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Objective This study aimed to compare the contribution of 18F-fluorodepxyglucose (FDG) positron (PET)/ computed tomography (CT) acquisition of early and delayed scan 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 (SUV mean) 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 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

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.

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.

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.

The conventional treatment goal for chronic thromboembolic pulmonary hypertension (CTEPH) is improving hemodynamic status, particularly mean pulmonary artery pressure (mPAP); however, some patients complain of impaired quality of life (QOL) caused by dyspnea on effort, even after hemodynamic status has fully improved. It remains unclear whether treatment for CTEPH can improve patients' QOL or whether quantitative measures of QOL correlate with hemodynamic status. This study quantified QOL among Japanese CTEPH patients and investigated whether balloon pulmonary angioplasty (BPA) improved QOL.We calculated the QOL scores of 45 CTEPH patients using the European Quality of Life Five Dimension scale (EQ-5D). The mean QOL score among 12 of those 45 not involved in any therapy except supplemental oxygen at the time of initial measurement was 0.673 ± 0.251. QOL was measured before and after BPA for 17 patients, and the mean significantly improved (QOL from 0.741 ± 0.195 to 0.802 ± 0.160, p 0.05; mPAP from 33.0 ± 8.4 to 23.4 ± 4.2 mmHg, p 0.05; pulmonary vascular resistance from 441.4 ± 214.2 to 268.4 ± 85.6 dyne/s/cmBPA improved QOL in patients with CTEPH mainly by improving "usual activities," besides the improvement in mPAP.

Background Balloon pulmonary angioplasty (BPA) has been performed in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). However, some patients have inoperable CTEPH despite having lesions suitable for surgical treatment. The effectiveness of BPA in such cases is unclear. The aim of this study was to clarify the effectiveness of BPA in these cases. Methods We retrospectively investigated patients with inoperable CTEPH and divided them into two groups: BPA-suitable and BPA-unsuitable groups based on the findings of pulmonary angiography, computed tomography, and perfusion scintigraphy. The BPA-unsuitable group included patients whose lesions are suitable for surgical treatment but who did not undergo the procedure for any specified reason. We analyzed the hemodynamic, respiratory, and functional status of the patients before and after BPA. Results Forty-three consecutive patients with inoperable CTEPH (age, 62.6 ± 13.5 years; 31 women) were included; all of them underwent BPA. There were 10 patients in the BPA-unsuitable group. In all patients, the mean pulmonary artery pressure, pulmonary vascular resistance, arterial oxygen saturation level, and 6-min walking distance significantly improved after BPA (mean pulmonary artery pressure, from 43.3 ± 7.8 mmHg to 23.9 ± 4.7 mmHg; pulmonary vascular resistance, from 924.1 ± 462.2 dynes/s/cm−5 to 319.7 ± 163.8 dynes/s/cm−5; arterial oxygen saturation level, from 89.3 ± 4.3% to 93.4 ± 3.3%; 6-min walking distance, from 370.0 ± 107.4 m to 443.8 ± 101.4 m). Notably, none of the parameters significantly differed between the groups after BPA. Importantly, the amount of lung bleeding did not differ between them. However, several sessions were required in the BPA-unsuitable group (BPA-unsuitable group: six sessions vs. BPA-suitable group: four sessions). Conclusions BPA safely improved the hemodynamic and functional statuses of the patients with CTEPH who are judged as inoperable for any reason despite lesion being suitable for surgical treatment. However, numerous BPA sessions were required in these patients.

Pulmonary hypertension (PH) is defined as a mean pulmonary artery pressure (PAP) ≥ 25 mmHg at rest as assessed by right heart catheterization (RHC), and Doppler-derived systolic PAP (sPAPECHO) or tricuspid regurgitation pressure gradient (TRPG) is widely used to screen for PH. However, the cutoff value of sPAPECHO or TRPG for detecting a mean PAP ≥ 25 mmHg that was determined invasively has not been well defined.We studied 189 patients who underwent RHC. Echocardiography was performed within 24 hours of invasive evaluation, and sPAPECHO was defined as the TRPG with right atrial pressure estimated on the basis of the current guideline.From the receiver operating characteristic (ROC) curve analysis, the optimal sPAPECHO, and TRPG cutoffs for detecting PH were 41 mmHg (sensitivity, 92%; specificity, 91%; area under the curve = 0.95) and 36 mmHg (sensitivity, 90%; specificity, 93%; area under the curve = 0.95), respectively. The area under the TRPG ROC curve was similar to the area under the sPAPECHO ROC curve.Given that Doppler echocardiography is required to accurately detect PH rather than to accurately estimate systolic PAP, our results provide useful information with regard to screening patients for PH and recommending further investigations on PH.

The precise physiological changes associated with the use of left ventricular assist device (LVAD) are not well characterized. We examined the impact of changes in hemodynamic state using LVAD on endothelial function. We measured flow-mediated vasodilation (FMD) to evaluate endothelial vasodilator function of the brachial artery in 53 patients (dilated cardiomyopathy: 39, ischemic cardiomyopathy: 4, and others: 10) with an implanted LVAD (DuraHeart, EVAHEART, or HeartMate II). We found that FMD value in the HeartMateII LVAD group (9.3% ± 2.9%) was significantly higher than those in the other two groups (EVAHEART: 6.7% ± 2.8% and DuraHeart: 6.2% ± 4.0%). Other factors that affected the FMD value were age (r = - 0.31, p = 0.026), Brinkman index (r = - 0.30, p = 0.029); however, aortic opening, aortic regurgitation, and other hemodynamic parameters such as cardiac index or pulmonary capillary wedge pressure did not correlate with FMD. Multivariate analyses revealed that the difference among the LVAD models most significantly affected the FMD values after adjusting for age and smoking status (t = 2.6, p = 0.014). Event free survival rate of death and cerebral infarction was not significantly different according to the value of FMD. The difference among the LVAD groups most significantly affected the state of endothelial function and it had more impact than other clinical factors.

Aims We assessed preoperative muscle wasting in patients undergoing left ventricular assist device (LVAD) implantations using abdominal skeletal muscle images on computed tomography (CT) and explored the associations between the preoperative muscle wasting and clinical outcomes after LVAD implantation. Methods and results We retrospectively examined the records of 111 patients who underwent continuous‐flow LVAD implantations as bridge‐to‐transplant therapy from January 2010 to December 2016 at our institution. After 33 patients were excluded, the study cohort consisted of 78 individuals. CT images used to calculate the skeletal muscle index (SMI) at the third lumbar vertebra level were obtained before the LVAD implantation procedures. Patients were classified as having muscle wasting if their SMI fell into the lowest gender‐based tertile. The median SMI for the study patients was 37.6 cm2/m2. The SMI cut‐off values for the lowest tertiles were 36.7 cm2/m2 for men and 28.2 cm2/m2 for women, resulting in 26 patients (33.3%) with muscle wasting in this study. During the mean follow‐up of 738 ± 379 days, there were 10 deaths (12.8% mortality). Seven of the 26 patients with muscle wasting (26.9%) died, and 3 of the 52 patients without muscle wasting (5.8%) died. The times to all‐cause mortality were significantly different between patients with and without muscle wasting (P = 0.0094). Muscle wasting was found to be associated with mortality in univariate and multivariate Cox analyses (hazard ratio: 4.32; 95% CI: 1.19–20.2). Conclusions Preoperative muscle wasting was associated with a higher mortality in patients with LVAD. Assessment of the abdominal skeletal muscle area on CT prior to LVAD implantation can help predict mortality.

Heart transplantation (HTx) is the gold standard therapy to improve quality and quantity of life in end‐stage heart failure patients. However, recipients are at risk of experiencing allograft rejection and post‐transplant complications, in the acute as well as chronic phase. A 43‐year‐old man with a history of left ventricular non‐compaction underwent orthotopic HTx. On Day 7, transthoracic echocardiography showed a sudden decrease in cardiac function with hypokinesis in a left ventricular anterior wall distribution. Coronary angiography revealed a large thrombus in the left main trunk. With intra‐aortic balloon pump support, emergency percutaneous coronary intervention was performed. Endomyocardial biopsy showed no rejection. A left main trunk thrombus is rare in the early phase after HTx, but it can be a life‐threatening complication. Transthoracic echocardiography is well known to be important in the management of heart transplant recipients, and coronary angiography as well as myocardial biopsy should be considered when left ventricular wall motion is impaired.

BackgroundTreatment 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.MethodsIn 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.ResultsThe 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 (pConclusionSelexipag 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.

BackgroundThe 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.MethodsA 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 (2) and High RAP (≥8 mmHg) (PRE-CI/H-RAP; n = 242); Reduced CI (2) and Low RAP (2) 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).ResultsThe 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).ConclusionsThe 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.

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.

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.

BackgroundThe 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.MethodsA 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) 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.ResultsThe 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],PP= 0.007).ConclusionsThe 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.

Background The current strategy of balloon pulmonary angioplasty (BPA) for chronic thromboembolic pulmonary hypertension (CTEPH) is to dilate branches as many as possible without lung injury to normalize mean pulmonary artery pressure and oxygenation. The shape of guiding catheter is one of the important factors to achieve this strategy. However, conventional guiding catheters which are typically used for BPA are difficult to introduce into particular branches. The Ikari-curve left (IL) guiding catheter may be suitable for this purpose by adjusting its curves (Figure 1); however, its utility and effectiveness for lung injury are unclear. Purpose The aim of this study is to clarify utility and safety of IL guiding catheter for BPA. Methods We retrospectively analyzed 202 consecutive BPA sessions of 40 patients with CTEPH from November 2016 to October 2019 and divided them into two groups; IL group, in which we used IL guiding catheter; and non-IL group in which we used others. IL guiding catheter was used for branches of left lung which are difficult to introduce by conventional catheter prior Nov. 2018. After Nov.2018, we also used it for the same type branches of right lung. The occurrence of lung injury was determined by the presence of bloody sputum during the perioperative period. We compared success rate of introduction into target vessels and of occurrence of lung injury. Results The average age of enrolled patients was 60.3±14.4 year-old and female was 65%. There were 99 sessions in IL group. The median treated branches significantly differed between groups (IL group: 15 vs. non-IL group: 10, p Conclusion IL guiding catheter can be introduced into branches that cannot be accessed via conventional guiding catheters and has potential to reduce the occurrence of lung injury. 2228 characters including space Figure1 Funding Acknowledgement Type of funding source: None

Supplemental Digital Content is available in the text, 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 ± 29.0 and 61.6 ± 23.8 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 a significant difference in peak VO2 (14.2 ± 3.4 [with fatigue] vs 17.4 ± 4.7 [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.

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 (P0.001) 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. P0.01), 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.

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): 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.

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

Anticentriole autoantibodies-positive systemic sclerosis (SSc) has been reported to develop pulmonary arterial hypertension (PAH) at a high rate. In this report, we describe two patients with anticentriole antibodies-positive SSc-PAH who were treated with pulmonary vasodilators. Both cases were elderly women with poor physical conditions and clinical findings of SSc. Case 1 was resistant to combination therapy with pulmonary vasodilators; in Case 2, hemodynamic improvement was obtained by upfront combination therapy at an early stage. Because anticentriole antibodies-positive SSc-PAH rapidly deteriorates, careful hemodynamic observation and timely aggressive use of pulmonary vasodilators should be considered.

Respiratory muscle weakness is often complicated in patients with heart failure. Its presence further worsens the clinical course of heart failure. However, the effect and appropriate method of inspiratory muscle training has not previously been elucidated. A 55-year-old man with dilated cardiomyopathy was admitted for intractable heart failure. His heart failure was dependent on catecholamine infusion and the implantation of left ventricular assist device was planned. He also had suffered from some muscle weakness, which was later diagnosed as lamin dystrophy due to mutation of LMNA c.G97T E33X. Preoperatively we started aerobic rehabilitation with inspiratory muscle training. Before training, inspiratory and expiratory muscle strength was significantly reduced and exercise capacity was decreased. The load of inspiratory training could be gradually increased along the result of regular evaluation of respiratory muscle strength. During 8 weeks of training, there was no worsening of heart failure and no significant events related to arrhythmia. After training, respiratory muscle strength and exercise capacity were improved significantly.

This study investigated the effectiveness and safety of interval training during in-hospital treatment of patients with advanced heart failure. Twenty-four consecutive patients with advanced symptomatic heart failure who were referred for cardiac transplant evaluation were recruited. After performing aerobic exercise for approximate intensity, high-intensity interval training (HIIT) was performed. The protocol consisted of 3 or 4 sessions of 1-min high-intensity exercise aimed at 80% of peak VO

Key Clinical Message We have presented a case of advanced HF, in which newly developed AF hastened the timing of the implantation of mechanical support. Newly developed AF in advanced HF may be intractable by medical therapies and could be a key event that determines the timing of mechanical support.

Background Fractional exhaled nitric oxide levels are related to various clinical diseases. This study investigated the associations between the clinical characteristics and the level of fractional exhaled nitric oxide in patients with adult congenital heart disease. Methods and results Fractional exhaled nitric oxide values were measured in 30 adult patients with stable congenital heart disease who had undergone right heart catheterization and 17 healthy individuals (controls). There was no significant difference in fractional exhaled nitric oxide values between patients with congenital heart disease and healthy controls. Depending on whether their fractional exhaled nitric oxide values were above or below the median value, patients with congenital heart disease were divided into two groups (low vs. high fractional exhaled nitric oxide groups). The relationship between fractional exhaled nitric oxide values and clinical characteristics was investigated. There was a higher percentage of patients with cyanosis in the low fractional exhaled nitric oxide group (50%) than in the high fractional exhaled nitric oxide group (7.1%). There was no significant difference in right heart catheterization data between the low and high fractional exhaled nitric oxide groups. The fractional exhaled nitric oxide value was correlated to the number of neutrophils in patients with cyanosis (r = 0.84 (N = 8), p = 0.005). Conclusions In this cohort of patients with adult congenital heart disease, lower levels of fractional exhaled nitric oxide corresponded to the presence of cyanosis.

Riociguat, a soluble guanylate cyclase stimulator, induces pulmonary artery dilatation through blood flow and is effective in treating chronic thromboembolic pulmonary hypertension (CTEPH). There are two types of vasculopathies in CTEPH based upon its location, in other words, proximal or distal to the thrombus-medicated obstruction. Distal vasculopathy is characterized by intrapulmonary shunts due to diminished blood flow. While other therapeutic interventions for CTEPH including pulmonary endarterectomy and balloon pulmonary angioplasty achieve reperfusion to the distal vasculopathy vessels, the effects of riociguat on distal vasculopathy vessels remain undetermined. Herein, we describe a case of a 66-year-old woman who exhibited deterioration of mean pulmonary artery pressure and exercise tolerance after a 4-month treatment with riociguat. She received balloon pulmonary angioplasty prior to riociguat administration. Her lung perfusion scintigraphy and pulmonary angiography findings did not change over the course of treatment. Notably, after the discontinuation of riociguat, her clinical values returned to their levels prior to riociguat administration. Her intrapulmonary shunt ratio followed a similar course as her hemodynamic status. We demonstrate that riociguat can deteriorate hemodynamic status, which may mediate the dilatation of intrapulmonary shunts. We should perform close monitoring of symptoms and hemodynamic status after riociguat administration, especially in patients in whom the reperfused DVs occurred due to invasive treatment.

Current therapeutic methods for chronic thromboembolic pulmonary hypertension (CTEPH) can improve hemodynamic status and are expected to improve prognoses. However, some patients experience dyspnea during effort and continue supplemental oxygenation despite their hemodynamic status being fully improved. Considering the pathogenesis of CTEPH, the dead space and intrapulmonary shunt are assumed to be responsible for hypoxia in CTEPH, but their contributions are unclear. It is also unclear whether they are improved after treatment. The aim of this study was to investigate the implications of the dead space ratio (DSR) and the intrapulmonary shunt ratio (ISR) for hypoxia in CTEPH and treatment for CTEPH.We retrospectively measured the DSR and ISR of 23 consecutive patients with CTEPH. For 11 of these 23 (10 were treated by balloon pulmonary angioplasty, one with riociguat), we also measured these parameters before and after CTEPH treatments. Overall, the DSR and ISR were abnormally elevated (DSR: 0.63 ± 0.06; ISR: 0.20 ± 0.05). After treatment, mean pulmonary artery pressure was improved (from 40.3 ± 8.1 to 25.5 ± 2.7 mmHg). Although atrial oxygen saturation (SaO2), DSR and ISR were improved (SaO2: from 90.2 ± 3.2 to 93.7 ± 1.8%; DSR: from 0.64 ± 0.06 to 0.58 ± 0.05; ISR: from 0.20 ± 0.04 to 0.18 ± 0.02), these improvements were slight compared with that of mean pulmonary artery pressure.The DSR and ISR were abnormally elevated in patients with CTEPH and their improvement by treatment was limited. Only DSR can be a useful marker for normalization of hypoxia in CTEPH.

Pulmonary hypertension (PH) is defined as a mean pulmonary artery pressure (PAP) ≥ 25 mmHg at rest as assessed by right heart catheterization (RHC), and Doppler-derived systolic PAP (sPAP

Background Continuous-flow left ventricular assist devices (LVADs) improve survival and morbidity in patients with stage D heart failure. Management of LVADs for longer durations is necessary in some clinical settings, and a better understanding of the hemodynamics of patients using LVADs is warranted. Arrhythmia, including atrial (AA) and ventricular (VAs) arrhythmias, is a modifying factor of hemodynamics that is highly prevalent among patients with LVADs. However, the clinical impact of arrhythmias in various clinical settings in patients with LVAD, in which the hemodynamic load is likely to present as worsening of right heart failure, remains to be completely elucidated. Case presentation We describe the case of a patient under sustained ventricular fibrillation for extraordinarily long duration who was stabilized using LVAD support and in whom newly developed atrial fibrillation led to a significant worsening of right heart failure while using an LVAD. Conclusion This case demonstrates the substantial clinical impact of AAs in the management of right heart failure using an LVAD. Electronic supplementary material The online version of this article (10.1186/s12872-019-1132-1) contains supplementary material, which is available to authorized users.

Endothelial dysfunction is a hallmark of vasculopathy associated with systemic sclerosis (SSc). Reactive hyperemia peripheral arterial tonometry is a rapid and non-invasive technique to assess peripheral microvascular endothelial function by measuring changes in digital pulse volume during reactive hyperemia. Low scores of the reactive hyperemia index (RHI) imply an impaired vasodilatory response and, accordingly, impaired endothelial and vascular health. To investigate the clinical significance of the RHI in SSc patients, RHI values were measured in 43 SSc patients and 10 healthy controls. In diffuse cutaneous SSc (dcSSc) patients, RHI values were significantly decreased compared with healthy controls, and inversely correlated with disease duration. In total SSc patients, there was a significant inverse correlation between RHI values and skin score, and interstitial lung disease was associated with the decrease in RHI values. Among vascular symptoms, the current and past history of digital ulcers was seen more frequently in patients with decreased RHI values than in those with normal RHI values. Although no SSc patients had pulmonary arterial hypertension, an inverse correlation was evident between RHI values and mean pulmonary arterial pressure measured by right heart catheterization. These results indicate that the decrease in RHI values is associated with skin fibrosis, interstitial lung disease, digital ulcers and pulmonary vascular involvement leading to pulmonary arterial hypertension, supporting the canonical idea that endothelial dysfunction is a critical event underlying the development of tissue fibrosis and vascular complications in SSc.

Although a correlation between the nutritional status and the prognosis of patients with heart failure has been suggested, a correlation between the nutritional status and outcomes after the left ventricular assist device (LVAD) implantation remains unclear. We aimed to investigate the efficacy of the Controlling Nutritional Status (CONUT) score (range 0-12, including serum albumin, total cholesterol, and lymphocytes) as a nutritional index in speculating the prognosis of patients undergoing LVAD implantation. We examined 63 consecutive patients who underwent the continuous-flow LVAD implantation. Using the preoperative CONUT score, patients were categorized into two groups: lower CONUT score (0-4: normal to mild malnutrition) and higher CONUT score (5-12: moderate to severe malnutrition). We compared for the backgrounds and the clinical events after LVAD implantation. The higher CONUT group exhibited a significantly higher mean right atrial pressure (10.9 ± 4.7 vs. 7.3 ± 4.1 mmHg; p = 0.0019). In that group, the mortality rate was significantly higher (25% vs. 2.6%; p = 0.0059) and the Kaplan-Meier analysis showed lower survival rate. Furthermore, more bleeding events significantly occurred in the higher CONUT group. The preoperative CONUT score may reflect systemic venous congestion and offer a useful prognostic index of clinical courses after LVAD implantation.