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BACKGROUND AND AIMS: Implantable cardioverter-defibrillators (ICDs) are critical for preventing sudden cardiac death (SCD) in arrhythmogenic right ventricular cardiomyopathy (ARVC). This study aims to identify cross-continental differences in utilization of primary prevention ICDs and survival free from sustained ventricular arrhythmia (VA) in ARVC. METHODS: This was a retrospective analysis of ARVC patients without prior VA enrolled in clinical registries from 11 countries throughout Europe and North America. Patients were classified according to whether they received treatment in North America or Europe and were further stratified by baseline predicted VA risk into low- (<10%/5 years), intermediate- (10%-25%/5 years), and high-risk (>25%/5 years) groups. Differences in ICD implantation and survival free from sustained VA events (including appropriate ICD therapy) were assessed. RESULTS: One thousand ninety-eight patients were followed for a median of 5.1 years; 554 (50.5%) received a primary prevention ICD, and 286 (26.0%) experienced a first VA event. After adjusting for baseline risk factors, North Americans were more than three times as likely to receive ICDs {hazard ratio (HR) 3.1 [95% confidence interval (CI) 2.5, 3.8]} but had only mildly increased risk for incident sustained VA [HR 1.4 (95% CI 1.1, 1.8)]. North Americans without ICDs were at higher risk for incident sustained VA [HR 2.1 (95% CI 1.3, 3.4)] than Europeans. CONCLUSIONS: North American ARVC patients were substantially more likely than Europeans to receive primary prevention ICDs across all arrhythmic risk strata. A lower rate of ICD implantation in Europe was not associated with a higher rate of VA events in those without ICDs.
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Displasia Arritmogênica Ventricular Direita , Desfibriladores Implantáveis , Humanos , Desfibriladores Implantáveis/efeitos adversos , Displasia Arritmogênica Ventricular Direita/complicações , Displasia Arritmogênica Ventricular Direita/epidemiologia , Displasia Arritmogênica Ventricular Direita/terapia , Estudos Retrospectivos , Arritmias Cardíacas/epidemiologia , Arritmias Cardíacas/terapia , Arritmias Cardíacas/etiologia , Morte Súbita Cardíaca/epidemiologia , Morte Súbita Cardíaca/prevenção & controle , Morte Súbita Cardíaca/etiologia , Fatores de Risco , América do Norte/epidemiologia , Europa (Continente)/epidemiologiaRESUMO
BACKGROUND AND AIMS: Pathogenic desmoplakin (DSP) gene variants are associated with the development of a distinct form of arrhythmogenic cardiomyopathy known as DSP cardiomyopathy. Patients harbouring these variants are at high risk for sustained ventricular arrhythmia (VA), but existing tools for individualized arrhythmic risk assessment have proven unreliable in this population. METHODS: Patients from the multi-national DSP-ERADOS (Desmoplakin SPecific Effort for a RAre Disease Outcome Study) Network patient registry who had pathogenic or likely pathogenic DSP variants and no sustained VA prior to enrolment were followed longitudinally for the development of first sustained VA event. Clinically guided, step-wise Cox regression analysis was used to develop a novel clinical tool predicting the development of incident VA. Model performance was assessed by c-statistic in both the model development cohort (n = 385) and in an external validation cohort (n = 86). RESULTS: In total, 471 DSP patients [mean age 37.8 years, 65.6% women, 38.6% probands, 26% with left ventricular ejection fraction (LVEF) < 50%] were followed for a median of 4.0 (interquartile range: 1.6-7.3) years; 71 experienced first sustained VA events {2.6% [95% confidence interval (CI): 2.0, 3.5] events/year}. Within the development cohort, five readily available clinical parameters were identified as independent predictors of VA and included in a novel DSP risk score: female sex [hazard ratio (HR) 1.9 (95% CI: 1.1-3.4)], history of non-sustained ventricular tachycardia [HR 1.7 (95% CI: 1.1-2.8)], natural logarithm of 24-h premature ventricular contraction burden [HR 1.3 (95% CI: 1.1-1.4)], LVEF < 50% [HR 1.5 (95% CI: .95-2.5)], and presence of moderate to severe right ventricular systolic dysfunction [HR 6.0 (95% CI: 2.9-12.5)]. The model demonstrated good risk discrimination within both the development [c-statistic .782 (95% CI: .77-.80)] and external validation [c-statistic .791 (95% CI: .75-.83)] cohorts. The negative predictive value for DSP patients in the external validation cohort deemed to be at low risk for VA (<5% at 5 years; n = 26) was 100%. CONCLUSIONS: The DSP risk score is a novel model that leverages readily available clinical parameters to provide individualized VA risk assessment for DSP patients. This tool may help guide decision-making for primary prevention implantable cardioverter-defibrillator placement in this high-risk population and supports a gene-first risk stratification approach.
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Desmoplaquinas , Humanos , Desmoplaquinas/genética , Feminino , Masculino , Medição de Risco/métodos , Adulto , Pessoa de Meia-Idade , Arritmias Cardíacas/genética , Heterozigoto , Taquicardia Ventricular/genéticaRESUMO
BACKGROUND: A smartphone 12-Lead ECG that enables layman ECG screening is still lacking. We aimed to validate D-Heart ECG device, a smartphone 8/12 Lead electrocardiograph with an image processing algorithm to guide secure electrode placement by non-professional users. METHODS: One-hundred-fourty-five patients with HCM were enrolled. Two uncovered chest images were acquired using the smartphone camera. An image with virtual electrodes placement by imaging processing algorithm software was compared to the 'gold standard' electrode placement by a doctor. D-Heart 8 and 12-Lead ECG were obtained, immediately followed by 12lead ECGs and were assessed by 2 independent observers. Burden of ECG abnormalities was defined by a score based on the sum of 9 criteria, identifying four classes of increasing severity. RESULTS: A total of 87(60%) patients presented a normal/mildly abnormal ECG, whereas 58(40%) had moderate or severe ECG alteration. Eight(6%) patients had ≥1 misplaced electrode. D-Heart 8-Lead and 12lead ECGs concordance according to Cohen's weighted kappa test was 0,948 (p < 0,001, agreement of 97.93%). Concordance was high for the Romhilt-Estes score (kw = 0,912; p < 0.01). Concordance between D-Heart 12-Lead ECG and standard 12-Lead ECG was perfect (kw = 1). PR and QRS intervals measurements comparison with Bland-Altman method showed good accuracy (95% limit of agreement ±18 ms for PR and ± 9 ms for QRS). CONCLUSIONS: D-Heart 8/12-Lead ECGs proved accurate, allowing an assessment of ECG abnormalities comparable to the standard 12lead ECG in patients with HCM. The image processing algorithm provided accurate electrode placement, standardizing exam quality, potentially opening perspectives for layman ECG screening campaigns.
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Cardiomiopatia Hipertrófica , Eletrocardiografia , Humanos , Eletrocardiografia/métodos , Smartphone , Arritmias Cardíacas/diagnóstico , Cardiomiopatia Hipertrófica/diagnóstico , Coração , AntraciclinasRESUMO
AIMS: Arrhythmogenic right ventricular cardiomyopathy (ARVC) causes ventricular arrhythmias (VAs) and sudden cardiac death (SCD). In 2019, a risk prediction model that estimates the 5-year risk of incident VAs in ARVC was developed (ARVCrisk.com). This study aimed to externally validate this prediction model in a large international multicentre cohort and to compare its performance with the risk factor approach recommended for implantable cardioverter-defibrillator (ICD) use by published guidelines and expert consensus. METHODS AND RESULTS: In a retrospective cohort of 429 individuals from 29 centres in North America and Europe, 103 (24%) experienced sustained VA during a median follow-up of 5.02 (2.05-7.90) years following diagnosis of ARVC. External validation yielded good discrimination [C-index of 0.70 (95% confidence interval-CI 0.65-0.75)] and calibration slope of 1.01 (95% CI 0.99-1.03). Compared with the three published consensus-based decision algorithms for ICD use in ARVC (Heart Rhythm Society consensus on arrhythmogenic cardiomyopathy, International Task Force consensus statement on the treatment of ARVC, and American Heart Association guidelines for VA and SCD), the risk calculator performed better with a superior net clinical benefit below risk threshold of 35%. CONCLUSION: Using a large independent cohort of patients, this study shows that the ARVC risk model provides good prognostic information and outperforms other published decision algorithms for ICD use. These findings support the use of the model to facilitate shared decision making regarding ICD implantation in the primary prevention of SCD in ARVC.
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Displasia Arritmogênica Ventricular Direita , Desfibriladores Implantáveis , Arritmias Cardíacas/etiologia , Displasia Arritmogênica Ventricular Direita/complicações , Displasia Arritmogênica Ventricular Direita/diagnóstico , Displasia Arritmogênica Ventricular Direita/terapia , Morte Súbita Cardíaca/epidemiologia , Morte Súbita Cardíaca/etiologia , Morte Súbita Cardíaca/prevenção & controle , Desfibriladores Implantáveis/efeitos adversos , Humanos , Estudos Retrospectivos , Fatores de RiscoRESUMO
PURPOSE OF REVIEW: Pharmacological treatment options for hypertrophic cardiomyopathy (HCM) are currently limited and comprise non-disease specific therapies such as ß-blockers, non-dihydropyridine calcium channel blockers, and disopyramide. These agents that offer a variable degree of symptomatic relief, often suboptimal, are often limited by side-effects and fail to address the key molecular abnormalities of the disease. RECENT FINDINGS: Mavacamten is a novel, first-in-class, allosteric inhibitor of cardiac myosin ATPase, which reduces actin-myosin cross-bridge formation, thereby reducing myocardial contractility and improving myocardial energetic consumption in experimental HCM models. Following a successful Phase 2 study, the recently published phase III, placebo-controlled, randomized EXPLORER-HCM trial demonstrated the efficacy and safety of mavacamten in reducing left ventricular outflow tract obstruction and ameliorating exercise capacity, New York Heart Association functional class and health status in patients with obstructive HCM. Mavacamten represents the first agent specifically developed for HCM successfully tested in a Phase III trial, to be registered soon for clinical use, representing a radical change of paradigm in the pharmacological treatment of HCM.
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Benzilaminas , Cardiomiopatia Hipertrófica , Uracila , Benzilaminas/uso terapêutico , Miosinas Cardíacas , Cardiomiopatia Hipertrófica/tratamento farmacológico , Ensaios Clínicos Fase III como Assunto , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Uracila/análogos & derivadosRESUMO
AIMS: Whether pregnancy is a modifier of the long-term course and outcome of women with hypertrophic cardiomyopathy (HCM) is unknown. We assessed the association of pregnancy with long-term outcomes in HCM women. METHODS AND RESULTS: Retrospective evaluation of women with HCM from 1970 to 2021. Only women with pregnancy-related information (pregnancy present or absent) and a follow-up period lasting ≥1 year were included. The peri-partum period was defined as -1 to 6 months after delivery. The primary endpoint was a composite for major adverse cardiovascular events [MACE: cardiovascular death, sudden cardiac death, appropriate defibrillator shock and heart failure (HF) progression]. Overall, 379 (58%) women were included. There were 432 pregnancies in 242 (63%) patients. In 29 (7.6%) cases, pregnancies (n = 39) occurred after HCM diagnosis. Among these, three carrying likely pathogenic sarcomeric variants suffered MACEs in the peri-partum period. At 10 ± 9 years of follow-up, age at diagnosis [hazard ratio (HR) 1.034, 95% confidence interval (CI) 1.018-1.050, P < 0.001] and New York Heart Association (NYHA) class (II vs. I: HR 1.944, 95% CI 0.896-4.218; III vs. I: HR 5.291, 95% CI 2.392-11.705, P < 0.001) were associated with MACE. Conversely, pregnancy was associated with reduced risk (HR 0.605; 95% CI 0.380-0.963, P = 0.034). Among women with pregnancy, multiple occurrences did not modify risk. CONCLUSIONS: Pregnancy is not a modifier of long-term outcome in women with HCM and mostly occurs before a cardiac diagnosis. Most patients tolerate pregnancy well and do not show a survival disadvantage compared to women without. Pregnancy should not be discouraged, except in the presence of severe HF symptoms or high-risk features.
Hypertrophic cardiomyopathy (HCM) is the most common genetic disorder of the myocardium and is characterized by important gender-related differences: women are typically 5 years older than men at diagnosis, over half are diagnosed >50 years of age and consistently show greater propensity than men for heart failure (HF)-related complications and adverse outcome. Whether pregnancy is a modifier of the long-term course and outcome of women with HCM is unknown. In this study, pregnancy was not a modifier of long-term outcome in women with HCM. In particular: At 10 ± 7 years, most patients tolerated pregnancy well and did not show a survival disadvantage compared to women without pregnancies. Only baseline heart failure symptoms and age were associated with adverse outcome.Pregnancy should not be discouraged, except in the presence of severe HF symptoms or high-risk features. Nevertheless, cardio-obstetric counselling and close supervision are key in all instances, particularly in the peri-partum period.
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Cardiomiopatia Hipertrófica , Gravidez , Humanos , Feminino , Masculino , Estudos Retrospectivos , Fatores de Risco , Cardiomiopatia Hipertrófica/diagnóstico , Cardiomiopatia Hipertrófica/epidemiologia , Cardiomiopatia Hipertrófica/terapia , Morte Súbita Cardíaca/epidemiologia , Morte Súbita Cardíaca/etiologia , Modelos de Riscos ProporcionaisRESUMO
Background: Patients with likely pathogenic/pathogenic desmoplakin (DSP) variants are poorly characterized. Some of them meet diagnostic criteria for arrhythmogenic right ventricular cardiomyopathy (ARVC), but it is unclear how risk stratification strategies for ARVC perform in this setting. Objectives: The purpose of this study was to characterize arrhythmic outcomes and to test the performance of the recently validated ARVC risk calculator in patients with DSP likely pathogenic/pathogenic variants fulfilling definite 2010 ARVC Task Force Criteria (DSP-TFC+). Methods: DSP-TFC+ patients were enrolled from 20 institutions across 3 continents. Ventricular arrhythmias (VA), defined as a composite of sustained ventricular tachycardia (VT), appropriate implantable cardioverter defibrillator therapies, and ventricular fibrillation/sudden cardiac death events in follow-up, were reported as the primary outcome. We tested the performance of the ARVC risk calculator for VA prediction, reporting c-statistics. Results: Among 252 DSP-TFC+ patients (age 39.6 ± 16.9 years, 35.3% male), 94 (37.3%) experienced VA over 44.5 [IQR: 19.6-78.3] months. Patients with left ventricle involvement (n = 194) were at higher VA risk (log-rank P = 0.0239). History of nonsustained VT (aHR 2.097; P = 0.004) showed the strongest association with VA occurrence during the first 5-year follow-up. Neither age (P = 0.723) nor male sex (P = 0.200) was associated with VAs at follow-up. In 204 patients without VA at diagnosis, incident VA rate was high (32.8%; 7.37%/y). The ARVC risk calculator performed poorly overall (c-statistic 0.604 [0.594-0.614]) and very poorly in patients with left ventricular disease (c-statistic 0.558 [0.556-0.560]). Conclusions: DSP-TFC+ patients are at substantial risk for VAs. The ARVC risk calculator performs poorly in DSP-TFC+ patients suggesting need for a gene-specific risk algorithm. Meanwhile, DSP-TFC+ patients with nonsustained VT should be considered as high-risk.
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AIMS: Diagnosis of arrhythmogenic cardiomyopathy (ACM) may be challenging, as it comprises diverse phenotypes (right dominant, biventricular, and left dominant), and each may overlap with other clinical entities. The issue of differential diagnosis with conditions mimicking ACM has been previously highlighted; however, a systematic analysis of ACM diagnostic delay, and of its clinical implications, is lacking. METHODS AND RESULTS: Data of all ACM patients from three Italian Cardiomyopathy Referral Centres were reviewed to assess the time from first medical contact to definitive ACM diagnosis; a significant diagnostic delay was defined as a time to ACM diagnosis ≥2 years. Baseline characteristics and clinical course of patients with and without diagnostic delay were compared. Of 174 ACM patients, 31% experienced diagnostic delay, with a median time to diagnosis of 8 years (20% in right-dominant ACM, 33% in left-dominant ACM, and 39% in biventricular). Patients with diagnostic delay, when compared with those without, more frequently exhibited an ACM phenotype with left ventricular (LV) involvement (74 vs. 57%, P = 0.04) and a specific genetic background (none had plakophilin-2 variants). The most common initial (mis)diagnoses were dilated cardiomyopathy (51%), myocarditis (21%), and idiopathic ventricular arrhythmia (9%). At follow-up, all-cause mortality was greater in those with diagnostic delay (P = 0.03). CONCLUSION: Diagnostic delay is common in patients with ACM, particularly in the presence of LV involvement, and is associated with greater mortality at follow-up. Clinical suspicion and increasing use of tissue characterization by cardiac magnetic resonance in specific clinical settings are of key importance for the timely identification of ACM.
Almost one-third of patients with arrhythmogenic cardiomyopathy (ACM) experience a diagnostic delay >2 years. These patients are mostly affected by an ACM phenotype with left ventricular (LV) involvement and present worse mortality compared with those without diagnostic delay.Diagnostic delay is common in patients with ACM, particularly in the presence of LV involvement, and is associated with greater mortality at follow-up.The most common initial (mis)diagnoses were dilated cardiomyopathy, myocarditis, and idiopathic ventricular arrhythmia. Clinical suspicion and increasing use of tissue characterization by cardiac magnetic resonance in these specific clinical settings are of key importance to identify ACM in a timely fashion.
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Displasia Arritmogênica Ventricular Direita , Cardiomiopatias , Humanos , Diagnóstico Tardio , Displasia Arritmogênica Ventricular Direita/diagnóstico , Displasia Arritmogênica Ventricular Direita/genética , Cardiomiopatias/diagnóstico , Cardiomiopatias/genética , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/genética , Imageamento por Ressonância MagnéticaRESUMO
Background: Although disopyramide has been widely used to reduce left ventricular outflow obstruction (LVOTO) and to improve symptoms in patients with obstructive hypertrophic cardiomyopathy (oHCM), its use in real world as well as patient characteristics associated with a positive treatment response are still unclear. Methods: From 1980 to 2021, 1527 patients with HCM were evaluated and 372 (23%) had a LVOTO with active follow-up. The efficacy and safety of disopyramide were assessed systematically during 12 months (2-, 6-, and 12-month visits). Responders were patients with a final NYHA = I and a LVOTO < 30 mmHg; incomplete responders were those patients with NYHA > I and a LVOTO < 30 mmHg; and non-responders were symptomatic patients with no change in functional class NYHA and a LVOT gradient > 30 mmHg. Results: Two-hundred-fifty-four (66%) patients were in functional class NYHA I/II and 118 (34%) in NYHA III/IV. A total of 118/372 (32%, 55 ± 16 years) underwent disopyramide therapy. Twenty-eight (24%) patients responded to therapy, 39 (33%) were incomplete responders, and 51 (43%) did not respond. Responder were mainly patients in functional NYHA class I/II (24/28, 86%), whereas incomplete responders and non-responders were more often in functional NYHA class III/IV (50/54 (93%)). An independent predictor of response to disopyramide treatment was the presence of NYHA I/II at the initiation of therapy (HR 1.5 (95% CI 1.1-4.5), p = 0.03). No major life-threatening arrhythmic events or syncope occurred, despite 19 (16%) patients showing reduced QTc from baseline, 19 (16%) having no difference, while 80 (69%) patients had prolonged QTc interval. Thirty-one (26%) patients experienced side effects, in particular, 29 of the anticholinergic type. Conclusions: Disopyramide was underused in oHCM but effective in reducing LVOTO gradients and symptoms in slightly symptomatic patients with less severe disease phenotype with a safe pro-arrhythmic profile.
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Hypertrophic cardiomyopathy is the most common genetic cardiomyopathy. Main complications include the development of arrhythmias and heart failure, and the latter may be triggered by left ventricular outflow tract obstruction. The treatment of left ventricular outflow tract obstruction includes pharmacological therapies (beta-blockers, calcium channel blockers, disopyramide) and septal reduction therapies (alcohol septal ablation, surgical myectomy). Myosin inhibitors represent a new therapeutic opportunity and in recent clinical trials proved effective in symptom relief, improvement of functional capacity and quality of life in patients with obstructive hypertrophic cardiomyopathy. In this narrative review we will summarize the available and under development therapeutic approaches for hypertrophic cardiomyopathy.
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Cardiomiopatia Hipertrófica , Insuficiência Cardíaca , Obstrução da Via de Saída Ventricular Esquerda , Humanos , Qualidade de Vida , Cardiomiopatia Hipertrófica/tratamento farmacológicoRESUMO
BACKGROUND: Clinical guidelines recommend regular screening for arrhythmogenic right ventricular cardiomyopathy (ARVC) to monitor at-risk relatives, resulting in a significant burden on clinical resources. Prioritizing relatives on their probability of developing definite ARVC may provide more efficient patient care. OBJECTIVES: The aim of this study was to determine the predictors and probability of ARVC development over time among at-risk relatives. METHODS: A total of 136 relatives (46% men, median age 25.5 years [IQR: 15.8-44.4 years]) from the Netherlands Arrhythmogenic Cardiomyopathy Registry without definite ARVC by 2010 task force criteria were included. Phenotype was ascertained using electrocardiography, Holter monitoring, and cardiac imaging. Subjects were divided into groups with "possible ARVC" (only genetic or familial predisposition) and "borderline ARVC" (1 minor task force criterion plus genetic or familial predisposition). Cox regression was performed to determine predictors and multistate modeling to assess the probability of ARVC development. Results were replicated in an unrelated Italian cohort (57% men, median age 37.0 years [IQR: 25.4-50.4 years]). RESULTS: At baseline, 93 subjects (68%) had possible ARVC, and 43 (32%) had borderline ARVC. Follow-up was available for 123 relatives (90%). After 8.1 years (IQR: 4.2-11.4 years), 41 (33%) had developed definite ARVC. Independent of baseline phenotype, symptomatic subjects (P = 0.014) and those 20 to 30 years of age (P = 0.002) had a higher hazard of developing definite ARVC. Furthermore, patients with borderline ARVC had a higher probability of developing definite ARVC compared with those with possible ARVC (1-year probability 13% vs 0.6%, 3-year probability 35% vs 5%; P < 0.01). External replication showed comparable results (P > 0.05). CONCLUSIONS: Symptomatic relatives, those 20 to 30 years of age, and those with borderline ARVC have a higher probability of developing definite ARVC. These patients may benefit from more frequent follow-up, while others may be monitored less often.
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Displasia Arritmogênica Ventricular Direita , Humanos , Displasia Arritmogênica Ventricular Direita/diagnóstico , Displasia Arritmogênica Ventricular Direita/epidemiologia , Displasia Arritmogênica Ventricular Direita/genética , Eletrocardiografia/métodos , Fenótipo , Países BaixosRESUMO
BACKGROUND: Electrocardiographic (ECG) findings in arrhythmogenic left ventricular cardiomyopathy (ALVC) are limited to small case series. OBJECTIVES: This study aimed to analyze the ECG characteristics of ALVC patients and to correlate ECG with cardiac magnetic resonance and genotype data. METHODS: We reviewed data of 54 consecutive ALVC patients (32 men, age 39 ± 15 years) and compared them with 84 healthy controls with normal cardiac magnetic resonance. RESULTS: T-wave inversion was often noted (57.4%), particularly in the inferior and lateral leads. Low QRS voltages in limb leads were observed in 22.2% of patients. The following novel ECG findings were identified: left posterior fascicular block (LPFB) (20.4%), pathological Q waves (33.3%), and a prominent R-wave in V1 with a R/S ratio ≥0.5 (24.1%). The QRS voltages were lower in ALVC compared with controls, particularly in lead I and II. At receiver-operating characteristic analysis, the sum of the R-wave in I to II ≤8 mm (AUC: 0.909; P < 0.0001) and S-wave in V1 plus R-wave in V6 ≤12 mm (AUC: 0.784; P < 0.0001) effectively discriminated ALVC patients from controls. It is noteworthy that 4 of the 8 patients with an apparently normal ECG were recognized by these new signs. Transmural late gadolinium enhancement was associated to LPFB, a R/S ratio ≥0.5 in V1, and inferolateral T-wave inversion, and a ringlike pattern correlated to fragmented QRS, SV1+RV6 ≤12 mm, low QRS voltage, and desmoplakin alterations. CONCLUSIONS: Pathological Q waves, LPFB, and a prominent R-wave in V1 were common ECG signs in ALVC. An R-wave sum in I to II ≤8 mm and SV1+RV6 ≤12 mm were specific findings for ALVC phenotypes compared with controls.
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Cardiomiopatias , Meios de Contraste , Masculino , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Gadolínio , Eletrocardiografia , Arritmias Cardíacas , Bloqueio de RamoRESUMO
Background: Sudden cardiac arrest (SCA) in young people represents a dramatic event, often leading to severe neurologic outcomes or sudden cardiac death (SCD), and is frequently caused by genetic heart diseases. In this study, we report the results of the Tuscany registry of sudden cardiac death (ToRSADE) registry, aimed at monitoring the incidence and investigating the genetic basis of SCA and SCD occurring in subjects < 50 years of age in Tuscany, Italy. Methods and results: Creation of the ToRSADE registry allowed implementation of a repository for clinical, molecular and genetic data. For 22 patients, in whom a genetic substrate was documented or suspected, blood samples could be analyzed; 14 were collected at autopsy and 8 from resuscitated patients after SCA. Next generation sequencing (NGS) analysis revealed likely pathogenetic (LP) variants associated with cardiomyopathy (CM) or channelopathy in four patients (19%), while 17 (81%) carried variants of uncertain significance in relevant genes (VUS). In only one patient NGS confirmed the diagnosis obtained during autopsy: the p.(Asn480Lysfs*20) PKP2 mutation in a patient with arrhythmogenic cardiomyopathy (AC). Conclusion: Systematic genetic screening allowed identification of LP variants in 19% of consecutive patients with SCA/SCD, including subjects carrying variants associated with hypertrophic cardiomyopathy (HCM) or AC who had SCA/SCD in the absence of structural cardiomyopathy phenotype. Genetic analysis combined with clinical information in survived patients and post-mortem evaluation represent an essential multi-disciplinary approach to manage juvenile SCD and SCA, key to providing appropriate medical and genetic assistance to families, and advancing knowledge on the basis of arrhythmogenic mechanisms in inherited cardiomyopathies and channelopathies.
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IMPORTANCE: A high burden of premature ventricular contractions (PVCs) at disease diagnosis has been associated with an overall higher risk of ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy (ARVC). Data regarding dynamic modification of PVC burden at follow-up with Holter monitoring and its impact on arrhythmic risk in ARVC are scarce. OBJECTIVE: To describe changes in the PVC burden and to assess whether serial Holter monitoring is dynamically associated with sustained ventricular arrhythmias during follow-up in patients with ARVC. DESIGN, SETTINGS, AND PARTICIPANTS: In this cohort study, patients with a definite ARVC diagnosis, available Holter monitoring results at disease diagnosis, and at least 2 additional results of Holter monitoring during follow-up were enrolled from 6 ARVC registries in North America and Europe. Data were collected from June 1 to September 15, 2021. MAIN OUTCOMES AND MEASURES: The association between prespecified variables retrieved at each Holter monitoring follow-up (ie, overall PVC burden; presence of sudden PVC spikes, defined as absolute increase in PVC burden ≥5000 per 24 hours or a relative ≥75% increase, with an absolute increase of ≥1000 PVCs; presence of nonsustained ventricular tachycardia [NSVT]; and use of ß-blockers and class III antiarrhythmic drugs) and sustained ventricular arrhythmias occurring within 12 months after that Holter examination was assessed using a mixed logistical model. RESULTS: In 169 enrolled patients with ARVC (mean [SD] age, 36.3 [15.0] years; 95 men [56.2%]), a total of 723 Holter examinations (median, 4 [IQR, 4-5] per patient) were performed during a median follow-up of 54 (IQR, 42-63) months and detected 75 PVC spikes and 67 sustained ventricular arrhythmias. The PVC burden decreased significantly from the first to the second Holter examination (mean, 2906 [95% CI, 1581-4231] PVCs per 24 hours; P < .001). A model including 24-hour PVC burden (odds ratio [OR] 1.50 [95% CI, 1.10-2.03]; P = .01), PVC spikes (OR, 6.20 [95 CI, 2.74-13.99]; P < .001), and NSVT (OR, 2.29 [95% CI, 1.10-4.51]; P = .03) at each follow-up Holter examination was associated with sustained ventricular arrhythmia occurrence in the following 12 months. CONCLUSIONS AND RELEVANCE: These findings suggest that in patients with ARVC, changes in parameters derived from each Holter examination performed during follow-up are associated with the risk of sustained ventricular arrhythmias within 12 months of disease diagnosis.
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Displasia Arritmogênica Ventricular Direita , Taquicardia Ventricular , Complexos Ventriculares Prematuros , Adulto , Feminino , Humanos , Masculino , Displasia Arritmogênica Ventricular Direita/complicações , Displasia Arritmogênica Ventricular Direita/diagnóstico , Estudos de Coortes , Eletrocardiografia Ambulatorial , Complexos Ventriculares Prematuros/complicações , Complexos Ventriculares Prematuros/diagnósticoRESUMO
AIMS: Exercise performance is known to predict outcome in hypertrophic cardiomyopathy (HCM), but whether sex-related differences exist is unresolved. We explored whether functional impairment, assessed by exercise echocardiography, has comparable predictive accuracy in females and males with HCM. METHODS: We retrospectively evaluated 292 HCM patients (46 ± 16 years, 72% males), consecutively referred for exercise echocardiography; 242 were followed for 5.9 ± 4.2 years. RESULTS: Peak exercise capacity was 6.5 ± 1.6 metabolic equivalents (METs). Sixty patients (21%) showed impaired exercise capacity (≤5 METs). Exercise performance was reduced in females, compared with males (5.6 ± 1.6 vs 6.9 ± 1.5 METs, p < 0.001; peak METs ≤ 5 in 40% vs 13%, p < 0.001), largely driven by a worse performance in women >50 years of age. At multivariable analysis, female sex was independently associated with impaired exercise capacity (odds ratio: 4.67; 95% confidence interval (CI): 1.83-11.90; p = 0.001). During follow-up, 24 patients (10%) met the primary endpoint (a combination of cardiac death, heart failure requiring hospitalization, sustained ventricular tachycardia, appropriate implantable cardioverter defibrillator discharge, resuscitated sudden cardiac death and cardioembolic stroke). Event-free survival was reduced in females (p = 0.035 vs males). Peak METs were inversely related to outcome in males (hazard ratio (HR) per unit increase: 0.57; 95% CI: 0.39-0.84; p = 0.004) but not in females (HR: 1.22; 95% CI: 0.66-2.24; p = 0.53). CONCLUSIONS: Female patients with HCM showed significant age-related impairment in functional capacity compared with males, particularly evident in post-menopausal age groups. While women were at greater risk of HCM-related complications and death, impaired exercise capacity predicted adverse outcome only in men. These findings suggest the need for sex-specific management strategies in HCM.
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Cardiomiopatia Hipertrófica , Desfibriladores Implantáveis , Morte Súbita Cardíaca , Ecocardiografia , Feminino , Humanos , Masculino , Estudos RetrospectivosRESUMO
BACKGROUND: Whether early vs. delayed referral to septal reduction therapies (SRT, alcohol septal ablation or surgical myectomy) bears prognostic relevance in hypertrophic obstructive cardiomyopathy (HOCM) is unresolved. We analyzed the impact of SRT timing on the outcome of HOCM patients. METHODS: We followed 126 patients for 5⯱â¯4â¯years after SRT (mean age 53⯱â¯15â¯years; 55 post-ASA and 71 post-SM). Based on time-to-treatment (TTT; from HOCM diagnosis to SRT), patients were divided into three groups: "<3" years, Nâ¯=â¯50; "3-5" years, Nâ¯=â¯25; ">5" years, Nâ¯=â¯51. RESULTS: Patients with TTTâ¯>â¯5â¯years were younger at diagnosis and more often had atrial fibrillation (AF). Left ventricular outflow tract (LVOT) gradients were comparable in the 3 TTT groups. Two patients died peri-operatively, all with TTTâ¯>â¯5. Long-term, 8 patients died (3 suddenly and 5 due to heart failure). Mortality increased progressively with TTT (2% vs. 4% vs. 12% for TTT "<3", "3-5", and ">5" years, p for trendâ¯=â¯0.039). Independent predictors of disease progression (new-onset AF, worsening to NYHA III/IV symptoms, re-intervention or death) were TTT ("3-5" vs. "<3" years: HR: 4.988, 95%CI: 1.394-17.843; ">5" vs. "<3" years: HR: 3.420, 95%CI: 1.258-9.293, overall p-valueâ¯=â¯0.025), AF at baseline (HR: 1.896, 95%CI: 1.002-3.589, pâ¯=â¯0.036) and LVOT gradient (HR per mmâ¯Hg increase: 1.022, 95%CI: 1.007-1.024, pâ¯=â¯0.023). CONCLUSIONS: Delay in SRT referral has significant impact on long-term outcome of patients with HOCM, particularly when >5â¯years from first detection of gradient, even when successful relief of symptoms and gradient is achieved. Earlier interventions are associated with lower complication rates and better prognosis, suggesting the importance of timely SRT to maximize treatment benefit and prevent late HOCM-related complications.
Assuntos
Cardiomiopatia Hipertrófica/mortalidade , Cardiomiopatia Hipertrófica/cirurgia , Ablação por Cateter/mortalidade , Ablação por Cateter/métodos , Septos Cardíacos/cirurgia , Tempo para o Tratamento , Adulto , Idoso , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Ablação por Cateter/tendências , Feminino , Seguimentos , Septos Cardíacos/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Estudos Retrospectivos , Tempo para o Tratamento/tendências , Resultado do TratamentoRESUMO
Importance: Predictors of lethal arrhythmic events (LAEs) after a pediatric diagnosis of hypertrophic cardiomyopathy (HCM) are unresolved. Existing algorithms for risk stratification are limited to patients older than 16 years because of a lack of data on younger individuals. Objective: To describe the long-term outcome of pediatric-onset HCM and identify age-specific arrhythmic risk factors. Design, Setting, and Participants: This study assessed patients with pediatric-onset hypertrophic cardiomyopathy diagnosed from 1974 to 2016 in 2 national referral centers for cardiomyopathies in Florence, Italy. Patients with metabolic and syndromic disease were excluded. Exposures: Patients were assessed at 1-year intervals, or more often, if their clinical condition required. Main Outcomes and Measures: Lethal arrhythmic events (LAEs) and death related to heart failure. Results: Of 1644 patients with HCM, 100 (6.1%) were 1 to 16 years old at diagnosis (median [interquartile range], 12.2 [7.3-14.1] years). Of these, 63 (63.0%) were boys. Forty-two of the 100 patients (42.0%) were symptomatic (defined as an New York Heart Association classification higher than 1 or a Ross score greater than 2). The yield of sarcomere gene testing was 55 of 70 patients (79%). During a median of 9.2 years during which a mean of 1229 patients were treated per year, 24 of 100 patients (24.0%) experienced cardiac events (1.9% per year), including 19 LAEs and 5 heart failure-related events (3 deaths and 2 heart transplants). Lethal arrhythmic events occurred at a mean (SD) age of 23.1 (11.5) years. Two survivors of LAEs with symptoms of heart failure experienced recurrent cardiac arrest despite an implantable cardioverter defibrillator. Risk of LAE was associated with symptoms at onset (hazard ratio [HR], 8.2; 95% CI, 1.5-68.4; P = .02) and Troponin I or Troponin T gene mutations (HR, 4.1; 95% CI, 0.9-36.5; P = .06). Adult HCM risk predictors performed poorly in this population. Data analysis occurred from December 2016 to October 2017. Conclusions and Relevance: Pediatric-onset HCM is rare and associated with adverse outcomes driven mainly by arrhythmic events. Risk extends well beyond adolescence, which calls for unchanged clinical surveillance into adulthood. In this study, predictors of adverse outcomes differ from those of adult populations with HCM. In secondary prevention, the implantable cardioverter defibrillator did not confer absolute protection in the presence of limiting symptoms of heart failure.
Assuntos
Arritmias Cardíacas/epidemiologia , Cardiomiopatia Hipertrófica/complicações , Adolescente , Adulto , Idade de Início , Cardiomiopatia Hipertrófica/diagnóstico , Cardiomiopatia Hipertrófica/mortalidade , Criança , Pré-Escolar , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Itália , Masculino , Fatores de Risco , Taxa de Sobrevida , Adulto JovemRESUMO
BACKGROUND: MHealth technologies are revolutionizing cardiovascular medicine. However, a low-cost, user-friendly smartphone-based electrocardiograph is still lacking. D-Heart® is a portable device that enables the acquisition of the ECG on multiple leads which streams via Bluetooth to any smartphone. Because of the potential impact of this technology in low-income settings, we determined the accuracy of D-Heart® tracings in the stratification of ECG morphological abnormalities, compared with 12-lead ECGs. METHODS: Consecutive African patients referred to the Ziguinchor Regional Hospital (Senegal) were enrolled (n=117; 69 males, age 39±11years). D-Heart® recordings (3 peripheral leads plus V5) were obtained immediately followed by 12 lead ECGs and were assessed blindly by 2 independent observers. Global burden of ECG abnormalities was defined by a semi-quantitative score based on the sum of 9 criteria, identifying four classes of increasing severity. RESULTS: D-Heart® and 12-lead ECG tracings were respectively classified as: normal: 72 (61%) vs 69 (59%); mildly abnormal: 42 (36%) vs 45 (38%); moderately abnormal: 3 (3%) vs 3 (3%). None had markedly abnormal tracings. Cohen's weighted kappa (kw) test demonstrated a concordance of 0,952 (p<0,001, agreement 98,72%). Concordance was high as well for the Romhilt-Estes score (kw=0,893; p<0,001 agreement 97,35%). PR and QRS intervals comparison with Bland-Altman method showed good accuracy for D-Heart® measurements (95% limit of agreement ±20ms for PR and ±10ms for QRS). CONCLUSIONS: D-Heart® proved effective and accurate stratification of ECG abnormalities comparable to the 12-lead electrocardiographs, thereby opening new perspectives for low-cost community cardiovascular screening programs in low-income settings.