Cardiomiopatia hipertrófica : avaliação genético-molecular, rastreamento de familiares e papel dos microRNAs como biomarcadores

A cardiomiopatia hipertrófica (CMH) é a doença cardiovascular de origem genética mais prevalente. Embora a avaliação de familiares em primeiro grau para CMH seja recomendada por diretrizes internacionais através de testes genéticos, estes podem não estar disponíveis ou serem negativos. Estratégias de rastreamento de CMH baseadas em critérios clínicos ainda não foram suficientemente testadas nesta população. Além disso, é desconhecido o papel de microRNAs como biomarcadores para a doença com esta finalidade. Foram avaliados 23 probandos com CMH e 58 familiares em primeiro grau. O rastreamento clínico identificou 10 (17%) familiares acometidos pela CMH. Marcadores clínicos como sintomas relacionados à CMH, história familiar de morte súbita, sopro sistólico e eletrocardiograma (ECG) anormal demonstraram boa acurácia para detecção da doença. Contudo, ECG anormal isoladamente apresentou a melhor performance. Critérios modificados de ECG para o rastreamento de CMH entre os familiares foram capazes de elevar a acurácia da estratégia empregada. Uma revisão sistemática foi realizada para identificar microRNAs diferencialmente expressos na CMH e sua correlação fenotípica. Identificou-se 87 microRNAs em um total de 329 indivíduos estudados. Os microRNAs na CMH apresentaram padrão de up-regulation em sua maioria. Entre os analisados, evidenciaram maior correlação fenotípico o mir-21 e mais marcadamente o mir-29a. O rastreamento clínico de familiares em primeiro grau de pacientes com CMH é factível e apresenta boa acurácia, principalmente quando baseado no ECG. Os microRNAs mir-21 e mir-29a apresentam marcada expressão na CMH e poderão ser candidatos a biomarcadores para reconhecimento da doença em fase clínica e pré-clínica.Hypertrophic cardiomyopathy (HCM) is the most common cardiovascular genetic disorder. Although the first-degree relatives evaluation for detecting HCM based on genetic testing is recommended by international guidelines, they may not be available or be negative. The HCM screening strategies based on clinical criteria are still not sufficiently tested in this population. Moreover, the role of microRNAs as biomarkers in HCM for this purpose is still unknown. Twenty-three probands with HCM were evaluated and 58 first-degree relatives. The clinical screening was able to identify 10 (17%) relatives with HCM. Clinical markers such as HCM related symptoms, family history of sudden cardiac death, heart murmur, and abnormal electrocardiogram (ECG) showed good accuracy for detecting the disease. However, an abnormal ECG alone presented with the highest performance. A modified abnormal ECG model was able to improve the accuracy of the applied strategy. A systematic review was performed for identifying differentially expressed microRNAs and their phenotypic expression. A total of 87 microRNAs in 329 studied individuals were identified. MicroRNAs in HCM showed a pattern of up-regulation in most cases. Among several microRNAs, mir-21 and mir-29a showed the greatest phenotypic correlation, with the most consistent findings for the latter. HCM clinical screening of first-degree relatives is feasible and showed good accuracy, mainly when an ECG strategy was applied. The microRNAs mir-21 and mir-29a showed pronounced expression in HCM and may be good candidates as biomarkers to recognize the disease in clinical and pre-clinical stages

Impact of COVID-19 infection among heart transplant recipients : a southern brazilian experience

Purpose: The coronavirus-2019 (COVID-19) infection is associated with a high risk of complications and death among heart transplant recipients. However, most cohorts are from high-income countries, while data from Latin America are sparse. Methods: This is a retrospective cohort of heart transplant recipients followed at a hospital in Rio Grande do Sul, Brazil, between March 1st 2020 and October 1st 2021. Results: Of the 62 heart transplant recipients on follow-up, 21 (34%) were infected by COVID-19, 58 (36-63) years of age, 67% male, body mass index of 26 (23-29) kg/m2, 48% with hypertension, 43% with chronic kidney disease, 5% with diabetes, within 2 (1-4) years of post-transplant follow-up. At presentation, the main symptoms were fever (62%), myalgia (33%), cough (33%), headache (33%), and dyspnea (19%). Hospitalization was required for 13 (62%) patients, with a time from first symptoms to the admission of 5 (1-12) days. In 38%, supplementary oxygen was needed, 19% required intensive care, and 10% mechanical ventilation. Three (14%) were infected after at least a first dose of COVID-19 vaccine. The main complications were bacterial pneumonia (38%), renal replacement therapy (19%), sepsis (10%) and venous thromboembolism (10%). Immunosuppression therapy was modified in 48%, with a reduction in the majority (89%). Two (10%) patients died in the hospital due to refractory hypoxemia and multiple organ dysfunction. The incidence of COVID-19 among transplant patients was comparable to the general population in the State of Rio Grande do Sul with a peak in December 2020. Conclusion: Heart transplant recipients shown a high rate of COVID-19 infection in Southern Brazil, with typical symptom presentation in most cases. There was an elevated rate of hospitalization, supplementary oxygen support, and complications. In-hospital lethality among infected heart transplanted recipients was similar to previously reported data worldwide despite the high rates of infection in Latin America