 6, 12, 24, 36, and 52. The baseline KCCQ-12 overall summary score (OSS) mean ± standard error was 38.7 ± 0.9 (FCM group) and 37.1 ± 0.8 (placebo group); corresponding values for the clinical summary score (CSS) were 40.9 ± 0.9 and 40.1 ± 0.9. At Week 2, changes in OSS and CSS were similar for FCM and placebo. From Week 4 to Week 24, patients assigned to FCM had significantly greater improvements in OSS and CSS scores vs. placebo [adjusted mean difference (95% confidence interval, CI) at Week 4: 2.9 (0.5-5.3, P = 0.018) for OSS and 2.8 (0.3-5.3, P = 0.029) for CSS; adjusted mean difference (95% CI) at Week 24: 3.0 (0.3-5.6, P = 0.028) for OSS and 2.9 (0.2-5.6, P = 0.035) for CSS]. At Week 52, the treatment effect had attenuated but remained in favour of FCM. CONCLUSION: In iron-deficient patients with HF and left ventricular ejection fraction <50% who had stabilized after an episode of acute HF, treatment with IV FCM, compared with placebo, results in clinically meaningful beneficial effects on HRQoL as early as 4 weeks after treatment initiation, lasting up to Week 24.

[RECOMMENDATIONS FOR CHANGING CARDIOVASCULAR SCREENING OF ATHLETES WHO ARE REQUIRED FOR PRE-PARTICIPATION SCREENING UNDER THE SPORTS LAW - A POSITION PAPER ON BEHALF OF THE ISRAEL HEART SOCIETY].

INTRODUCTION: For many years routine screening of athletes in Israel includes frequently performed ECGs and exercise tests that overload the system with questionable benefits. The purpose of the current document is to reevaluate the need for pre-participation testing and establish new evidence-based guidelines. It should be noted that our proposal for a change of approach relates only to subjects whose health questionnaire is normal, who do not have a family history of sudden and unexpected death at an early age, or a family history of hereditary heart disease and whose physical examination from a cardiovascular point of view is normal.

Ferric carboxymaltose for iron deficiency at discharge after acute heart failure: a multicentre, double-blind, randomised, controlled trial.

BACKGROUND: Intravenous ferric carboxymaltose has been shown to improve symptoms and quality of life in patients with chronic heart failure and iron deficiency. We aimed to evaluate the effect of ferric carboxymaltose, compared with placebo, on outcomes in patients who were stabilised after an episode of acute heart failure. METHODS: AFFIRM-AHF was a multicentre, double-blind, randomised trial done at 121 sites in Europe, South America, and Singapore. Eligible patients were aged 18 years or older, were hospitalised for acute heart failure with concomitant iron deficiency (defined as ferritin <100 µg/L, or 100-299 µg/L with transferrin saturation <20%), and had a left ventricular ejection fraction of less than 50%. Before hospital discharge, participants were randomly assigned (1:1) to receive intravenous ferric carboxymaltose or placebo for up to 24 weeks, dosed according to the extent of iron deficiency. To maintain masking of patients and study personnel, treatments were administered in black syringes by personnel not involved in any study assessments. The primary outcome was a composite of total hospitalisations for heart failure and cardiovascular death up to 52 weeks after randomisation, analysed in all patients who received at least one dose of study treatment and had at least one post-randomisation data point. Secondary outcomes were the composite of total cardiovascular hospitalisations and cardiovascular death; cardiovascular death; total heart failure hospitalisations; time to first heart failure hospitalisation or cardiovascular death; and days lost due to heart failure hospitalisations or cardiovascular death, all evaluated up to 52 weeks after randomisation. Safety was assessed in all patients for whom study treatment was started. A pre-COVID-19 sensitivity analysis on the primary and secondary outcomes was prespecified. This study is registered with ClinicalTrials.gov, NCT02937454, and has now been completed. FINDINGS: Between March 21, 2017, and July 30, 2019, 1525 patients were screened, of whom 1132 patients were randomly assigned to study groups. Study treatment was started in 1110 patients, and 1108 (558 in the carboxymaltose group and 550 in the placebo group) had at least one post-randomisation value. 293 primary events (57·2 per 100 patient-years) occurred in the ferric carboxymaltose group and 372 (72·5 per 100 patient-years) occurred in the placebo group (rate ratio [RR] 0·79, 95% CI 0·62-1·01, p=0·059). 370 total cardiovascular hospitalisations and cardiovascular deaths occurred in the ferric carboxymaltose group and 451 occurred in the placebo group (RR 0·80, 95% CI 0·64-1·00, p=0·050). There was no difference in cardiovascular death between the two groups (77 [14%] of 558 in the ferric carboxymaltose group vs 78 [14%] in the placebo group; hazard ratio [HR] 0·96, 95% CI 0·70-1·32, p=0·81). 217 total heart failure hospitalisations occurred in the ferric carboxymaltose group and 294 occurred in the placebo group (RR 0·74; 95% CI 0·58-0·94, p=0·013). The composite of first heart failure hospitalisation or cardiovascular death occurred in 181 (32%) patients in the ferric carboxymaltose group and 209 (38%) in the placebo group (HR 0·80, 95% CI 0·66-0·98, p=0·030). Fewer days were lost due to heart failure hospitalisations and cardiovascular death for patients assigned to ferric carboxymaltose compared with placebo (369 days per 100 patient-years vs 548 days per 100 patient-years; RR 0·67, 95% CI 0·47-0·97, p=0·035). Serious adverse events occurred in 250 (45%) of 559 patients in the ferric carboxymaltose group and 282 (51%) of 551 patients in the placebo group. INTERPRETATION: In patients with iron deficiency, a left ventricular ejection fraction of less than 50%, and who were stabilised after an episode of acute heart failure, treatment with ferric carboxymaltose was safe and reduced the risk of heart failure hospitalisations, with no apparent effect on the risk of cardiovascular death. FUNDING: Vifor Pharma.

Prevalence and impact of concomitant malignancy on outcomes among ambulatory heart failure population.

INTRODUCTION: Heart failure (HF) and cancer are medical conditions with a rising prevalence resulting in increased co-occurrence. We assessed the impact of cancer on clinical outcome in patients with HF and the prognostic impact of specific types of cancers on different HF subpopulations. METHODS: All patients with HF were evaluated for the occurrence of malignant neoplasm at a health maintenance organization and were followed for cardiac-related hospitalizations and death. RESULTS: The study cohort included 7106 HF patients, 1564 of them (22%) had a diagnosis of malignant neoplasm. HF patients with concomitant cancer were older, had more comorbidities and were more likely to have NYHA class III/IV (42% vs. 37%, P < .01), compared with patients with no malignancy. The overall 2-year mortality rate of the entire HF cohort was 23.2%. Survival rate by Kaplan-Meier analysis demonstrated that the presence of a malignancy was directly associated with reduced survival: 67.2 ± 1.2% vs 79.5 ± 0.5%, P < .001. Malignancy was associated with an increase in mortality with a hazard ratio (HR) of 1.36, 95% confidence interval (CI) 1.21-1.54, P < .001. The strongest impact of malignancy on outcomes was related to age; among patients <70 years old, the increase in the risk of mortality was the highest with a HR of 2.07, 95% CI 1.54-2.80, P < .001. CONCLUSIONS: Malignancy is common among patients with HF. Patients with concomitant HF and malignancies have poor outcomes, and the impact of cancer on outcome is stronger among young patients.

Survival Benefit in Patients with Heart Failure Treated in Specialized Heart Failure Center within the Community.

BACKGROUND: Heart failure centers with specialized nurse-supervised management programs have been proposed to improve prognosis. The Heart Failure Center in Beit Shemesh, Israel, is located within a large primary care facility. The specialist team supervised the managememt of patients both within the frame of the center and while they were hospitalized. OBJECTIVES: To evaluate the health services utilization by heart failure patients treated at a heart failure center and their clinical outcome. METHODS: In this retrospective study, we compared the clinical outcome of patients treated at a heart failure center to patients who received the standard care in 2013-2014. The clinical outcome included primary care visits, emergency room visits, hospitalizations, and death. RESULTS: The study comprised 430 heart failure patients; 82 were treated at the heart failure center and 348 under standard care. At baseline, no significant differences were seen in clinical parameters between the groups. Healthcare utilization was higher among the study group. No significant changes in healthcare utilization were found. During follow-up, patients treated in a heart failure center were more likely to get recommended heart failure medications. Mortality was significantly lower in patients treated in the heart failure center compared with those receiving standard care 3.6% vs. 24%, respectively (P = 0.001), hazard ratio 0.19, 95% confidence interval 0.06-0.62, P = 0.005. CONCLUSIONS: Joint management of heart failure by primary clinics and a specialized community heart failure center reduced mortality. There was no decrease in healthcare utilizations among heart failure center patients, despite the reduction in mortality.

International External Validation Study of the 2014 European Society of Cardiology Guidelines on Sudden Cardiac Death Prevention in Hypertrophic Cardiomyopathy (EVIDENCE-HCM).

BACKGROUND: Identification of people with hypertrophic cardiomyopathy (HCM) who are at risk of sudden cardiac death (SCD) and require a prophylactic implantable cardioverter defibrillator is challenging. In 2014, the European Society of Cardiology proposed a new risk stratification method based on a risk prediction model (HCM Risk-SCD) that estimates the 5-year risk of SCD. The aim was to externally validate the 2014 European Society of Cardiology recommendations in a geographically diverse cohort of patients recruited from the United States, Europe, the Middle East, and Asia. METHODS: This was an observational, retrospective, longitudinal cohort study. RESULTS: The cohort consisted of 3703 patients. Seventy three (2%) patients reached the SCD end point within 5 years of follow-up (5-year incidence, 2.4% [95% confidence interval {CI}, 1.9-3.0]). The validation study revealed a calibration slope of 1.02 (95% CI, 0.93-1.12), C-index of 0.70 (95% CI, 0.68-0.72), and D-statistic of 1.17 (95% CI, 1.05-1.29). In a complete case analysis (n= 2147; 44 SCD end points at 5 years), patients with a predicted 5-year risk of <4% (n=1524; 71%) had an observed 5-year SCD incidence of 1.4% (95% CI, 0.8-2.2); patients with a predicted risk of ≥6% (n=297; 14%) had an observed SCD incidence of 8.9% (95% CI, 5.96-13.1) at 5 years. For every 13 (297/23) implantable cardioverter defibrillator implantations in patients with an estimated 5-year SCD risk ≥6%, 1 patient can potentially be saved from SCD. CONCLUSIONS: This study confirms that the HCM Risk-SCD model provides accurate prognostic information that can be used to target implantable cardioverter defibrillator therapy in patients at the highest risk of SCD.

Electrocardiographic Predictors of Morbidity and Mortality in Patients With Acute Myocarditis: The Importance of QRS-T Angle.

BACKGROUND: Acute myocarditis carries a variable prognosis. We evaluated the morbidity and mortality rates in patients with acute myocarditis and admission electrocardiographic predictors of outcome. METHODS AND RESULTS: Patients admitted to a tertiary hospital with a clinical diagnosis of acute myocarditis were evaluated; 193 patients were included. Median follow-up was 5.7 years, 82% were male, and overal median age was 30 years (range 21-39). The most common clinical presentations were chest pain (77%) and fever (53%). The 30-day survival rate was 98.9%. Overall survival during follow-up was 94.3%. The most common abnormalities observed on electrocardiography were T-wave changes (36%) and ST-segment changes (32%). Less frequent changes included abnormal T-wave axis (>105° or < -15°; 16%), abnormal QRS axis (12%), QTc >460 ms (11%), and QRS interval ≥120 ms (5%). Wide QRS-T angle (≥100°) was demonstrated in 13% of the patients and was associated with an increased mortality rate compared with patients with a narrow QRS-T angle (20% vs 4%; P = .007). The rate of heart failure among patients with a wide QRS-T angle was significantly higher (36% vs 10%; P = .001). Cox regression analysis demonstrated that a wide QRS-T angle (≥100°) was a significant independent predictor of heart failure (hazard ratio [HR] 3.20, 95% confidence interval [CI] 1.35-7.59; P < .01) and of the combined end point of death or heart failure (HR 2.56, 95% CI 1.14-5.75; P < .05). CONCLUSIONS: QRS-T angle is a predictor of increased morbidity and mortality in acute myocarditis.

Acute viral myocarditis: current concepts in diagnosis and treatment.

Acute myocarditis is one of the most challenging diseases to diagnose and treat in cardiology. The true incidence of the disease is unknown. Viral infection is the most common etiology. Modern techniques have improved the ability to diagnose specific viral pathogens in the myocardium. Currently, parvovirus B19 and adenoviruses are most frequently identified in endomyocardial biopsies. Most patients will recover without sequelae, but a subset of patients will progress to chronic inflammatory and dilated cardiomyopathy. The pathogenesis includes direct viral myocardial damage as well as autoimmune reaction against cardiac epitopes. The clinical manifestations of acute myocarditis vary widely--from asymptomatic changes on electrocardiogram to fulminant heart failure, arrhythmias and sudden cardiac death. Magnetic resonance imaging is emerging as an important tool for the diagnosis and follow-up of patients, and for guidance of endomyocardial biopsy. In the setting of acute myocarditis endomyocardial biopsy is required for the evaluation of patients with a clinical scenario suggestive of giant cell myocarditis and of those who deteriorate despite supportive treatment. Treatment of acute myocarditis is still mainly supportive, except for giant cell myocarditis where immunotherapy has been shown to improve survival. Immunotherapy and specific antiviral treatment have yet to demonstrate definitive clinical efficacy in ongoing clinical trials. This review will focus on the clinical manifestations, the diagnostic approach to the patient with clinically suspected acute myocarditis, and an evidence-based treatment strategy for the acute and chronic form of the disease.

Echocardiographic Characteristics and Clinical Outcomes of the Hyperdynamic Heart: A 'Super-Normal' Heart is not a Normal Heart.

A hyperdynamic heart is defined as a left ventricular (LV) with an ejection fraction (EF) above the normal range. Is this favorable? We looked at the diastolic properties of subjects with a hyperdynamic heart and its impact on outcome. Consecutive echocardiography examinations during 5 years were evaluated by EF subgroups, including a hyperdynamic heart (EF >70%). All examinations with significant LV hypertrophy or valve disease were excluded. The study included 16,994 subjects. A total of 720 subjects (4.2%) had a hyperdynamic heart. Subjects with a hyperdynamic heart were older, more likely to be women, and more likely to have hypertension, diabetes, and obesity. A total of 20% of patients had a diagnosis of heart failure. This group had a higher heart rate, smaller ventricular size, and the highest relative wall thickness. All indexes of diastolic dysfunction were significantly more prevalent in the hyperdynamic group. This included a higher LV mass, larger left atrial volume, reduced relaxation (smaller mitral e'), longer deceleration time, and higher LV end-diastolic pressures (high mitral E/e' ratio) and peak tricuspid regurgitation gradient. Diastolic dysfunction, defined by an abnormal functional or structural parameter, was present in 78% of the subjects. Survival was significantly lower in the group with a hyperdynamic heart. The Cox regression analysis after adjustment demonstrated reduced survival during a median 9-year follow-up in the hyperdynamic group compared with those with a normal EF (hazard ratio 1.56, 95% confidence interval 1.38 to 1.76, p <0.001). In conclusion, subjects with a hyperdynamic systolic function have increased prevalence of diastolic dysfunction and reduced survival. A hyperdynamic heart is not a normally functioning heart.

Incidence, risk assessment and prevention of sudden cardiac death in cardiomyopathies.

Cardiomyopathies are a significant contributor to cardiovascular morbidity and mortality, mainly due to the development of heart failure and increased risk of sudden cardiac death (SCD). Despite improvement in survival with contemporary treatment, SCD remains an important cause of mortality in cardiomyopathies. It occurs at a rate ranging between 0.15% and 0.7% per year (depending on the cardiomyopathy), which significantly surpasses SCD incidence in the age- and sex-matched general population. The risk of SCD is affected by multiple factors including the aetiology, genetic basis, age, sex, physical exertion, the extent of myocardial disease severity, conduction system abnormalities, and electrical instability, as measured by various metrics. Over the past decades, the knowledge on the mechanisms and risk factors for SCD has substantially improved, allowing for a better-informed risk stratification. However, unresolved issues still challenge the guidance of SCD prevention in patients with cardiomyopathies. In this review, we aim to provide an in-depth discussion of the contemporary concepts pertinent to understanding the burden, risk assessment and prevention of SCD in cardiomyopathies (dilated, non-dilated left ventricular, hypertrophic, arrhythmogenic right ventricular, and restrictive). The review first focuses on SCD incidence in cardiomyopathies and then summarizes established and emerging risk factors for life-threatening arrhythmias/SCD. Finally, it discusses validated approaches to the risk assessment and evidence-based measures for SCD prevention in cardiomyopathies, pointing to the gaps in evidence and areas of uncertainties that merit future clarification.

State-of-the-art document on optimal contemporary management of cardiomyopathies.

Cardiomyopathies represent significant contributors to cardiovascular morbidity and mortality. Over the past decades, a progress has occurred in characterization of the genetic background and major pathophysiological mechanisms, which has been incorporated into a more nuanced diagnostic approach and risk stratification. Furthermore, medications targeting core disease processes and/or their downstream adverse effects have been introduced for several cardiomyopathies. Combined with standard care and prevention of sudden cardiac death, these novel and emerging targeted therapies offer a possibility of improving the outcomes in several cardiomyopathies. Therefore, the aim of this document is to summarize practical approaches to the treatment of cardiomyopathies, which includes the evidence-based novel therapeutic concepts and established principles of care, tailored to the individual patient aetiology and clinical presentation of the cardiomyopathy. The scope of the document encompasses contemporary treatment of dilated, hypertrophic, restrictive and arrhythmogenic cardiomyopathy. It was based on an expert consensus reached at the Heart Failure Association online Workshop, held on 18 March 2021.