Deep Learning Models for Predicting Left Heart Abnormalities From Single-Lead Electrocardiogram for the Development of Wearable Devices.

BACKGROUND: Left heart abnormalities are risk factors for heart failure. However, echocardiography is not always available. Electrocardiograms (ECGs), which are now available from wearable devices, have the potential to detect these abnormalities. Nevertheless, whether a model can detect left heart abnormalities from single Lead I ECG data remains unclear.Methods and Results: We developed Lead I ECG models to detect low ejection fraction (EF), wall motion abnormality, left ventricular hypertrophy (LVH), left ventricular dilatation, and left atrial dilatation. We used a dataset comprising 229,439 paired sets of ECG and echocardiography data from 8 facilities, and validated the model using external verification with data from 2 facilities. The area under the receiver operating characteristic curves of our model was 0.913 for low EF, 0.832 for wall motion abnormality, 0.797 for LVH, 0.838 for left ventricular dilatation, and 0.802 for left atrial dilatation. In interpretation tests with 12 cardiologists, the accuracy of the model was 78.3% for low EF and 68.3% for LVH. Compared with cardiologists who read the 12-lead ECGs, the model's performance was superior for LVH and similar for low EF. CONCLUSIONS: From a multicenter study dataset, we developed models to predict left heart abnormalities using Lead I on the ECG. The Lead I ECG models show superior or equivalent performance to cardiologists using 12-lead ECGs.

Diagnostic values of delayed additional FDG PET/CT scan in the evaluation of cardiac sarcoidosis.

OBJECTIVE: This study aimed to compare the contribution of 18F-fluorodepxyglucose (FDG) positron (PET)/ computed tomography (CT) acquisition of early and delayed scans in patients with cardiac sarcoidosis (CS). METHODS: Twenty-three patients with CS (median age: 69 years; 11 women) were retrospectively evaluated using dual-phase FDG PET/CT. All patients were instructed to consume a low-carbohydrate diet followed by fasting for 18 h before FDG injection to reduce physiological myocardial uptake. PET/CT was acquired at 60 min (early) and 100 min (delayed) after FDG administration. Focal and focal on diffuse uptake on visual analysis was considered positive for CS. A semi-quantitative analysis was performed using the maximum standardized uptake value (SUVmax) of the cardiac lesion and the mean SUV (SUVmean) of the blood pool. RESULTS: Significant myocardial FDG uptake was observed in 21 patients (91.3%) in the early acquisition group and in 23 patients in the delayed scan group (100%). Compared to the early scan, the delayed scan showed a significantly higher SUVmax of the cardiac lesion [median, 4.0; IQR (interquartile range, 2.9 to 7.0) vs. 5.8 (IQR 3.7 to 10.1); P = 0.0030] and a significantly lower SUVmean of blood pool [median, 1.3 (IQR, 1.2 to 1.4) vs. 1.1 (IQR, 0.9 to 1.2); P < 0.0001]. CONCLUSION: Delayed FDG PET/CT acquisition improves detection accuracy in patients with CS compared to early scans with washout of the blood pool activity. Therefore, it can contribute to a more accurate assessment of CS.

Prognostic value of follow-up vasoreactivity test in pulmonary arterial hypertension.

BACKGROUND: Acute vasoreactivity test with inhaled nitric oxide (NO) is performed during diagnostic right heart catheterization (RHC) to identify patients with pulmonary arterial hypertension (PAH) who respond to calcium channel blockers. Our purpose was to investigate the prognostic importance of follow-up vasoreactivity test after treatment. METHODS: We retrospectively analyzed 36 PAH patients (mean age, 47 years; 61 % treatment-naïve), who underwent diagnostic and follow-up RHC and vasoreactivity tests at our center. The primary outcome was all-cause mortality. RESULTS: The median time between baseline and follow-up RHC was 9.7 months. Absolute change in mean pulmonary arterial pressure (ΔmPAP) during NO challenge was less pronounced after treatment, but there was great variability among patients. Overall cohort was dichotomized into two groups: preserved vasoreactivity (ΔmPAP ≤ -1 mmHg) and less vasoreactivity (ΔmPAP ≥0 mmHg) at follow-up RHC. Less vasoreactivity group had higher usage rate of endothelin receptor antagonists and parenteral prostacyclin analogues. During a median observation period of 6.3 years after follow-up RHC, 7 patients died, of which 6 showed less vasoreactivity at follow-up. Absolute ΔmPAP ≥0 at follow-up RHC was associated with all-cause mortality in univariable Cox regression analysis (hazard ratio, 8.728; 95 % confidence interval, 1.045-72.887; p = 0.045), whereas other hemodynamic parameters were not. Absolute ΔmPAP ≥0 at follow-up RHC was associated with all-cause mortality in multivariable Cox analysis adjusted for age and known PAH prognostic factors (HR, 12.814; 95 % CI, 1.088-150.891; p = 0.043). Kaplan-Meier survival analysis revealed a significantly worse survival of less vasoreactivity group compared to preserved vasoreactivity group (log-rank test, p = 0.016). CONCLUSIONS: Follow-up vasoreactivity test after treatment could contribute to the detection of high-risk subgroups who might need careful monitoring and referral for lung transplantation.

Renal replacement therapy as a therapeutic option for right heart failure in severe pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a progressively life-threatening disease that causes right heart failure (RHF). Renal dysfunction frequently complicates PAH with RHF and is associated with a worse prognosis. Renal replacement therapy (RRT) may be a therapeutic option, although its efficacy and safety are unclear. We describe a 30-year-old male with severe PAH who developed renal insufficiency and diuretic-refractory volume overload complicated with RHF but was successfully managed with intermittent RRT via a subcutaneously fixed superficial artery for 4 years. RRT led to haemodynamic stability, which enabled us to carefully de-titrate parenteral PAH drugs without worsening RHF. This case highlights that RRT may be a potential alternative for haemodynamic and volume control of refractory fluid retention complicated with RHF in severe PAH cases. Further studies are warranted to gain more insight into patient selection and the optimal timing of RRT in PAH patients with deteriorating RHF.

DMD exon 2 duplication due to a complex genomic rearrangement is associated with a somatic mosaicism.

We report the case of a patient with dystrophinopathy caused by DMD exon 2 duplication, showing marked asymmetric muscle atrophy. Immunostaining of the biopsied muscle tissue showed a mosaic staining, suggesting a somatic mosaicism. Polymerase chain reaction (PCR) analysis showed only one breakpoint, and long-read whole-genome sequencing revealed the entire structure of the rearranged sequence. The complex rearrangement was composed of two tandem duplications: one showed a microhomology near the breakpoint, suggesting a microhomology-mediated mechanism, whereas the other was associated with flanking short tandem repeats. The long-read sequencing also suggested the presence of a wild-type nonduplicated sequence, supporting somatic mosaicism. Whereas complementary DNA and western blot analyses were not useful, droplet digital PCR (ddPCR) analysis showed an average copy number of 1.61, enabling accurate estimation of the proportion of cells containing the duplication. Long-read sequencing and ddPCR analysis were useful for revealing the rearrangements and the precise copy number.

Selexipag for the treatment of chronic thromboembolic pulmonary hypertension.

BACKGROUND: Treatment options for inoperable chronic thromboembolic pulmonary hypertension (CTEPH) remain limited. Selexipag, an oral selective IP prostacyclin receptor agonist approved for pulmonary arterial hypertension, is a potential treatment option for CTEPH. METHODS: In this multicentre, randomised, double-blind, placebo-controlled study, 78 Japanese patients with inoperable CTEPH or persistent/recurrent pulmonary hypertension after pulmonary endarterectomy and/or balloon pulmonary angioplasty were randomly assigned to receive placebo or selexipag. The primary end-point was the change in pulmonary vascular resistance (PVR) from baseline to week 20. Secondary end-points were changes in other haemodynamic parameters: 6-min walk distance (6MWD), Borg dyspnoea scale score, World Health Organization (WHO) functional class, EuroQol five-dimension five-level tool and N-terminal pro-brain natriuretic peptide. RESULTS: The change in PVR was -98.2±111.3 dyn·s·cm-5 and -4.6±163.6 dyn·s·cm-5 in the selexipag and placebo groups, respectively (mean difference -93.5 dyn·s·cm-5; 95% CI -156.8 to -30.3; p=0.006). The changes in cardiac index (p<0.001) and Borg dyspnoea scale score (p=0.036) were also significantly improved over placebo. 6MWD and WHO functional class were not significantly improved. The common adverse events in the selexipag group corresponded to those generally observed following administration of a prostacyclin analogue. CONCLUSION: Selexipag significantly improved PVR and other haemodynamic variables in patients with CTEPH, although exercise capacity remained unchanged. Further large-scale investigation is necessary to prove the role of selexipag in CTEPH.

Cardiac index predicts long-term outcomes in patients with heart failure.

BACKGROUND: The role of cardiac index (CI) and right atrial pressure (RAP) for predicting long-term outcomes of heart failure has not been well established. The aim of this study was to investigate long-term cardiac outcomes in patients with heart failure having various combinations of CI and RAP. METHODS: A total of 787 heart failure patients who underwent right-heart catheterization were retrospectively categorized into the following four groups: Preserved CI (≥2.5 L/min/m2) and Low RAP (<8 mmHg) (PRE-CI/L-RAP; n = 285); Preserved CI (≥2.5 L/min/m2) and High RAP (≥8 mmHg) (PRE-CI/H-RAP; n = 242); Reduced CI (<2.5 L/min/m2) and Low RAP (<8 mmHg) (RED-CI/L-RAP; n = 123); and Reduced CI (<2.5 L/min/m2) and High RAP (≥8 mmHg) (RED-CI/H-RAP; n = 137). Survival analysis was applied to investigate which groups were associated with major adverse cardiovascular events (MACE). RESULTS: The RED-CI/L-RAP and RED-CI/H-RAP groups were significantly associated with MACE as compared with the PRE-CI/L-RAP and PRE-CI/H-RAP groups after adjustment for confounding factors (RED-CI/L-RAP vs. PRE-CI/L-RAP: HR 2.11 [95% CI 1.33-3.37], p = 0.002; RED-CI/H-RAP vs. PRE-CI/L-RAP: HR 2.18 [95% CI 1.37-3.49], p = 0.001; RED-CI/L-RAP vs. PRE-CI/H-RAP: HR 1.86 [95% CI 1.16-3.00], p = 0.01; RED-CI/H-RAP vs. PRE-CI/H-RAP: HR 1.92 [95% CI 1.26-2.92], p = 0.002), whereas the difference between the RED-CI/H-RAP and RED-CI/L-RAP groups was not significant (HR 1.03 [95% CI 0.64-1.66], p = 0.89). CONCLUSIONS: The hemodynamic severity categorized by CI and RAP levels provided clear risk stratification in patients with symptomatic heart failure. Low CI was an independent predictor of long-term cardiac outcomes.

Axitinib Induces and Aggravates Hypertension Regardless of Prior Treatment With Tyrosine Kinase Inhibitors.

Background: Axitinib is a tyrosine kinase inhibitor (TKI) that inhibits vascular endothelial growth factor receptor signaling and is approved for second-line treatment of advanced renal cell carcinoma (RCC). Although the occurrence of hypertension with axitinib use has been documented, it is unclear whether a first-line TKI regimen can significantly affect the development of hypertension when axitinib is used as second-line therapy. Methods and Results: In this single-center retrospective study, advanced RCC patients treated with axitinib after first-line chemotherapy were divided into 2 groups according to the use of TKIs as part of first-line treatment before the initiation of axitinib. Clinical outcomes were compared between patients who were treated with (TKI(+); n=11) or without (TKI(-); n=11) a TKI. Although 63.6% of all patients had hypertension at baseline, axitinib-induced hypertension developed in 81.8% of patients, and 36.4% of patients experienced Grade 3 hypertension. After initiation of axitinib, both systolic and diastolic blood pressures and the hypertension grade were significantly elevated both in the TKI(+) and TKI(-) groups, and the number of antihypertensive drugs was significantly increased among all patients. Conclusions: This study suggests the need for proper monitoring and management of blood pressure in RCC patients treated with axitinib, regardless of a prior regimen with or without TKIs.

Association of serum CCL20 levels with pulmonary vascular involvement and primary biliary cholangitis in patients with systemic sclerosis.

AIM: Systemic sclerosis (SSc) is a chronic autoimmune disease resulting in vasculopathy and fibrosis of the skin and major internal organs. Especially, interstitial lung disease and pulmonary arterial hypertension are the leading causes of mortality. C-C motif ligand 20 (CCL20) is known as a homeostatic and inflammatory chemokine, which is associated with fibrosis and angiogenesis and constantly expressed in organs involved in SSc. Therefore, we investigated the potential contribution of CCL20 to the development of SSc. METHOD: We conducted cross-sectional analyses of 67 SSc patients and 20 healthy controls recruited in a single center for 9 years. Serum CCL20 levels were measured by enzyme-linked immunosorbent assay. Statistical analyses were performed with the Mann-Whitney U test, the Kruskal-Wallis test followed by Dunn's multiple comparison test, Fisher's exact probability test and the Spearman's rank correlation coefficient. RESULTS: SSc patients had significantly higher serum CCL20 levels than healthy controls. In SSc patients, serum CCL20 levels correlated inversely with the percentage of predicated diffusion lung capacity for carbon monoxide and positively with mean pulmonary artery pressure (mPAP). In addition, SSc patients with increased serum CCL20 levels had anti-mitochondrial antibody M2 titer significantly elevated relative to those with normal levels, and SSc patients with asymptomatic primary biliary cholangitis (PBC) possessed higher serum CCL20 levels than those without. Importantly, serum CCL20 levels were associated positively with mPAP values and PBC presence by multivariate regression analysis. CONCLUSION: Serum CCL20 levels may be involved in the development of pulmonary vascular involvement leading to pulmonary arterial hypertension and asymptomatic PBC in SSc patients.

Case Report: A Case of Acute Cellular Rejection Due to Atopic Dermatitis Exacerbation 3 Years After Heart Transplantation.

Background: Little evidence has been presented about the association between previous atopic/allergic disease and graft rejection after solid organ transplantation. Thus, we present a case wherein acute cellular rejection (ACR) after heart transplantation (HTx) was noted along with exacerbation of atopic disease. Case Summary: A 32-year-old man was admitted at our hospital for regular monitoring of graft rejection. He had undergone heart transplant 3 years prior due to dilated cardiomyopathy. Echocardiogram revealed good biventricular function, and no abnormal findings were found in blood sampling tests. However, biopsy showed moderate ACR [Grade 2R(ISHLT 2004)/3A(ISHLT 1990)], which required twice-repeated steroid pulses with intensified immunosuppression. Meanwhile, his atopic dermatitis, which was diagnosed before having heart failure, was getting worse for the past 6 months. The exacerbation of atopic dermatitis was presumed to be related to the development of the intractable cellular rejection. Discussion: This case suggested the association of atopic disease and graft rejection after HTx. We examined 76 patients from a cohort of previous studies who underwent HTx at our hospital, which suggested that patients with atopic/allergic disorders such as atopic dermatitis and asthma tended to have a significantly higher frequency of moderate rejection than non-allergic patients. (p = 0.012; Fisher's exact test). Our case also suggests that exacerbation of atopic dermatitis might cause graft rejection of the transplanted organ, so that it is important to carefully evaluate the risk of graft rejection if there is a previous history of atopic/allergic disease.

Combined pre- and post-capillary pulmonary hypertension: The clinical implications for patients with heart failure.

BACKGROUND: The prognostic implications of combined pre- and post-capillary pulmonary hypertension (Cpc-PH) in patients with pulmonary hypertension due to left heart disease (PH-LHD) remain controversial. The aim of this retrospective study was to evaluate the new PH-LHD criteria, recommended by the 6th World Symposium on Pulmonary Hypertension and to determine the prognostic value of Cpc-PH. METHODS: A total of 701 patients with symptomatic heart failure who had undergone right-heart catheterization were divided into the following four groups: (i) Isolated post-capillary PH (Ipc-PH) group; mean pulmonary artery pressure (mPAP) >20 mmHg, pulmonary artery wedge pressure (PAWP) >15 mmHg, and pulmonary vascular resistance (PVR) <3 Wood units (WU) (ii) Cpc-PH group; mPAP >20 mmHg, PAWP >15 mmHg, and PVR ≥3 WU (iii) borderline-PH group; mPAP >20 mmHg and PAWP ≤15 mmHg (iv) non-PH group; mPAP ≤20 mmHg. Multivariate Cox hazard analysis was used to investigate whether Cpc-PH was associated with cardiac outcomes. RESULTS: The study subjects were allocated into the Ipc-PH (n = 268), Cpc-PH (n = 54), borderline-PH (n = 112), or non-PH (n = 267) groups. The Cpc-PH group was associated significantly with adverse cardiac events even after adjustment for clinically relevant confounding factors for heart failure prognosis (vs. non-PH group: HR 2.98 [95% CI 1.81-4.90], P <0.001; vs. Ipc-PH group: HR: 1.92 [95% CI 1.19-3.08], P = 0.007). CONCLUSIONS: The new definitions of PH-LHD stratified patients into 4 categories. Long-term clinical outcomes were significantly different between the four categories, with Cpc-PH having the worst cardiac outcomes.

Carbon Monoxide Diffusing Capacity Predicts Cardiac Readmission in Patients Undergoing Left Ventricular Assist Device Implantation in Japan.

Carbon monoxide diffusion capacity (DLCO) is impaired in heart failure patients; however, its clinical impact has not been well investigated in the left ventricular assist device (LVAD) population. We explored the predictive value of preoperative DLCO in the survival and cardiac readmission rates after LVAD implantation. Seventy-six patients who received continuous-flow LVAD as bridge-to-transplant therapy from November 2007 to September 2018 and underwent pulmonary function test before LVAD implantation were included. The primary study endpoints were death and readmission for heart failure or arrhythmia (cardiac readmission). Patients were stratified into two groups according to the percent of predicted DLCO (%DLCO). Pulmonary vascular resistance (PVR) was equivocal between the groups preoperatively, whereas the low DLCO group (%DLCO < 80%) showed significantly high PVR postoperatively. The mortality rate was not different between the groups. The 2 year cardiac readmission rate was 33.5% in the low DLCO group and 8.7% in the high DLCO group (%DLCO ≥ 80%) (P = 0.028). The %DLCO was associated with cardiac readmission in univariate and multivariate analyses (hazard ratio: 4.32; 95% CI: 1.50-15.9; P = 0.005). Low %DLCO was associated with high PVR postoperatively and was a risk factor for cardiac readmission after LVAD implantation.

Association between infectious event and de novo malignancy after heart transplantation.

The aim of the study was to investigate the incidence of and risk factors for de novo malignancy after heart transplantation (HTx) in a single center. We assessed 102 consecutive patients who received HTx and were followed-up in our center regularly for > 1 year from June 2006 to May 2018. We investigated the incidence of and risk factors for de novo malignancy. The cumulative incidence of each malignancy type during the follow-up period was one (0.98%) for skin cancer, four (3.92%) for nonskin solid organ cancer, and six (5.88%) for posttransplant lymphoproliferative disorder (PTLD). The percentage of patients with more than one infectious event ≤ 1 year after HTx was higher in the malignancy group than in the non-malignancy group. Furthermore, Kaplan-Meier analysis revealed that the incidence rate of infectious events was higher in patients with malignancies than in those without (log-rank P < 0.001). After dividing malignancies into a PTLD group and a solid organ malignancy group, we found that negative Epstein-Barr virus serostatus, cytomegalovirus-positive antigenemia, and the occurrence of any viral or gastrointestinal infectious event at ≤ 1 year were more frequent in patients with PTLD than in patients without it. The survival rate was significantly lower for patients with solid organ malignancy than for patients without malignancy. In conclusion, there was a correlation between infectious events and de novo malignancy, particularly in patients with PTLD. We should confirm this finding by conducting a larger cohort study.

Differences in the prognoses of patients referred to an advanced heart failure center from hospitals with different bed volumes.

Few reports have discussed appropriate strategies for patient referrals to advanced heart failure (HF) centers with available left ventricular assist devices (LVADs). We examined the association between the characteristics and prognoses of referred patients with advanced HF and the bed volume of the referring hospitals. This retrospective analysis evaluated 186 patients with advanced HF referred to our center for consultation about the indication of LVAD between January 1, 2015, and August 31, 2018. We divided the patients into two groups according to the bed volume of their referring hospital (high bed volume hospitals (HBHs): ≥ 500 beds in the hospital; low bed volume hospitals (LBHs): < 500 beds). We compared the primary outcome measure, a composite of LVAD implantation and all-cause death, between the patients referred from HBHs and patients referred from LBHs. The 186 patients with advanced HF referred to our hospital, who were referred from 130 hospitals (87 from LBHs and 99 from HBHs), had a mean age of 43.0 ± 12.6 years and a median left ventricular ejection fraction of 22% [15-33%]. The median follow-up duration of the patients was 583 days (119-965 days), and the primary outcome occurred during follow-up in 42 patients (43%) in the HBH group and 20 patients (23%) in the LBH group. Patients referred from HBHs tended to require catecholamine infusion on transfer more often than those referred from LBLs (36.5% (HBH), 20.2% (LBL), P = 0.021). Kaplan-Meier analysis indicates that the occurrence of the primary outcome was significantly higher in the HBH patients than in the LBH patients (log-rank P = 0.0022). Multivariate Cox proportional hazards analysis revealed that catecholamine support on transfer and long disease duration were statistically significant predictors of the primary outcome. Patients from HBHs had a greater risk of the primary outcome. However, the multivariate analysis did not indicate an association between referral from an HBH and the primary outcome. In contrast, catecholamine support on transfer, long duration of disease, and low blood pressure were independent predictors of the primary outcome. Therefore, these should be considered when determining the timing of a referral to an advanced HF center, irrespective of the bed volume of the referring hospital.

Novel Balloon Pulmonary Angioplasty Technique for Chronic Thromboembolic Pulmonary Hypertension.

This study aimed to clarify the usefulness of the Ikari-curve left (IL) guiding catheter for balloon pulmonary angioplasty (BPA).The current BPA strategy for chronic thromboembolic pulmonary hypertension is dilation of as many branches as possible to normalize hemodynamics and oxygenation. The shape of the guiding catheter is a major factor in achieving this. However, conventional guiding catheters are difficult to introduce into particular branches. The IL guiding catheter may be suitable; however, its utility remains unclear.We retrospectively analyzed 202 consecutive BPA sessions of 40 patients from November 2016 to October 2019 and divided these sessions into two groups: the IL group where the IL guiding catheter was used and the non-IL group where other catheters were utilized. The occurrence of lung injury was determined by the presence of bloody sputum. We compared the rates of successful introduction into target vessels and assessed for the occurrence of lung injury.The average age of enrolled patients was 60.3 ± 14.4 years, with females comprising 65%. There were 99 sessions in the IL group. The median treated branches per session differed between the 2 groups (IL group: 15 versus non-IL group: 10, P < 0.05). The occurrence of lung injury was lower in the IL group (4.0% versus 11.7%, P = 0.07). The IL group had more successful vessel insertions than the non-IL group (78.8% versus 42.7%, P < 0.01).The IL guiding catheter may be introduced into branches that cannot be accessed by conventional guiding catheters.

Takotsubo syndrome in the same heart before and after heart transplantation.

Heart transplantation is an effective therapy for patients with end-stage heart failure. In some cases, Takotsubo syndrome (TTS) was seen in the donor heart. We report a case of TTS in a 40-year-old woman with a history of epileptic seizures who underwent heart transplantation from a donor with TTS. The donor was brain-dead due to severe hypoxic encephalopathy during cardiac arrest with TTS. Fifteen months after heart transplantation, she was readmitted for epileptic seizures. Electrocardiogram showed T-wave inversion, and transthoracic echocardiography showed apical ballooning. Coronary angiography was normal, and endomyocardial biopsy was negative for rejection. Iodine-123 metaiodobenzylguanidine imaging demonstrated a low heart-to-mediastinum ratio and high washout rate. Eighteen days after admission, recovery of left ventricular dysfunction was confirmed, and she was diagnosed with TTS triggered by epileptic seizures. It is important to recognize the risk of recurrent TTS in heart transplantation patients from a donor with TTS.

Clinical importance of respiratory muscle fatigue in patients with cardiovascular disease.

Patients with cardiovascular diseases frequently experience exertional dyspnea. However, the relationship between respiratory muscle strength including its fatigue and cardiovascular dysfunctions remains to be clarified.The maximal inspiratory pressure/maximal expiratory pressure (MIP/MEP) before and after cardiopulmonary exercise testing (CPX) in 44 patients with heart failure and ischemic heart disease were measured. Respiratory muscle fatigue was evaluated by calculating MIP (MIPpost/MIPpre) and MEP (MEPpost/MEPpre) changes.The mean MIPpre and MEPpre values were 67.5 ±â€Š29.0 and 61.6 ±â€Š23.8 cm H2O, respectively. After CPX, MIP decreased in 25 patients, and MEP decreased in 22 patients. We evaluated the correlation relationship between respiratory muscle function including respiratory muscle fatigue and exercise capacity evaluated by CPX such as peak VO2 and VE/VCO2 slope. Among MIP, MEP, change in MIP, and change in MEP, only the value of change in MIP had an association with the value of VE/VCO2 slope (R = -0.36, P = .017). In addition, multivariate analysis for determining factor of change in MIP revealed that the association between the change in MIP and eGFR was independent from other confounding parameters (beta, 0.40, P = .017). The patients were divided into 2 groups, with (MIP change < 0.9) and without respiratory muscle fatigue (MIP change > 0.9), and a significant difference in peak VO2 (14.2 ±â€Š3.4 [with fatigue] vs 17.4 ±â€Š4.7 [without fatigue] mL/kg/min; P = .020) was observed between the groups.Respiratory muscle fatigue demonstrated by the change of MIP before and after CPX significantly correlated with exercise capacity and renal function in patients with cardiovascular disease.

The Clinical Efficacy of Endothelin Receptor Antagonists in Patients with Pulmonary Arterial Hypertension.

Therapeutic strategies for pulmonary arterial hypertension (PAH) have made remarkable progress over the last two decades. Currently, 3 types of drugs can be used to treat PAH; prostacyclins, phosphodiesterase 5 inhibitors, and endothelin receptor antagonists (ERA). In Japan, the first generation ERA bosentan was reimbursed in 2005, following which the 2nd generation ERAs ambrisentan and macitentan were reimbursed in 2009 and 2015, respectively. The efficacy of each ERA on hemodynamics in PAH patients remains to be elucidated. The aims of this study were to evaluate the hemodynamic effects of ERAs and compare these effects among each generation of ERAs.We retrospectively examined the clinical parameters of 42 PAH patients who were prescribed an ERA (15 bosentan, 12 ambrisentan, and 15 macitentan) and who underwent a hemodynamic examination before and after ERA introduction at our institution from January 2007 to July 2019.In a total of 42 patients, mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR) were significantly decreased and cardiac index was significantly increased after ERA introduction (P < 0.001) and the World Health Organization-Functional class (WHO-Fc) was significantly improved after ERA introduction (P = 0.005). Next, in a comparison between 1st and 2nd generation ERAs, 2nd generation ERAs were found to have brought about greater improvements in hemodynamic parameters (mPAP and PVR. P < 0.01), heart rate, brain natriuretic peptide, arterial oxygen saturation, and mixed venous oxygen saturation than the 1st generation ERA bosentan.We conclude that all ERAs could successfully improve the hemodynamics of PAH patients and that the newer generation ERAs, ambrisentan and macitentan, seemed to be preferable to bosentan.