RESUMEN
BACKGROUND: Although spironolactone has been shown to decrease morbidity and mortality in patients with heart failure and reduced left ventricular ejection fraction, its role in patients with heart failure and preserved left ventricular ejection fraction (HFpEF) is not well defined. In this study we investigated the mechanisms involved when elderly women with HFpEF are treated with spironolactone. METHODS AND RESULTS: Forty-eight women with HFpEF were enrolled in a randomized placebo-controlled trial and were assigned to 25 mg spironolactone daily (n = 24) or placebo (n = 24) for 6 months. Six-minute walk distance, clinical composite score, Doppler echocardiography, and biomarkers were determined at baseline and after 3 and 6 months of therapy. Six months of spironolactone treatment stabilized clinical symptoms, as demonstrated by significant worsening of the clinical composite score in the placebo group (P = .02). In addition, spironolactone treatment improved diastolic function by significantly increasing early diastolic tissue Doppler velocity of the lateral mitral annulus (lateral e'; P = .003) and significantly reducing the mitral peak E velocity to lateral e' ratio (lateral E/e'; P = .0001). Finally, spironolactone favorably affected remodeling through a reduction in myocardial fibrosis measured by a reduction in type III procollagen levels (P = .035). Six-minute walk distance did not significantly improve with spironolactone treatment compared with placebo. CONCLUSIONS: Spironolactone stabilizes functional capacity and symptoms and improves diastolic function, possibly through its ability to suppress type III procollagen synthesis.
Asunto(s)
Insuficiencia Cardíaca/tratamiento farmacológico , Espironolactona/administración & dosificación , Volumen Sistólico/fisiología , Función Ventricular Izquierda/fisiología , Anciano , Diástole , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Ecocardiografía Doppler , Femenino , Estudios de Seguimiento , Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/fisiopatología , Humanos , Antagonistas de Receptores de Mineralocorticoides/administración & dosificación , Estudios Retrospectivos , Volumen Sistólico/efectos de los fármacos , Resultado del Tratamiento , Función Ventricular Izquierda/efectos de los fármacosRESUMEN
OBJECTIVES: We sought to determine the mechanisms linking dynamic obstruction and exercise tolerance in patients with hypertrophic obstructive cardiomyopathy (HOCM). BACKGROUND: Patients with HOCM have reduced exercise tolerance. However, the association between dynamic obstruction and peak oxygen consumption (VO2max) is weak. METHODS: We enrolled 25 patients with HOCM, 20 with hypertrophic cardiomyopathy (HCM), and 20 normal control patients. Two-dimensional, Doppler, strain, and left ventricular (LV) twist mechanics by speckle tracking echocardiography were obtained. The 25 HOCM patients had left heart catheterization, and 16 were re-examined after septal reduction. RESULTS: Deformation measurements were the lowest in HOCM patients and increased (p<0.05) after septal reduction. Twist and untwisting rate were not different between patients with HCM and control patients, but untwisting was significantly delayed in HCM patients and longest in HOCM patients. The delay related well with LV end-diastolic pressure (r=0.76) and volume (r=-0.73), and VO2max (r=-0.75, all p<0.01). After septal reduction, untwisting occurred earlier and accounted for the increase in end-diastolic volume (r=0.65), and VO2max (r=0.74, both p<0.05). CONCLUSIONS: Dynamic obstruction leads to delayed untwisting in HOCM, which accounts well for the increased LV filling pressures, the reduced LV volumes, and VO2max. After septal reduction, untwisting occurs earlier and leads to an improvement in LV filling and exercise tolerance.