RESUMO
BACKGROUND: A novel risk calculator based on clinical characteristics and noninvasive tests that predicts the onset of clinical sustained ventricular arrhythmias (VA) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) has been proposed and validated by recent studies. It remains unknown whether programmed ventricular stimulation (PVS) provides additional prognostic value. METHODS: All patients with a definite ARVC diagnosis, no history of sustained VAs at diagnosis, and PVS performed at baseline were extracted from 6 international ARVC registries. The calculator-predicted risk for sustained VA (sustained or implantable cardioverter defibrillator treated ventricular tachycardia [VT] or fibrillation, [aborted] sudden cardiac arrest) was assessed in all patients. Independent and combined performance of the risk calculator and PVS on sustained VA were assessed during a 5-year follow-up period. RESULTS: Two hundred eighty-eight patients (41.0±14.5 years, 55.9% male, right ventricular ejection fraction 42.5±11.1%) were enrolled. At PVS, 137 (47.6%) patients had inducible ventricular tachycardia. During a median of 5.31 [2.89-10.17] years of follow-up, 83 (60.6%) patients with a positive PVS and 37 (24.5%) with a negative PVS experienced sustained VA (P<0.001). Inducible ventricular tachycardia predicted clinical sustained VA during the 5-year follow-up and remained an independent predictor after accounting for the calculator-predicted risk (HR, 2.52 [1.58-4.02]; P<0.001). Compared with ARVC risk calculator predictions in isolation (C-statistic 0.72), addition of PVS inducibility showed improved prediction of VA events (C-statistic 0.75; log-likelihood ratio for nested models, P<0.001). PVS inducibility had a 76% [67-84] sensitivity and 68% [61-74] specificity, corresponding to log-likelihood ratios of 2.3 and 0.36 for inducible (likelihood ratio+) and noninducible (likelihood ratio-) patients, respectively. In patients with a ARVC risk calculator-predicted risk of clinical VA events <25% during 5 years (ie, low/intermediate subgroup), PVS had a 92.6% negative predictive value. CONCLUSIONS: PVS significantly improved risk stratification above and beyond the calculator-predicted risk of VA in a primary prevention cohort of patients with ARVC, mainly for patients considered to be at low and intermediate risk by the clinical risk calculator.
Assuntos
Displasia Arritmogênica Ventricular Direita , Prevenção Primária , Feminino , Humanos , Masculino , Arritmias Cardíacas/epidemiologia , Displasia Arritmogênica Ventricular Direita/epidemiologia , Displasia Arritmogênica Ventricular Direita/prevenção & controle , Morte Súbita Cardíaca/epidemiologia , Desfibriladores Implantáveis , Prevenção Primária/métodos , Medição de Risco/métodos , Fatores de Risco , Volume Sistólico , Taquicardia Ventricular/epidemiologia , Função Ventricular Direita , Adulto , Pessoa de Meia-IdadeRESUMO
AIMS: Arrhythmic mitral valve syndrome is linked to life-threatening ventricular arrhythmias. The incidence, morphology and methods for risk stratification are not well known. This prospective study aimed to describe the incidence and the morphology of ventricular arrhythmia and propose risk stratification in patients with arrhythmic mitral valve syndrome. METHODS: Arrhythmic mitral valve syndrome patients were monitored for ventricular tachyarrhythmias by implantable loop recorders (ILR) and secondary preventive implantable cardioverter-defibrillators (ICD). Severe ventricular arrhythmias included ventricular fibrillation, appropriate or aborted ICD therapy, sustained ventricular tachycardia and non-sustained ventricular tachycardia with symptoms of hemodynamic instability. RESULTS: During 3.1 years of follow-up, severe ventricular arrhythmia was recorded in seven (12%) of 60 patients implanted with ILR [first event incidence rate 4% per person-year, 95% confidence interval (CI) 2-9] and in four (20%) of 20 patients with ICD (re-event incidence rate 8% per person-year, 95% CI 3-21). In the ILR group, severe ventricular arrhythmia was associated with frequent premature ventricular complexes, more non-sustained ventricular tachycardias, greater left ventricular diameter and greater posterolateral mitral annular disjunction distance (all P < 0.02). CONCLUSIONS: The yearly incidence of ventricular arrhythmia was high in arrhythmic mitral valve syndrome patients without previous severe arrhythmias using continuous heart rhythm monitoring. The incidence was even higher in patients with secondary preventive ICD. Frequent premature ventricular complexes, non-sustained ventricular tachycardias, greater left ventricular diameter and greater posterolateral mitral annular disjunction distance were predictors of first severe arrhythmic event.
Assuntos
Desfibriladores Implantáveis , Taquicardia Ventricular , Complexos Ventriculares Prematuros , Humanos , Valva Mitral/diagnóstico por imagem , Estudos Prospectivos , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/epidemiologia , Taquicardia Ventricular/etiologia , Fibrilação Ventricular/diagnóstico , Fibrilação Ventricular/epidemiologia , Fibrilação Ventricular/etiologia , Complexos Ventriculares Prematuros/complicações , Síndrome , Desfibriladores Implantáveis/efeitos adversos , Morte Súbita Cardíaca/epidemiologiaRESUMO
AIMS: Cardiac disease progression prior to first ventricular arrhythmia (VA) in LMNA genotype-positive patients is not described. METHODS AND RESULTS: We performed a primary prevention cohort study, including consecutive LMNA genotype-positive patients from our centre. Patients underwent repeated clinical, electrocardiographic, and echocardiographic examinations. Electrocardiographic and echocardiographic disease progression as a predictor of first-time VA was evaluated by generalized estimation equation analyses. Threshold values at transition to an arrhythmic phenotype were assessed by threshold regression analyses. We included 94 LMNA genotype-positive patients without previous VA (age 38 ± 15 years, 32% probands, 53% females). Nineteen (20%) patients experienced VA during 4.6 (interquartile range 2.1-7.3) years follow up, at mean age 50 ± 11 years. We analysed 536 echocardiographic and 261 electrocardiogram examinations. Individual patient disease progression was associated with VA [left ventricular ejection fraction (LVEF) odds ratio (OR) 1.4, 95% confidence interval (CI) 1.2-1.6 per 5% reduction, left ventricular end-diastolic volume index (LVEDVi) OR 1.2 (95% CI 1.1-1.3) per 5 mL/m2 increase, PR interval OR 1.2 (95% CI 1.1-1.4) per 10 ms increase]. Threshold values for transition to an arrhythmic phenotype were LVEF 44%, LVEDVi 77 mL/m2, and PR interval 280 ms. CONCLUSIONS: Incidence of first-time VA was 20% during 4.6 years follow up in LMNA genotype-positive patients. Individual patient disease progression by ECG and echocardiography were strong predictors of VA, indicating that disease progression rate may have additional value to absolute measurements when considering primary preventive ICD. Threshold values of LVEF <44%, LVEDVi >77 mL/m2, and PR interval >280 ms indicated transition to a more arrhythmogenic phenotype.
Assuntos
Desfibriladores Implantáveis , Laminopatias , Feminino , Masculino , Humanos , Volume Sistólico , Estudos de Coortes , Função Ventricular Esquerda , Fatores de Risco , Desfibriladores Implantáveis/efeitos adversos , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/genética , Laminopatias/complicações , Prevenção Primária , Progressão da DoençaRESUMO
BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is predominantly caused by desmosomal genetic variants, and clinical hallmarks include arrhythmias and systolic dysfunction. We aimed at studying the impact of the implicated gene(s) on the disease course. METHODS: The Nordic ARVC Registry holds data on a multinational cohort of ARVC families. The effects of genotype on electrocardiographic features, imaging findings and clinical events were analysed. RESULTS: We evaluated 419 patients (55% men), with a mean follow-up of 11.2±7.4 years. A pathogenic desmosomal variant was identified in 62% of the 230 families: PKP2 in 41%, DSG2 in 13%, DSP in 7% and DSC2 in 3%. Reduced left ventricular ejection fraction (LVEF) ≤45% on cardiac MRI was more frequent among patients with DSC2/DSG2/DSP than PKP2 ARVC (27% vs 4%, p<0.01). In contrast, in Cox regression modelling of patients with definite ARVC, we found a higher risk of arrhythmias among PKP2 than DSC2/DSG2/DSP carriers: HR 0.25 (0.10-0.68, p<0.01) for atrial fibrillation/flutter, HR 0.67 (0.44-1.0, p=0.06) for ventricular arrhythmias and HR 0.63 (0.42-0.95, p<0.05) for any arrhythmia. Gene-negative patients had an intermediate risk (16%) of LVEF ≤45% and a risk of the combined arrhythmic endpoint comparable with DSC2/DSG2/DSP carriers. Male sex was a risk factor for both arrhythmias and reduced LVEF across all genotype groups (p<0.01). CONCLUSION: In this large cohort of ARVC families with long-term follow-up, we found PKP2 genotype to be more arrhythmic than DSC2/DSG2/DSP or gene-negative carrier status, whereas reduced LVEF was mostly seen among DSC2/DSG2/DSP carriers. Male sex was associated with a more severe phenotype.
Assuntos
Displasia Arritmogênica Ventricular Direita , Insuficiência Cardíaca , Arritmias Cardíacas/genética , Displasia Arritmogênica Ventricular Direita/complicações , Displasia Arritmogênica Ventricular Direita/genética , Desmossomos , Feminino , Estudos de Associação Genética , Humanos , Masculino , Placofilinas/genética , Volume Sistólico/genética , Função Ventricular EsquerdaRESUMO
AIMS: This study aimed to explore the incidence of severe cardiac events in paediatric arrhythmogenic right ventricular cardiomyopathy (ARVC) patients and ARVC penetrance in paediatric relatives. Furthermore, the phenotype in childhood-onset ARVC was described. METHODS: Consecutive ARVC paediatric patients and genotype positive relatives ≤18 years of age were followed with electrocardiographic, structural, and arrhythmic characteristics according to the 2010 revised Task Force Criteria. Penetrance of ARVC disease was defined as fulfilling definite ARVC criteria and severe cardiac events were defined as cardiac death, heart transplantation (HTx) or severe ventricular arrhythmias. Childhood-onset disease was defined as meeting definite ARVC criteria ≤12 years of age. RESULTS: Among 62 individuals [age 9.8 (5.0-14.0) years, 11 probands], 20 (32%) fulfilled definite ARVC diagnosis, of which 8 (40%) had childhood-onset disease. The incidence of severe cardiac events was 23% (n = 14) by last follow-up and half of them occurred in patients ≤12 years of age. Among the eight patients with childhood-onset disease, five had biventricular involvement needing HTx and three had severe arrhythmic events. Among the 51 relatives, 6% (n = 3) met definite ARVC criteria at time of genetic diagnosis, increasing to 18% (n = 9) at end of follow-up. CONCLUSIONS: In a paediatric ARVC cohort, there was a high incidence of severe cardiac events and half of them occurred in children ≤12 years of age. The ARVC penetrance in genotype positive paediatric relatives was 18%. These findings of a high-malignant phenotype in childhood-onset ARVC indicate a need for ARVC family screening at younger age than currently recommended.
Assuntos
Displasia Arritmogênica Ventricular Direita , Humanos , Displasia Arritmogênica Ventricular Direita/diagnóstico , Displasia Arritmogênica Ventricular Direita/epidemiologia , Displasia Arritmogênica Ventricular Direita/genética , Fatores de Risco , Arritmias Cardíacas/epidemiologia , Eletrocardiografia , Estudos de CoortesRESUMO
AIMS: We aimed to characterize the substrate of T-wave inversion (TWI) using cardiac magnetic resonance (CMR) and the association between diffuse fibrosis and ventricular arrhythmias (VA) in patients with mitral valve prolapse (MVP). METHODS AND RESULTS: TWI was defined as negative T-wave ≥0.1 mV in ≥2 adjacent ECG leads. Diffuse myocardial fibrosis was assessed by T1 relaxation time and extracellular volume (ECV) fraction by T1-mapping CMR. We included 162 patients with MVP (58% females, age 50 ± 16 years), of which 16 (10%) patients had severe VA (aborted cardiac arrest or sustained ventricular tachycardia). TWI was found in 34 (21%) patients. Risk of severe VA increased with increasing number of ECG leads displaying TWI [OR 1.91, 95% CI (1.04-3.52), P = 0.04]. The number of ECG leads displaying TWI increased with increasing lateral ECV (26 ± 3% for TWI 0-1leads, 28 ± 4% for TWI 2leads, 29 ± 5% for TWI ≥3leads, P = 0.04). Patients with VA (sustained and non-sustained ventricular tachycardia) had increased lateral T1 (P = 0.004), also in the absence of late gadolinium enhancement (LGE) (P = 0.008). CONCLUSIONS: Greater number of ECG leads with TWI reflected a higher arrhythmic risk and higher degree of lateral diffuse fibrosis by CMR. Lateral diffuse fibrosis was associated with VA, also in the absence of LGE. These results suggest that TWI may reflect diffuse myocardial fibrosis associated with VA in patients with MVP. T1-mapping CMR may help risk stratification for VA.
Assuntos
Cardiomiopatias , Prolapso da Valva Mitral , Taquicardia Ventricular , Adulto , Idoso , Arritmias Cardíacas/complicações , Arritmias Cardíacas/etiologia , Cardiomiopatias/complicações , Cardiomiopatias/diagnóstico por imagem , Meios de Contraste , Feminino , Fibrose , Gadolínio , Humanos , Imagem Cinética por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Prolapso da Valva Mitral/complicações , Prolapso da Valva Mitral/diagnóstico por imagem , Prolapso da Valva Mitral/patologia , Miocárdio/patologia , Valor Preditivo dos Testes , Taquicardia Ventricular/complicações , Taquicardia Ventricular/etiologiaRESUMO
AIMS: We aimed to assess sex-specific phenotypes and disease progression, and their relation to exercise, in arrhythmogenic cardiomyopathy (AC) patients. METHODS AND RESULTS: In this longitudinal cohort study, we included consecutive patients with AC from a referral centre. We performed echocardiography at baseline and repeatedly during follow-up. Patients' exercise dose at inclusion was expressed as metabolic equivalents of task (MET)-h/week. Ventricular arrhythmia (VA) was defined as aborted cardiac arrest, sustained ventricular tachycardia, or appropriate therapy by implantable cardioverter-defibrillator. We included 190 AC patients (45% female, 51% probands, age 41 ± 17 years). Ventricular arrhythmia had occurred at inclusion or occurred during follow-up in 85 patients (33% of females vs. 55% of males, P = 0.002). Exercise doses were higher in males compared with females [25 (interquartile range, IQR 14-51) vs. 12 (IQR 7-22) MET-h/week, P < 0.001]. Male sex was a marker of proband status [odds ratio (OR) 2.6, 95% confidence interval (CI) 1.4-5.0, P = 0.003] and a marker of VA (OR 2.6, 95% CI 1.4-5.0, P = 0.003), but not when adjusted for exercise dose and age (adjusted OR 1.8, 95% CI 0.9-3.6, P = 0.12 and 1.5, 95% CI 0.7-3.1, P = 0.30, by 5 MET-h/week increments). In all, 167 (88%) patients had ≥2 echocardiographic examinations during 6.9 (IQR 4.7-9.8) years of follow-up. We observed no sex differences in deterioration of right or left ventricular dimensions and functions. CONCLUSION: Male AC patients were more often probands and had higher prevalence of VA than female patients, but not when adjusting for exercise dose. Importantly, disease progression was similar between male and female patients.
Assuntos
Displasia Arritmogênica Ventricular Direita , Desfibriladores Implantáveis , Adulto , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/epidemiologia , Arritmias Cardíacas/terapia , Displasia Arritmogênica Ventricular Direita/diagnóstico por imagem , Displasia Arritmogênica Ventricular Direita/epidemiologia , Progressão da Doença , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Caracteres Sexuais , Adulto JovemRESUMO
AIMS: We aimed to assess structural progression in arrhythmogenic cardiomyopathy (AC) patients and mutation-positive family members and its impact on arrhythmic outcome in a longitudinal cohort study. METHODS AND RESULTS: Structural progression was defined as the development of new Task Force imaging criteria from inclusion to follow-up and progression rates as annual changes in imaging parameters. We included 144 AC patients and family members (48% female, 47% probands, 40 ± 16 years old). At genetic diagnosis and inclusion, 58% of family members had penetrant AC disease. During 7.0 [inter-quartile range (IQR) 4.5-9.4] years of follow-up, 47% of family members without AC at inclusion developed AC criteria, resulting in a yearly new AC penetrance of 8%. Probands and family members had a similar progression rate of right ventricular outflow tract diameter (0.5 mm/year vs. 0.6 mm/year, P = 0.28) by mixed model analysis of 598 echocardiographic examinations. Right ventricular fractional area change progression rate was even higher in family members (-0.6%/year vs. -0.8%/year, P < 0.01). Among 86 patients without overt structural disease or arrhythmic history at inclusion, a first severe ventricular arrhythmic event occurred in 8 (9%), of which 7 (88%) had concomitant structural progression. Structural progression was associated with higher incidence of severe ventricular arrhythmic events adjusted for age, sex, and proband status (HR 21.24, 95% CI 2.47-182.81, P < 0.01). CONCLUSION: More than half of family members had AC criteria at genetic diagnosis and yearly AC penetrance was 8%. Structural progression was similar in probands and family members and was associated with higher incidence of severe ventricular arrhythmic events.
Assuntos
Displasia Arritmogênica Ventricular Direita , Adulto , Displasia Arritmogênica Ventricular Direita/genética , Progressão da Doença , Família , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Penetrância , Adulto JovemRESUMO
OBJECTIVE: Changes in right ventricular (RV) structure and function following prolonged endurance training in athletes arise due to its unique anatomy and physiology. Arrhythmogenic cardiomyopathy (AC) should be differentiated from electrical, functional and structural adaptation of the heart in response to repetitive intense physical activity due to the negative contribution of exercise on AC progression and arrhythmic risk. DESIGN: For this review we performed a systematic search of the PubMed database up to October 2017 using terms and keywords pertaining to RV, athlete's heart (AH), AC, sudden cardiac death. RESULTS: This review summarizes currently available data on the impact of exercise on cardiac structure and function, discusses the debatable hypothesis of exercise-induced RV remodeling, compares the common features and search for distinctive characteristics between AH and AC. CONCLUSION: Exercise has a more profound impact on the structure and function of the RV than of the left ventricle. Differentiating physiologic RV remodeling following prolonged endurance exercise from subclinical cardiac pathology can be challenging. A multimodality approach is recommended to differentiate between exercise-induced physiological adaptations and cardiomyopathy.
Assuntos
Displasia Arritmogênica Ventricular Direita/fisiopatologia , Atletas , Cardiomegalia Induzida por Exercícios , Resistência Física , Função Ventricular Direita , Remodelação Ventricular , Adaptação Fisiológica , Animais , Displasia Arritmogênica Ventricular Direita/diagnóstico por imagem , Displasia Arritmogênica Ventricular Direita/genética , Displasia Arritmogênica Ventricular Direita/mortalidade , Morte Súbita Cardíaca/etiologia , Humanos , Fatores de Risco , Fatores de Tempo , Função Ventricular EsquerdaRESUMO
BACKGROUND: The implications of exercise-induced cardiac troponin elevation in healthy individuals are unclear. This study aimed to determine if individuals with a high exercise-induced cardiac troponin I (cTnI) response have alterations in myocardial function following high-intensity endurance exercise compared with normal-cTnI responders. METHODS AND RESULTS: Study individuals were recruited from previous participants in a 91-km mountain bike cycling race (the North Sea Race) and were classified as high- (n=34) or normal-cTnI responders (n=25) based on maximal cTnI values after the recruitment race. The present study exposed all participants to 2 prolonged high-intensity exercises: a combined lactate threshold and cardiopulmonary exercise test and repeated participation in the North Sea Race. Echocardiography was performed before, immediately after, and 24 hours following exercise. All study individuals (n=59) had normal coronary arteries, and were aged 51±10 years; 46 (74%) were men. There were no differences in baseline characteristics between the high- and normal-cTnI responders. Maximal cTnI levels 3 hours after exercise were significantly higher in the high- compared with normal-cTnI group (P<0.001-0.027). Following exercise, there were no differences in global ventricular function between the 2 groups. In contrast, high-cTnI responders had significantly lower regional strain in the anteroseptal segments following exercise, with more profound changes after the race. CONCLUSIONS: High-cTnI responders had lower anteroseptal segmental strain shortly after exercise than normal-cTnI responders. However, there were no permanent alterations in myocardial strain, indicating no short- or long-term adverse consequences of these exercise-induced alterations in myocardial function. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02166216.
Assuntos
Biomarcadores , Troponina I , Função Ventricular Esquerda , Humanos , Masculino , Troponina I/sangue , Feminino , Pessoa de Meia-Idade , Função Ventricular Esquerda/fisiologia , Adulto , Biomarcadores/sangue , Exercício Físico/fisiologia , Teste de Esforço , Ciclismo/fisiologia , Regulação para Cima , EcocardiografiaRESUMO
BACKGROUND: LMNA genotype-positive patients have high risk of experiencing life-threatening ventricular tachyarrhythmias (VTAs). The LMNA-risk VTA calculator published in 2019 has not been externally validated. OBJECTIVE: The purpose of this study was to validate the LMNA-risk VTA calculator. METHODS: We included LMNA genotype-positive patients without previous VTAs from 2 large Scandinavian centers. Patients underwent electrocardiography, 24-hour Holter monitoring, and echocardiographic examinations at baseline and repeatedly during follow-up. Validation of the LMNA-risk VTA calculator was performed using Harrell's C-statistic derived from multivariable Cox regression analysis. RESULTS: We included 118 patients (age 37 years [IQR 27-49 years]; 39 [33%] probands; 65 [55%] women; 100 [85%] with non-missense LMNA variants). Twenty-three patients (19%) experienced VTA during 6.1 years (interquartile range 3.0-9.1 years) follow-up, resulting in 3.0% (95% confidence interval 2.0%-4.5%) yearly incidence rate. Atrioventricular block and reduced left ventricular ejection fraction were independent predictors of VTAs, while nonsustained ventricular tachycardia, male sex, and non-missense LMNA variants were not. The LMNA-risk VTA calculator showed 83% sensitivity and 26% specificity for identifying patients with VTAs during the coming 5 years, and a Harrell's C-statistic of 0.85, when applying ≥7% predicted 5-year VTA risk as threshold. The sensitivity increased to 100% when reevaluating risk at the time of last consultation before VTA. The calculator overestimated arrhythmic risk in patients with mild and moderate phenotype, particularly in men. CONCLUSION: Validation of the LMNA-risk VTA calculator showed high sensitivity for subsequent VTAs, but overestimated arrhythmic risk when using ≥7% predicted 5-year risk as threshold. Frequent reevaluation of risk was necessary to maintain the sensitivity of the model.
Assuntos
Desfibriladores Implantáveis , Laminopatias , Taquicardia Ventricular , Masculino , Feminino , Humanos , Volume Sistólico , Função Ventricular Esquerda , Desfibriladores Implantáveis/efeitos adversos , Taquicardia Ventricular/etiologia , Eletrocardiografia , Laminopatias/complicações , Lamina Tipo ARESUMO
BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by fibrofatty replacement of primarily the right ventricular myocardium, a substrate for life-threatening ventricular arrhythmias (VAs). Repeated cardiac imaging of at-risk relatives is important for early disease detection. However, it is not known whether screening should be age-tailored. OBJECTIVES: The goal of this study was to assess the need for age-tailoring of follow-up protocols in early ARVC by evaluating myocardial disease progression in different age groups. METHODS: We divided patients with early-stage ARVC and genotype-positive relatives without overt structural disease and VA at first evaluation into 3 groups: age <30 years, 30 to 50 years, and ≥50 years. Longitudinal biventricular deformation characteristics were used to monitor disease progression. To link deformation abnormalities to underlying myocardial disease substrates, Digital Twins were created using an imaging-based computational modeling framework. RESULTS: We included 313 echocardiographic assessments from 82 subjects (57% female, age 39 ± 17 years, 10% probands) during 6.7 ± 3.3 years of follow-up. Left ventricular global longitudinal strain slightly deteriorated similarly in all age groups (0.1%-point per year [95% CI: 0.05-0.15]). Disease progression in all age groups was more pronounced in the right ventricular lateral wall, expressed by worsening in longitudinal strain (0.6%-point per year [95% CI: 0.46-0.70]) and local differences in myocardial contractility, compliance, and activation delay in the Digital Twin. Six patients experienced VA during follow-up. CONCLUSIONS: Disease progression was similar in all age groups, and sustained VA also occurred in patients aged >50 years without overt ARVC phenotype at first evaluation. Unlike recommended by current guidelines, our study suggests that follow-up of ARVC patients and relatives should not stop at older age.
Assuntos
Displasia Arritmogênica Ventricular Direita , Feminino , Masculino , Humanos , Displasia Arritmogênica Ventricular Direita/diagnóstico por imagem , Miocárdio , Coração , Simulação por Computador , Progressão da DoençaRESUMO
AIMS: We aimed to study the progression of cardiac dysfunction in patients with lamin A/C mutations and explore markers of adverse cardiac outcome. METHODS AND RESULTS: We followed consecutive lamin A/C genotype-positive patients divided into tertiles according to age. Patients underwent repeated clinical examinations, electrocardiograms (ECGs), and echocardiograms. We followed left ventricular (LV) and right ventricular (RV) size and function, and the severity atrioventricular-valve regurgitations. Outcome was death, LVAD implant, or cardiac transplantation. We included 101 patients [age 44 (29-54) years, 39% probands, 50% female]. We analysed 576 echocardiograms and 258 ECGs during a follow-up of 4.9 (interquartile range 2.5-8.2) years. The PR-interval increased at young age from 204 ± 73 to 212 ± 69 ms (P < 0.001), LV ejection fraction (LVEF) declined from middle age from 50 ± 12% to 47 ± 13% (P < 0.001), while LV volumes remained unchanged. RV function and tricuspid regurgitation worsened from middle age with accelerating rates. Progression of RV dysfunction [odds ratio (OR) 1.3, 95% confidence interval (CI) (1.03-1.65), P = 0.03] and tricuspid regurgitation [OR 4.9, 95% CI (1.64-14.9), P = 0.004] were associated with outcome when adjusted for age, sex, comorbidities, LVEF, and New York Heart Association functional class. CONCLUSION: In patients with lamin A/C genotype, electrical disease started at young age. From middle age, LV function deteriorated progressively, while LV size remained unchanged. Worsening of RV function and tricuspid regurgitation accelerated in older age and were associated with outcome. Our systematic map on cardiac deterioration may help optimal monitoring and prognostication in lamin A/C disease.
Assuntos
Insuficiência da Valva Tricúspide , Adulto , Ecocardiografia , Feminino , Humanos , Lamina Tipo A/genética , Masculino , Pessoa de Meia-Idade , Mutação , Volume Sistólico , Insuficiência da Valva Tricúspide/complicações , Insuficiência da Valva Tricúspide/diagnóstico por imagem , Insuficiência da Valva Tricúspide/genética , Função Ventricular Esquerda , Função Ventricular DireitaRESUMO
Background: The effect of prolonged, high-intensity endurance exercise on myocardial function is unclear. This study aimed to determine the left ventricular (LV) response to increased exercise duration and intensity using novel echocardiographic tools to assess myocardial work and fatigue. Materials and methods: LV function was assessed by echocardiography before, immediately, and 24 h after a cardiopulmonary exercise test (CPET) and a 91-km mountain bike leisure race. Cardiac Troponin I (cTnI) was used to assess myocyte stress. Results: 59 healthy recreational athletes, 52 (43-59) years of age, 73% males, were included. The race was longer and of higher intensity generating higher cTnI levels compared with the CPET (p < 0.0001): Race/CPET: exercise duration: 230 (210, 245)/43 (40, 45) minutes, mean heart rate: 154 ± 10/132 ± 12 bpm, max cTnI: 77 (37, 128)/12 (7, 23) ng/L. Stroke volume and cardiac output were higher after the race than CPET (p < 0.005). The two exercises did not differ in post-exercise changes in LV ejection fraction (LVEF) or global longitudinal strain (GLS). There was an increase in global wasted work (p = 0.001) following the race and a persistent reduction in global constructive work 24 h after exercise (p = 0.003). Conclusion: Increased exercise intensity and duration were associated with increased myocardial wasted work post-exercise, without alterations in LVEF and GLS from baseline values. These findings suggest that markers of myocardial inefficiency may precede reduction in global LV function as markers of myocardial fatigue.
RESUMO
Arrhythmic mitral valve prolapse syndrome is associated with a high risk of death. A 60-year-old man with arrhythmic mitral valve prolapse syndrome was monitored with an implantable loop recorder. Nine months later dyspnea developed, followed by cardiac arrest. Echocardiography showed mitral valve chordal rupture. He underwent successful surgical mitral valve repair. (Level of Difficulty: Intermediate.).
RESUMO
OBJECTIVES: This study aimed to perform an external validation of the value of right ventricular (RV) deformation patterns and RV mechanical dispersion in patients with arrhythmogenic cardiomyopathy (AC). Secondly, this study assessed the association of these parameters with life-threatening ventricular arrhythmia (VA). BACKGROUND: Subtle RV dysfunction assessed by echocardiographic deformation imaging is valuable in AC diagnosis and risk prediction. Two different methods have emerged, the RV deformation pattern recognition and RV mechanical dispersion, but these have neither been externally validated nor compared. METHODS: We analyzed AC probands and mutation-positive family members, matched from 2 large European referral centers. We performed speckle tracking echocardiography, whereby we classified the subtricuspid deformation patterns from normal to abnormal and assessed RV mechanical dispersion from 6 segments. We defined VA as sustained ventricular tachycardia, appropriate implantable cardioverter-defibrillator therapy, or aborted cardiac arrest. RESULTS: We included 160 subjects, 80 from each center (43% proband, 55% women, age 41 ± 17 years). VA had occurred in 47 (29%) subjects. In both cohorts, patients with a history of VA showed abnormal deformation patterns (96% and 100%) and had greater RV mechanical dispersion (53 ± 30 ms vs. 30 ± 21 ms; p < 0.001 for the total cohort). Both parameters were independently associated to VA (adjusted odds ratio: 2.71 [95% confidence interval: 1.47 to 5.00] per class step-up, and 1.26 [95% confidence interval: 1.07 to 1.49]/10 ms, respectively). The association with VA significantly improved when adding RV mechanical dispersion to pattern recognition (net reclassification improvement 0.42; p = 0.02 and integrated diagnostic improvement 0.06; p = 0.01). CONCLUSIONS: We externally validated 2 RV dysfunction parameters in AC. Adding RV mechanical dispersion to RV deformation patterns significantly improved the association with life-threatening VA, indicating incremental value.
Assuntos
Displasia Arritmogênica Ventricular Direita , Taquicardia Ventricular , Adulto , Arritmias Cardíacas/diagnóstico por imagem , Arritmias Cardíacas/etiologia , Displasia Arritmogênica Ventricular Direita/diagnóstico por imagem , Displasia Arritmogênica Ventricular Direita/genética , Ecocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Taquicardia Ventricular/diagnóstico por imagem , Taquicardia Ventricular/etiologia , Adulto JovemRESUMO
Background Arrhythmogenic cardiomyopathy (AC) is characterized by biventricular dysfunction, exercise intolerance, and high risk of ventricular tachyarrhythmias and sudden death. Predisposing factors for left ventricular (LV) disease manifestation and its prognostic implication in AC are poorly described. We aimed to assess the associations of exercise exposure and genotype with LV dysfunction in AC, and to explore the impact of LV disease progression on adverse arrhythmic outcome. Methods and Results We included 168 patients with AC (50% probands, 45% women, 40±16 years old) with 715 echocardiographic exams (4.1±1.7 exams/patient, follow-up 7.6 [interquartile range (IQR), 5.4-10.9] years) and complete exercise and genetic data in a longitudinal study. LV function by global longitudinal strain was -18.8% [IQR, -19.2% to -18.3%] at presentation and was worse in patients with greater exercise exposure (global longitudinal strain worsening, 0.09% [IQR, 0.01%-0.17%] per 5 MET-hours/week, P=0.02). LV function by global longitudinal strain worsened, with 0.08% [IQR, 0.05%-0.12%] per year; (P<0.001), and progression was most evident in patients with desmoplakin genotype (P for interaction <0.001). Deterioration of LV function predicted incident ventricular tachyarrhythmia (aborted cardiac arrest, sustained ventricular tachycardia, or implantable cardioverter defibrillator shock) (adjusted odds ratio, 1.1 [IQR, 1.0-1.3] per 1% worsening by global longitudinal strain; P=0.02, adjusted for time and previous arrhythmic events). Conclusions Greater exercise exposure was associated with worse LV function at first visit of patients with AC but did not significantly affect the rate of LV progression during follow-up. Progression of LV dysfunction was most pronounced in patients with desmoplakin genotypes. Deterioration of LV function during follow-up predicted subsequent ventricular tachyarrhythmia and should be considered in risk stratification.
Assuntos
Displasia Arritmogênica Ventricular Direita/complicações , Exercício Físico/fisiologia , Previsões , Predisposição Genética para Doença , Ventrículos do Coração/diagnóstico por imagem , Disfunção Ventricular Esquerda/etiologia , Função Ventricular Esquerda/fisiologia , Adulto , Displasia Arritmogênica Ventricular Direita/genética , Displasia Arritmogênica Ventricular Direita/fisiopatologia , Progressão da Doença , Ecocardiografia/métodos , Feminino , Seguimentos , Ventrículos do Coração/fisiopatologia , Humanos , Imagem Cinética por Ressonância Magnética/métodos , Masculino , Prognóstico , Fatores de Risco , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
OBJECTIVES: This study aimed to assess whether patients with MAD also have disjunction of the tricuspid annulus. BACKGROUND: Mitral annulus disjunction (MAD) is an abnormal atrial displacement of the mitral annulus. Whether the disjunction extends to the right side of the heart is not known. METHODS: In a cohort of patients with MAD, we assessed the presence of tricuspid annulus disjunction (TAD) with the use of cardiac magnetic resonance. We explored the associations between TAD and MAD characteristics and the relationship to ventricular arrhythmias (nonsustained/sustained ventricular tachycardias and aborted cardiac arrest). RESULTS: We included 84 patients (mean age: 48 ± 16 years; 63% female). We observed TAD in 42 (50%). Patients with TAD were older (age 52 ± 16 years vs. 43 ± 15 years; p = 0.02), had greater circumferential extent of MAD (164 ± 57° vs. 115 ± 58°; p = 0.002), greater maximum longitudinal MAD distance (9.4 ± 2.9 mm vs. 6.2 ± 2.8 mm; p < 0.001), and more frequent mitral valve prolapse (n = 39 [92%] vs. n = 24 [57%]; p < 0.001). Ventricular arrhythmias had occurred in 34 patients (41%), who were younger (age 39 ± 14 years vs. 54 ± 14 years; p < 0.001) and had lower prevalence of TAD (n = 22 [29%] vs. n = 12 [52%]; p = 0.03). TAD was not associated with ventricular arrhythmias when adjusted for age (odds ratio adjusted for age: 0.54; 95% confidence interval: 0.20 to 1.45; p = 0.22). CONCLUSIONS: We report for the first time the existence of right-sided annulus disjunction as a common finding in patients with MAD. TAD was associated with more severe left-sided annulus disjunction and mitral valve prolapse, but not with ventricular arrhythmias.
Assuntos
Insuficiência da Valva Mitral , Prolapso da Valva Mitral , Adulto , Idoso , Feminino , Humanos , Lactente , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Valva Mitral/diagnóstico por imagem , Prolapso da Valva Mitral/diagnóstico por imagem , Valor Preditivo dos TestesRESUMO
AIMS: We aimed to assess the prevalence of mitral annulus disjunction (MAD) and to explore the association with aortic disease and mitral valve surgery in patients with Marfan syndrome (MFS) and Loeys-Dietz syndrome (LDS). METHODS AND RESULTS: We included consecutive MFS patients fulfilling Revised Ghent Criteria and LDS patients fulfilling Loeys-Dietz Revised Nosology. MAD was identified by echocardiography and was quantified as the longitudinal distance from the ventricular myocardium to the hinge point of the posterior mitral leaflet. Aortic events were defined as aortic dissection or prophylactic aortic surgery. We recorded the need of mitral valve surgery including mitral valve repair or replacement. We included 168 patients (103 with MFS and 65 with LDS). The prevalence of MAD was 41%. MAD was present in all age groups. Aortic events occurred in 112 (67%) patients (27 with dissections and 85 with prophylactic surgical interventions). Patients with MAD were younger at aortic event than those without MAD (log rank = 0.02) Patients with aortic events had greater MAD distance in posterolateral wall [8 (7-10) mm vs. 7 (6-8) mm, P = 0.04]. Mitral events occurred more frequently in patients with MAD (P < 0.001). CONCLUSION: MAD was highly prevalent in patients with MFS and LDS. MAD was a marker of severe disease including aortic events at younger age and need of mitral valve surgery. Screening patients with MFS an LDS for MAD may provide prognostic information and may be relevant in planning surgical intervention. Detection of MAD in patients with MFS and LDS may infer closer clinical follow-up from younger age.
Assuntos
Procedimentos Cirúrgicos Cardíacos , Síndrome de Loeys-Dietz , Síndrome de Marfan , Aorta , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Humanos , Síndrome de Loeys-Dietz/diagnóstico por imagem , Síndrome de Loeys-Dietz/epidemiologia , Síndrome de Loeys-Dietz/cirurgia , Síndrome de Marfan/complicações , Síndrome de Marfan/diagnóstico por imagem , Síndrome de Marfan/epidemiologia , Valva Mitral/diagnóstico por imagem , Valva Mitral/cirurgiaRESUMO
OBJECTIVES: This study aimed to assess the presence of echocardiographic and electrocardiographic similarities in patients with Brugada syndrome (BrS) and arrhythmogenic cardiomyopathy (AC) and the prevalence and prognostic value of AC structural/electrical features in patients with BrS. BACKGROUND: BrS and AC are genetic cardiac diseases with high risk for sudden cardiac death. Although BrS and AC display different features, previous reports suggest a phenotypic overlap. METHODS: We acquired clinical data, electrocardiogram, and transthoracic echocardiography in patients with BrS and AC. We assessed the presence of AC diagnostic criteria according to the 2010 AC task force criteria for right ventricular outflow tract (RVOT), fractional area change, depolarization, and repolarization in the patients with BrS. We compared arrhythmic outcome in BrS patients with and without AC structural/electrical criteria. RESULTS: A total of 116 BrS and 141 AC patients were included. AC electrical features were present in 28 (24%) BrS patients and structural features in 97 (84%) BrS patients. BrS patients with an RVOT or depolarization AC criterion showed a trend towards worse severe arrhythmia-free survival compared to BrS patients without (p = 0.05). The criterion for RVOT dilation showed high sensitivity and improved detection of arrhythmic BrS patients when added to type 1 electrocardiogram pattern and syncope (area under the curve 0.73 [95% confidence interval: 0.59 to 0.87] vs. area under the curve 0.79 [95% confidence interval: 0.69 to 0.90]); p = 0.009). CONCLUSIONS: In this large cohort comparison, Brugada syndrome (BrS) and arrhythmogenic cardiomyopathy patients had phenotypic overlap. The presence of arrhythmogenic cardiomyopathy diagnostic criteria in BrS patients was associated with a trend towards higher arrhythmic risk. The right ventricular outflow tract dilation criterion improved detection of arrhythmic BrS patients.