Impact of additional selexipag on prostacyclin infusion analogs in patients with pulmonary arterial hypertension.

The effective therapy for pulmonary arterial hypertension (PAH) with inadequate clinical response is scarce except for lung transplantation when prostacyclin infusion is ineffective. The purpose of this study is to investigate the efficacy and safety of selexipag in addition to the infusion of prostacyclin. Nine patients [median 38 (36-49) years of age; 78% female] with PAH whose clinical response was inadequate despite the use of prostacyclin infusion analogs, were evaluated. Addition of selexipag significantly improved hemodynamics and no serious adverse events were observed. Selexipag with prostacyclin infusion analogs can be an effective therapeutic strategy for the PAH patients with inadequate clinical response.

Factors related to instrumental activities of daily living in persons with chronic thromboembolic pulmonary hypertension.

Instrumental activities of daily living (IADL) are significantly related to quality of life and mortality among individuals with heart disease. However, few reports have examined IADL in persons with chronic thromboembolic pulmonary hypertension (CTEPH). The aim of this study was to clarify factors related to IADL in persons with CTEPH. This retrospective, observational study enrolled 163 persons with CTEPH (mean ± standard deviation age = 65 ± 13 years; 68% female) admitted to the Department of Cardiology at Keio University Hospital between January 2015 and July 2019. The Frenchay Activities Index (FAI) was used to assess IADL. Age, sex, body mass index, World Health Organization functional class (WHO-FC), cardiac function (mean pulmonary arterial pressure, mean right atrial pressure, pulmonary capillary wedge pressure, and cardiac index), pulmonary function (percentage vital capacity, percentage forced expiratory volume in 1 s, diffusion capacity of carbon monoxide (DLCO)/alveolar volume (VA)), physical function (knee extension strength and walking speed), and 6-min walking distance (6MWD) were assessed. Multiple regression analysis was performed to identify factors significantly associated with FAI. Mean FAI was 25 ± 8. Univariate analysis showed that sex, WHO-FC, DLCO/VA, walking speed, and 6MWD were correlated with FAI. Multiple regression analysis showed that 6MWD (sß = 0.338, 95% CI 0.014-0.034, p < .001), sex (sß = 0.268, 95% CI 2.238-7.165, p < .001), and DLCO/VA (sß = 0.257, 95% CI 1.011-3.528, p < .001) were significantly correlated with FAI (R2 = 0.261). IADL were associated with exercise tolerance, sex, and DLCO/VA in persons with CTEPH. In the future, more details of IADL are expected to be clarified by analyzing individual components of IADL and investigating social background characteristics, including living environment.

Exercise tolerance and quality of life in hemodynamically partially improved patients with chronic thromboembolic pulmonary hypertension treated with balloon pulmonary angioplasty.

The efficacy of extensive balloon pulmonary angioplasty (BPA) beyond hemodynamic improvement in chronic thromboembolic pulmonary hypertension (CTEPH) patients has been verified. However, the relationship between extensive BPA in CTEPH patients after partial hemodynamic improvement and exercise tolerance or quality of life (QOL) remains unclear. We prospectively enrolled 22 CTEPH patients (66±10 years, females: 59%) when their mean pulmonary artery pressure initially decreased to <30 mmHg during BPA sessions. Hemodynamic and echocardiographic data, cardiopulmonary exercise testing, and QOL scores using the 36-item short form questionnaire (SF-36) were evaluated at enrollment (entry), just after the final BPA session (finish), and at the 6-month follow-up (follow-up). We analyzed whether extensive BPA improves exercise capacity and QOL scores over time. Moreover, the clinical characteristics leading to improvement were elucidated. The peak oxygen uptake (VO2) showed significant improvement at entry, finish, and follow-up (17.3±5.5, 18.4±5.9, and 18.9±5.3 mL/kg/min, respectively; P<0.001). Regarding the QOL, the physical component summary (PCS) scores significantly improved (32±11, 38±13, and 43±13, respectively; P<0.001), but the mental component summary scores remained unchanged. Linear regression analysis revealed that age and a low peak VO2 at entry were predictors of improvement in peak VO2, while low PCS scores and low TAPSE at entry were predictors of improvement in PCS scores. In conclusion, extensive BPA led to improved exercise tolerance and physical QOL scores, even in CTEPH patients with partially improved hemodynamics.

Triple oral combination therapy with macitentan, riociguat, and selexipag for pulmonary arterial hypertension.

BACKGROUND: The evidence regarding triple oral combination therapy for patients with pulmonary arterial hypertension (PAH) is scarce. This study was performed to investigate the effectiveness and safety of triple oral combination therapy with macitentan, riociguat, and selexipag. METHODS: Among consecutive patients with PAH who were referred to our hospital from 2009 to 2020, those who underwent triple oral combination therapy using macitentan, riociguat, and selexipag were retrospectively analyzed. Hemodynamic and echocardiographic assessments and Kaplan-Meier analyses of all-cause death and initiation of prostacyclin infusion were conducted. RESULTS: Twenty-six patients underwent this combination therapy. These patients were predominantly female (73.1%) with a median age of 38 years at baseline and nine patients were taking some PAH medications at baseline. The median time from initiation of the first PAH drug to the third PAH drug in treatment naïve patients was 24 days (interquartile range, 12-47 days). Four patients (15.0%) discontinued taking any of the three vasodilators because of adverse events, and 17 patients (65.4%) reached the maximum dose of all three drugs. The mean pulmonary arterial pressure, pulmonary vascular resistance, and cardiac output improved by 29%, 65%, and 82%, respectively (median observation period: 441 days) and similar improvements were observed in treatment-naïve patients at baseline. The survival rate and prostacyclin infusion-free rate since administration of all three vasodilators was 93.3% and 74.6% at 3 years, respectively. When patients were divided by risk stratification, the prostacyclin-free rate at 3 years was 92.9% in low-/intermediate-risk patients and 55.0% in high-risk patients. CONCLUSION: Triple oral combination therapy with macitentan, riociguat, and selexipag sufficiently improved clinical parameters and was well tolerated in patients with PAH. This combination could be a particularly promising strategy in patients with low/intermediate risk and possibly even in half of patients with high risk. Further studies are needed to validate these findings.The reviews of this paper are available via the supplemental material section.

Activities of daily living among elderly persons with severe aortic stenosis.

PURPOSE: To determine the level of limitations in activities of daily living (ADL) and instrumental ADL, and identify related factors to instrumental ADL among elderly persons with severe aortic stenosis (AS). MATERIALS AND METHODS: We prospectively enrolled 112 consecutive elderly persons (mean age, 84.6 ± 4.4 y) with severe AS. We assessed ADL and instrumental ADL using the Barthel index (BI) and the Frenchay activities index (FAI), respectively. Cardiac, physical, cognitive and kidney functions, nutritional status, medical histories, and comorbidities were assessed. A multiple logistic analysis was developed to explore related factors to the FAI. RESULTS: The medians (ranges) of BI and FAI were 100 (15-100) and 21 (0-38), respectively. The multiple logistic analysis revealed that a history of heart failure (sß = -0.189), a history of cerebrovascular disease (sß = -0.233), the short physical performance battery score ≤ 8 (sß = -0.272), the mini-mental state examination score ≤ 23 (sß = -0.168) were significantly related to the FAI (p < 0.05). CONCLUSIONS: Physical frailty, a history of heart failure, cerebrovascular disease, and cognitive decline were independently related to declined instrumental ADL. IMPLICATIONS FOR REHABILIATION Activities of daily living was well-preserved among elderly persons with severe aortic stenosis. Instrumental activities of daily living varied among patients with aortic stenosis and was sometimes impaired. Physical frailty, a history of heart failure, and a history of cerebrovascular disease were independently associated with instrumental activities of daily living in elderly persons with severe aortic stenosis.

Preoperative Instrumental Activities of Daily Living Predicts Survival After Transcatheter Aortic Valve Implantation.

Background: This aim of this study was to clarify prognosis after transcatheter aortic valve implantation (TAVI) in patients with aortic stenosis (AS) and to identify baseline factors associated with mortality. Methods and Results: We prospectively enrolled 257 consecutive elderly persons with AS who were referred to Keio University Hospital and who underwent assessment of cardiac, physical (walking speed), cognitive, and renal functions, nutritional status, activities of daily living (ADL), instrumental ADL (IADL) assessed with the Frenchay activities index (FAI), and comorbidities. The primary outcome was postoperative death. Differences in basic characteristics were compared between a group that survived for a median of 661 days (IQR, 0-1,289 days) after TAVI and a group that did not. Multivariate hazard ratios (HR) were calculated for independent factors selected in Cox proportional hazard models. Thirty-one individuals died during follow-up. Walking speed was significantly faster (0.87±0.25 vs. 0.70±0.24 m/s, P<0.001) and FAI was significantly higher (21.2±8.0 vs. 15.7±8.0, P=0.026) in the survival group compared with those who died. Multivariate HR for mortality according to walking speed was 0.05 (95% CI: 0.028-0.091) in model 1 and 0.04 (95% CI: 0.020-0.081) in model 2, and those for FAI were 0.94 (95% CI: 0.92-0.95) and 0.92 (95% CI: 0.90-0.92), respectively. Conclusions: Preoperative walking speed and IADL are crucial factors associated with prognosis after TAVI even after adjustment.

Malnutrition among elderly patients with severe aortic stenosis.

BACKGROUND: Most patients with aortic stenosis (AS) are elderly. To achieve favorable outcomes after interventional treatments, careful management including adequate nutritional support is required. However, there has been a lack of knowledge about the prevalence of malnutrition and factors related to it. AIMS: To explore the prevalence of malnutrition and its related factors in patients with severe AS. METHODS: This was a single-institution, cross-sectional study. A total of 300 consecutive older patients (mean age, 83.8 ± 0.5 years) with AS were prospectively enrolled. Nutritional status was evaluated with the Mini Nutritional Assessment-Short Form (MNA-SF). Cardiac, kidney, physical, cognitive functions, instrumental activities of daily living (IADL) as measured with the Frenchay Activities Index (FAI), medical history, and comorbidities were evaluated as potentially related factors. Multiple logistic regression analysis was performed to identify factors that were significantly associated with the MNA-SF. RESULTS: The mean (SD) score of the MNA-SF was 10.9 (2.5). 34 patients (11.3%) and 127 patients (42.3%) met the criteria for malnutrition and at risk of malnutrition, respectively. On multiple logistic regression analysis, female sex (OR 3.455, 95% CI 1.045-11.42, P = 0.042), NYHA class (OR 3.625, 95% CI 1.627-8.074, P = 0.002), left ventricular ejection fraction (/10%) (OR 0.961, 95% CI 0.932-0.991, P = 0.010), and FAI score (/10 points) (OR 0.911, 95% CI 0.864-0.961, P < 0.001) were significantly related to malnutrition. CONCLUSIONS: The prevalence of malnutrition was high among older persons with severe AS, and female sex, poor cardiac function, and lower IADL were independently related to it.

Physical frailty in older people with severe aortic stenosis.

BACKGROUND: Assessment of physical frailty is important among elderly with severe aortic stenosis (AS) when considering treatment. AIMS: We aimed to: (1) investigate the prevalence of physical frailty in older people with severe AS and (2) examine factors related to physical frailty. METHODS: A total of 125 consecutive elderly AS patients (mean age 84.6 ± 4.4 year) were enrolled. Physical frailty was defined as scoring ≤8 points on the short physical performance battery (SPPB). Factors likely related to physical frailty, including cardiac function, nutritional and metabolic status, kidney function, medical history, and comorbidities, were evaluated. Logistic regression analyses were used to examine which factors were related to physical frailty. RESULTS: Physical frailty was prevalent in 38.4 %. After sex and age adjusted, the following were significantly related to physical frailty: LVEF (adjusted OR per 10 % decrease: 1.39, p < 0.05), the Mini Nutritional Assessment-Short Form (adjusted OR per 1 point decrease: 1.21, p < 0.05), serum albumin (adjusted OR per 1 g/dL decrease: 2.64, p < 0.05), HDL-C (adjusted OR per 10 mg/dL decrease: 1.52, p < 0.01), eGFR (adjusted OR per 10 mL/min decrease: 1.59, p < 0.05), grip strength (adjusted OR per 10 kg decrease: 3.60, p < 0.01), coronary heart disease (adjusted OR: 2.78, p < 0.01), cerebrovascular disease (adjusted OR: 6.06, p < 0.01), and musculoskeletal disorders (adjusted OR: 3.28, p < 0.01). CONCLUSIONS: The prevalence of physical frailty is high and related to nutritional status, comorbidities, and cardiac status.