Circulating miRNA in functional tricuspid regurgitation. Unveiling novel links to heart failure: A pilot study.

AIM: Severe functional tricuspid regurgitation (FTR) is associated with high risk of cardiovascular events, particularly heart failure (HF) and mortality. MicroRNAs (miRNAs) have been recently identified as novel biomarkers in different cardiovascular conditions, but no studies have focused on FTR. We sought to (1) to identify and validate circulating miRNAs as regulators of FTR and (2) to test association of miRNA with heart failure and mortality in FTR. METHODS AND RESULTS: Consecutive patients with isolated severe FTR (n = 100) evaluated in the outpatient Heart Valve Clinic and age- and gender-matched subjects with no TR (controls, n = 50) were prospectively recruited. The experimental design included (1) a screening phase to identify candidate miRNA differentially expressed in FTR (n = 8) compared with controls (n = 8) through miRNA array profiling of 192 miRNAs using quantitative reverse transcription PCR arrays [qRT-PCR]) and (2) a validation phase in which candidate miRNAs identified in the initial screening were selected for further validation by qRT-PCR in a prospectively recruited cohort of FTR (n = 92) and controls (n = 42). Bioinformatics analysis was used to predict their potential target genes and functional pathways elicited. A combined endpoint of hospital admission due to heart failure (HF) and all-cause mortality was defined. Initial screening identified 16 differentially expressed miRNAs in FTR compared with controls, subsequently confirmed in the validation phase (n = 16 were excluded due to significant haemolysis). miR-186-5p, miR-30e-5p, and miR-152-3p identified FTR with high predictive value [AUC of 0.93 (0.88-0.97), 0.83 (0.75-0.91) and 0.84 (0.76-0.92), respectively]. During a median follow-up of 20.4 months (IQR 8-35 months), 32% of FTR patients reached the combined endpoint. Patients with low relative expression of miR-15a-5p, miR-92a-3p, miR101-3p, and miR-363-3p, miR-324-3p, and miR-22-3p showed significantly higher rates of events (log-rank test for all P < 0.01). Both miR-15a-5p [hazard ratio: 0.21 (0.06-0.649, P = 0.007) and miR-92a-3p (0.27 (0.09-0.76), P = 0.01] were associated with outcomes after adjusting for age, gender, and New York Heart Association functional class. CONCLUSIONS: Circulating miRNAs are novel diagnostic and prognostic biomarkers in severe FTR. The quantification of miR-186-5p, miR-30e-5p, and miR-152-3p held strong diagnostic value, and the quantification of miR-15a-5p and miR-92a-3p are independently associated with outcomes. The recognition of specific miRNAs offers a novel perspective for TR evaluation.

La clasificación 4A para pacientes con insuficiencia tricuspídea / The 4A classification for patients with tricuspid regurgitation

Introducción y objetivos: La insuficiencia tricuspídea (IT) significativa se asocia con un aumento de la morbimortalidad. La valoración clínica del paciente con IT es un reto. Nuestro objetivo es establecer una nueva clasificación clínica, específica para pacientes con IT, denominada clasificación 4A, y evaluar su impacto pronóstico. Métodos: Se incluyó a pacientes evaluados en la clínica valvular, con IT aislada al menos grave y ausencia de antecedentes de insuficiencia cardiaca (IC). Se recogieron síntomas y signos de astenia, edema en extremidades inferiores, dolor o distensión abdominal y anorexia (asthenia, ankle swelling, abdominal pain or distention and anorexia) y se realizó un seguimiento cada 6 meses. La clasificación 4A abarca desde A0 (ninguna A) a A3 (3 o 4 Aes). Se definió un resultado combinado de ingreso hospitalario debido a IC derecha o muerte de causa cardiovascular. Resultados: Se incluyó a 135 pacientes con IT significativa entre 2016 y 2021 (el 69% mujeres; media de edad, 78±7 años). Durante un seguimiento medio de 26 [intervalo intercuartílico, 10-41] meses, 53 pacientes (39%) alcanzaron el resultado combinado. Ingresaron por IC 46 (34%) y murió un 5% (n=7). Al inicio, el 94% de los pacientes se encontraban en NYHA I o II, mientras que el 24% ya presentaba A2 o A3. La presencia de A2 o A3 se asoció con una alta incidencia de eventos. El cambio en la puntuación de la clasificación 4A fue un marcador independiente de IC y muerte cardiovascular (HR ajustada por unidad de cambio de la clasificación 4A=1,95 [1,37-2,77]; p <0,001). Conclusiones: Se muestra una nueva clasificación clínica específica para pacientes con IT basada en signos y síntomas de IC derecha y predictora de eventos.

Introduction and objectives: Significant tricuspid regurgitation (TR) is associated with increased morbidity and mortality. Clinical evaluation of TR patients is challenging. Our aim was to establish a new clinical classification specific for patients with TR, the 4A classification, and evaluate its prognostic performance. Methods: We included patients with isolated TR that was at least severe and without previous episodes of heart failure (HF) who were assessed in the heart valve clinic. We registered signs and symptoms of asthenia, ankle swelling, abdominal pain or distention and/or anorexia and followed up the patients every 6 months. The 4A classification ranged from A0 (no A) to A3 (3 or 4 As present). We defined a combined endpoint consisting of hospital admission due to right HF or cardiovascular mortality. Results: We included 135 patients with significant TR between 2016 and 2021 (69% females, mean age 78±7 years). During a median follow-up of 26 [IQR, 10-41] months, 39% (n=53) patients had the combined endpoint: 34% (n=46) were admitted for HF and 5% (n=7) died. At baseline, 94% of the patients were in NYHA I or II, while 24% were in classes A2 or A3. The presence of A2 or A3 conferred a high incidence of events. The change in 4A class remained an independent marker of HF and cardiovascular mortality (adjusted HR per unit of change of 4A class, 1.95 [1.37-2.77]; P<.001). Conclusions: This study reports a novel clinical classification specifically for patients with TR that is based on signs and symptoms of right HF and has prognostic value for events.(AU)

La consulta telemática para el paciente con valvulopatías o enfermedad aórtica en tiempos de la COVID-19 / Telemedicine for patients with valvular heart disease or aortic disease in the era of COVID-19

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Fusión eco-escopia, una ayuda durante la punción transeptal / Eco-X ray fusion for transseptal puncture

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