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.

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.

Treatments targeting inotropy.

Acute heart failure (HF) and in particular, cardiogenic shock are associated with high morbidity and mortality. A therapeutic dilemma is that the use of positive inotropic agents, such as catecholamines or phosphodiesterase-inhibitors, is associated with increased mortality. Newer drugs, such as levosimendan or omecamtiv mecarbil, target sarcomeres to improve systolic function putatively without elevating intracellular Ca2+. Although meta-analyses of smaller trials suggested that levosimendan is associated with a better outcome than dobutamine, larger comparative trials failed to confirm this observation. For omecamtiv mecarbil, Phase II clinical trials suggest a favourable haemodynamic profile in patients with acute and chronic HF, and a Phase III morbidity/mortality trial in patients with chronic HF has recently begun. Here, we review the pathophysiological basis of systolic dysfunction in patients with HF and the mechanisms through which different inotropic agents improve cardiac function. Since adenosine triphosphate and reactive oxygen species production in mitochondria are intimately linked to the processes of excitation-contraction coupling, we also discuss the impact of inotropic agents on mitochondrial bioenergetics and redox regulation. Therefore, this position paper should help identify novel targets for treatments that could not only safely improve systolic and diastolic function acutely, but potentially also myocardial structure and function over a longer-term.

Novel EIF2AK4 mutations in histologically proven pulmonary capillary hemangiomatosis and hereditary pulmonary arterial hypertension.

BACKGROUND: Pulmonary hypertension (PH) remains one of the rarest and deadliest diseases. Pulmonary Capillary Hemangiomatosis (PCH) is one of the sub-classes of PH. It was identified using histological and molecular tools and is characterized by the proliferation of capillaries into the alveolar septae. Mutations in the gene encoding the eukaryotic translation initiation factor 2 alpha kinase 4 (EIF2AK4) have recently been linked to this particular subgroup of PH. METHODS: In our effort to unveil the genetic basis of idiopathic and familial cases of PH in Lebanon, we have used whole exome sequencing to document known and/or novel mutations in genes that could explain the underlying phenotype. RESULTS: We showed bi-allelic mutations in EIF2AK4 in two non-consanguineous families: a novel non-sense mutation c.1672C > T (p.Q558*) and a previously documented deletion c.560_564drlAAGAA (p.K187Rfs9*). Our histological analysis coupled with the CT-scan results showed that the two patients with the p.Q558* mutation have PH. In contrast, only one of the individuals harboring the p.K187Rfs9* variant has a documented PCH while his older brother remains asymtomatic. Differential analysis of the variants in the genes of the neighboring network of EIF2AK4 between the two siblings identified a couple of interesting missense mutations that could account for this discrepancy. CONCLUSION: These findings represent a novel documentation of the involvement of EIF2AK4 in the different aspects of pulmonary hypertension. The absence of a molecular mechanism that relates the abrogated function of the protein to the phenotype is still a major hurdle in our understanding of the disease.

Establishing an ECMO program in a developing country: challenges and lessons learned.

AIM: The ECMO (extracorporeal membrane oxygenation) Program at the American University of Beirut Medical Center was established in November 2015 as the first program serving adult and pediatric population in a low-resource setting. The aim of the study is to describe the challenges faced during the establishment of the program and factors leading to its success. METHODS: The program establishment is described. The preparation phase, included the strategic, financial, and clinical planning by administration, nursing, and a multidisciplinary team of physicians. The training and education phase included all the involved nurses, perfusionists, and physicians. Concerns were heard from various stakeholders, and the challenges were analyzed and discussed. RESULTS: The preparation committee chose the adequate equipment, responded to the concerns, defined roles and responsibilities through credentialing and privileging, wrote policies and protocols, and established a strategy to decide for the ECMO indication. Selected team of nurses, physicians, and perfusionists are identified and trained locally, and abroad. A full-time ECMO physician was recruited to launch the program. Twelve patients (6 adults, 3 children, and 3 neonates) were supported by ECMO, for cardiac and respiratory indications. Eleven patients were supported by veno-arterial ECMO, and 1 patient (a neonate) with veno-venous ECMO. Overall, 75% survived to decannulation and 41% survived to discharge. CONCLUSION: With limited human and financial resources, new ECMO centers need to carefully establish selection criteria that may differ from those used in developed countries. Indications should be discussed on a case by case basis, taking into account clinical, social, and financial issues. This experience might help other institutions in developing countries to build their own program despite financial and human limitations.

Clinical and genetic characteristics of pulmonary arterial hypertension in Lebanon.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare disease with an incidence rate of 2-6 cases per million per year. Our knowledge of the disease in the Middle East and North Africa (MENA) region is limited by the small number of clinical studies and the complete absence of genetic studies. METHODS: Our aim was to shed light on the clinical and genetic characteristics of PAH in Lebanon and the region by using exome sequencing on PAH patients referred to the American University of Beirut Medical Center (AUBMC). Twenty-one idiopathic, hereditary and Congenital Heart Disease (CHD) PAH patients were prospectively recruited, their clinical data summarized, and sequencing performed. RESULTS: The mean age at diagnosis was 33 years with a female preponderance of 70%. The mean pulmonary artery pressure at the time of diagnosis was 55. Genetic testing showed that 5 out of 19 idiopathic and Congenital Heart Disease PAH patients had Bone Morphogenetic Protein Receptor 2 (BMPR2) mutations at 25% prevalence, with 2 of these patients exhibiting a novel mutation. It also showed the presence of 1 BMPR2 mutation with 100% penetrance in a heritable PAH family. In the remaining cases, the lack of a complete genotype/phenotype correlation entailed a multigenic inheritance; suspected interactions involved previously associated genes T-box transcription factor 4 (TBX4), Bone Morphogenic Protein 10 (BMP10) and Growth Differentiation Factor 2 (GDF2). CONCLUSIONS: This is the first study that looks into the genetic causes of PAH, including known and new BMPR2 mutations, in the MENA region. It is also the first study to characterize the clinical features of the disease in Lebanon.

Readmission rates and related factors in heart failure patients: A study in Lebanon.

BACKGROUND: Heart failure is the leading cause of hospitalization among older adults in the United States and other developed countries. Readmission rates of heart failure patients is one of the key outcome performance measures used in evaluating the quality of care of these patients. In Lebanon, there are no published data on readmission of heart failure patients. The aim of the study was to examine the readmission rates of heart failure patients within 30, 60 and 90 days of discharge from the hospital, and factors associated with readmission. METHODS: The medical records of all 187 patients admitted with heart failure to Rafic Hariri University Hospital in Beirut between January 1, 2010 and December 31, 2010 were reviewed. Data on demographic and relevant clinical variables were retrieved. RESULTS: Readmission rates were 15%, 22.2%, and 27.8% at 30, 60 and 90 days following discharge, respectively. The majority of readmissions (73.61%) were due to heart failure exacerbations. Significant predictors of readmission were: history of diabetes mellitus, coronary artery disease, length of stay at the index admission and gamma glutamyl transpeptidase levels. Management of the patients did not always conform to the evidence based guidelines. CONCLUSION: The findings suggest the need for better adherence to clinical guidelines in caring for heart failure patients and improved documentation of discharge instructions.

Isolated Left Ventricular Diastolic Collapse Due to Extra-Thoracic Compression.

Isolated collapse of the left ventricle (LV) in diastole is not a very common finding on two-dimensional echocardiography. Reported cases in the literature were due to either loculated postoperative pericardial effusion/hematoma or left pleural effusion. To our knowledge, this is the first case report of LV diastolic collapse secondary to extra-thoracic compression.

Advanced heart failure therapies in the Eastern Mediterranean Region: current status, challenges, and future directions.

While there has been a global decrease in rates of heart failure (HF) prevalence between 1990 and 2019, the Eastern Mediterranean region (EMR) is experiencing an increase. In 2019, approximately 1,229,766 individuals lived with moderate to severe HF in the EMR. Despite the growth in the utilization of advanced heart failure (AHF) therapies in the EMR in the past two decades, current volumes are yet to meet the growing AHF burden in the region. Heart transplantation (HT) volumes in EMR have grown from 9 in the year 2000 to 179 HTs in 2019. However, only a few centers provide the full spectrum of AHF therapies, including durable mechanical circulatory support (MCS) and HT. Published data on the utilization of left ventricular assist devices (LVAD) in the EMR are scarce. Notably, patients undergoing LVAD implantation in the EMR are on average, 13 year younger, and more likely to present with critical cardiogenic shock, as compared to their counterparts in the Western world. Furthermore, AHF care in the region is hampered by the paucity of multidisciplinary HF programs, inherent costs of AHF therapies, limited access to short and long-term MCS, organ shortage, and lack of public awareness and acceptance of AHF therapeutics. All stakeholders in the EMR should work together to strategize tackling the challenging AHF burden in the region.

Heart failure with preserved ejection fraction epidemiology, pathophysiology, diagnosis and treatment strategies.

The prevalence of HF with preserved ejection raction (HFpEF, with EF ≥50%) is increasing across all populations with high rates of hospitalization and mortality, reaching up to 80% and 50%, respectively, within a 5-year timeframe. Comorbidity-driven systemic inflammation is thought to cause coronary microvascular dysfunction and increased epicardial adipose tissue, leading to downstream friborsis and molecular changes in the cardiomyocyte, leading to increased stiffness and diastolic dynsfunction. HFpEF poses unique challenges in terms of diagnosis due to its complex and diverse nature. The diagnosis of HFpEF relies on a combination of clinical assessment, imaging studies, and biomarkers. An additional important step in diagnosing HFpEF involves excluding certain cardiac diagnoses that may be specific underlying causes of HFpEF or may be masquerading as HFpEF and require specific alternative treatment approaches. In addition to administering sodium-glucose cotransporter 2 inhibitors to all patients, the most effective approach to enhance clinical outcomes may involve tailored therapy based on each patient's unique clinical profile. Exercise should be recommended for all patients to improve the quality of life. Glucagon-like peptide-1 1 agonists are a promising treatment option in obese HFpEF patients. Novel approaches targeting inflammation are also in early phase trials.

Expert Recommendations to Bridge Gaps in Heart Failure Patient Support in the Middle East and Africa Region.

Heart failure (HF) remains a serious health and socioeconomic problem in the Middle East and Africa (MEA). The age-standardized prevalence rate for HF in the MEA region is higher compared to countries in Eastern Europe, Latin America, and Southeast Asia. Also cardiovascular-related deaths remain high compared to their global counterparts. Moreover, in MEA, 66% of HF readmissions are elicited by potentially preventable factors, including delay in seeking medical attention, nonadherence to HF medication, suboptimal discharge planning, inadequate follow-up, and poor social support. Patient support in the form of activation, counseling, and caregiver education has been shown to improve outcomes in patients with HF. A multidisciplinary meeting with experts from different countries across the MEA region was convened to identify the current gaps and unmet needs for patient support for HF in the region. The panel provided insights into the real-world challenges in HF patient support and contributed strategic recommendations for optimizing HF care.

How to tackle therapeutic inertia in heart failure with reduced ejection fraction. A scientific statement of the Heart Failure Association of the ESC.

Guideline-directed medical therapy (GDMT) in patients with heart failure and reduced ejection fraction (HFrEF) reduces morbidity and mortality, but its implementation is often poor in daily clinical practice. Barriers to implementation include clinical and organizational factors that might contribute to clinical inertia, i.e. avoidance/delay of recommended treatment initiation/optimization. The spectrum of strategies that might be applied to foster GDMT implementation is wide, and involves the organizational set-up of heart failure care pathways, tailored drug initiation/optimization strategies increasing the chance of successful implementation, digital tools/telehealth interventions, educational activities and strategies targeting patient/physician awareness, and use of quality registries. This scientific statement by the Heart Failure Association of the ESC provides an overview of the current state of GDMT implementation in HFrEF, clinical and organizational barriers to implementation, and aims at suggesting a comprehensive framework on how to overcome clinical inertia and ultimately improve implementation of GDMT in HFrEF based on up-to-date evidence.

Differences in presentation, diagnosis and management of heart failure in women. A scientific statement of the Heart Failure Association of the ESC.

Despite the progress in the care of individuals with heart failure (HF), important sex disparities in knowledge and management remain, covering all the aspects of the syndrome, from aetiology and pathophysiology to treatment. Important distinctions in phenotypic presentation are widely known, but the mechanisms behind these differences are only partially defined. The impact of sex-specific conditions in the predisposition to HF has gained progressive interest in the HF community. Under-recruitment of women in large randomized clinical trials has continued in the more recent studies despite epidemiological data no longer reporting any substantial difference in the lifetime risk and prognosis between sexes. Target dose of medications and criteria for device eligibility are derived from studies with a large predominance of men, whereas specific information in women is lacking. The present scientific statement encompasses the whole scenario of available evidence on sex-disparities in HF and aims to define the most challenging and urgent residual gaps in the evidence for the scientific and clinical HF communities.

Clinical features, socioeconomic status, management, short and long-term outcomes of patients with acute myocardial infarction: Phase I results of PEACE MENA registry.

BACKGROUND: The Program for the Evaluation and Management of Cardiac Events in the Middle East and North Africa (PEACE MENA) is a prospective registry program in Arabian countries that involves in patients with acute myocardial infarction (AMI) or acute heart failure (AHF). METHODS: This prospective, multi-center, multi-country study is the first report of the baseline characteristics and outcomes of inpatients with AMI who were enrolled during the first 14-month recruitment phase. We report the clinical characteristics, socioeconomic, educational levels, and management, in-hospital, one month and one-year outcomes. RESULTS: Between April 2019 and June 2020, 1377 patients with AMI were enrolled (79.1% males) from 16 Arabian countries. The mean age (± SD) was 58 ± 12 years. Almost half of the population had a net income < $500/month, and 40% had limited education. Nearly half of the cohort had a history of diabetes mellitus, hypertension, or hypercholesterolemia; 53% had STEMI, and almost half (49.7%) underwent a primary percutaneous intervention (PCI) (lowest 4.5% and highest 100%). Thrombolytics were used by 36.2%. (Lowest 6.45% and highest (90.9%). No reperfusion occurred in 13.8% of patients (lowest was 0% and highest 72.7%).Primary PCI was performed less frequently in the lower income group vs. high income group (26.3% vs. 54.7%; P<0.001). Recurrent ischemia occurred more frequently in the low-income group (10.9% vs. 7%; P = 0.018). Re-admission occurred in 9% at 1 month and 30% at 1 year, whereas 1-month mortality was 0.7% and 1-year mortality 4.7%. CONCLUSION: In the MENA region, patients with AMI present at a young age and have a high burden of cardiac risk factors. Most of the patients in the registry have a low income and low educational status. There is heterogeneity among key performance indicators of AMI management among various Arabian countries.

Integration of implantable device therapy in patients with heart failure. A clinical consensus statement from the Heart Failure Association (HFA) and European Heart Rhythm Association (EHRA) of the European Society of Cardiology (ESC).

Implantable devices form an integral part of the management of patients with heart failure (HF) and provide adjunctive therapies in addition to cornerstone drug treatment. Although the number of these devices is growing, only few are supported by robust evidence. Current devices aim to improve haemodynamics, improve reverse remodelling, or provide electrical therapy. A number of these devices have guideline recommendations and some have been shown to improve outcomes such as cardiac resynchronization therapy, implantable cardioverter-defibrillators and long-term mechanical support. For others, more evidence is still needed before large-scale implementation can be strongly advised. Of note, devices and drugs can work synergistically in HF as improved disease control with devices can allow for further optimization of drug therapy. Therefore, some devices might already be considered early in the disease trajectory of HF patients, while others might only be reserved for advanced HF. As such, device therapy should be integrated into HF care programmes. Unfortunately, implementation of devices, including those with the greatest evidence, in clinical care pathways is still suboptimal. This clinical consensus document of the Heart Failure Association (HFA) and European Heart Rhythm Association (EHRA) of the European Society of Cardiology (ESC) describes the physiological rationale behind device-provided therapy and also device-guided management, offers an overview of current implantable device options recommended by the guidelines and proposes a new integrated model of device therapy as a part of HF care.

Outcomes of Patients with Monoclonal Gammopathy of Undetermined Significance with and without Atrial Fibrillation: A Retrospective Cohort Analysis of the Nationwide Inpatient Sample Database.

BACKGROUND: Monoclonal gammopathy of undetermined significance (MGUS) is a non-malignant precursor of multiple myeloma (MM). MGUS has been suggested to be associated with a higher risk of cardiovascular diseases, including AFIB, but it is still unclear whether this association is real. Studies are lacking on the impact of atrial fibrillation on health outcomes in this population. The association of AFIB in this population is lagging and merits further investigation. METHODS: The study conducted a retrospective analysis of the Nationwide Inpatient Sample (NIS) for 2018, including adult patients with primary diagnoses of MGUS and AFIB. Patients were divided into two groups based on AFIB presence. Outcomes assessed included complications, length of stay, mortality, hospital charges, and discharge disposition. RESULTS: The study included 9007 patients with MGUS of whom 2404 had AFIB. Patients with both MGUS and AFIB had higher rates of acute kidney injury [AKI] (31.5% vs. 27.5%; p = 0.002) and pericarditis (2% vs. 1.2%; p = 0.029). They also had longer hospital stays (5 vs. 4 days; p < 0.001) and higher hospitalization costs ($43,729 vs. $41,169; p < 0.001). CONCLUSIONS: The study showed that the prevalence of AFIB in MGUS patients is high. Patients with AFIB had increased rates of complications (AKI and pericarditis) and higher mortality compared to patients without AFIB. Further studies screening for AFIB in this patient population are warranted.

Regional expert opinion: Management of heart failure with preserved ejection fraction in the Middle East, North Africa and Turkey.

Although epidemiological data on heart failure (HF) with preserved ejection fraction (HFpEF) are scarce in the Middle East, North Africa and Turkey (MENAT) region, Lancet Global Burden of Disease estimated the prevalence of HF in the MENAT region in 2019 to be 0.78%, versus 0.71% globally. There is also a high incidence of HFpEF risk factors and co-morbidities in the region, including coronary artery disease, diabetes, obesity, hypertension, anaemia and chronic kidney disease. For instance, 14.5-16.2% of adults in the region reportedly have diabetes, versus 7.0% in Europe. Together with increasing life expectancy, this may contribute towards a higher burden of HFpEF in the region than currently reported. This paper aims to describe the epidemiology and burden of HFpEF in the MENAT region, including unique risk factors and co-morbidities. It highlights challenges with diagnosing HFpEF, such as the prioritization of HF with reduced ejection fraction (HFrEF), the specific profile of HFpEF patients in the region and barriers to effective management associated with the healthcare system. Guidance is given on the diagnosis, prevention and management of HFpEF, including the emerging role of sodium-glucose co-transporter-2 inhibitors. Given the high burden of HFpEF coupled with the fact that its prevalence is likely to be underestimated, healthcare professionals need to be alert to its signs and symptoms and to manage patients accordingly. Historically, HFpEF treatments have focused on managing co-morbidities and symptoms, but new agents are now available with proven effects on outcomes in patients with HFpEF.

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.