RESUMEN
The increasing prevalence of type 2 diabetes mellitus (T2DM) is a significant worldwide health concern caused by sedentary lifestyles and unhealthy diets. Beyond glycemic control, T2DM impacts multiple organ systems, leading to various complications. While traditionally associated with cardiovascular and microvascular complications, emerging evidence indicates significant effects on pulmonary health. Pulmonary vascular dysfunction and fibrosis, characterized by alterations in vascular tone and excessive extracellular matrix deposition, are increasingly recognized in individuals with T2DM. The onset of T2DM is often preceded by prediabetes, an intermediate hyperglycemic state that is associated with increased diabetes and cardiovascular disease risk. This review explores the relationship between T2DM, pulmonary vascular dysfunction and pulmonary fibrosis, with a focus on potential links with prediabetes. Pulmonary vascular function, including the roles of nitric oxide (NO), prostacyclin (PGI2), endothelin-1 (ET-1), thromboxane A2 (TxA2) and thrombospondin-1 (THBS1), is discussed in the context of T2DM and prediabetes. Mechanisms linking T2DM to pulmonary fibrosis, such as oxidative stress, dysregulated fibrotic signaling, and chronic inflammation, are explained. The impact of prediabetes on pulmonary health, including endothelial dysfunction, oxidative stress, and dysregulated vasoactive mediators, is highlighted. Early detection and intervention during the prediabetic stage may reduce respiratory complications associated with T2DM, emphasizing the importance of management strategies targeting blood glucose regulation and vascular health. More research that looks into the mechanisms underlying pulmonary complications in T2DM and prediabetes is needed.
Asunto(s)
Diabetes Mellitus Tipo 2 , Fibrosis Pulmonar , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/fisiopatología , Fibrosis Pulmonar/fisiopatología , Estado Prediabético/complicaciones , Estado Prediabético/fisiopatología , Estado Prediabético/metabolismo , Animales , Pulmón/fisiopatología , Pulmón/patologíaRESUMEN
OBJECTIVES: The aim of this study was to test the hypothesis that the acute left ventricular (LV) unloading effect of transcatheter aortic valve replacement (TAVR) would improve right ventricular (RV) function and RV-pulmonary artery (PA) coupling in patients with severe aortic stenosis (AS). BACKGROUND: RV dysfunction is an ominous prognostic marker in patients undergoing TAVR, suggesting that relief of obstruction might be less beneficial in this cohort. However, the left ventricle and right ventricle influence each other through ventricular interaction, which could lead to improved RV function through LV unloading. METHODS: Prospective invasive hemodynamic measurements with simultaneous echocardiography were performed in symptomatic patients with severe AS before and immediately after TAVR. RESULTS: Forty-four patients (mean age 81 ± 8 years, 27% women) with severe AS underwent TAVR. At baseline, right atrial, PA mean (27 ± 7 mm Hg), and pulmonary capillary wedge (16 ± 4 mm Hg) pressures were mildly elevated, with a low normal cardiac index (2.3 l/min/m2). Pulmonary vascular resistance was mildly elevated (222 ± 133 dynes · s/cm5) and PA compliance mildly reduced (3.4 ± 01.4 ml/mm Hg). Following TAVR, aortic valve area increased (from 0.8 ± 0.3 to 2.7 ± 1.1 cm2; p < 0.001) with a reduction in mean aortic gradient (from 37 ± 11 to 7 ± 4 mm Hg; p < 0.001) and an increase in cardiac index (from 2.3 ± 0.5 to 2.5 ± 0.6 l/min/m2; p = 0.03). LV stroke work, end-systolic wall stress, and systolic ejection period decreased by 23% to 27% (p < 0.001 for all), indicating substantial LV unloading. RV stroke work (from 16 ± 7 to 18 ± 7 mm Hg · ml; p = 0.04) and tricuspid annular systolic velocities (from 9.5 ± 2.0 to 10.4 ± 3.5 cm/s; p = 0.01) increased, along with a decrease in PVR (194 ± 113 dynes · s/cm5; p = 0.03), indicating improvement in RV-PA coupling. Increased RV stroke work following TAVR directly correlated with the magnitude of increase in aortic valve area (r = 0.58; p < 0.001). CONCLUSIONS: Acute relief in obstruction to LV ejection with TAVR is associated with improvements in RV function and RV-PA coupling. These findings provide new insights into the potential benefits of LV unloading with TAVR on RV dysfunction in patients with severe AS.
Asunto(s)
Estenosis de la Válvula Aórtica/cirugía , Válvula Aórtica/cirugía , Hemodinámica , Arteria Pulmonar/fisiopatología , Reemplazo de la Válvula Aórtica Transcatéter , Función Ventricular Izquierda , Función Ventricular Derecha , Anciano , Anciano de 80 o más Años , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/fisiopatología , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/fisiopatología , Femenino , Humanos , Masculino , Estudios Prospectivos , Recuperación de la Función , Índice de Severidad de la Enfermedad , Factores de Tiempo , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: Non-invasive estimates have suggested that asymptomatic BMPR2 mutation carriers may have an abnormal pulmonary vascular response to exercise and hypoxia. However, this has not been assessed with "gold standard" invasive measures. METHODS: Eight controls and 8 asymptomatic BMPR2 mutation carriers underwent cardiac magnetic resonance imaging with simultaneous invasive pressure recording during bicycle exercise in normoxia, hypoxia and after sildenafil administration. Abnormal pulmonary vascular reserve was defined as an increase in mean pulmonary artery pressure relative to cardiac output (P/Q slope) >3 mm Hg/liter/min. RESULTS: During normoxic exercise, BMPR2 mutation carriers had a similar P/Q slope when compared with healthy subjects. Only 1 of 8 BMPR2 mutation carriers had a P/Q slope >3 mm Hg/liter/min. During exercise in hypoxia, 3 of 8 BMPR2 mutation carriers had P/Q slopes >3 mm Hg/liter/min compared with none of the controls. Sildenafil decreased the P/Q slope both in controls and BMPR2 mutation carriers. The exercise-induced increase in right ventricular ejection fraction was similar between groups. None of the BMPR2 mutation carriers developed pulmonary arterial hypertension within 2 (range 1.3 to 2.8) years. CONCLUSIONS: The presence of a BMPR2 mutation, per se, is not associated with an abnormal pulmonary vascular and right ventricular functional response to exercise in asymptomatic individuals. Longer follow-up will be required to determine whether a P/Q slope of >3 mm Hg/liter/min during exercise in normoxia or hypoxia is a sign of pre-clinical disease expression.