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Myocarditis is defined as myocardial inflammation and its etiology is highly diverse, including infectious agents, drugs, and autoimmune diseases. The clinical presentation also varies widely, extending beyond the classic clinical picture of acute chest pain, and includes cases of cardiomyopathy of unknown cause whose etiology may be inflammatory. Because certain patients may benefit from targeted treatments, the search for the etiology should begin when myocarditis is first suspected. There remain several areas of uncertainty in the diagnosis and treatment of this disease. Consequently, this consensus document aims to provide clear recommendations for its diagnosis and treatment. Hence, a diagnostic algorithm is proposed, specifying when non-invasive diagnosis with cardiac MR is appropriate vs a noninvasive approach with endomyocardial biopsy. In addition, more novel aspects are discussed, such as when to suspect an underlying genetic etiology. The recommendations cover the management of myocarditis and inflammatory cardiomyopathy, both for general complications and specific clinical entities.
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Cardiomiopatias , Consenso , Miocardite , Humanos , Miocardite/diagnóstico , Miocardite/terapia , Miocardite/etiologia , Cardiomiopatias/diagnóstico , Cardiomiopatias/terapia , Cardiomiopatias/etiologia , Biópsia , Algoritmos , Miocárdio/patologiaRESUMO
BACKGROUND: The pathogenicity of the different genetic variants causing hypertrophic cardiomyopathy (HCM) and the genotype/phenotype correlations are difficult to assess in clinical practice, as most mutations are unique or identified in non-informative families. Pathogenic variants in the sarcomeric gene MYBPC3 inherited with an autosomal dominant pattern, whereas incomplete and age-dependent penetrance are the most common causes of HCM. METHODS: We describe the clinical characteristics of a new truncating MYBPC3 variant, p.Val931Glyfs*120, in 75 subjects from 18 different families from northern Spain with the p.Val931Glyfs*120 variant. RESULTS: Our cohort allows us to estimate the penetrance and prognosis of this variant. The penetrance of the disease increases with age, whereas 50% of males in our sample developed HCM by the age of 36 years old, and 50% of women developed the disease by the time they reached 48 years of age (p = 0.104). Men have more documented arrhythmias with potential risk of sudden death (p = 0.018), requiring implantation of cardioverter defibrillators (p = 0.024). Semi-professional/competitive sport among males is related to earlier onset of HCM (p = 0.004). CONCLUSIONS: The p.Val931Glyfs*120 truncating variant in MYBPC3 is associated with a moderate phenotype of HCM, with a high penetrance, onset in middle age, and a worse outcome in males due to higher risk of sudden death due to arrhythmias.
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Cardiomiopatia Hipertrófica , Masculino , Feminino , Humanos , Espanha , Cardiomiopatia Hipertrófica/genética , Fenótipo , Penetrância , Proteínas do Citoesqueleto/genética , Morte SúbitaRESUMO
BACKGROUND: Variants in myosin heavy chain 7 (MYH7) are responsible for disease in 1% to 5% of patients with dilated cardiomyopathy (DCM); however, the clinical characteristics and natural history of MYH7-related DCM are poorly described. OBJECTIVES: We sought to determine the phenotype and prognosis of MYH7-related DCM. We also evaluated the influence of variant location on phenotypic expression. METHODS: We studied clinical data from 147 individuals with DCM-causing MYH7 variants (47.6% female; 35.6 ± 19.2 years) recruited from 29 international centers. RESULTS: At initial evaluation, 106 (72.1%) patients had DCM (left ventricular ejection fraction: 34.5% ± 11.7%). Median follow-up was 4.5 years (IQR: 1.7-8.0 years), and 23.7% of carriers who were initially phenotype-negative developed DCM. Phenotypic expression by 40 and 60 years was 46% and 88%, respectively, with 18 patients (16%) first diagnosed at <18 years of age. Thirty-six percent of patients with DCM met imaging criteria for LV noncompaction. During follow-up, 28% showed left ventricular reverse remodeling. Incidence of adverse cardiac events among patients with DCM at 5 years was 11.6%, with 5 (4.6%) deaths caused by end-stage heart failure (ESHF) and 5 patients (4.6%) requiring heart transplantation. The major ventricular arrhythmia rate was low (1.0% and 2.1% at 5 years in patients with DCM and in those with LVEF of ≤35%, respectively). ESHF and major ventricular arrhythmia were significantly lower compared with LMNA-related DCM and similar to DCM caused by TTN truncating variants. CONCLUSIONS: MYH7-related DCM is characterized by early age of onset, high phenotypic expression, low left ventricular reverse remodeling, and frequent progression to ESHF. Heart failure complications predominate over ventricular arrhythmias, which are rare.
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Cardiomiopatia Dilatada , Insuficiência Cardíaca , Cadeias Pesadas de Miosina , Adolescente , Adulto , Arritmias Cardíacas/complicações , Arritmias Cardíacas/epidemiologia , Arritmias Cardíacas/genética , Miosinas Cardíacas/genética , Cardiomiopatia Dilatada/genética , Feminino , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/genética , Humanos , Masculino , Pessoa de Meia-Idade , Cadeias Pesadas de Miosina/genética , Fenótipo , Remodelação Ventricular/genética , Adulto JovemRESUMO
AIMS: The aim of this study was to determine the frequency of heterozygous truncating ALPK3 variants (ALPK3tv) in patients with hypertrophic cardiomyopathy (HCM) and confirm their pathogenicity using burden testing in independent cohorts and family co-segregation studies. METHODS AND RESULTS: In a discovery cohort of 770 index patients with HCM, 12 (1.56%) were heterozygous for ALPK3tv [odds ratio(OR) 16.11, 95% confidence interval (CI) 7.94-30.02, P = 8.05e-11] compared to the Genome Aggregation Database (gnomAD) population. In a validation cohort of 2047 HCM probands, 32 (1.56%) carried heterozygous ALPK3tv (OR 16.17, 95% CI 10.31-24.87, P < 2.2e-16, compared to gnomAD). Combined logarithm of odds score in seven families with ALPK3tv was 2.99. In comparison with a cohort of genotyped patients with HCM (n = 1679) with and without pathogenic sarcomere gene variants (SP+ and SP-), ALPK3tv carriers had a higher prevalence of apical/concentric patterns of hypertrophy (60%, P < 0.001) and of a short PR interval (10%, P = 0.009). Age at diagnosis and maximum left ventricular wall thickness were similar to SP- and left ventricular systolic impairment (6%) and non-sustained ventricular tachycardia (31%) at baseline similar to SP+. After 5.3 ± 5.7 years, 4 (9%) patients with ALPK3tv died of heart failure or had cardiac transplantation (log-rank P = 0.012 vs. SP- and P = 0.425 vs. SP+). Imaging and histopathology showed extensive myocardial fibrosis and myocyte vacuolation. CONCLUSIONS: Heterozygous ALPK3tv are pathogenic and segregate with a characteristic HCM phenotype.
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Cardiomiopatia Hipertrófica , Proteínas Musculares/genética , Proteínas Quinases/genética , Cardiomiopatia Hipertrófica/genética , Heterozigoto , Humanos , Mutação , SarcômerosRESUMO
AIMS: Dilated cardiomyopathy (DCM) associated with dystrophin gene (DMD) mutations in individuals with mild or absent skeletal myopathy is often indistinguishable from other DCM forms. We sought to describe the phenotype and prognosis of DMD associated DCM in DMD mutation carriers without severe skeletal myopathy. METHODS AND RESULTS: At 26 European centres, we retrospectively collected clinical characteristics and outcomes of 223 DMD mutation carriers (83% male, 33 ± 15 years). A total of 112 individuals (52%) had DCM at first evaluation [n = 85; left ventricular ejection fraction (LVEF) 34 ± 11.2%] or developed DCM (n = 27; LVEF 41.3 ± 7.5%) after a median follow-up of 96 months (interquartile range 5-311 months). DCM penetrance was 45% in carriers older than 40 years. DCM appeared earlier in males and was independent of the type of mutation, presence of skeletal myopathy, or elevated serum creatine kinase levels. Major adverse cardiac events (MACE) occurred in 22% individuals with DCM, 18% developed end-stage heart failure and 9% sudden cardiac death or equivalent. Skeletal myopathy was not associated with survival free of MACE in patients with DCM. Decreased LVEF and increased left ventricular end-diastolic diameter at baseline were associated with MACE. Individuals without DCM had favourable prognosis without MACE or death during follow-up. CONCLUSIONS: DMD-associated DCM without severe skeletal myopathy is characterized by incomplete penetrance but high risk of MACE, including progression to end-stage heart failure and ventricular arrhythmias. DCM onset is the major determinant of prognosis with similar survival regardless of the presence of skeletal myopathy.
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Cardiomiopatia Dilatada , Insuficiência Cardíaca , Doenças Musculares , Adolescente , Adulto , Cardiomiopatia Dilatada/epidemiologia , Cardiomiopatia Dilatada/genética , Distrofina/genética , Feminino , Insuficiência Cardíaca/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Volume Sistólico , Função Ventricular Esquerda , Adulto JovemRESUMO
OBJECTIVES: This study aimed to investigate the accuracy of a broad range of echocardiographic variables to develop multiparametric scores to diagnose CA in patients with proven light chain (AL) amyloidosis or those with increased heart wall thickness who had amyloid was suspected. We also aimed to further characterize the structural and functional changes associated with amyloid infiltration. BACKGROUND: Cardiac amyloidosis (CA) is a serious but increasingly treatable cause of heart failure. Diagnosis is challenging and frequently unclear at echocardiography, which remains the most often used imaging tool. METHODS: We studied 1,187 consecutive patients evaluated at 3 referral centers for CA and analyzed morphological, functional, and strain-derived echocardiogram parameters with the aim of developing a score-based diagnostic algorithm. Cardiac amyloid burden was quantified by using extracellular volume measurements at cardiac magnetic resonance. RESULTS: A total of 332 patients were diagnosed with AL amyloidosis and 339 patients with transthyretin CA. Concentric remodeling and strain-derived parameters displayed the best diagnostic performance. A multivariable logistic regression model incorporating relative wall thickness, E wave/e' wave ratio, longitudinal strain, and tricuspid annular plane systolic excursion had the greatest diagnostic performance in AL amyloidosis (area under the curve: 0.90; 95% confidence interval: 0.87 to 0.92), whereas the addition of septal apical-to-base ratio yielded the best diagnostic accuracy in the increased heart wall thickness group (area under the curve: 0.80; 95% confidence interval: 0.85 to 0.90). CONCLUSIONS: Specific functional and structural parameters characterize different burdens of CA deposition with different diagnostic performances and enable the definition of 2 scores that are sensitive and specific tools with which diagnose or exclude CA.
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Neuropatias Amiloides Familiares/diagnóstico por imagem , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Ecocardiografia , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Neuropatias Amiloides Familiares/patologia , Neuropatias Amiloides Familiares/fisiopatologia , Biópsia , Diagnóstico Diferencial , Europa (Continente) , Feminino , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/patologia , Amiloidose de Cadeia Leve de Imunoglobulina/fisiopatologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Valor Preditivo dos Testes , Função Ventricular Esquerda , Remodelação VentricularRESUMO
Objective: Cardiac amyloid infiltration can lead to systolic heart failure (HF) or to conduction disorders (CD). Patients with transthyretin (ATTR) amyloidosis are particularly exposed. We sought to determine the prevalence of ATTR and AL among patients >60 years admitted with CD or unexplained systolic HF and increased wall thickness. Materials and Methods: We studied 143 patients (57% males, 79 ± 9 years) with HF (N = 28) or CD requiring pacemaker implantation (N = 115). In total, 139 (97%) patients (28 with HF and 111 with CD) underwent 99mTc-DPD scintigraphy to detect ATTR, and 105 (73%; 19 HF and 86 CD) underwent AL screening. Results: Five patients (4%; 95%CI:0-7%) exhibited wild-type ATTR (ATTRwt) amyloidosis, 2 (2%; 95%CI:0-4%) had CD and 3 (11%; 95%CI:0-23%) HF. No patient showed AL. The 2 ATTRwt patients with CD were previously asymptomatic, did not show classical ECG signs and exhibited mild LV hypertrophy with preserved LVEF. By contrast, all ATTRwt patients with HF had ECG and echocardiographic signs of amyloid. During a mean follow-up of 18 ± 11 months, 3(60%) patients with ATTRwt amyloidosis (1 CD and 2 HF) and 14(10.4%) without died. Conclusion: Prevalence of ATTRwt amyloidosis in patients with CD requiring pacemaker is low. Although, additional studies are needed, prevalence seems to be higher in elderly patients with systolic HF.
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Neuropatias Amiloides Familiares/diagnóstico por imagem , Arritmias Cardíacas/diagnóstico por imagem , Cardiomiopatias/diagnóstico por imagem , Insuficiência Cardíaca Sistólica/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Neuropatias Amiloides Familiares/complicações , Neuropatias Amiloides Familiares/mortalidade , Neuropatias Amiloides Familiares/cirurgia , Arritmias Cardíacas/complicações , Arritmias Cardíacas/mortalidade , Arritmias Cardíacas/cirurgia , Biomarcadores/metabolismo , Cardiomiopatias/complicações , Cardiomiopatias/mortalidade , Cardiomiopatias/cirurgia , Estudos Transversais , Ecocardiografia , Feminino , Insuficiência Cardíaca Sistólica/complicações , Insuficiência Cardíaca Sistólica/mortalidade , Insuficiência Cardíaca Sistólica/cirurgia , Humanos , Hipertrofia Ventricular Esquerda/complicações , Hipertrofia Ventricular Esquerda/mortalidade , Hipertrofia Ventricular Esquerda/cirurgia , Masculino , Marca-Passo Artificial , Pré-Albumina/metabolismo , Estudos Prospectivos , Cintilografia , Análise de SobrevidaRESUMO
Never judge a book by its cover, nor assume hypertrophic cardiomyopathy (HCM) as sarcomeric, as appearances can deceive. HCM phenocopies account for a 5-10% of the cases, mainly represented by storage diseases, flagged by the increasing prevalence of senile cardiac amyloid in developing countries. Multisystemic and heterogeneous presentation of these entities is a challenge for clinicians, and time delay in diagnosis is a major concern. Promising drugs and gene-specific tailored therapies are under development, therefore, more than ever, appropriate understanding of these conditions is mandatory for adequate early treatment and counselling. In this review, storage disorders will be classified as extracellular and intracellular deposit storage diseases, focusing our attention on the most prevalent conditions from the cardiologist's perspective.
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INTRODUCTION AND OBJECTIVES: Bioresorbable vascular scaffolds (BVS) have the potential to restore vasomotion but the clinical implications are unknown. We sought to evaluate angina and ischemia in the long-term in patients treated with BVS and metallic drug-eluting stents (mDES). METHODS: Multicenter study including patients with 24 ± 6 months of uneventful follow-up, in which stress echocardiography was performed and functional status was assessed by the Seattle Angina Questionnaire (SAQ). The primary endpoint was a positive result in stress echocardiography. RESULTS: The study included 102 patients treated with BVS and 106 with mDES. There were no differences in the patients' baseline characteristics. Recurrent angina was found in 18 patients (17.6%) in the BVS group vs 25 (23.5%) in the mDES group (P = .37), but SAQ results were significantly better in the BVS group (angina frequency 96.0 ± 8.0 vs 89.2 ± 29.7; P = .02). Stress echocardiography was positive in 11/92 (11.9%) of BVS patients vs 9/96 (9.4%) of mDES patients in the (P = .71) and angina was induced in 2/102 (1.9%) vs 7/106 (6.6%) (P = .18), respectively, but exercise performance was better in the BVS group even in those with positive tests (exercise duration 9.0 ± 2.0minutes vs 7.7 ± 1.8minutes; P = .02). A propensity score matching analysis yielded similar results. CONCLUSIONS: The primary endpoint was similar in both groups. In addition, recurrent angina was similar in patients with BVS and mDES. The better functional status, assessed by means of SAQ and exercise performance, detected in patients receiving BVS should be confirmed in further studies.
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Angina Pectoris/terapia , Stents Farmacológicos , Ecocardiografia sob Estresse/métodos , Isquemia Miocárdica/terapia , Intervenção Coronária Percutânea/instrumentação , Alicerces Teciduais , Implantes Absorvíveis , Idoso , Angina Pectoris/diagnóstico , Estudos de Coortes , Eletrocardiografia/métodos , Everolimo/farmacologia , Feminino , Seguimentos , Humanos , Masculino , Metais , Pessoa de Meia-Idade , Isquemia Miocárdica/diagnóstico , Intervenção Coronária Percutânea/métodos , Pontuação de Propensão , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Centros de Atenção Terciária , Fatores de Tempo , Resultado do TratamentoRESUMO
PURPOSE: Late adverse myocardial remodeling after acute myocardial infarction (AMI) is strongly associated with sudden cardiac death (SCD). Cardiac magnetic resonance (CMR) performed early after AMI can predict late remodeling and SCD risk with moderate accuracy. This study assessed the ability of CMR-measured circumferential strain (CS) to add incremental predictive information to late gadolinium enhancement (LGE). METHODS: Patients with an AMI and LVEF < 50% were screened for inclusion. A total of 27 patients, totaling 432 myocardial segments, prospectively underwent CMR 7 ± 5 days after percutaneous coronary intervention (PCI). LGE, microvascular obstruction (MVO), and myocardial CS were measured for each segment. The primary endpoint was late segmental adverse remodeling defined as segmental wall motion score (WMS) > 1 measured by echocardiography 3 months after PCI. RESULTS: A total of 141 segments experienced the primary endpoint at 3 months. The mean LGE volume was higher in these segments, but LGE was also present in many segments with normal WMS (40 ± 28 versus 20 ± 26%, p < 0.01). Segments that met the primary endpoint also showed greater impairment of CS. Segments with both LGE > 17% and impaired CS >- 7.2% on CMR were more likely to experience late adverse remodeling (73%) as compared to segments with neither (9%, p < 0.001) or one abnormal parameter (36%, p < 0.001). CS >- 7.2% also added incremental accuracy to LGE > 17% for predicting late adverse remodeling (AUC 0.81 from 0.70, p < 0.001). CONCLUSIONS: When performed early after AMI, LGE is a moderate predictor of late remodeling and CS is a powerful predictor of late myocardial remodeling. When combined, they can predict late remodeling, a surrogate of SCD, with high accuracy.