Sex differences in left ventricular afterload and diastolic function are independent from the aortic size.

学位記番号：医博甲175

A case of a middle-aged patient with a ventricular septal defect complicated by severe pulmonary hypertension-stepwise surgical repair with pulmonary vasodilators-

We report a case of ventricular septal defect (VSD) in which we attempted to treat pulmonary arterial hypertension (PAH) with the goal of VSD closure in an adult with suspected Eisenmenger syndrome in childhood. Four years previously (age 41 years), she was referred to our department due to repeated hemoptysis requiring further treatment of PAH. We started combination therapy with several pulmonary vasodilators. Two years later, her pulmonary vascular resistance (PVR) was improved but still not at the level where VSD closure was possible. To control the increased PA flow resulting from intensive PAH treatment and to reduce the risk of hemoptysis, we performed pulmonary artery banding (PAB). As the risk of hemoptysis decreased, a prostacyclin analog was introduced, and the dose was increased. More than 1 year after PAB, active vasoactivity testing became positive, suggesting that the pulmonary vascular lesion was now “reversible”. We performed VSD closure and atrial septal defect creation even though her PVR was still high. After the operation, her exercise capacity was remarkably improved. We suggest that stepwise surgical repair with pulmonary vasodilators is an important treatment option for select patients with VSD with severe PAH.Learning objectiveAdvances in pulmonary arterial hypertension (PAH) treatment have led to the use of a “treat-and-repair” strategy to close the intracardiac shunt after PAH treatment in select patients with adult congenital heart disease. In our case, ventricular septal defect (VSD) closure was achieved with stepwise surgical repair and a combination of pulmonary vasodilators, even though long-standing severe PAH with persistent hemoptysis remained. Even after a long period of exposure to high blood flow, this strategy may reduce pulmonary vascular resistance and permit eventual closure of the VSD

Sex differences in left ventricular afterload and diastolic function are independent from the aortic size.

BackgroundWomen have a greater risk of heart failure with preserved ejection fraction (HFPEF) than men do, yet the basis for this disparity remains unclear. Greater arterial stiffness and afterload causes left ventricular (LV) diastolic dysfunction, a central mechanism of HFPEF. Because of smaller body habitus, previous reports have used body surface area as a surrogate of the size of the aorta. We performed a comprehensive hemodynamic evaluation of elderly patients with preserved EF and evaluated sex differences in the associations between LV function and afterload, before and after adjusting for the aortic sizes.Methods and resultsFour hundred and forty-three patients (mean age: 73 years, 169 women) who underwent clinically indicated echocardiography and computed tomography (CT) were identified. Linear regression analyses were performed to assess the independent contributions of sex to and its interaction with LV function before and after adjusting for CT-derived aortic length and volume. Although blood pressures were similar between the sexes, women had greater arterial elastance, lower arterial compliance, and greater LV ejection fraction (all pConclusionWomen had worse LV relaxation than men did against the same degree of afterload, before and even after adjusting for the aortic sizes

Interleukin-6 in Patients With Heart Failure and Preserved Ejection Fraction

Background: Interleukin (IL)-6 is a central inflammatory mediator and potential therapeutic target in heart failure (HF). Prior studies have shown that IL-6 concentrations are elevated in patients with HF, but much fewer data are available in heart failure with preserved ejection fraction (HFpEF). Objectives: This study aims to determine how IL-6 relates to changes in cardiac function, congestion, body composition, and exercise tolerance in HFpEF. Methods: Clinical, laboratory, body composition, exercise capacity, physiologic and health status data across 4 National Heart, Lung, and Blood Institute–sponsored trials were analyzed according to the tertiles of IL-6. Results: IL-6 was measured in 374 patients with HFpEF. Patients with highest IL-6 levels had greater body mass index; higher N-terminal pro–B-type natriuretic peptide, C-reactive protein, and tumor necrosis factor-α levels; worse renal function; and lower hemoglobin levels, and were more likely to have diabetes. Although cardiac structure and function measured at rest were similar, patients with HFpEF and highest IL-6 concentrations had more severely impaired peak oxygen consumption (12.3 ± 3.3 mL/kg/min 13.1 ± 3.1 mL/kg/min 14.4 ± 3.9 mL/kg/min, P &lt; 0.0001) as well as 6-minute walk distance (276 ± 107 m vs 332 ± 106 m vs 352 ± 116 m, P &lt; 0.0001), even after accounting for increases in IL-6 related to excess body mass. IL-6 concentrations were associated with increases in total body fat and trunk fat, more severe symptoms during submaximal exercise, and poorer patient-reported health status. Conclusions: IL-6 levels are commonly elevated in HFpEF, and are associated with greater symptom severity, poorer exercise capacity, and more upper body fat accumulation. These findings support testing the hypothesis that therapies that inhibit IL-6 in patients with HFpEF may improve clinical status.</p

Interleukin-6 in Patients With Heart Failure and Preserved Ejection Fraction

Background: Interleukin (IL)-6 is a central inflammatory mediator and potential therapeutic target in heart failure (HF). Prior studies have shown that IL-6 concentrations are elevated in patients with HF, but much fewer data are available in heart failure with preserved ejection fraction (HFpEF). Objectives: This study aims to determine how IL-6 relates to changes in cardiac function, congestion, body composition, and exercise tolerance in HFpEF. Methods: Clinical, laboratory, body composition, exercise capacity, physiologic and health status data across 4 National Heart, Lung, and Blood Institute–sponsored trials were analyzed according to the tertiles of IL-6. Results: IL-6 was measured in 374 patients with HFpEF. Patients with highest IL-6 levels had greater body mass index; higher N-terminal pro–B-type natriuretic peptide, C-reactive protein, and tumor necrosis factor-α levels; worse renal function; and lower hemoglobin levels, and were more likely to have diabetes. Although cardiac structure and function measured at rest were similar, patients with HFpEF and highest IL-6 concentrations had more severely impaired peak oxygen consumption (12.3 ± 3.3 mL/kg/min 13.1 ± 3.1 mL/kg/min 14.4 ± 3.9 mL/kg/min, P &lt; 0.0001) as well as 6-minute walk distance (276 ± 107 m vs 332 ± 106 m vs 352 ± 116 m, P &lt; 0.0001), even after accounting for increases in IL-6 related to excess body mass. IL-6 concentrations were associated with increases in total body fat and trunk fat, more severe symptoms during submaximal exercise, and poorer patient-reported health status. Conclusions: IL-6 levels are commonly elevated in HFpEF, and are associated with greater symptom severity, poorer exercise capacity, and more upper body fat accumulation. These findings support testing the hypothesis that therapies that inhibit IL-6 in patients with HFpEF may improve clinical status.</p

Interleukin-6 in Patients With Heart Failure and Preserved Ejection Fraction

Background: Interleukin (IL)-6 is a central inflammatory mediator and potential therapeutic target in heart failure (HF). Prior studies have shown that IL-6 concentrations are elevated in patients with HF, but much fewer data are available in heart failure with preserved ejection fraction (HFpEF). Objectives: This study aims to determine how IL-6 relates to changes in cardiac function, congestion, body composition, and exercise tolerance in HFpEF. Methods: Clinical, laboratory, body composition, exercise capacity, physiologic and health status data across 4 National Heart, Lung, and Blood Institute–sponsored trials were analyzed according to the tertiles of IL-6. Results: IL-6 was measured in 374 patients with HFpEF. Patients with highest IL-6 levels had greater body mass index; higher N-terminal pro–B-type natriuretic peptide, C-reactive protein, and tumor necrosis factor-α levels; worse renal function; and lower hemoglobin levels, and were more likely to have diabetes. Although cardiac structure and function measured at rest were similar, patients with HFpEF and highest IL-6 concentrations had more severely impaired peak oxygen consumption (12.3 ± 3.3 mL/kg/min 13.1 ± 3.1 mL/kg/min 14.4 ± 3.9 mL/kg/min, P &lt; 0.0001) as well as 6-minute walk distance (276 ± 107 m vs 332 ± 106 m vs 352 ± 116 m, P &lt; 0.0001), even after accounting for increases in IL-6 related to excess body mass. IL-6 concentrations were associated with increases in total body fat and trunk fat, more severe symptoms during submaximal exercise, and poorer patient-reported health status. Conclusions: IL-6 levels are commonly elevated in HFpEF, and are associated with greater symptom severity, poorer exercise capacity, and more upper body fat accumulation. These findings support testing the hypothesis that therapies that inhibit IL-6 in patients with HFpEF may improve clinical status.</p

Interleukin-6 in Patients With Heart Failure and Preserved Ejection Fraction

Background: Interleukin (IL)-6 is a central inflammatory mediator and potential therapeutic target in heart failure (HF). Prior studies have shown that IL-6 concentrations are elevated in patients with HF, but much fewer data are available in heart failure with preserved ejection fraction (HFpEF). Objectives: This study aims to determine how IL-6 relates to changes in cardiac function, congestion, body composition, and exercise tolerance in HFpEF. Methods: Clinical, laboratory, body composition, exercise capacity, physiologic and health status data across 4 National Heart, Lung, and Blood Institute–sponsored trials were analyzed according to the tertiles of IL-6. Results: IL-6 was measured in 374 patients with HFpEF. Patients with highest IL-6 levels had greater body mass index; higher N-terminal pro–B-type natriuretic peptide, C-reactive protein, and tumor necrosis factor-α levels; worse renal function; and lower hemoglobin levels, and were more likely to have diabetes. Although cardiac structure and function measured at rest were similar, patients with HFpEF and highest IL-6 concentrations had more severely impaired peak oxygen consumption (12.3 ± 3.3 mL/kg/min 13.1 ± 3.1 mL/kg/min 14.4 ± 3.9 mL/kg/min, P &lt; 0.0001) as well as 6-minute walk distance (276 ± 107 m vs 332 ± 106 m vs 352 ± 116 m, P &lt; 0.0001), even after accounting for increases in IL-6 related to excess body mass. IL-6 concentrations were associated with increases in total body fat and trunk fat, more severe symptoms during submaximal exercise, and poorer patient-reported health status. Conclusions: IL-6 levels are commonly elevated in HFpEF, and are associated with greater symptom severity, poorer exercise capacity, and more upper body fat accumulation. These findings support testing the hypothesis that therapies that inhibit IL-6 in patients with HFpEF may improve clinical status.</p

Effects of Mineralocorticoid Receptor Antagonists in Early-Stage Heart Failure With Preserved Ejection Fraction

Background: Hospitalization with a first episode of heart failure (HF) is a serious event associated with poor clinical outcomes in HF with preserved ejection fraction (HFpEF). Identification of HFpEF via detection of elevated left ventricular filling pressure at rest or during exercise may allow early intervention. Benefits of treatment with mineralocorticoid receptor antagonists (MRAs) in established HFpEF have been reported, but use of MRAs is not well studied in early HFpEF without prior HF hospitalization. Methods: We retrospectively studied 197 patients with HFpEF who did not have prior hospitalization but had been diagnosed by exercise stress echocardiography or catheterization. We examined changes in natriuretic peptide levels and echocardiographic parameters reflecting diastolic function following MRA initiation. Results: Of the 197 patients with HFpEF, MRA treatment was initiated for 47 patients. After a median 3-month follow-up, reduction in N-terminal pro-B-type natriuretic peptide levels from baseline to follow-up was greater in patients treated with MRA than in those who were not (median, -200 pg/mL [interquartile range, -544 to -31] vs 67 pg/mL [interquartile range, -95 to 456], P < 0.0001 in 50 patients with paired data). Similar results were observed for the changes in B-type natriuretic peptide levels. Reduction in the left atrial volume index was also greater in the MRA-treated group than in the non-MRA-treated group after a median 7-month follow-up (77 patients with paired echocardiographic data). Patients with lower left ventricular global longitudinal strain experienced a greater reduction in N-terminal pro-B-type natriuretic peptide levels following MRA treatment. In the safety assessment, MRA modestly decreased renal function but did not change potassium levels. Conclusions: Our results suggest that MRA treatment has potential benefits for early-stage HFpEF. Résumé: Contexte: L'hospitalisation consécutive à un premier épisode d'insuffisance cardiaque (IC) est un événement grave associé à des résultats cliniques médiocres dans l'IC à fraction d’éjection préservée (ICFEP). Or, la détection d'une pression de remplissage ventriculaire gauche élevée au repos ou à l'effort peut permettre de déceler une ICFEP et d’intervenir de façon précoce. Par ailleurs, le recours à des antagonistes des récepteurs minéralocorticoïdes (ARM) serait bénéfique dans les cas d’ICFEP, mais leur utilisation n'a pas été bien étudiée dans l’ICFEP précoce sans hospitalisation préalable pour cause d'insuffisance cardiaque. Méthodologie: Nous avons étudié rétrospectivement 197 patients atteints d’ICFEP qui n'avaient pas été hospitalisés auparavant, mais dont la maladie avait été diagnostiquée par une échocardiographie de stress ou un cathétérisme. Après l’instauration des ARM, nous avons examiné les variations des taux de peptides natriurétiques et des paramètres échocardiographiques reflétant la fonction diastolique. Résultats: Sur les 197 patients atteints d’ICFEP, 47 ont entamé un traitement par des ARM. Après un suivi médian de trois mois, la réduction des taux de propeptides natriurétiques de type B N-terminal (NT-proBNP) entre la valeur initiale et le suivi était plus importante chez les patients traités par des ARM que chez ceux qui ne l'étaient pas (médiane : -200 pg/ml [écart interquartile : -544 à -31] contre 67 pg/ml [écart interquartile : -95 à 456], p < 0,0001 chez 50 patients ayant des données appariées). Des résultats similaires ont été observés pour la variation des taux de peptides natriurétiques de type B. La réduction du volume de l'oreillette gauche était également plus importante dans le groupe traité par des ARM que dans le groupe témoin après un suivi médian de sept mois (données échocardiographiques appariées pour 77 patients). Les patients présentant une déformation longitudinale globale du ventricule gauche plus faible ont connu une réduction plus importante des taux de NT-proBNP après le traitement par des ARM. Enfin, lors de l'évaluation de l’innocuité, les ARM ont légèrement altéré la fonction rénale, mais sans modifier les taux de potassium. Conclusions: Ces résultats semblent indiquer que le traitement par des ARM présente des avantages potentiels dans les cas d’ICFEP au stade précoce

Interleukin-6 in Patients With Heart Failure and Preserved Ejection Fraction

Background: Interleukin (IL)-6 is a central inflammatory mediator and potential therapeutic target in heart failure (HF). Prior studies have shown that IL-6 concentrations are elevated in patients with HF, but much fewer data are available in heart failure with preserved ejection fraction (HFpEF). Objectives: This study aims to determine how IL-6 relates to changes in cardiac function, congestion, body composition, and exercise tolerance in HFpEF. Methods: Clinical, laboratory, body composition, exercise capacity, physiologic and health status data across 4 National Heart, Lung, and Blood Institute–sponsored trials were analyzed according to the tertiles of IL-6. Results: IL-6 was measured in 374 patients with HFpEF. Patients with highest IL-6 levels had greater body mass index; higher N-terminal pro–B-type natriuretic peptide, C-reactive protein, and tumor necrosis factor-α levels; worse renal function; and lower hemoglobin levels, and were more likely to have diabetes. Although cardiac structure and function measured at rest were similar, patients with HFpEF and highest IL-6 concentrations had more severely impaired peak oxygen consumption (12.3 ± 3.3 mL/kg/min 13.1 ± 3.1 mL/kg/min 14.4 ± 3.9 mL/kg/min, P &lt; 0.0001) as well as 6-minute walk distance (276 ± 107 m vs 332 ± 106 m vs 352 ± 116 m, P &lt; 0.0001), even after accounting for increases in IL-6 related to excess body mass. IL-6 concentrations were associated with increases in total body fat and trunk fat, more severe symptoms during submaximal exercise, and poorer patient-reported health status. Conclusions: IL-6 levels are commonly elevated in HFpEF, and are associated with greater symptom severity, poorer exercise capacity, and more upper body fat accumulation. These findings support testing the hypothesis that therapies that inhibit IL-6 in patients with HFpEF may improve clinical status.</p