Immunoadsorption therapy in refractory heart failure patients with dilated cardiomyopathy: a potential therapeutic option

SUMMARY OBJECTIVE: Removal of cardiac autoantibodies by immunoadsorption might confer clinical improvement in dilated cardiomyopathy. In this pilot study, we investigated the efficacy and safety of immunoadsorption therapy in refractory heart failure patients with dilated cardiomyopathy. METHODS: This study consisted of 9 heart failure patients with dilated cardiomyopathy, NYHA III-IV, left ventricular ejection fraction <30%, unresponsive to heart failure therapy, and with cardiac autoantibodies. Patients underwent immunoadsorption therapy for five consecutive days using a tryptophan column. Changes in cardiac function (left ventricular ejection fraction, left ventricular end-diastolic diameter, left ventricular end-systolic diameter), exercise capacity (6-minute walk distance), neurohormonal (N-terminal pro-brain natriuretic peptide), proinflammatory (high-sensitive C-reactive protein), and myocardial (cardiac troponin-I), biochemical, and hematological variables were obtained at baseline and after 3 and 6 months of immunoadsorption therapy. RESULTS: Mean left ventricular ejection fraction and 6-minute walk distance significantly increased at 3 months (from 23.27±5.09 to 32.1±1.7%, p=0.01 for left ventricular ejection fraction and from 353±118 to 434±159 m, p=0.04 for 6-minute walk distance) and further increased at 6 months after immunoadsorption therapy (to 34.5±7.7%, p=0.02 for ejection fraction and to 441±136 m, p=0.04 for 6-minute walk distance). NT-proBNP level reduced from 1161(392.8-3034) to 385(116.1-656.5) ng/L (p=0.04), and high-sensitive C-reactive protein decreased from 9.74±0.96 to 4.3±5.8 mg/L (p=0.04) at 6 months. Left ventricular end-diastolic diameter (66.1±5.8 vs. 64.7±8.9 mm) and left ventricular end-systolic diameter (56.1±8.6 vs. 52.3±10.8 mm) tended to decrease but did not reach statistical significance. No significant worsening was observed in creatinine, cardiac troponin-I, and hemoglobin levels after the immunoadsorption procedure. CONCLUSION: In dilated cardiomyopathy patients with refractory heart failure, immunoadsorption may be considered a potentially useful therapeutic option to improve a patient's clinical status.

Desafios e Aplicações dos Testes Genéticos na Cardiomiopatia Dilatada: Genótipo, Fenótipo e Implicações Clínicas / Challenges and Applications of Genetic Testing in Dilated Cardiomyopathy: Genotype, Phenotype and Clinical Implications

Resumo Os testes genéticos para cardiomiopatia dilatada (CMD) apresentam uma positividade de até 40%, mas há uma grande heterogeneidade genética e outros desafios decorrentes de expressividade variável e penetrância incompleta. O heredograma é fundamental para diferenciar os casos de CMD esporádica e familiar, por meio da avaliação do histórico familiar. A CMD familiar apresenta um rendimento maior nos testes genéticos, mas a CMD esporádica não exclui a possibilidade de causa genética. Alguns genes têm fenótipos específicos, sendo o gene da Lamina ( LMNA ) o mais fortemente associado a um fenótipo de arritmias malignas e quadros de insuficiência cardíaca (IC) avançada. A presença de uma variante genética causal também pode ajudar na avaliação prognóstica, identificando quadros mais graves e com menores taxas de remodelamento reverso em comparação com indivíduos com genótipo negativo. As diretrizes atuais recomendam a avaliação e aconselhamento genético em indivíduos com CMD, além do rastreamento em cascata nos familiares de primeiro grau nos casos em que há uma ou mais variantes identificadas, sendo uma oportunidade para o diagnóstico e tratamento precoces. Familiares com genótipo positivo e fenótipo negativo são candidatos à avaliação seriada, com periodicidade que varia conforme a idade. O genótipo também auxilia na indicação individualizada de cardiodesfibrilador implantável e em recomendações quanto à atividade física e planejamento familiar. Estudos em curso esclarecem progressivamente os detalhes das relações genótipo/fenótipo de um grande número de variantes e fazem com que a genética molecular esteja cada vez mais presente na prática clínica.

Abstract Genetic tests for dilated cardiomyopathy (DCM) have a diagnostic yield of up to 40%, but there is significant genetic heterogeneity and other challenges, such as variable expressivity and incomplete penetrance. Pedigree analysis is essential for distinguishing between sporadic and familial DCM cases by assessing family history. Familial DCM yields higher results in genetic testing, but sporadic DCM does not rule out the possibility of a genetic cause. Some genes have specific phenotypes, with the Lamin gene ( LMNA ) being associated with a phenotype of malignant arrhythmias and advanced heart failure (HF). The presence of a causal genetic variant can also aid in prognostic evaluation, identifying more severe cases with lower rates of reverse remodeling (RR) compared to individuals with a negative genotype. Current guidelines recommend genetic evaluation and counseling for individuals with DCM, along with cascade screening in first-degree relatives in cases where one or more variants are identified, offering an opportunity for early diagnosis and treatment. Relatives with a positive genotype and negative phenotype are candidates for serial evaluation, with frequency varying by age. Genotype also assists in individualized recommendations for implantable cardioverter-defibrillator (ICD) placement and advice regarding physical activity and family planning. Ongoing studies are progressively elucidating the details of genotype/phenotype relationships for a large number of variants, making molecular genetics increasingly integrated into clinical practice.

Quantitative analysis of myocardial fibrosis in dilated cardiomyopathy with deep learning joint segmentation model / 中华放射学杂志

Objective:To explore the effect of joint segmentation model of myocardial-fibrotic region based on deep learning in quantitative analysis of myocardial fibrosis in patients with dilated cardiomyopathy(DCM).Methods:The data of 200 patients with confirmed DCM and myocardial fibrosis in the left ventricle detected by cardiac MR-late gadolinium enhancement (CMR-LGE) in Xuzhou Central Hospital from January 2015 to April 2022 were retrospectively analyzed. Using a complete randomized design, the patients were divided into training set ( n=120), validation set ( n=30) and test set ( n=50). The left ventricle myocardium was outlined and the normal myocardial region was selected by radiologists. Fibrotic myocardium was extracted through calculating the threshold with standard deviation (SD) as a reference standard for left ventricle segmentation and fibrosis quantification. The left ventricular myocardium was segmented by convex prior U-Net network. Then the normal myocardial image block was recognized by VGG image classification network, and the fibrosis myocardium was extracted by SD threshold. The myocardial segmentation effect was evaluated using precision, recall, intersection over union (IOU) and Dice coefficient. The consistency of myocardial fibrosis ratio in left ventricle obtained by joint segmentation model and manual extraction was evaluated with intra-class correlation coefficient (ICC). According to the median of fibrosis rate, the samples were divided into mild and severe fibrosis, and the quantitative effect of fibrosis was compared by Mann-Whitney U test. Results:In the test set, the precision of myocardial segmentation was 0.827 (0.799, 0.854), the recall was 0.849 (0.822, 0.876), the IOU was 0.788 (0.760, 0.816), and the Dice coefficient was 0.832 (0.807, 0.857). The consistency of fibrosis ratio between joint segmentation model and manual extraction was high (ICC=0.991, P<0.001). No statistically significant difference was found in the ratio error between mild and severe fibrosis ( P>0.05). Conclusions:The joint segmentation model realizes the automatic calculation of myocardial fibrosis ratio in left ventricle, which is highly consistent with the results of manual extraction. Therefore, it can accurately realize the automatic quantitative analysis of myocardial fibrosis in patients with dilated cardiomyopathy.

Valores de referencia de T1 mapping en individuos sanos en Resonancia Magnética Cardíaca 3.0 Tesla. Relación con edad y sexo. Comparación con diferentes poblaciones / Reference values for T1 mapping in healthy adults at 3.0T. Relation to age and sex. Comparison with different populations

RESUMEN Introducción: El T1 mapping es una técnica que permite mejorar la caracterización tisular por resonancia magnética cardíaca (RMC), y posee creciente evidencia a su favor como herramienta de diagnóstico precoz y estratificación. Presentamos los resultados de la cuantificación del T1 nativo miocárdico en individuos sanos, estudiados en un campo de 3.0 T, a fin de proveer valores de referencia para el medio local. Material y métodos: Se incluyeron 124 individuos consecutivos derivados a nuestro centro para realización de RMC, cuyos estudios resultaron normales. Se midió el T1 mapping en un eje corto medioventricular. Se analizaron los resultados según edad y sexo. Se incluyeron también 27 pacientes con diagnóstico de miocardiopatía hipertrófica, 11 con diagnóstico de miocardiopatía dilatada y 8 con amiloidosis cardíaca. Resultados: Se analizaron 124 estudios. La media global de T1 mapping fue de 1220,7 ± 21,2 mseg. Redondeando a valores enteros, se consideró 1178-1263 mseg como "rango de normalidad" (p5-p95). Se observó un tiempo T1 ligeramente superior en mujeres. No hubo diferencias con respecto a la edad. Se observó una excelente reproducibilidad, evaluada por el coeficiente de correlación intraclase (0,97) y el método de Bland-Altman. Los valores de T1 mapping fueron significativamente superiores en los grupos de individuos portadores de miocardiopatía. Conclusiones: Reportamos valores normales de T1 mapping nativo en una población adulta local. Los mismos son levemente mayores en mujeres, diferencia que no impresiona relevante desde el punto de vista clínico. Al comparar con individuos portadores de miocardiopatía hipertrófica, dilatada o con amiloidosis cardíaca, se obtuvo una muy buena discriminación. La variabilidad interobservador fue muy baja.

ABSTRACT Background: T1mapping is a technique that improves tissue characterization by cardiovascular magnetic resonance (CMR), and there is growing evidence favoring its use as a tool for early diagnosis and stratification. We present the results of native myocardial T1 quantification in a 3.0 T field in healthy individuals, in order to provide local reference values. Methods: A total of 124 consecutive adults with normal studies, referred to our center for CMR, were included in the study. T1 relaxation time was measured in a midventricular short axis slice, analyzing age and sex dependance. For comparison, 27 patients with hypertrophic cardiomyopathy, 11 with dilated cardiomyopathy and 8 with cardiac amyloidosis were also included. Results: Mean global T1mapping of the 124 studies analyzed was 1220.7 ±21.2 msec, and rounding to unity, 1178-1263 msec (p5-p95) was considered as "normal range". A slightly longer T1 time was observed in women and no differences were found with respect to age. Excellent reproducibility was obtained, evaluated by intraclass correlation coefficient (0.97) and BlandAltman plot. T1 mapping values were significantly higher in both groups of individuals with cardiomyopathy. Conclusions: We report normal values of native T1 mapping in a local healthy adult population. Times were slightly higher in women, a difference that was not considered clinically relevant. When comparing with individuals with hypertrophic or dilated cardiomyopathy, a very good discrimination was obtained between the 3 populations. The interobserver variability was very low.

Correlation analysis of NLRP3 gene promoter polymorphism and clinical characteristics of patients with dilated cardiomyopathy / 中国医师杂志

Objective:To investigate the relationship between NOD-like receptor protein 3 (NLRP3) gene promoter region-30 single nucleotide polymorphism (SNP) (rs3738448) G/T and dilated cardiomyopathy (DCM) and its related risk factors.Methods:A case-control study method was used to collect 137 patients and 140 healthy controls; polymerase chain reaction-restriction endonuclease fragment length polymorphism technology combined with sequence alignment after DNA sequencing was used for data statistics; After Hardy-Weinberg balance test, the χ 2 test was used for correlation analysis; logistic regression was used to analyze the correlation between multiple risk factors and the SNP site and the incidence of DCM; SNPinfo database was used to predict and analyze the transcription factors affected by the SNP. Results:A total of GG and GT genotypes were detected at this SNP locus, and their genotype distributions were in line with Hardy-Weinberg equilibrium ( P>0.05). At the same time, the difference between the DCM group and the control group was significant ( P<0.05). Multivariate logistic regression analysis indicated that mean arterial pressure, C-reactive protein and B-type brain natriuretic peptide were independent risk factors for the onset of DCM (all P<0.05). The incidence of DCM in -30(RS3738448)G/T genotype GT group was 2.243 times higher than that in GG group (95% CI: 1.043-4.827, P<0.05). Logistic regression analysis under dominant, recessive and additive genetic models showed that there was a correlation between the dominant inheritance of SNP and the occurrence of DCM ( OR=0.44, AIC=370.4, BIC=381.3, P<0.05). Conclusions:The -30 (rs3738448) G/T SNP in the promoter region of the NLRP3 gene is associated with the pathogenesis of DCM, and provides population genetic data for the study of polymorphisms in the promoter region of NLRP3 gene.

Efficacy and safety of ivabradine in dilated cardiomyopathy patients: a meta-analysis of randomized controlled trials / 中国医师杂志

Objective:This study aimed to systematically evaluate the efficacy and safety of ivabradine in patients with dilated cardiomyopathy, and to provide evidence-based reference for clinical treatment.Methods:We searched PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wan Fang, VIP databases from inception to 1 September 2021 for randomized controlled trials (RCTs) that compared conventional therapies and ivabradine with conventional therapies in dilated cardiomyopathy patients. Studies meeting the inclusion criteria were included and analyzed. After data extraction and literature quality evaluation, we use the Review Manager 5.4 to perform the meta-analysis and publication bias test.Results:5 studies enrolling 494 patients were included. Compared with conventional therapies (control group), ivabradine and conventional therapies (observation group) significantly reduced resting heart rate [ MD=-7.58, 95% CI(-12.40, -2.76), Z=3.08, P=0.002], left ventricular end diastolic diameter (LVEDD) [ MD=-4.48, 95% CI(-7.33, -1.64), Z=3.09, P=0.002], left ventricular end systolic diameter (LVESD) [ MD=-4.94, 95% CI(-7.29, -2.59), Z=4.12, P<0.001], B-type natriuretic peptide (BNP) [ MD=-212.39, 95% CI(-230.55, -194.23), Z=22.92, P<0.001], New York Heart Association (NYHA) class [ MD=-0.36, 95% CI(-0.44, -0.27), Z=8.46, P<0.001] and Minnesota Questionnaire Score [ MD=-10.43, 95% CI(-15.72, -5.13), Z=3.86, P=0.001]. The left ventricular ejection fraction (LVEF) levels [ MD=1.31, 95% CI(0.64, 1.97), Z=3.85, P=0.001], 6-minute walk test level (6MWT) [ MD=54.83, 95% CI(40.58, 69.08), Z=7.54, P<0.001], systolic blood pressure [ MD=4.72, 95% CI(0.91, 8.54), Z=2.43, P=0.02], the incidence of visual symptoms (phosphene) [ OR=7.22, 95% CI(1.32, 45.00), P=0.02] and symptomatic bradycardia [ OR=8.90, 95% CI(1.21, 65.75), P=0.03] in the observation group were higher than those in the control group after treatment. In addition, there were no significant difference in the incidence of acute event between the two groups [ OR=0.72, 95% CI(0.12, 4.29), P=0.72]. Conclusions:Meta analysis showed that ivabradine combined β receptor blockers can effectively reduce resting heart rate and improve cardiac function in patients with dilated cardiomyopathy, but may increase the incidence of hallucinations and symptomatic bradycardia.

Left atrial function analysis in patients with functional mitral regurgitation associated with dilated cardiomyopathy / Análise da função atrial esquerda em pacientes com insuficiência mitral funcional associada à miocardiopatia dilatada

BACKGROUND: Functional mitral regurgitation (FMR) is associated with dilated cardiomyopathy (DC), heart failure (HF), and worsening left atrial function (LAF). Patients with DC and FMR may present left atrial dysfunction resulting from both ventricular dysfunction and valve disease, but it is unknown whether the presence of valve disease will lead to greater LAF impairment. OBJECTIVE: This study aimed to evaluate the relationship between LAF parameters and FMR degree in patients with DC. METHODS: This cross-sectional observational study included 214 patients with DC, 46 without FMR (control group) and 168 with mild, moderate or severe FMR. An LAF analysis was performed by speckle tracking echocardiography (STE) and atrial volumetric variation. RESULTS: LAF analyzed by STE by means of reservoir strain, conduit strain and active contraction strain was reduced in the sample, with values of 14.3%, 8.49% and 5.92%, respectively. FMR degree was significantly associated with reservoir strain (0.27 ± 0.16 versus 0.15 ± 0.09; p < 0.001) and contraction strain (19.2 ± 7.3 versus 11.2 ± 2.7; p < 0.001). FMR was also associated with a reduced LAF assessed by volumetric analysis: total atrial emptying fraction of 0.51 ± 0.13 versus 0.34 ± 0.11 and active atrial emptying fraction of 0 .27 ± 0.16 versus 0.15 ± 0.09 (p < 0.001). CONCLUSION: In a population with DC, FMR was associated with reduced LAF assessed by STE and atrial volume variation.

FUNDAMENTO: A insuficiência mitral funcional (IMF) está associada à miocardiopatia dilatada (MD), à insuficiência cardíaca (IC) e à piora da função atrial esquerda (FAE). A FAE pode decair tanto pela disfunção ventricular quanto pela valvopatia, mas não se sabe se esta leva a um prejuízo maior da FAE. OBJETIVO: Avaliar a relação entre a piora de parâmetros de FAE com o grau de IMF, em pacientes com MD. MÉTODOS: Trata-se de estudo observacional transversal, que incluiu 214 pacientes com MD, sendo 46 sem IMF (controle) e 168 com IMF discreta, moderada ou grave. A análise da FAE foi realizada por ecocardiografia por speckle tracking (STE) e por variação volumétrica atrial. RESULTADOS: A FAE, analisada por STE­ por meio do strain de reservatório, conduto e contração ativa ­ encontrou-se reduzida na amostra, com valores respectivos de 14,3%, 8,49% e 5,92%. O grau de IMF associou-se significativamente com os valores do strain de reservatório (0,27±0,16 versus 0,15±0,09; p <0,001. CONCLUSÃO: Em uma população com MD, a presença de IMF associa-se à redução da FAE de reservatório e de contração, avaliada por STE e pela variação volumétrica atrial.

Estratificação da Insuficiência Cardíaca Clínica através do Mapa T1 Nativo: Experiência de um Serviço de Referência / Clinical Heart Failure Stratification Through Native T1 Mapping: Experience of a Referral Service

Resumo Fundamento: Fibrose cardíaca difusa é fator importante na avaliação prognóstica dos pacientes com disfunção ventricular. Mapeamento T1 nativo pela ressonância magnética cardíaca (RMC) apresenta elevada sensibilidade e é considerado preditor independente de mortalidade por todas as causas e desenvolvimento de insuficiência cardíaca (IC) nos pacientes com cardiomiopatia. Objetivos: Avaliar aplicabilidade da avaliação com mapa T1 nativo em pacientes com IC em um hospital de referência de cardiologia e sua associação com parâmetros estruturais e perfil funcional. Métodos: Estudo transversal com pacientes adultos com IC classes funcionais NYHA I e II, isquêmicos e não isquêmicos, acompanhados em hospital de referência, que realizaram RMC. Os valores de T1 nativo foram analisados em relação a parâmetros estruturais, comorbidades, etiologia e categorização da IC pela fração de ejeção do ventrículo esquerdo (FEVE). Análises foram realizadas com nível de significância de 5%. Resultados: Analisados 134 pacientes. Valores de T1 nativo elevados foram encontrados em pacientes com maior dilatação (1004,9 vs 1042,7ms, p=0,001), volume (1021,3 vs 1050,3ms, p<0,01) e disfunção ventricular (1010,1 vs 1053,4ms, p<0,001), mesmo quando analisados isoladamente os não isquêmicos. Pacientes classificados com IC com fração de ejeção reduzida apresentaram maiores valores T1 em relação aos com IC e fração de ejeção preservada (ICFEP) (992,7 vs 1054,1ms, p<0,001). Dos com ICFEP, 55,2% apresentavam T1 elevado. Conclusões: Mapeamento T1 por RMC é factível para avaliação da IC clínica. Houve associação direta entre maior valor nativo de T1 e menor fração de ejeção, maiores diâmetros e volumes do VE, independentemente da etiologia da IC.

Abstract Background: Diffuse cardiac fibrosis is an important factor in the prognostic assessment of patients with ventricular dysfunction. Cardiovascular magnetic resonance imaging (CMR) native T1 mapping is highly sensitive and considered an independent predictor of all-cause mortality and heart failure (HF) development in patients with cardiomyopathy. Objectives: To evaluate the feasibility of native T1 mapping assessment in patients with HF in a cardiology referral hospital and its association with structural parameters and functional profile. Methods: Cross-sectional study with adult patients with HF NYHA functional classes I and II, ischemic and non-ischemic, followed in a referral hospital, who underwent CMR. Native T1 values were analyzed for structural parameters, comorbidities, etiology, and categorization of HF by left ventricular ejection fraction (LVEF). Analyses were performed with a significance level of 5%. Results: Enrollment of 134 patients. Elevated native T1 values were found in patients with greater dilation (1004.9 vs 1042.7ms, p = 0.001), ventricular volumes (1021.3 vs 1050.3ms, p <0.01) and ventricular dysfunction (1010.1 vs 1053.4ms, p <0.001), also present when the non-ischemic group was analyzed separately. Patients classified as HF with reduced ejection fraction had higher T1 values than those with HF and preserved ejection fraction (HFPEF) (992.7 vs 1054.1ms, p <0.001). Of those with HFPEF, 55.2% had higher T1. Conclusions: CMR T1 mapping is feasible for clinical HF evaluation. There was a direct association between higher native T1 values and lower ejection fraction, and with larger LV diameters and volumes, regardless of the etiology of HF.

Iatrogenic Complications During the Diagnostic Work-Up of an Inflammatory Cardiomyopathy

Abstract A 72-year-old woman was admitted for acute heart failure. The echocardiography revealed moderate depression of the left ventricular ejection fraction. Coronary disease was excluded by coronarography. Cardiac magnetic resonance showed predominantly left ventricular septal hypertrophy and severe depression of the left ventricular systolic function. There was also a bright, multifocal and patchy late gadolinium enhancement with subendocardial, mesocardial and subepicardial involvement, suggestive of sarcoidosis. Biochemical study, thoracic computed tomography and positron emission tomography were inconclusive for extra-cardiac sarcoidosis. Therefore, an endomyocardial biopsy was performed. The procedure was complicated by the development of complete atrioventricular block, requiring implantation of a cardiac resynchronization pacing device. A few days after device implantation, the patient developed fever. The echocardiography revealed extensive vegetations, and thus the diagnosis of a device-associated infective endocarditis was made. Even though antibiotic therapy was promptly started, the patient ended up dying. Biopsy results revealed lymphocytic myocarditis. This case is paradigmatic because it shows how the etiologic diagnosis of dilated cardiomyopathy can be challenging. Non-invasive diagnostic exams may not provide a definite diagnosis, requiring an endomyocardial biopsy. However, the benefits versus risks of such procedure must always be carefully weighted.

Registro Multicêntrico de Takotsubo (REMUTA) - Aspectos Clínicos, Desfechos Intra-Hospitalares e Mortalidade a Longo Prazo / Takotsubo Multicenter Registry (REMUTA) - Clinical Aspects, In-Hospital Outcomes, and Long-Term Mortality

Resumo Fundamento A síndrome de takotsubo (takotsubo) é uma forma de cardiomiopatia adquirida. Dados nacionais sobre essa condição são escassos. O Registro REMUTA é o primeiro a incluir dados multicêntricos dessa condição no nosso país. Objetivo Descrever as características clínicas, prognóstico, tratamento intra-hospitalar e mortalidade hospitalar e em 1 ano de seguimento. Métodos Estudo observacional, retrospectivo, tipo registro. Incluídos pacientes internados com diagnóstico de takotsubo ou que desenvolveram esta condição durante internação por outra causa. Os desfechos avaliados incluíram fator desencadeador, análise dos exames, uso de medicações, complicações e óbito intra-hospitalar e em 1 ano de seguimento. O nível de significância adotado foi de 5%. Resultados Foram incluídos 169 pacientes, em 12 centros no Estado do Rio de Janeiro. A idade média foi de 70,9 ± 14,1 anos e 90,5% eram do sexo feminino; 63% dos casos foram de takotsubo primário e 37% secundário. Troponina I foi positiva em 92,5% dos pacientes e a mediana de BNP foi de 395 (176,5; 1725). Supradesnivelamento do segmento ST esteve presente em 28% dos pacientes. A fração de ejeção do ventrículo esquerdo teve mediana de 40 (35; 48)%. Observamos taxa de 25,7% de ventilação mecânica invasiva e 17,4% de choque. Suporte circulatório mecânico foi utilizado em 7,7%. A mortalidade intra-hospitalar foi de 10,6% e a mortalidade ao final de 1 ano foi de 16,5%. Takotsubo secundário e choque cardiogênico foram preditores independentes de mortalidade. Conclusão Os resultados do REMUTA mostram que takotsubo não se trata de patologia benigna como se pensava, especialmente no grupo de takotsubo secundário que acarreta elevada taxa de complicações e de mortalidade. (Arq Bras Cardiol. 2020; 115(2):207-216)

Abstract Background Takotsubo syndrome (TTS) is an acquired form of cardiomyopathy. National Brazilian data on this condition are scarce. The Takotsubo Multicenter Registry (REMUTA) is the first to include multicenter data on this condition in Brazil. Objective To describe the clinical characteristics, prognosis, in-hospital treatment, in-hospital mortality, and mortality during 1 year of follow-up. Methods This is an observational, retrospective registry study including patients admitted to the hospital with diagnosis of TTS and patients admitted for other reasons who developed this condition. Evaluated outcomes included triggering factor, analysis of exams, use of medications, complications, in-hospital mortality, and mortality during 1 year of follow-up. A significance level of 5% was adopted. Results The registry included 169 patients from 12 centers in the state of Rio de Janeiro, Brazil. Mean age was 70.9 ± 14.1 years, and 90.5% of patients were female; 63% of cases were primary TTS, and 37% were secondary. Troponin I was positive in 92.5% of patients, and median BNP was 395 (176.5; 1725). ST-segment elevation was present in 28% of patients. Median left ventricular ejection fraction was 40 (35; 48)%. We observed invasive mechanical ventilation in 25.7% of cases and shock in 17.4%. Mechanical circulatory support was used in 7.7%. In-hospital mortality was 10.6%, and mortality at 1 year of follow-up was 16.5%. Secondary TTS and cardiogenic shock were independent predictors of mortality. Conclusion The results of the REMUTA show that TTS is not a benign pathology, as was once thought, especially regarding the secondary TTS group, which has a high rate of complications and mortality. (Arq Bras Cardiol. 2020; 115(2):207-216)

Doença de Coronavírus-19 e o Miocárdio / Coronavirus Disease 2019 and the Myocardium

Resumo A infecção pelo coronavírus denominada COVID-19 promoveu crescente interesse de cardiologistas, emergencistas, intensivistas e pesquisadores, pelo estudo do acometimento miocárdico partindo de diferentes formas clínicas decorrentes de desmodulação imunoinflamatória e neuro-humoral.O acometimento miocárdico pode ser mínimo e apenas identificado a partir de alterações eletrocardiográficas, principalmente por aumento de troponinas cardíacas, ou no outro lado do espectro pelas formas de miocardite fulminante e síndrome de takotsubo.A descrição de provável miocardite aguda tem sido comumente apoiada pela observação da troponina elevada em associação com disfunção. A clássica definição de miocardite, respaldada pela biópsia endomiocárdica de infiltrado inflamatório é rara, e foi observada em um único relato de caso até o momento, não se identificando o vírus no interior dos cardiomiócitos.Assim, o fenômeno que se tem documentado é de injúria miocárdica aguda, sendo obrigatório afastar doença coronária obstrutiva a partir da elevação de marcadores de necrose miocárdica, associada ou não à disfunção ventricular, provavelmente associada à tempestade de citoquinas e outros fatores que podem sinergicamente promover lesão miocárdica, tais como hiperativação simpática, hipoxemia, hipotensão arterial e fenômenos trombóticos microvasculares.Fenômenos inflamatórios sistêmicos e miocárdicos após infecção viral estão bem documentados, podendo evoluir para remodelamento cardíaco e disfunção miocárdica. Portanto, será importante a cardiovigilância desses indivíduos para monitorar o desenvolvimento do fenótipo de miocardiopatia dilatada.A presente revisão apresenta os principais achados etiofisiopatológicos, descrição da taxonomia desses tipos de acometimento cardíaco e sua correlação com as principais formas clínicas do componente miocárdico presente nos pacientes na fase aguda de COVID-19.

Abstract Infection with the coronavirus known as COVID-19 has promoted growing interest on the part of cardiologists, emergency care specialists, intensive care specialists, and researchers, due to the study of myocardial involvement based on different clinical forms resulting from immunoinflammatory and neurohumoral demodulation.Myocardial involvement may be minimal and identifiable only by electrocardiographic changes, mainly increased cardiac troponins, or, on the other side of the spectrum, by forms of fulminant myocarditis and takotsubo syndrome.The description of probable acute myocarditis has been widely supported by the observation of increased troponin in association with dysfunction. Classical definition of myocarditis, supported by endomyocardial biopsy of inflammatory infiltrate, is rare; it has been observed in only one case report to date, and the virus has not been identified inside cardiomyocytes.Thus, the phenomenon that has been documented is acute myocardial injury, making it necessary to rule our obstructive coronary disease based on increased markers of myocardial necrosis, whether or not they are associated with ventricular dysfunction, likely associated with cytokine storms and other factors that may synergistically promote myocardial injury, such as sympathetic hyperactivation, hypoxemia, arterial hypotension, and microvascular thrombotic phenomena.Systemic inflammatory and myocardial phenomena following viral infection have been well documented, and they may progress to cardiac remodeling and myocardial dysfunction. Cardiac monitoring of these patients is, therefore, important in order to monitor the development of the phenotype of dilated myocardiopathy.This review presents the main etiological and physiopathological findings, a description of the taxonomy of these types of cardiac involvement, and their correlation with the main clinical forms of the myocardial component present in patients in the acute phase of COVID-19.

Late gadolinium enhancement distribution pattern of left ventricular wall in patients with dilated cardiomyopathy: a preliminary study / 中华心血管病杂志

Objective: To investigate the distribution pattern of late gadolinium enhancement (LGE) in left ventricular free wall of patients with dilated cardiomyopathy (DCM). Methods: A total of 130 consecutive DCM patients who were hospitalized in our hospital, underwent both CMR and CTA examinations and met the inclusion and exclusion criteria including negative results of coronary angiography or coronary CTA, were retrospective included in this study. The LGE pattern, extent and distribution in left ventricular free wall were analyzed. Results: Left ventricular free wall LGE was detected in 56 out of 130 DCM patients. LGE was observed in both septal and free wall in 53 out of 56 patients with LGE (94.6%). Prevalence of NYHA classification Ⅲ/Ⅳ, intraventricular block, paroxysmal ventricular tachycardia, and secondary mitral insufficiency was significantly higher, while left ventricular ejection fraction was significantly lower, left ventricular end-diastolic/systolic volume, left ventricular end-diastolic/systolic volume index and left ventricular end-diastolic diameters values were larger in patients with LGE than without LGE (all P<0.05). In terms LGE pattern among these 56 patients, percent of involved myocardial segments in patients with subepicardial LGE (n=19) was significantly higher than patients with intermural LGE (n=30), patients with transmural LGE (n=21), and patients with subendocardial LGE (n=9)(60.8%(127/209) vs. 32.4%(107/330), 32.5%(75/231), 26.3%(26/99), respectively, all P < 0.01). Transmural LGE was most likely to involve the left ventricular inferior lateral basal (18/21) and mid (13/21) segment, followed by anterior lateral basal (15/21) and mid (11/21) segments and inferior mid segment (9/21). Subepicardial LGE was more likely to occur in the inferior lateral basal (13/19) and mid (16/19) segment, anterior lateral basal (13/19) and mid (15/19) segment, anterior lateral basal (13/19) and mid (15/19) segment, lateral apical (13/19), anterior and inferior mid segment (12/19 and 10/19), and apical segment (15/19 and 10/19). Intermural LGE mostly involved the anterior and inferior basal (19/30, 16/30) and mid (18/30 and 14/30) segment. There were 33 cases of single LGE pattern and 23 cases of multiple LGE pattern. Percent of involved myocardial segments was significantly higher in multiple LGE group than single LGE group (60.9% (154/253) vs. 49.9%(181/363), P = 0.007). Of 130 patients, 23 received heart transplantation, of which 6 patients had septal LGE alone and 17 patients had septal and free wall LGE. The rate of heart transplantation in the latter group was higher (32.1% (17/53)vs. 13.6%(6/44), P=0.034). Conclusions: There are several LGE distribution patterns in left ventricular wall among DCM patients.

Fourteen Years' Survival After Batista Operation: The Short History of a Long Journey

Abstract A 41-year-old man with end-stage heart failure due to nonischemic dilated cardiomyopathy was submitted to the Batista procedure as an alternative to heart transplantation. With surgery, the patient showed progressive clinical amelioration, achieving long-term stable NYHA functional class II, despite gradual dilation of the heart chambers. Persistent atrial fibrillation appeared on the last year of life, his clinical condition deteriorated, and the patient died 14 years, four months, and 13 days after the operation. To the best of our knowledge this seems to be the longest reported survival for a patient submitted to Batista operation.

Importance of Genetic Testing in Dilated Cardiomyopathy: Applications and Challenges in Clinical Practice / Importância do Teste Genético na Miocardiopatia Dilatada: Aplicações e Desafios na Prática Clínica

Abstract Dilated cardiomyopathy (DCM) is a clinical syndrome characterized by left ventricular dilatation and contractile dysfunction. It is the most common cause of heart failure in young adults. The advent of next-generation sequencing has contributed to the discovery of a large amount of genomic data related to DCM. Mutations involving genes that encode cytoskeletal proteins, the sarcomere, and ion channels account for approximately 40% of cases previously classified as idiopathic DCM. In this scenario, geneticists and cardiovascular genetics specialists have begun to work together, building knowledge and establishing more accurate diagnoses. However, proper interpretation of genetic results is essential and multidisciplinary teams dedicated to the management and analysis of the obtained information should be considered. In this review, we approach genetic factors associated with DCM and their prognostic relevance and discuss how the use of genetic testing, when well recommended, can help cardiologists in the decision-making process.

Resumo A miocardiopatia dilatada (MCD) é uma síndrome caracterizada por dilatação ventricular esquerda e disfunção contrátil, sendo considerada a causa mais comum de insuficiência cardíaca em adultos jovens. O uso do sequenciamento de nova geração tem contribuído com a descoberta de uma grande quantidade de dados genômicos relacionados à MCD, identificando mutações que envolvem genes que codificam proteínas do citoesqueleto, sarcômero e canais iônicos, os quais são responsáveis por aproximadamente 40% dos casos classificados como MCD idiopática. Nesse cenário, geneticistas e especialistas em genética cardiovascular passaram a atuar em conjunto, agregando conhecimento e estabelecendo diagnósticos mais precisos. No entanto, é fundamental interpretar corretamente os resultados genéticos, sendo necessário criar e fomentar equipes multidisciplinares dedicadas à gestão e análise das informações coletadas. Nesta revisão, abordamos os fatores genéticos associados à MCD, aspectos prognósticos, além de discutirmos como o emprego dos testes genéticos, quando bem indicados, pode ser útil na tomada de decisão na prática clínica dos cardiologistas.

Clinical research of Yangxin-Fulv decoction combined with amiodarone hydrochloride in the treatment of dilated cardiomyopathy complicated with ventricular arrhythmia / 国际中医中药杂志

Objective@#To explore the clinical efficacy of Yangxin-Fulv decoction combined with amiodarone hydrochloride in the treatment of dilated cardiomyopathy (DCM) complicated with ventricular arrhythmia (VA).@*Methods@#According to the random table method, 103 DCM patients with VA were divided into the control group (n=51) and the research group (n=52). The patients in the control group were given amiodarone hydrochloride orally on the basis of routine treatment, while the research group was given Yangxin-Fulv decoction on the basis of the control group. The treatment course of two groups was 3 months. The total number of ventricular premature beats, ventricular premature second rhythm, triple rhythm, short-term ventricular tachycardia,left ventricular ejection fraction (LVEF), left ventricular diastolic internal diameter (LVEDD), left ventricular end systolic diameter (LVESV) and left ventricular posterior wall thickness (LVPWT) were recorded by dynamic electrocardiogram analyzer. The Dynamic electrocardiogram was used to monitor QT interphase dispersion (QTd) and calibrate QT interphase dispersion (QTcd) and change of QTc interval. Clinical efficacy was evaluated and adverse reactions were recorded.@*Results@#The total effective rate of the research group was 88.5% while the control group was 62.8%, where the difference between two groups was statistically significant (χ2=6.106, P=0.014). After treatment, the total number of ventricular premature beats, ventricular premature second rhythm, triple rhythm, and short-term ventricular tachycardia in the research group were significantly lower than those in the control group (t=-7.005,-4.760,-16.111,-12.059, P<0.001). After treatment, the LVEF of the research group was significantly higher than that of the control group (t=4.024, P<0.01), while the LVEDD, LVESV and LVPWT of the research group were significantly lower than those of the control group (t=-3.913,-6.623,-5.719, P<0.001). After treatment, the changes of QTc interval (402.08 ± 30.14 ms vs. 421.08 ± 32.19 ms, t=-3.093), QTd (65.25 ± 5.63 ms vs. 72.18 ± 5.92 ms, t=-6.089) and QTcd (72.18 ± 10.56 ms vs. 80.53 ± 12.09 ms, t=-3.735) in the research group were significantly lower than those in the control group (P<0.01). During the treatment period, the incidence of adverse reactions in the control group was 7.8% (4/51) and in the research group was 5.8% (3/52). There was no significant difference in the incidence of adverse reactions between the two groups (χ2=0.175, P=0.676).@*Conclusions@#The Yangxin-Fulv decoction combined with amiodarone hydrochloride can improve the clinical symptoms and clinical efficacy of DCM patients with VA by inhibiting ventricular remodeling and arrhythmia.

Screening of pathogenic genes in a Chinese familial dilated cardiomyopathy pedigree from Inner Mongolia / 中华心血管病杂志

Objective@#Screen the pathogenic genes of a pedigree with clinical manifestation of familial dilated cardiomyopathy in Inner Mongolia.@*Methods@#A total of 3 patients with dilated cardiomyopathy and 20 family members from the same family were examined in Ordos Central Hospital in Inner Mongolia from October, 2003 to August, 2017. Data on medical history, physical examinations, electrocardiograms, and echocardiography were obtained. 5 ml peripheral blood was sampled for per person. Chip Capture Sequencing technology was used to capture all the exons and splice sites of the genes that associated with hereditary cardiomyopathy and hereditary arrhythmia. The mutations in these genes were detected by high-throughput sequencing. All suspected pathogenic loci identified by high-throughput sequencing were verified by Sanger sequencing used for mutation detection. One hundred and fifty gender, age and race matched healthy people were included as the control group.@*Results@#Pathogenic gene variations were detected in 3 symptomatic family members and 1 carrier from the pedigree. Five pathogenic gene variations were identified in the proband (Ⅱ1), a pSer236Gly and a pArg215Cys variation in the MYBPC3 gene, a pGln90Arg variation in the DSP gene, and pAsn2912Asp and pGlu2910Val variation in the DMD gene. One pathogenic variation was detected in Ⅲ3, which was a pArg215Cys variation in the MYBPC3 gene. Two pathogenic variations were detected in Ⅲ7, a pSer236Gly variation in the MYBPC3 gene and a pGln90Arg variation in the DSP gene. Two pathogenic variations were detected in the Ⅳ7, a pSer236Gly variation in the MYBPC3 gene and a pGln90Arg variation in the DSP gene. No gene variation loci were detected in the other family members and the control group.@*Conclusion@#MYBPC3 gene, DSP gene and DMD gene variations are present in the familial dilated cardiomyopathy pedigree from Inner Mongolia, and these variations may be related with familial dilated cardiomyopathy.

Clinical research of Yangxin-Fulv decoction combined with amiodarone hydrochloride in the treatment of dilated cardiomyopathy complicated with ventricular arrhythmia / 国际中医中药杂志

Objective To explore the clinical efficacy of Yangxin-Fulv decoction combined with amiodarone hydrochloride in the treatment of dilated cardiomyopathy (DCM) complicated with ventricular arrhythmia (VA). Methods According to the random table method, 103 DCM patients with VA were divided into the control group (n=51) and the research group (n=52). The patients in the control group were given amiodarone hydrochloride orally on the basis of routine treatment, while the research group was given Yangxin-Fulv decoction on the basis of the control group. The treatment course of two groups was 3 months. The total number of ventricular premature beats, ventricular premature second rhythm, triple rhythm, short-term ventricular tachycardia,left ventricular ejection fraction (LVEF), left ventricular diastolic internal diameter (LVEDD), left ventricular end systolic diameter (LVESV) and left ventricular posterior wall thickness (LVPWT) were recorded by dynamic electrocardiogram analyzer. The Dynamic electrocardiogram was used to monitor QT interphase dispersion (QTd) and calibrate QT interphase dispersion (QTcd) and change of QTc interval. Clinical efficacy was evaluated and adverse reactions were recorded. Results The total effective rate of the research group was 88.5% while the control group was 62.8%, where the difference between two groups was statistically significant (χ2=6.106, P=0.014). After treatment, the total number of ventricular premature beats, ventricular premature second rhythm, triple rhythm, and short-term ventricular tachycardia in the research group were significantly lower than those in the control group (t=-7.005,-4.760,-16.111,-12.059, P<0.001). After treatment, the LVEF of the research group was significantly higher than that of the control group (t=4.024, P<0.01), while the LVEDD, LVESV and LVPWT of the research group were significantly lower than those of the control group (t=-3.913,-6.623,-5.719, P<0.001). After treatment, the changes of QTc interval (402.08 ± 30.14 ms vs. 421.08 ± 32.19 ms, t=-3.093), QTd (65.25 ± 5.63 ms vs. 72.18 ± 5.92 ms, t=-6.089) and QTcd (72.18 ± 10.56 ms vs. 80.53 ± 12.09 ms, t=-3.735) in the research group were significantly lower than those in the control group (P<0.01). During the treatment period, the incidence of adverse reactions in the control group was 7.8% (4/51) and in the research group was 5.8% (3/52). There was no significant difference in the incidence of adverse reactions between the two groups (χ2=0.175, P=0.676). Conclusions The Yangxin-Fulv decoction combined with amiodarone hydrochloride can improve the clinical symptoms and clinical efficacy of DCM patients with VA by inhibiting ventricular remodeling and arrhythmia.