The Role of the Immune System in Pathobiology and Therapy of Myocarditis: A Review.

The role of the immune system in myocarditis onset and progression involves a range of complex cellular and molecular pathways. Both innate and adaptive immunity contribute to myocarditis pathogenesis, regardless of its infectious or non-infectious nature and across different histological and clinical subtypes. The heterogeneity of myocarditis etiologies and molecular effectors is one of the determinants of its clinical variability, manifesting as a spectrum of disease phenotype and progression. This spectrum ranges from a fulminant presentation with spontaneous recovery to a slowly progressing, refractory heart failure with ventricular dysfunction, to arrhythmic storm and sudden cardiac death. In this review, we first examine the updated definition and classification of myocarditis at clinical, biomolecular and histopathological levels. We then discuss recent insights on the role of specific immune cell populations in myocarditis pathogenesis, with particular emphasis on established or potential therapeutic applications. Besides the well-known immunosuppressive agents, whose efficacy has been already demonstrated in human clinical trials, we discuss the immunomodulatory effects of other drugs commonly used in clinical practice for myocarditis management. The immunological complexity of myocarditis, while presenting a challenge to simplistic understanding, also represents an opportunity for the development of different therapeutic approaches with promising results.

Long-term efficacy and safety of tailored immunosuppressive therapy in immune-mediated biopsy-proven myocarditis: A propensity-weighted study.

AIMS: Standardized immunosuppressive therapy (IS) had been previously investigated in biopsy-proven (BP) lymphocytic myocarditis with heart failure (HF). This study evaluated efficacy and safety of tailored IS in BP immune-mediated myocarditis, irrespective of histology and clinical presentation. METHODS AND RESULTS: Consecutive BP myocarditis patients treated with long-term tailored IS on top of optimal medical therapy (OMT), were compared with OMT non-IS controls using propensity-score weighting. The primary outcome was a composite of death or heart transplant, the secondary outcome was a composite of biventricular function, New York Heart Association (NYHA) class variation, and relapse. IS was managed by a multidisciplinary Cardioimmunology Team, involved a safety checklist and active patients' education. Ninety-one IS patients were compared with 267 non-IS patients. IS patients more frequently had systemic immune-mediated diseases (35% vs. 9.7%), lower baseline echocardiographic left ventricular ejection fraction (35% vs. 43%), lower right ventricular fractional area change (34% vs. 41%) and higher frequency of active lymphocytic, eosinophilic and giant cell myocarditis (71% vs. 58%, 12% vs. 1.1%, and 6.6% vs. 1.5%, respectively). At 5-year follow up, no difference was observed in the primary outcome (survival rate 93% in IS vs. 87% in non-IS), but IS patients had a higher relapse rate. Thus, IS patients, with a lower biventricular function and a higher risk profile at baseline, presented similar biventricular function and NYHA class to non-IS patients at follow-up. Minor adverse drug reactions occurred in 13% of patients, all resolved with therapy switch. CONCLUSIONS: Prolonged tailored IS is effective and safe in BP immune-mediated myocarditis irrespective of histology and clinical presentation.

CMR Predictors of Favorable Outcome in Myocarditis: A Single-Center Experience.

Background: Cardiovascular magnetic resonance (CMR) has emerged as the most accurate, non-invasive method to support the diagnosis of clinically suspected myocarditis and as a risk-stratification tool in patients with cardiomyopathies. We aim to assess the diagnostic and prognostic role of CMR at diagnosis in patients with myocarditis. Methods: We enrolled consecutive single-center patients with 2013 ESC consensus-based endomyocardial biopsy (EMB)-proven or clinically suspected myocarditis undergoing CMR at diagnosis. The pre-specified outcome was defined as NYHA class > I and echocardiographic left ventricular ejection fraction (LVEF) < 50% at follow-up. Results: We included 207 patients (74% male, median age 36 years; 25% EMB-proven). CMR showed the highest sensitivity in myocarditis with infarct-like presentation. Patients with EMB-proven myocarditis were more likely to have diffuse LGE and right ventricular LGE (p < 0.001), which was also more common among patients with arrhythmic presentation (p = 0.001). The outcome was met in 17 patients at any follow-up time point, more commonly in those with larger biventricular volumes (p < 0.001), CMR-based diagnosis of dilated cardiomyopathy (p < 0.001), and ischemic LGE (p = 0.005). Higher biventricular systolic function (p < 0.001) and greater LGE extent (p = 0.033) at diagnosis had a protective effect. Conclusions: In our single-center cohort of rigorously defined myocarditis patients, higher biventricular systolic function and greater LGE extent on CMR at diagnosis identified patients with better functional class and higher left ventricular ejection fraction at follow-up. Conversely, larger biventricular volumes, CMR-based DCM features, and the presence of an ischemic LGE pattern at diagnosis were predictors of worse functional class and LV systolic dysfunction at follow-up. Larger prospective studies are warranted to extend our findings to multi-center cohorts.

Endomyocardial biopsy: safety and prognostic utility in paediatric and adult myocarditis in the European Society of Cardiology EURObservational Research Programme Cardiomyopathy and Myocarditis Long-Term Registry.

BACKGROUND AND AIMS: Contemporary multicentre data on clinical and diagnostic spectrum and outcome in myocarditis are limited. Study aims were to describe baseline features, 1-year follow-up, and baseline predictors of outcome in clinically suspected or biopsy-proven myocarditis (2013 European Society of Cardiology criteria) in adult and paediatric patients from the EURObservational Research Programme Cardiomyopathy and Myocarditis Long-Term Registry. METHODS: Five hundred eighty-one (68.0% male) patients, 493 adults, median age 38 (27-52) years, and 88 children, aged 8 (3-13) years, were divided into 3 groups: Group 1 (n = 233), clinically suspected myocarditis with abnormal cardiac magnetic resonance; Group 2 (n = 222), biopsy-proven myocarditis; and Group 3 (n = 126) clinically suspected myocarditis with normal or inconclusive or no cardiac magnetic resonance. Baseline features were analysed overall, in adults vs. children, and among groups. One-year outcome events included death/heart transplantation, ventricular assist device (VAD) or implantable cardioverter defibrillator (ICD) implantation, and hospitalization for cardiac causes. RESULTS: Endomyocardial biopsy, mainly right ventricular, had a similarly low complication rate in children and adults (4.7% vs. 4.9%, P = NS), with no procedure-related death. A classical myocarditis pattern on cardiac magnetic resonance was found in 31.3% of children and in 57.9% of adults with biopsy-proven myocarditis (P < .001). At 1-year follow-up, 11/410 patients (2.7%) died, 7 (1.7%) received a heart transplant, 3 underwent VAD (0.7%), and 16 (3.9%) underwent ICD implantation. Independent predictors at diagnosis of death or heart transplantation or hospitalization or VAD implantation or ICD implantation at 1-year follow-up were lower left ventricular ejection fraction and the need for immunosuppressants for new myocarditis diagnosis refractory to non-aetiology-driven therapy. CONCLUSIONS: Endomyocardial biopsy was safe, and cardiac magnetic resonance using Lake Louise criteria was less sensitive, particularly in children. Virus-negative lymphocytic myocarditis was predominant both in children and adults, and use of immunosuppressive treatments was low. Lower left ventricular ejection fraction and the need for immunosuppressants at diagnosis were independent predictors of unfavourable outcome events at 1 year.

Cardiomyopathies in children and adolescents: aetiology, management, and outcomes in the European Society of Cardiology EURObservational Research Programme Cardiomyopathy and Myocarditis Registry.

BACKGROUND AND AIMS: Childhood-onset cardiomyopathies are rare and poorly characterized. This study examined the baseline characteristics and 1-year follow-up of children with cardiomyopathy in the first European Cardiomyopathy Registry. METHODS: Prospective data were collected on individuals aged 1-<18 years enrolled in the European Society of Cardiology EURObservational Research Programme Cardiomyopathy and Myocarditis long-term registry (June 2014-December 2016). RESULTS: A total of 633 individuals aged ≤18 years with hypertrophic [HCM; n = 388 (61.3%)], dilated [DCM; n = 206 (32.5%)], restrictive [RCM; n = 28 (4.4%)], and arrhythmogenic right ventricular cardiomyopathy [ARVC; n = 11 (1.7%)] were enrolled by 23 referral centres in 14 countries. Median age at diagnosis was 4.0 [interquartile range (IQR) 0-10] years, and there was a male predominance [n = 372 (58.8%)] across all subtypes, with the exception of DCM diagnosed <10 years of age; 621 (98.1%) patients were receiving cardiac medication and 80 (12.6%) had an implantable cardioverter-defibrillator. A total of 253 patients (253/535, 47.3%) had familial disease. Genetic testing was performed in 414 (67.8%) patients with a pathogenic or likely pathogenic variant reported in 250 (60.4%). Rare disease phenocopies were reported in 177 patients (28.0%) and were most frequent in patients under 10 years [142 (30.9%) vs. 35 (19.6%); P = .003]. Over a median follow-up of 12.5 months (IQR 11.3-15.3 months), 18 patients (3.3%) died [HCM n = 9 (2.6%), DCM n = 5 (3.0%), RCM n = 4 (16.0%)]. Heart failure events were most frequent in RCM patients (36.0%). CONCLUSIONS: The findings confirm the heterogeneous aetiology of childhood cardiomyopathies and show a high frequency of familial disease. Outcomes differed by cardiomyopathy subtype, highlighting a need for disease-specific evaluation and treatment.

Advances in myocarditis management in the light of the latest research and recent guidelines of the European Society of Cardiology.

Myocarditis remains an unknown disease with varying clinical manifestations, often leading to heart failure. The latest 2021 and 2022 guidelines of the European Society of Cardiology (ESC) are the first official European documents updating knowledge on the diagnosis and treatment of myocarditis since the 2013 ESC expert consensus statement. These guidelines and new studies allow standardization and improvements to the management of myocarditis. In this review, we discuss the most important aspects of myocarditis diagnosis, therapies and follow-up based on current knowledge.

Uneventful COVID-19 Infection and Vaccination in a Cohort of Patients with Prior Myocarditis.

Myocarditis has in rare cases been associated with COVID-19 infection and has emerged as a possible rare side effect of vaccination with anti-COVID-19 messenger RNA vaccines. However, little is known about possible COVID-19 infection- and/or vaccination-related myocarditis relapse in patients with previous clinically suspected or biopsy-proven myocarditis. Myocarditis may relapse, particularly in females with immune-mediated/autoimmune features and a predisposing immunogenetic background. We aimed to assess the prevalence of myocarditis relapse during the COVID-19 outbreak and following COVID-19 vaccination in a cohort of patients with prior myocarditis. We included in the analysis myocarditis patients on active follow-up, for whom COVID-19 infection and vaccination statuses were known, and collected data on clinical, laboratory and echocardiographic findings, and myocarditis relapse. We enrolled 409 patients, of whom 114 (28%) reported COVID-19 infection and 347 (85%) completed the vaccination scheme. Only one patient, having COVID-19 infection before the vaccination campaign started, was admitted to hospital because of pneumonia; the remaining patients had an uneventful COVID-19 infection course, with only mild symptoms. No myocarditis relapse was recorded following COVID-19 infection or vaccination. Moreover, the frequency of new myocarditis cases following the COVID-19 outbreak was not different compared to the three-year period preceding the COVID-19 era. In conclusion, in our cohort of patients with prior myocarditis, both COVID-19 infection and vaccination were uneventful.

Consensus on the assessment of systemic sclerosis-associated primary heart involvement: World Scleroderma Foundation/Heart Failure Association guidance on screening, diagnosis, and follow-up assessment.

Introduction: Heart involvement is a common problem in systemic sclerosis. Recently, a definition of systemic sclerosis primary heart involvement had been proposed. Our aim was to establish consensus guidance on the screening, diagnosis and follow-up of systemic sclerosis primary heart involvement patients. Methods: A systematic literature review was performed to investigate the tests used to evaluate heart involvement in systemic sclerosis. The extracted data were categorized into relevant domains (conventional radiology, electrocardiography, echocardiography, cardiac magnetic resonance imaging, laboratory, and others) and presented to experts and one patient research partner, who discussed the data and added their opinion. This led to the formulation of overarching principles and guidance statements, then reviewed and voted on for agreement. Consensus was attained when the mean agreement was ⩾7/10 and of ⩾70% of voters. Results: Among 2650 publications, 168 met eligibility criteria; the data extracted were discussed over three meetings. Seven overarching principles and 10 guidance points were created, revised and voted on. The consensus highlighted the importance of patient counseling, differential diagnosis and multidisciplinary team management, as well as defining screening and diagnostic approaches. The initial core evaluation should integrate history, physical examination, rest electrocardiography, trans-thoracic echocardiography and standard serum cardiac biomarkers. Further investigations should be individually tailored and decided through a multidisciplinary management. The overall mean agreement was 9.1/10, with mean 93% of experts voting above 7/10. Conclusion: This consensus-based guidance on screening, diagnosis and follow-up of systemic sclerosis primary heart involvement provides a foundation for standard of care and future feasibility studies that are ongoing to support its application in clinical practice.

Fulminant Myocarditis: When One Size Does Not Fit All - A Critical Review of the Literature.

Fulminant myocarditis, rather than being a distinct form of myocarditis, is instead a peculiar clinical presentation of the disease. The definition of fulminant myocarditis has varied greatly in the last 20 years, leading to conflicting reports on prognosis and treatment strategies, mainly because of varied inclusion criteria in different studies. The main conclusion of this review is that fulminant myocarditis may be due to different histotypes and aetiologies that can be diagnosed only by endomyocardial biopsy and managed by aetiology-directed treatment. This life-threatening presentation requires rapid, targeted management both in the short term (mechanical circulatory support, inotropic and antiarrhythmic treatment and endomyocardial biopsy) and in the long term (including prolonged follow-up). Fulminant presentation has also recently been identified as a risk factor for worsened prognosis, even long after the resolution of the acute phase of myocarditis.

Transient pericardial constriction: A not so rare entity.

Constrictive pericarditis is a rare, potentially treatable, cause of heart failure with preserved ejection fraction that is characterized by insidious onset, challenging diagnosis and dismal prognosis, even following complete surgical pericardiectomy, particularly in advanced disease stages. In recent years it has been proposed that transient pericardial constriction may occur, with an even rarer frequency, during early phases of acute pericarditis and may resolve following specific treatment without progressing to the chronic, irreversible form. We recently observed two cases of well-documented transient pericardial constriction. In the present work we describe these two cases and provide a review on this rare condition, that, if unrecognized and left untreated, may lead to irreversible constrictive pericarditis.

Myocarditis: Etiology, Pathogenesis, and Their Implications in Clinical Practice.

Myocarditis is an inflammatory disease of the myocardium caused by infectious or non-infectious agents. It can lead to serious short-term and long-term sequalae, such as sudden cardiac death or dilated cardiomyopathy. Due to its heterogenous clinical presentation and disease course, challenging diagnosis and limited evidence for prognostic stratification, myocarditis poses a great challenge to clinicians. As it stands, the pathogenesis and etiology of myocarditis is only partially understood. Moreover, the impact of certain clinical features on risk assessment, patient outcomes and treatment options is not entirely clear. Such data, however, are essential in order to personalize patient care and implement novel therapeutic strategies. In this review, we discuss the possible etiologies of myocarditis, outline the key processes governing its pathogenesis and summarize best available evidence regarding patient outcomes and state-of-the-art therapeutic approaches.

Immunosuppressive Therapy of Biopsy-Proven, Virus-Negative, Autoimmune/Immune-Mediated Myocarditis-Focus on Azathioprine: A Review of Existing Evidence and Future Perspectives.

The use of immunosuppressive therapy (IT) in biopsy-proven, autoimmune/immune-mediated (AI), virus-negative myocarditis has become the standard of care. In particular, according to recent guidelines, azathioprine (AZA), in association with steroids, is a cornerstone of first-line therapy regimens. IT may have a crucial impact on the natural history of AI myocarditis, preventing its progression to end-stage heart failure, cardiovascular death, or heart transplantation, provided that strict appropriateness and safety criteria are observed. In particular, AZA treatment for AI virus-negative myocarditis requires the consideration of some crucial aspects regarding its pharmacokinetics and pharmacodynamics, as well as a high index of suspicion to detect its overt and/or subclinical side effects. Importantly, besides a tight teamwork with a clinical immunologist/immuno-rheumatologist, before starting IT, it is also necessary to carry out a careful "safety check-list" in order to rule out possible contraindications to IT and minimize patient's risk. The aim of this review is to describe the pharmacological properties of AZA, as well as to discuss practical aspects of its clinical use, in the light of existing evidence, with particular regard to the new field of cardioimmunology.

A Machine-Learning Model for the Prognostic Role of C-Reactive Protein in Myocarditis.

Aims: The role of inflammation markers in myocarditis is unclear. We assessed the diagnostic and prognostic correlates of C-reactive protein (CRP) at diagnosis in patients with myocarditis. Methods and results: We retrospectively enrolled patients with clinically suspected (CS) or biopsy-proven (BP) myocarditis, with available CRP at diagnosis. Clinical, laboratory and imaging data were collected at diagnosis and at follow-up visits. To evaluate predictors of death/heart transplant (Htx), a machine-learning approach based on random forest for survival data was employed. We included 409 patients (74% males, aged 37 ± 15, median follow-up 2.9 years). Abnormal CRP was reported in 288 patients, mainly with CS myocarditis (p < 0.001), recent viral infection, shorter symptoms duration (p = 0.001), chest pain (p < 0.001), better functional class at diagnosis (p = 0.018) and higher troponin I values (p < 0.001). Death/Htx was reported in 13 patients, of whom 10 had BP myocarditis (overall 10-year survival 94%). Survival rates did not differ according to CRP levels (p = 0.23). The strongest survival predictor was LVEF, followed by anti-nuclear auto-antibodies (ANA) and BP status. Conclusions: Raised CRP at diagnosis identifies patients with CS myocarditis and less severe clinical features, but does not contribute to predicting survival. Main death/Htx predictors are reduced LVEF, BP diagnosis and positive ANA.

[ANMCO Position paper: Cardiovascular disease in women - prevention, diagnosis, treatment and organization of care]. / Position paper ANMCO: Malattie cardiovascolari nella donna ­ prevenzione, diagnosi, terapia e organizzazione delle cure.

Cardiovascular diseases are still the main cause of death among women despite the improvements in treatment and prognosis achieved in the last 30 years of research. The determinant factors and causes have not been completely identified but the role of "gender" is now recognized. It is well known that women tend to develop cardiovascular disease at an older age than men, and have a high probability of manifesting atypical symptoms not often recognized. Other factors may also co-exist in women, which may favor the onset of specific cardiac diseases such as those with a sex-specific etiology (differential effects of estrogens, pregnancy pathologies, etc.) and those with a different gender expression of specific and prevalent risk factors, inflammatory and autoimmune diseases and cancer. Whether the gender differences observed in cardiovascular outcomes are influenced by real biological differences remains a matter of debate.This ANMCO position paper aims at providing the state of the research on this topic, with particular attention to the diagnostic aspects and to care organization.

Arterial stiffness and atrial fibrillation: shared mechanisms, clinical implications and therapeutic options.

Arterial stiffness (AS) and atrial fibrillation (AF) share commonalities in molecular and pathophysiological mechanisms and numerous studies have analyzed their reciprocal influence. The gold standard for AS diagnosis is represented by aortic pulse wave velocity, whose measurement can be affected by arrhythmias characterized by irregularities in heart rhythm, such as AF. Growing evidence show that patients with AS are at high risk of AF development. Moreover, the subset of AF patients with AS seems to be more symptomatic and rhythm control strategies are less effective in this population. Reducing AS through de-stiffening interventions may be beneficial for patients with AF and can be a new appealing target for the holistic approach of AF management. In this review, we discuss the association between AS and AF, with particular interest in shared mechanisms, clinical implications and therapeutic options.

Primary systemic sclerosis heart involvement: A systematic literature review and preliminary data-driven, consensus-based WSF/HFA definition.

Introduction: Primary heart involvement in systemic sclerosis may cause morpho-functional and electrical cardiac abnormalities and is a common cause of death. The absence of a clear definition of primary heart involvement in systemic sclerosis limits our understanding and ability to focus on clinical research. We aimed to create an expert consensus definition for primary heart involvement in systemic sclerosis. Methods: A systematic literature review of cardiac involvement and manifestations in systemic sclerosis was conducted to inform an international and multi-disciplinary task force. In addition, the nominal group technique was used to derive a definition that was then subject to voting. A total of 16 clinical cases were evaluated to test face validity, feasibility, reliability and criterion validity of the newly created definition. Results: In total, 171 publications met eligibility criteria. Using the nominal group technique, experts added their opinion, provided statements to consider and ranked them to create the consensus definition, which received 100% agreement on face validity. A median 60(5-300) seconds was taken for the feasibility on a single case. Inter-rater agreement was moderate (mKappa (95% CI) = 0.56 (0.46-1.00) for the first round and 0.55 (0.44-1.00) for the second round) and intra-rater agreement was good (mKappa (95% CI) = 0.77 (0.47-1.00)). Criterion validity showed a 78 (73-84)% correctness versus gold standard. Conclusion: A preliminary primary heart involvement in systemic sclerosis consensus-based definition was created and partially validated, for use in future clinical research.

Predictors of relapse, death or heart transplantation in myocarditis before the introduction of immunosuppression: negative prognostic impact of female gender, fulminant onset, lower ejection fraction and serum autoantibodies.

AIMS: Outcome predictors in myocarditis are not well defined; we aimed at identifying predictors of death, heart transplantation (HTx) and relapse before the introduction of immunosuppression. METHODS AND RESULTS: From 1992 to 2012, 466 consecutive patients (68% male, mean age 37 ± 17 years, single centre recruitment, median follow-up 50 months) were included, of whom 216 had clinically suspected and 250 biopsy-proven myocarditis. Serum anti-heart (AHA) and anti-intercalated disk (AIDA) autoantibodies were measured by indirect immunofluorescence. Univariable and multivariable analyses of clinical and diagnostic features at diagnosis were performed. Survival free from death or HTx at 10 years was 83% in the whole study population and was lower in biopsy-proven versus clinically suspected myocarditis (76% vs. 94%, p < 0.001). Female gender (hazard ratio [HR] 2.7, 95% confidence interval [CI] 1.1-6.5), fulminant presentation (HR 13.77, 95% CI 9.7-261.73), high-titre organ-specific AHA (HR 4.2, 95% CI 1.2-14.7) and anti-nuclear antibodies (ANA) (HR 5.2, 95% CI 2.1-12.8) were independent predictors of death or HTx; higher echocardiographic left ventricular ejection fraction (LVEF) at diagnosis was protective, with a 0.93-fold risk reduction for each 1% LVEF increase (95% CI 0.89-0.96). History of myocarditis at diagnosis (HR 8.5, 95% CI 3.5-20.7) was an independent predictor of myocarditis relapse at follow-up; older age was protective (HR 0.95, 95% CI 0.91-0.99). Predictors of death, HTx and relapse did not differ in biopsy-proven versus clinically suspected myocarditis. CONCLUSIONS: Young age and a previous myocarditis were independent relapse predictors; female gender, fulminant onset, lower LVEF at presentation and high-titre organ-specific AHA and ANA were independent predictors of death and HTx, suggesting that autoimmune features predict worse prognosis.

Personalized Management of Myocarditis and Inflammatory Cardiomyopathy in Clinical Practice.

Myocarditis is an inflammatory heart disease induced by infectious and non-infectious causes frequently triggering immune-mediated pathologic mechanisms leading to myocardial damage and dysfunction. In approximately half of the patients, acute myocarditis resolves spontaneously while in the remaining cases, it may evolve into serious complications including inflammatory cardiomyopathy, arrhythmias, death, or heart transplantation. Due to the large variability in clinical presentation, unpredictable course of the disease, and lack of established causative treatment, myocarditis represents a challenging diagnosis in modern cardiology. Moreover, an increase in the incidence of myocarditis and inflammatory cardiomyopathy has been observed in recent years. However, there is a growing potential of available non-invasive diagnostic methods (biomarkers, serum anti-heart autoantibodies (AHA), microRNAs, speckle tracking echocardiography, cardiac magnetic resonance T1 and T2 tissue mapping, positron emission tomography), which may refine the diagnostic workup and/or noninvasive follow-up. Personalized management should include the use of endomyocardial biopsy and AHA, which may allow the etiopathogenetic subsets of myocarditis (infectious, non-infectious, and/or immune-mediated) to be distinguished and implementation of disease-specific therapies. In this review, we summarize current knowledge on myocarditis and inflammatory cardiomyopathy, and outline some practical diagnostic, therapeutic, and follow-up algorithms to facilitate comprehensive individualized management of these patients.

Association between common cardiovascular risk factors and clinical phenotype in patients with hypertrophic cardiomyopathy from the European Society of Cardiology (ESC) EurObservational Research Programme (EORP) Cardiomyopathy/Myocarditis registry.

AIMS: The interaction between common cardiovascular risk factors (CVRF) and hypertrophic cardiomyopathy (HCM) is poorly studied. We sought to explore the relation between CVRF and the clinical characteristics of patients with HCM enrolled in the EURObservational Research Programme (EORP) Cardiomyopathy registry. METHODS AND RESULTS: 1739 patients with HCM were studied. The relation between hypertension (HT), diabetes (DM), body mass index (BMI), and clinical traits was analysed. Analyses were stratified according to the presence or absence of a pathogenic variant in a sarcomere gene. The prevalence of HT, DM, and obesity (Ob) was 37, 10, and 21%, respectively. HT, DM, and Ob were associated with older age (P<0.001), less family history of HCM (HT and DM P<0.001), higher New York Heart Association (NYHA) class (P<0.001), atrial fibrillation (HT and DM P<0.001; Ob p = 0.03) and LV (left ventricular) diastolic dysfunction (HT and Ob P<0.001; DM P = 0.003). Stroke was more frequent in HT (P<0.001) and mutation-positive patients with DM (P = 0.02). HT and Ob were associated with higher provocable LV outflow tract gradients (HT P<0.001, Ob P = 0.036). LV hypertrophy was more severe in Ob (P = 0.018). HT and Ob were independently associated with NYHA class (OR 1.419, P = 0.017 and OR 1.584, P = 0.004, respectively). Other associations, including a higher proportion of females in HT and of systolic dysfunction in HT and Ob, were observed only in mutation-positive patients. CONCLUSION: Common CVRF are associated with a more severe HCM phenotype, suggesting a proactive management of CVRF should be promoted. An interaction between genotype and CVRF was observed for some traits.