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1.
J Cardiovasc Magn Reson ; 22(1): 84, 2020 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-33287829

RESUMO

BACKGROUND: Cardiovascular magnetic resonance (CMR) is part of the diagnostic work-up for cardiac amyloidosis (CA). Deep learning (DL) is an application of artificial intelligence that may allow to automatically analyze CMR findings and establish the likelihood of CA. METHODS: 1.5 T CMR was performed in 206 subjects with suspected CA (n = 100, 49% with unexplained left ventricular (LV) hypertrophy; n = 106, 51% with blood dyscrasia and suspected light-chain amyloidosis). Patients were randomly assigned to the training (n = 134, 65%), validation (n = 30, 15%), and testing subgroups (n = 42, 20%). Short axis, 2-chamber, 4-chamber late gadolinium enhancement (LGE) images were evaluated by 3 networks (DL algorithms). The tags "amyloidosis present" or "absent" were attributed when the average probability of CA from the 3 networks was ≥ 50% or < 50%, respectively. The DL strategy was compared to a machine learning (ML) algorithm considering all manually extracted features (LV volumes, mass and function, LGE pattern, early blood-pool darkening, pericardial and pleural effusion, etc.), to reproduce exam reading by an experienced operator. RESULTS: The DL strategy displayed good diagnostic accuracy (88%), with an area under the curve (AUC) of 0.982. The precision (positive predictive value), recall score (sensitivity), and F1 score (a measure of test accuracy) were 83%, 95%, and 89% respectively. A ML algorithm considering all CMR features had a similar diagnostic yield to DL strategy (AUC 0.952 vs. 0.982; p = 0.39). CONCLUSIONS: A DL approach evaluating LGE acquisitions displayed a similar diagnostic performance for CA to a ML-based approach, which simulates CMR reading by experienced operators.


Assuntos
Neuropatias Amiloides Familiares/diagnóstico por imagem , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Aprendizado Profundo , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Processamento de Imagem Assistida por Computador , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética , Idoso , Idoso de 80 Anos ou mais , Neuropatias Amiloides Familiares/patologia , Neuropatias Amiloides Familiares/fisiopatologia , Cardiomiopatia Hipertrófica/patologia , Cardiomiopatia Hipertrófica/fisiopatologia , Feminino , Humanos , Hipertrofia Ventricular Esquerda/patologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Amiloidose de Cadeia Leve de Imunoglobulina/patologia , Amiloidose de Cadeia Leve de Imunoglobulina/fisiopatologia , Masculino , Miocárdio/patologia , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Função Ventricular Esquerda , Remodelação Ventricular
2.
Sci Rep ; 10(1): 17026, 2020 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-33046745

RESUMO

The myocardial contraction fraction (MCF: stroke volume to myocardial volume) is a novel volumetric measure of left ventricular myocardial shortening. The purpose of the present study was to assess whether MCF could predict adverse outcomes for HCM patients. A retrospective cohort study of 438 HCM patients was conducted. The primary and secondary endpoints were all-cause mortality and HCM-related mortality. The association between MCF and endpoints was analysed. During a follow-up period of 1738.2 person-year, 76 patients (17.2%) reached primary endpoint and 50 patients (65.8%) reached secondary endpoint. Both all-cause mortality rate and HCM-related mortality rate decreased across MCF tertiles (24.7% vs. 17.9% vs. 9.5%, P trend = 0.003 for all-cause mortality; 16.4% vs. 9.7% vs. 6.1%, P trend = 0.021 for HCM-related mortality). Patients in the third tertile had a significantly lower risk of developing adverse outcomes than patients in the first tertile: all-cause mortality (adjusted HR: 0.26, 95% CI: 0.12-0.56, P = 0.001), HCM-related mortality (adjusted HR: 0.17, 95% CI: 0.07-0.42, P < 0.001). At 1-, 3-, and 5-year of follow-up, areas under curve were 0.699, 0.643, 0.618 for all-cause mortality and 0.749, 0.661, 0.613 for HCM-related mortality (all P value < 0.001), respectively. In HCM patients, MCF could independently predict all-cause mortality and HCM-related mortality, which should be considered for overall risk assessment in clinical practice.


Assuntos
Cardiomiopatia Hipertrófica/mortalidade , Insuficiência Cardíaca/mortalidade , Ventrículos do Coração/fisiopatologia , Contração Miocárdica/fisiologia , Adulto , Idoso , Cardiomiopatia Hipertrófica/fisiopatologia , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
3.
PLoS One ; 15(10): e0240296, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33027274

RESUMO

BACKGROUND: The peak velocity of early diastolic mitral annular motion (e`) is believed to provide sensitive detection of left ventricular (LV) diastolic dysfunction in hypertrophic cardiomyopathy (HCM), but other aspects of LV long-axis function in HCM have received less attention. Systolic mitral annular excursion (SExc) is also reduced in HCM and must be an intrinsic limitation to the extent of the subsequent motion during diastole. However, the effects of HCM on excursion during early diastole (EDExc) and atrial contraction (AExc), the duration of early diastolic motion (EDDur), and the relationships of EDExc with SExc, and of e`with EDExc and EDDur, are all unknown. METHODS: The study group was 22 subjects with HCM and there were 22 age and sex matched control subjects. SExc, EDExc, e`, AExc and EDDur were measured from pulsed wave tissue Doppler signals acquired from the septal and lateral walls. In the combined group of HCM and control subjects, multivariate analyses were performed to identify independent predictors of EDExc and e`for both LV walls. RESULTS: SExc, EDExc and e`were all lower, and EDDur was longer in the HCM group compared to the control group for both LV walls (p<0.05 for all). In contrast, AExc was lower for the septal wall in the HCM group (p<0.05), but not different between the groups for the lateral wall. In regression analyses of the combined group, EDExc was positively correlated with SExc, and SExc explained 57-86% of the variances in septal and lateral EDExc, e`was positively correlated with EDExc, and EDExc explained 58-68% of the variances of e`, whereas the combination of EDExc with EDDur explained 87-92% of the variances in e`. A diagnosis of HCM was not an independent predictor of EDExc when in combination with SExc, but was a minor contributor to the prediction of e`in combination with EDExc and EDDur. CONCLUSION: In HCM, the decrease in LV longitudinal contraction is the major mechanism accounting for a lower EDExc, the lower e`is accounted for by contributions from the lower EDExc and prolongation of early diastolic motion, and there is no atrial compensation for the reduction of long-axis contraction.


Assuntos
Cardiomiopatia Hipertrófica/fisiopatologia , Diástole/fisiologia , Sístole/fisiologia , Disfunção Ventricular Esquerda/fisiopatologia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino
4.
Lancet ; 396(10253): 759-769, 2020 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-32871100

RESUMO

BACKGROUND: Cardiac muscle hypercontractility is a key pathophysiological abnormality in hypertrophic cardiomyopathy, and a major determinant of dynamic left ventricular outflow tract (LVOT) obstruction. Available pharmacological options for hypertrophic cardiomyopathy are inadequate or poorly tolerated and are not disease-specific. We aimed to assess the efficacy and safety of mavacamten, a first-in-class cardiac myosin inhibitor, in symptomatic obstructive hypertrophic cardiomyopathy. METHODS: In this phase 3, randomised, double-blind, placebo-controlled trial (EXPLORER-HCM) in 68 clinical cardiovascular centres in 13 countries, patients with hypertrophic cardiomyopathy with an LVOT gradient of 50 mm Hg or greater and New York Heart Association (NYHA) class II-III symptoms were assigned (1:1) to receive mavacamten (starting at 5 mg) or placebo for 30 weeks. Visits for assessment of patient status occurred every 2-4 weeks. Serial evaluations included echocardiogram, electrocardiogram, and blood collection for laboratory tests and mavacamten plasma concentration. The primary endpoint was a 1·5 mL/kg per min or greater increase in peak oxygen consumption (pVO2) and at least one NYHA class reduction or a 3·0 mL/kg per min or greater pVO2 increase without NYHA class worsening. Secondary endpoints assessed changes in post-exercise LVOT gradient, pVO2, NYHA class, Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS), and Hypertrophic Cardiomyopathy Symptom Questionnaire Shortness-of-Breath subscore (HCMSQ-SoB). This study is registered with ClinicalTrials.gov, NCT03470545. FINDINGS: Between May 30, 2018, and July 12, 2019, 429 adults were assessed for eligibility, of whom 251 (59%) were enrolled and randomly assigned to mavacamten (n=123 [49%]) or placebo (n=128 [51%]). 45 (37%) of 123 patients on mavacamten versus 22 (17%) of 128 on placebo met the primary endpoint (difference +19·4%, 95% CI 8·7 to 30·1; p=0·0005). Patients on mavacamten had greater reductions than those on placebo in post-exercise LVOT gradient (-36 mm Hg, 95% CI -43·2 to -28·1; p<0·0001), greater increase in pVO2 (+1·4 mL/kg per min, 0·6 to 2·1; p=0·0006), and improved symptom scores (KCCQ-CSS +9·1, 5·5 to 12·7; HCMSQ-SoB -1·8, -2·4 to -1·2; p<0·0001). 34% more patients in the mavacamten group improved by at least one NYHA class (80 of 123 patients in the mavacamten group vs 40 of 128 patients in the placebo group; 95% CI 22·2 to 45·4; p<0·0001). Safety and tolerability were similar to placebo. Treatment-emergent adverse events were generally mild. One patient died by sudden death in the placebo group. INTERPRETATION: Treatment with mavacamten improved exercise capacity, LVOT obstruction, NYHA functional class, and health status in patients with obstructive hypertrophic cardiomyopathy. The results of this pivotal trial highlight the benefits of disease-specific treatment for this condition. FUNDING: MyoKardia.


Assuntos
Benzilaminas/uso terapêutico , Miosinas Cardíacas/antagonistas & inibidores , Cardiomiopatia Hipertrófica/tratamento farmacológico , Uracila/análogos & derivados , Antagonistas Adrenérgicos beta/uso terapêutico , Idoso , Benzilaminas/efeitos adversos , Bloqueadores dos Canais de Cálcio/uso terapêutico , Cardiomiopatia Hipertrófica/fisiopatologia , Fármacos Cardiovasculares/uso terapêutico , Método Duplo-Cego , Tolerância ao Exercício/fisiologia , Feminino , Hemodinâmica/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio/fisiologia , Avaliação de Resultados da Assistência ao Paciente , Uracila/efeitos adversos , Uracila/uso terapêutico
6.
Arch Cardiovasc Dis ; 113(8-9): 542-550, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32771348

RESUMO

BACKGROUND: Screening for Fabry disease is sub-optimal in non-specialised centres. AIM: To assess the diagnostic value of electrocardiographic scores of left ventricular hypertrophy and a combined electrocardiographic and echocardiographic model in Fabry disease. METHODS: We retrospectively reviewed the electrocardiograms and echocardiograms of 61 patients (mean age 55.6±11.5 years; 57% men) with Fabry disease and left ventricular hypertrophy, and compared them with those from 59 patients (mean age 44.8±18.3 years; 66% men) with sarcomeric hypertrophic cardiomyopathy. Six electrocardiography criteria for left ventricular hypertrophy were specifically analysed: Sokolow-Lyon voltage index; Cornell voltage index; Gubner index; Romhilt-Estes score; Sokolow-Lyon product (voltage index×QRS duration); and Cornell product (voltage index×QRS duration). RESULTS: Right bundle branch block was more frequent in patients with Fabry disease (54% vs. 22%; P=0.001). QRS duration, Gubner score and Sokolow-Lyon product were significantly higher in patients with Fabry disease. Maximal wall thickness was higher in patients with sarcomeric hypertrophic cardiomyopathy (21.9±5.1 vs. 15.5±2.9mm; P<0.001). Indexed sinus of Valsalva diameter was larger in patients with Fabry disease. After multivariable analysis, right bundle branch block, Sokolow-Lyon product, maximal wall thickness and aortic diameter were independently associated with Fabry disease. A model including these four variables yielded an area under the receiver operating characteristic curve of 0.918 (95% confidence interval 0.868-0.968) for Fabry disease. CONCLUSION: Our model combining easy-to-assess electrocardiographic and echocardiographic variables may be helpful in improving screening and reducing diagnosis delay in Fabry disease.


Assuntos
Cardiomiopatia Hipertrófica/diagnóstico , Ecocardiografia , Eletrocardiografia , Doença de Fabry/diagnóstico , Adulto , Idoso , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Cardiomiopatia Hipertrófica/fisiopatologia , Diagnóstico Diferencial , Doença de Fabry/diagnóstico por imagem , Doença de Fabry/fisiopatologia , Feminino , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Volume Sistólico , Função Ventricular Esquerda , Função Ventricular Direita , Remodelação Ventricular
7.
Am J Physiol Heart Circ Physiol ; 319(2): H306-H319, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32618513

RESUMO

Dilated cardiomyopathy (DCM) is clinically characterized by dilated ventricular cavities and reduced ejection fraction, leading to heart failure and increased thromboembolic risk. Mutations in thin-filament regulatory proteins can cause DCM and have been shown in vitro to reduce contractility and myofilament Ca2+-affinity. In this work we have studied the functional consequences of mutations in cardiac troponin T (R131W), cardiac troponin I (K36Q) and α-tropomyosin (E40K) using adenovirally transduced isolated guinea pig left ventricular cardiomyocytes. We find significantly reduced fractional shortening with reduced systolic Ca2+. Contraction and Ca2+ reuptake times were slowed, which contrast with some findings in murine models of myofilament Ca2+ desensitization. We also observe increased sarcoplasmic reticulum (SR) Ca2+ load and smaller fractional SR Ca2+ release. This corresponds to a reduction in SR Ca2+-ATPase activity and increase in sodium-calcium exchanger activity. We also observe dephosphorylation and nuclear translocation of the nuclear factor of activated T cells (NFAT), with concordant RAC-α-serine/threonine protein kinase (Akt) phosphorylation but no change to extracellular signal-regulated kinase activation in chronically paced cardiomyocytes expressing DCM mutations. These changes in Ca2+ handling and signaling are common to all three mutations, indicating an analogous pathway of disease pathogenesis in thin-filament sarcomeric DCM. Previous work has shown that changes to myofilament Ca2+ sensitivity caused by DCM mutations are qualitatively opposite from hypertrophic cardiomyopathy (HCM) mutations in the same genes. However, we find several common pathways such as increased relaxation times and NFAT activation that are also hallmarks of HCM. This suggests more complex intracellular signaling underpinning DCM, driven by the primary mutation.NEW & NOTEWORTHY Dilated cardiomyopathy (DCM) is a frequently occurring cardiac disorder with a degree of genetic inheritance. We have found that DCM mutations in proteins that regulate the contractile machinery cause alterations to contraction, calcium-handling, and some new signaling pathways that provide stimuli for disease development. We have used guinea pig cells that recapitulate human calcium-handling and introduced the mutations using adenovirus gene transduction to look at the initial triggers of disease before remodeling.


Assuntos
Sinalização do Cálcio , Cardiomiopatia Dilatada/genética , Proteínas dos Microfilamentos/genética , Mutação , Contração Miocárdica , Miócitos Cardíacos/enzimologia , Fatores de Transcrição NFATC/metabolismo , Proteína Oncogênica v-akt/metabolismo , Função Ventricular Esquerda , Animais , Cardiomiopatia Dilatada/metabolismo , Cardiomiopatia Dilatada/fisiopatologia , Cardiomiopatia Hipertrófica/genética , Cardiomiopatia Hipertrófica/metabolismo , Cardiomiopatia Hipertrófica/fisiopatologia , Células Cultivadas , Predisposição Genética para Doença , Cobaias , Masculino , Proteínas dos Microfilamentos/metabolismo , Fenótipo , Retículo Sarcoplasmático/metabolismo , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Trocador de Sódio e Cálcio/metabolismo , Tropomiosina/genética , Tropomiosina/metabolismo , Troponina I/genética , Troponina I/metabolismo , Troponina T/genética , Troponina T/metabolismo
8.
Am J Cardiol ; 131: 104-108, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32718552

RESUMO

Hypertrophic cardiomyopathy (HC) represents a major cause of sudden cardiac death in young adults. Late gadolinium enhancement (LGE) and extracellular volume (ECV) by T1 mapping are cardiac magnetic resonance (CMR) techniques to quantify fibrosis in HC. The relationships of LGE and ECV with ventricular arrhythmia, left ventricular (LV) diastolic function, and risk factors for sudden cardiac death (SCD) in HC are unclear. We studied 103 HC patients (mean age 51 ± 14, 42% women) who underwent CMR from 2012 to 2014. Global LGE and mean ECV were evaluated in relation to history of nonsustained ventricular tachycardia (NSVT), diastolic function by echocardiography, and SCD risk factors. LGE was present in 71 (69%) subjects. Wide variation was demonstrated in LGE (0.5% to 45.9%) and mean ECV (17.6% to 47.4%). Prevalence of NSVT increased continuously with LGE and was greater in subjects with ECV above the study population mean (27%). Increased LGE was associated with LV diastolic dysfunction and LV wall thickness. In conclusion, while ECV appears to have a threshold (27%) above which it is associated with NSVT, LGE demonstrates a more robust relationship with NSVT and measures of diastolic dysfunction.


Assuntos
Cardiomiopatia Hipertrófica/diagnóstico por imagem , Cardiomiopatia Hipertrófica/fisiopatologia , Imagem Cinética por Ressonância Magnética , Taquicardia Ventricular/diagnóstico por imagem , Taquicardia Ventricular/fisiopatologia , Adolescente , Adulto , Idoso , Meios de Contraste , Ecocardiografia , Feminino , Gadolínio , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
9.
Am J Cardiol ; 130: 130-136, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32636017

RESUMO

A mitral L-wave indicates advanced diastolic dysfunction with elevated left ventricular filling pressure. Previous studies have reported that the presence of a mitral L-wave is associated with a poor prognosis in patients with heart failure. However, whether the L-wave can predict adverse events in patients with hypertrophic cardiomyopathy (HC) is still unclear. Therefore, we aimed to investigate the prevalence of a mitral L-wave in patients with HC, and the prognosis of patients with or without an L-wave. We analyzed 445 patients with HC. The end points of this study were HC-related death, such as sudden death or potentially lethal arrhythmic events, heart failure-related death, and stroke-related death. A mitral L-wave was defined as a distinct mid-diastolic flow velocity after the E wave with a peak velocity >20 cm/s. The prevalence of an L-wave was 32.4% in patients with HC. Patients with an L-wave were significantly younger, more likely to be women, had higher New York Heart Association functional class, and had a higher prevalence of atrial fibrillation than did patients without an L-wave. Patients with an L-wave had a significantly higher incidence of HC-related death compared with those without an L-wave (log-rank, p < 0.001). The L-wave was an independent determinant of HC-related death in multivariate analysis adjusted for imbalanced baseline variables (adjusted hazard ratio 2.38; 95% confidence interval 1.42 to 4.01; p = 0.001). In conclusion, the presence of a mitral L-wave may be associated with adverse outcome in patients with HC.


Assuntos
Cardiomiopatia Hipertrófica/mortalidade , Cardiomiopatia Hipertrófica/fisiopatologia , Valva Mitral/fisiopatologia , Adulto , Idoso , Cardiomiopatia Hipertrófica/complicações , Diástole , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
10.
Int J Cardiovasc Imaging ; 36(11): 2129-2137, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32602022

RESUMO

We conducted this study to investigate left ventricle (LV) systolic function in endocardial, mid-myocardial, and epicardial layers by two-dimensional (2D) speckle tracking echocardiography (STE) in hypertrophic cardiomyopathy (HCM) patients with myocardial injury indexed by elevated serum cardiac troponin I (cTnI). Twenty-nine HCM patients with myocardial injury, thirty-five HCM patients without myocardial injury, and ninty-one healthy controls were enrolled in this study. Serum cTnI > 0.026 ng/mL was defined as myocardial injury. LV longitudinal and circumferential strain (LS and CS) were assessed in endocardial, mid-myocardial and epicardial layers. Layer-specific LS and CS differed significantly (all P < 0.001) among all three groups in all three layers, in a descending order from healthy controls to HCM patients without myocardial injury to HCM patients with myocardial injury. Layer-specific LS and CS were decreased the most in HCM patients with myocardial injury indexed by elevated seum cTnI (all P < 0.05). In HCM patients with myocardial injury, layer-specific LS and CS were significantly lower in the segments with greater hypertrophy (segmental thickness ≥ 15 mm) (all P < 0.001) except for endocardial CS (P > 0.05). Layer-specific evaluation of LV strain may improve understanding of impaired LV systolic function in HCM patients with myocardial injury, thus preventing further damage.


Assuntos
Cardiomiopatia Hipertrófica/diagnóstico por imagem , Ecocardiografia , Miocárdio/patologia , Disfunção Ventricular Esquerda/diagnóstico por imagem , Função Ventricular Esquerda , Adulto , Biomarcadores/metabolismo , Cardiomiopatia Hipertrófica/patologia , Cardiomiopatia Hipertrófica/fisiopatologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Sístole , Troponina I/sangue , Disfunção Ventricular Esquerda/patologia , Disfunção Ventricular Esquerda/fisiopatologia
11.
Circ Heart Fail ; 13(6): e006853, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32498620

RESUMO

BACKGROUND: Obstructive hypertrophic cardiomyopathy (oHCM) is characterized by unexplained left ventricular (LV) hypertrophy associated with dynamic LV outflow tract obstruction. Current medical therapies are nonspecific and have limited efficacy in relieving symptoms. Mavacamten is a first-in-class targeted inhibitor of cardiac myosin, which has been shown to reduce LV outflow tract obstruction, improve exercise capacity, and relieve symptoms of oHCM in the PIONEER-HCM phase 2 study. METHODS: EXPLORER-HCM is a multicenter, phase 3, randomized, double-blind, placebo-controlled trial to investigate the efficacy and safety of mavacamten in treating symptomatic oHCM. Eligible adults with oHCM and New York Heart Association Functional Class II or III are randomized 1:1 to receive once-daily, oral mavacamten, or matching placebo for 30 weeks. The primary composite functional end point is clinical response at week 30 compared to baseline defined as either (1) an increase in peak oxygen consumption ≥1.5 mL/kg/min and reduction of at least one New York Heart Association class; or (2) an improvement of ≥3.0 mL/kg/min in peak oxygen consumption with no worsening of New York Heart Association class. Secondary end points include change in postexercise LV outflow tract gradient, New York Heart Association class, peak oxygen consumption, and patient-reported outcomes assessed by the Kansas City Cardiomyopathy Questionnaire and a novel HCM-specific instrument. Exploratory end points aim to characterize the effect of mavacamten on multiple aspects of oHCM pathophysiology. CONCLUSIONS: EXPLORER-HCM is a phase 3 trial in oHCM testing a first-in-class, targeted strategy of myosin inhibition to improve symptom burden and exercise capacity through reducing LV outflow tract obstruction. Results of this trial will provide evidence to support the first disease-specific treatment for HCM. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03470545.


Assuntos
Benzilaminas/uso terapêutico , Cardiomiopatia Hipertrófica/tratamento farmacológico , Fármacos Cardiovasculares/uso terapêutico , Uracila/análogos & derivados , Benzilaminas/efeitos adversos , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Cardiomiopatia Hipertrófica/fisiopatologia , Fármacos Cardiovasculares/efeitos adversos , Ensaios Clínicos Fase III como Assunto , Método Duplo-Cego , Tolerância ao Exercício/efeitos dos fármacos , Humanos , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Recuperação de Função Fisiológica , Resultado do Tratamento , Uracila/efeitos adversos , Uracila/uso terapêutico , Função Ventricular Esquerda/efeitos dos fármacos
13.
Am J Med Sci ; 360(5): 517-524, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32540144

RESUMO

BACKGROUND: Gender plays a crucial role in the prevalence, clinical presentation, management and outcomes of various cardiovascular diseases. The aim of this study was to evaluate the impact of gender on clinical manifestations and outcomes in the Chinese patients with hypertrophic cardiomyopathy (HCM). METHODS: We evaluated 576 Chinese patients (316 males) who were diagnosed with HCM at West China Hospital from 2008 to 2016 and followed over 3.2 ± 2.3 years. RESULTS: Compared to male patients, female patients were older (57.2 ± 16.7 years vs. 53.0 ± 15.7 years, P = 0.002) and more symptomatic [New York Heart Association class III-IV symptoms 46.9% vs. 30.7%, P < 0.001] at the time of diagnosis, and had higher left ventricular outflow tract gradient at rest [33 (12-58) mmHg vs. 24 (8-42) mmHg, P = 0.007]. During the follow-up period, survival analysis showed no significant differences in the incidences of all-cause mortality (P = 0.657) and cardiovascular mortality (P = 0.214) but the rate of rehospitalization due to heart failure was higher in females than in males (P = 0.015). Multivariable Cox analysis showed that left ventricular ejection fraction (hazard ratio [HR], 0.96 [95% confidence interval [CI], 0.94-0.99]; P = 0.003) and New York Heart Association class III-IV (HR, 2.86 [95% CI, 1.38-5.94]; P = 0.005) were independently associated with cardiovascular mortality. CONCLUSIONS: Compared to males, females were older and more symptomatic at presentation, and had higher risk of progression to heart failure in Chinese HCM patients but there were no differences in cardiovascular mortality.


Assuntos
Cardiomiopatia Hipertrófica/diagnóstico por imagem , Cardiomiopatia Hipertrófica/epidemiologia , Caracteres Sexuais , Adolescente , Adulto , Idoso , Cardiomiopatia Hipertrófica/fisiopatologia , China/epidemiologia , Bases de Dados Factuais/tendências , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
14.
Am J Cardiol ; 127: 135-138, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32430163

RESUMO

A unique clinical circumstance involving middle-aged male identical twins with obstructive hypertrophic cardiomyopathy (HC) is reported. The concordance of morphologic (i.e., phenotype) findings and clinical course between the 2 patients is remarkable, including timing of the onset and progression of heart failure due to left ventricular outflow tract obstruction, frequency of paroxysmal atrial fibrillation and beneficial response to surgical myectomy and Cox-Maze IV procedure (performed 14 days apart). Histopathology of resected ventricular septal muscle showed identical hallmarks of HC including myocyte disorganization, small vessel disease, and myocardial fibrosis. A missense variant of the CRYAB gene was identified as potentially relevant to the pathogenesis of HC in the twins. Taken together, these observations support a powerful genetic determinant for the morphologic and clinical expression of HC, with little or no environmental influence.


Assuntos
Cardiomiopatia Hipertrófica/diagnóstico , Doenças em Gêmeos , Ecocardiografia/métodos , Função Ventricular Esquerda/fisiologia , Septo Interventricular/diagnóstico por imagem , Cardiomiopatia Hipertrófica/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gêmeos Monozigóticos
15.
Int J Cardiovasc Imaging ; 36(10): 1855-1885, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32462448

RESUMO

Exclusion of cardiac abnormalities should be performed at the beginning of the athlete's career. Myocarditis, right ventricular remodeling and coronary anomalies are well-known causes of life-threatening events of athletes, major cardiovascular events and sudden cardiac death. The feasibility of an extended comprehensive echocardiographic protocol for the detection of structural cardiac abnormalities in athletes should be tested. This standardized protocol of transthoracic echocardiography includes two- and three-dimensional imaging, tissue Doppler imaging, and coronary artery scanning. Post processing was performed for deformation analysis of all compounds including layer strain. During 2017 and 2018, the feasibility of successful image acquisition and post processing analysis was retrospectively analyzed in 54 male elite athletes. In addition, noticeable findings inside the analyzed cohort are described. The extended image acquisition and data analyzing was feasible from 74 to 100%, depending on the used modalities. One case of myocarditis was detected in the present cohort. Coronary anomalies were not found. Right ventricular size and function were within normal ranges. Isovolumetric right ventricular relaxation time showed significant regional differences. One case of hypertrophic cardiomyopathy and two subjects with bicuspid aortic valves were found. Due to the excessive cardiac stress in highly competitive sports, high-quality and precise screening modalities are necessary, especially with respect to acquired cardiac diseases like acute myocarditis and pathological changes of left ventricular and RV geometry. The documented feasibility of the proposed extended protocol underlines the suitability to detect distinct morphological and functional cardiac alterations and documents the potential added value of a comprehensive echocardiography.


Assuntos
Atletas , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Anomalias dos Vasos Coronários/diagnóstico por imagem , Ecocardiografia Doppler , Ecocardiografia Tridimensional , Miocardite/diagnóstico por imagem , Função Ventricular Direita , Remodelação Ventricular , Adulto , Cardiomiopatia Hipertrófica/complicações , Cardiomiopatia Hipertrófica/fisiopatologia , Anomalias dos Vasos Coronários/complicações , Morte Súbita Cardíaca/etiologia , Estudos de Viabilidade , Humanos , Masculino , Miocardite/complicações , Miocardite/fisiopatologia , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Adulto Jovem
16.
J Cardiovasc Transl Res ; 13(3): 265-273, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32410209

RESUMO

Imaging techniques have allowed knowing the structural adaptative changes observed in the hearts of highly trained athletes. Athletes can develop very marked structural changes and the need may rise for a differential diagnosis with real cardiomyopathy. In this chapter, authors review the physiologic and morphologic features associated with athletic training and the keys to differentiate normal adaptive athlete's heart from mild or initial expression forms of left-heart side cardiomyopathies such as hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), and left ventricle non-compaction (LVNC).


Assuntos
Atletas , Cardiomegalia Induzida por Exercícios , Cardiomiopatia Dilatada/diagnóstico por imagem , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Ecocardiografia , Miocárdio Ventricular não Compactado Isolado/diagnóstico por imagem , Imagem por Ressonância Magnética , Resistência Física , Adaptação Psicológica , Cardiomiopatia Dilatada/fisiopatologia , Cardiomiopatia Hipertrófica/fisiopatologia , Diagnóstico Diferencial , Eletrocardiografia , Humanos , Miocárdio Ventricular não Compactado Isolado/fisiopatologia , Valor Preditivo dos Testes , Prognóstico , Função Ventricular Esquerda , Remodelação Ventricular
17.
Cardiovasc Pathol ; 48: 107218, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32388447

RESUMO

Cardiac amyloid A (AA) amyloidosis is rare. We present the case of a 72-year-old woman with obstructive hypertrophic cardiomyopathy (HCM) and biopsy-proven renal AA amyloidosis whose dyspnea and exercise intolerance had worsened over the previous year. Her AA amyloidosis was suspected to be secondary to chronic diverticulitis for which she had undergone hemicolectomy and sigmoidectomy 3 years prior. Echocardiographic findings were consistent with worsening left ventricular outflow tract obstruction at rest. Cardiac magnetic resonance imaging revealed patchy areas of midwall late gadolinium enhancement. Right ventricular endomyocardial biopsy did not reveal amyloid deposition, and cardiac technetium-99m pyrophosphate scintigraphy did not suggest transthyretin amyloidosis. The patient underwent septal myectomy with resection of an accessory papillary muscle. Pathological examination of the myectomy specimen was consistent with HCM. In addition, there was a thick layer of diffuse endocardial and vascular amyloid deposition that was identified as AA type by laser-microdissection with liquid chromatography-coupled tandem-mass spectrometry. This case report highlights the presence of 2 distinct disease processes occurring simultaneously and the importance of tissue diagnosis of AA amyloidosis, a condition that is not commonly associated with HCM.


Assuntos
Amiloidose/complicações , Cardiomiopatia Hipertrófica/complicações , Insuficiência Cardíaca/etiologia , Nefropatias/complicações , Miocárdio/patologia , Obstrução do Fluxo Ventricular Externo/etiologia , Idoso , Amiloidose/metabolismo , Amiloidose/patologia , Amiloidose/fisiopatologia , Procedimentos Cirúrgicos Cardíacos , Cardiomiopatia Hipertrófica/metabolismo , Cardiomiopatia Hipertrófica/patologia , Cardiomiopatia Hipertrófica/fisiopatologia , Feminino , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Nefropatias/metabolismo , Nefropatias/patologia , Miocárdio/metabolismo , Proteína Amiloide A Sérica/metabolismo , Resultado do Tratamento , Função Ventricular Esquerda , Obstrução do Fluxo Ventricular Externo/metabolismo , Obstrução do Fluxo Ventricular Externo/patologia , Obstrução do Fluxo Ventricular Externo/fisiopatologia
18.
Int J Cardiovasc Imaging ; 36(9): 1751-1759, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32405733

RESUMO

Whether sex differences exist in cardiac magnetic resonance (CMR) findings in patients with hypertrophic cardiomyopathy (HCM) remain unknown. We sought to assess and compare CMR characteristics in male and female patients with HCM. From January-2006 to October-2017, 165 consecutive HCM patients evaluated with CMR were included. All clinical and complementary test information was prospectively collected. At the time of CMR evaluation women were older (70 [57-75] vs. 61 [47-72] years, p = 0.02) and more symptomatic in terms of dyspnea (New York Heart Association class II-IV 47.2 vs. 24.1%, p = 0.003) and palpitations (19.6 vs. 4.6%, p = 0.006) and received more frequently treatment with diuretics (49.1% vs. 23.4%, p = 0.001). On echocardiographic examination more women had obstructive physiology (45.1 vs. 20.6%, p = 0.002). On CMR evaluation, women showed smaller left ventricular end-systolic volume index (13 [10-15] vs. 16 [13-21] ml/m2, p < 0.001), higher left ventricular ejection fraction (77 [74-80] vs. 72 [66-78]%, p = 0.004), more marked left ventricular outflow tract acceleration (54.7 vs. 26.4%, p < 0.001) and mitral regurgitation (33.3 vs. 12.7%, p = 0.002). In multivariable analysis, female sex [OR 2.44 (1.04-5.73), p = 0.04] and left ventricular end-systolic volume index [OR 1.60 (1.08-2.38), p = 0.018] were independently associated with obstructive physiology. Women with HCM have more frequently obstructive physiology, a finding that could be related to the smaller left ventricular end-systolic volume.


Assuntos
Cardiomiopatia Hipertrófica/diagnóstico por imagem , Disparidades nos Níveis de Saúde , Imagem Cinética por Ressonância Magnética , Idoso , Cardiomiopatia Hipertrófica/complicações , Cardiomiopatia Hipertrófica/tratamento farmacológico , Cardiomiopatia Hipertrófica/fisiopatologia , Diuréticos/uso terapêutico , Feminino , Disparidades em Assistência à Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/etiologia , Insuficiência da Valva Mitral/fisiopatologia , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Fatores de Risco , Fatores Sexuais , Volume Sistólico , Fatores de Tempo , Função Ventricular Esquerda
19.
J Cardiovasc Magn Reson ; 22(1): 30, 2020 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-32366254

RESUMO

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is thought to be associated with microvascular dysfunction. Adenosine stress-perfusion cardiovascular magnetic resonance imaging (CMR) is a sensitive method for assessing microvascular perfusion abnormalities. We evaluated the prevalence and clinical characteristics of HCM patients with adenosine-induced perfusion defects on CMR. METHODS: Among 189 consecutive patients with HCM who underwent adenosine-stress perfusion CMR, 115 patients who had clinical, echocardiography, 24-h Holter monitoring and treadmill exercise test data were analyzed. We calculated myocardial perfusion ratio index from the intensity-over-time curve to quantify perfusion defects. The presence and extent of the stress-induced perfusion defect were compared with clinical characteristics, presence and extent of late gadolinium enhancement (LGE), left ventricular (LV) mass index and volume, presence of non-sustained ventricular tachycardia (NSVT) and results of treadmill exercise test. RESULTS: The mean age of enrolled patients was 51.8 ± 11.3 years. Most patients were asymptomatic except 25 subjects presented with New York Heart Association Class II dyspnea and 16 patients with atypical non-exertional chest discomfort. LGE was present in 103 (89.6%) subjects. Adenosine stress-induced perfusion defects were present in 48 (42%) subjects. None of the perfusion defects corresponded with a single or multiple coronary artery territories, showing a multiple patchy pattern in 24 (50.0%), a concentric subendocardial pattern in 20 subjects (41.7%), and as a single blot-like defect in the remaining 4 (8.3%). A perfusion defect was associated with NSVT, LV apical aneurysm, higher LV mass index, and higher LGE volume on univariate analysis. Multivariate analysis revealed female gender (P = 0.008), presence of apical aneurysm and NSVT (P = 0.036 and 0.047, respectively), and LV mass index (P = 0.022) to be independently associated with adenosine stress-induced perfusion defects. CONCLUSIONS: In patients with HCM, adenosine-stress perfusion defects on CMR are present in more than 40% of subjects. This perfusion defect is associated with NSVT, higher LV mass index, and apical aneurysms. The prognostic value of this finding needs further elucidation.


Assuntos
Adenosina/administração & dosagem , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Circulação Coronária , Imagem Cinética por Ressonância Magnética , Microcirculação , Imagem de Perfusão do Miocárdio/métodos , Vasodilatadores/administração & dosagem , Cardiomiopatia Hipertrófica/epidemiologia , Cardiomiopatia Hipertrófica/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Estudos Prospectivos , Fatores de Risco , Seul/epidemiologia , Função Ventricular Esquerda , Remodelação Ventricular
20.
J Cardiovasc Transl Res ; 13(3): 296-305, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32436168

RESUMO

Exercise training induces morphological and functional cardiovascular adaptation known as the "athlete's heart" with changes including dilatation, hypertrophy, and increased stroke volume. These changes may overlap with pathological appearances. Distinguishing athletic cardiac remodelling from cardiomyopathy is important and is a frequent medical dilemma. Cardiac magnetic resonance (CMR) has a role in clinical care as it can refine discrimination of health from a disease where ECG and echocardiography alone have left or generated uncertainty. CMR can more precisely assess cardiac structure and function as well as characterise the myocardium detecting key changes including myocardial scar and diffuse fibrosis. In this review, we will review the role of CMR in sports cardiology.


Assuntos
Displasia Arritmogênica Ventricular Direita/diagnóstico por imagem , Atletas , Cardiomegalia Induzida por Exercícios , Cardiomiopatia Dilatada/diagnóstico por imagem , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Miocárdio Ventricular não Compactado Isolado/diagnóstico por imagem , Imagem por Ressonância Magnética , Medicina Esportiva , Adaptação Fisiológica , Displasia Arritmogênica Ventricular Direita/fisiopatologia , Cardiologia , Cardiomiopatia Dilatada/fisiopatologia , Cardiomiopatia Hipertrófica/fisiopatologia , Diagnóstico Diferencial , Humanos , Miocárdio Ventricular não Compactado Isolado/fisiopatologia , Resistência Física , Valor Preditivo dos Testes , Prognóstico , Função Ventricular Esquerda , Função Ventricular Direita , Remodelação Ventricular
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