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Purpose: We sought to investigate the clinical results of preemptive temporary right ventricular assist device (RVAD) placement with left ventricular assist device (LVAD) implantation for anticipated right ventricular failure., Methods: Patients at risk for right ventricular failure were identified by the heart team. After median sternotomy, Protekduo (LivaNova, London, UK) dual-stage cannula was inserted from the right internal jugular vein under fluoroscopy guidance, and advanced into the pulmonary artery to the bifurcation of the main pulmonary artery. This was then connected to the venous drainage from the right atrium for cardiopulmonary bypass (CPB). After LVAD implantation, we connected the Protekduo cannula to the RVAD with oxygenator, and weaned CPB., Results: A total of 17 patients have received BiVAD implantation with this technique. The median age of patients was 55 years [Interquartile range (IQR): 51-63.5] and 94% (16/17) patients were male. 63.6% (7/11) of the patients were INTERMACS profile 1 or 2. Preoperatively, the median pulmonary artery pulsatility index was 4.0 [1.5-4.9] and median right ventricular stroke work index was 454.1 g/m/beat/m 2 [436.5-530.2]. Postoperatively, the oxygenators were removed on median postoperative day (POD) 3.5 [3 - 5]. Patients received mechanical ventilation for a median of 4 days [1.5-12] and RVADs were explanted on median POD 8 [7-19] at bedside with local anesthesia. Median ICU stay was 15 days [11.4-24]. Perioperative complications included delayed sternal closure [54.5% (6/11)], re-exploration for bleeding [18% (2/11)], acute kidney injury [36% (4/11)], and heparin induced thrombocytopenia [18% (2/11)]. 30-day mortality was 0% (0/11) and 1 year survival was 85.9%., Conclusion: Preemptive temporary RVAD implantation strategy for right heart failure post-LVAD showed acceptable clinical outcomes without any 30-day mortality., (© 2024 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Aims: Although patients with heart failure (HF) frequently experience considerable symptom burden and require significant care, most HF patients do not receive timely intervention due to the absence of a standardized method for identifying those in need of palliative care. The Needs Assessment Tool: Progressive Disease-Heart Failure (NAT: PD-HF) assesses the palliative care needs of patients with HF. However, its validity and reliability have yet to be fully examined. We aimed to assess the validity and reliability of the NAT: PD-HF in Japanese patients with HF., Methods: We prospectively enrolled 106 consecutive patients with chronic HF admitted to our university hospital between February 2023 and July 2023. Their caregivers (n = 95) and healthcare providers (n = 17) were also included. The NAT: PD-HF was translated from English to Japanese using a forward-backward translation procedure and adapted based on Japanese cultural and medical backgrounds by our professional multidisciplinary team. We assessed the internal consistency of the Japanese NAT: PD-HF version with Cronbach's alpha coefficient and the inter-rater and test-retest reliabilities with Cohen's kappa coefficient. After using the tool, all participants were asked to complete a questionnaire about the tool to determine its validity., Results: The proportion of female patients in this study was 47 (44%). The median age was 72 years [interquartile range (IQR) 59-81]. The median time spent assessing the patients' and their caregivers' needs using the Japanese NAT: PD-HF was 14 min (IQR 12-17). The Cronbach's alpha coefficient was 0.82, and the minimum kappa coefficient was 0.77 for inter-rater reliability and 0.88 for test-retest reliability. In total, 103 patients (97%) and all caregivers responded that the tool was easy to understand. One hundred (94%) patients and 89 (94%) caregivers felt that the tool would improve the quality of care, and 102 (96%) patients and 91 (96%) caregivers indicated that the discussions using this tool allowed them to confide in all their burdens and care needs. All healthcare providers expressed that this tool is helpful in understanding the burden and care needs of both patients and caregivers comprehensively., Conclusions: The NAT: PD-HF is a reliable and valid tool for Japanese patients with HF and their caregivers. This tool was very well accepted by patients, caregivers and healthcare providers to identify burdens and care needs., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Sacubitril/valsartan has become an important first-line drug for symptomatic heart failure (HF) patients, especially with left ventricular (LV) ejection fraction (LVEF) < 50%. However, the impact of sacubitril/valsartan on cardiovascular outcomes, especially LV reverse remodeling for such patients with low blood pressure, remains uncertain. We retrospectively studied 164 HF patients with LVEF < 50% who were treated with sacubitril/valsartan from two institutions. Echocardiography was performed before and 9.5 ± 5.1 months after initiation of maximum tolerated dose of sacubitril/valsartan. The maximum tolerated dose of sacubitril/valsartan was lower for the low blood pressure group (≤ 100 mmHg in systole) than for the non-low blood pressure group (> 100 mmHg in systole) (165 ± 106 mg vs. 238 ± 124 mg, P = 0.017). As expected, significant LV reverse remodeling was observed in the non-low blood pressure group after initiation of sacubitril/valsartan. It was noteworthy that significant LV reverse remodeling was also observed in the low blood pressure group after initiation of sacubitril/valsartan (LV end-diastolic volume: 177.3 ± 66.0 mL vs. 137.7 ± 56.1 mL, P < 0.001, LV end-systolic volume: 131.6 ± 60.3 mL vs. 94.6 ± 55.7 mL, P < 0.001, LVEF: 26.8 ± 10.3% vs. 33.8 ± 13.6%, P = 0.015). Relative changes in LV volumes and LVEF after initiation of sacubitril/valsartan were similar for the two groups. In conclusion, significant LV reverse remodeling occurred after initiation of sacubitril/valsartan, even in HF patients with LVEF < 50% and systolic blood pressure ≤ 100 mmHg., (© 2023. Springer Nature Japan KK, part of Springer Nature.)

Patients with persistent heart failure (HF) with reduced ejection fraction (HFrEF) have a poorer prognosis than those with HF with improved ejection fraction (HFimpEF). However, data on the predictive value of echocardiographic parameters for persistent HFrEF are lacking. We retrospectively studied 443 patients who were diagnosed with HFrEF (EF ≤ 40%) during hospitalization and underwent echocardiography at the 1-year follow-up. We divided them into the 2 groups: HFimpEF (EF > 40%) and persistent HFrEF group at 1-year follow-up, and assessed the predictive value of echocardiographic parameters at discharge for persistent HFrEF. In total, 301/443 patients (68%) were diagnosed with persistent HFrEF and 142/443 (32%) with HFimpEF at the 1-year follow-up. Kaplan-Meier analysis revealed that the persistent HFrEF group had a poorer prognosis than the HFimpEF group (log-rank, P < 0.001). Receiver operating characteristic curve analysis revealed that left ventricular end-systolic diameter (LVESD) had the highest area under the curve (AUC) (0.70; 95% confidence interval [CI]: 0.64-0.75; cutoff value: 55 mm) among various echocardiographic parameters. LVESD was an independent predictor of persistent HFrEF at the 1-year follow-up (odds ratio: 1.07, 95%CI: 1.02-1.12) upon multivariable logistic regression analysis. The incidence of persistent HFrEF was higher in patients with an LVESD ≥ 55 mm than in those with an LVESD < 55 mm (81% versus 55%, Fisher's exact test, P < 0.001). In conclusion, an LVESD (≥ 55 mm) was associated with persistent HFrEF. Focusing on LVESD in daily practice may help clinicians with risk stratification for decision-making regarding management in patients with advanced HF refractory to guideline-directed medical therapy.

Functional mitral regurgitation (FMR) often coexists with atrial fibrillation (AF) and may have a causal relation with AF persistence and exacerbation of heart failure (HF). The purpose of this study was to investigate the impact of FMR on AF catheter ablation (AFCA) outcomes and improvement in FMR after AFCA in patients with HF with preserved ejection fraction (HFpEF) and nonparoxysmal AF. Excluding patients with primary valve disease or post-mitral valve repair, 280 patients with HFpEF who underwent CA for nonparoxysmal AF were retrospectively included. All patients completed 1-year follow-up and were assessed for FMR, AF recurrence and HF parameters, including echocardiography. At baseline, FMR was present in 153 (54.6%) patients (mild, n = 112; moderate, n = 40; severe, n = 1), and these were decreased to 70 (25%) significantly 1 year after AFCA (mild, n = 64; moderate, n = 6), 119 patients (78%) had improvement in MR (a decrease of ≥1 level in the severity from baseline to 1 year on echocardiography). Overall, 274 patients (97.9%) had sinus rhythm at the 1-year examination, and recurrent AF-free survival did not differ in patients with and without MR improvement (83.2% vs 82.4%, p = 0.908). However, the MR improvement group had a significantly lower cardiothoracic ratio, left atrial diameter, E/e', and B-type natriuretic peptide levels after 1 year than those in the MR nonimprovement group. In conclusion, the majority of the HFpEF patients with nonparoxysmal AF had improvement of FMR after AFCA with the high maintenance of sinus rhythm, leading to a virtuous cycle of cardiac function., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Less data are available regarding the impact of cardiac power output on exercise capacity or clinical outcome in patients with chronic heart failure (CHF). The study enrolled 280 consecutive patients with CHF referred for cardiopulmonary exercise testing and right-sided heart catheterization between 2013 and 2018. The primary outcome was composite of heart failure hospitalization or death. Cardiac power output was calculated as (mean arterial pressure × CO) ÷ 451. Patients with low cardiac power output (<0.53 W, n = 99) were older and had a higher brain natriuretic peptide level than patients with high cardiac power output (≥0.53W, n = 181). Cardiac power output was correlated with peak oxygen consumption (peak V̇O 2 ), peak workload achievement, and ventilatory efficiency (V̇ E /V̇CO 2 slope) in cardiopulmonary exercise testing, whereas each of cardiac output or mean arterial pressure was not. There were 48 patients with events over a median follow-up period of 3.5 (interquartile range 1.0 to 6.0) years. Patients with low cardiac power output had about a 2-fold higher risk of events than those with a high cardiac power output (hazard ratio 1.97, 95% confidence interval 1.12 to 3.48). In the multivariable Cox regression, a 0.1-W decrease in cardiac power output was associated with 19% increased adverse events (hazard ratio 0.81, 95% confidence interval 0.67 to 0.99). In conclusion, cardiac power output was associated with reduced exercise capacity and poor clinical outcome, suggesting that cardiac power output is useful for risk stratification in patients with CHF. Further study is required to identify therapies targeting cardiac power output to improve the exercise capacity or clinical outcome in patients with CHF., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

A 39-year-old man was admitted with acute heart failure due to severe aortic regurgitation induced by annuloaortic ectasia associated with Takayasu's arteritis. Because of the active inflammatory phase associated with Takayasu's arteritis, surgery is typically performed following immune suppression by steroid therapy. Herein, we report a favorable recovery in the active inflammatory phase. Steroid therapy was initiated shortly following surgery. The decision to perform aortic root replacement without prior steroid therapy was made because the patient's risk of subsequent heart failures was deemed high and was complicated by other comorbidities.

Several liver fibrotic markers are associated with prognosis in patients with heart failure (HF). However, the optimal markers for outcome prediction remain unclear. This study aimed to simultaneously investigate the prognostic value of liver fibrotic markers and the associations between these markers and clinical parameters in patients with HF without organic liver disease. We prospectively examined 211 consecutive patients with chronic HF between April 2018 and August 2021, excluding those with organic liver disease, using liver magnetic resonance imaging and ultrasound. A total of 7 representative liver fibrotic markers were measured in all patients. The primary outcome of interest was the composite of all-cause death and hospitalization for worsening HF. During a median follow-up period of 747 (interquartile range 465 to 1,042) days, the primary outcome occurred in 45 patients. Patients with higher hyaluronic acid and type III procollagen N-terminal peptide (P-III-P) levels showed a significantly higher incidence of the primary outcome than those without (p <0.001 and p = 0.005, respectively). The multivariable Cox regression analysis revealed that hyaluronic acid and P-III-P levels were independently associated with the risk of adverse events (hazard ratio 1.84, 95% confidence interval 1.18 to 2.87 and hazard ratio 2.89, 95% confidence interval 1.32 to 6.34, respectively) even after adjustment for a mortality prediction model, whereas the other 5 markers were not associated with the primary outcome. In conclusion, among the representative liver fibrotic markers, hyaluronic acid and P-III-P might be the optimal markers for outcome prediction in patients with HF., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The prognostic impact of peak workload-to-weight ratio (PWR) during cardiopulmonary exercise testing (CPET) and its determinants in patients with chronic heart failure (CHF) are not well understood. Consecutive 514 patients with CHF referred for CPET at the Hokkaido University Hospital between 2013 and 2018 were identified. The primary outcome was a composite of hospitalization because of worsening heart failure and death. PWR was calculated as peak workload normalized to body weight (W/kg) by CPET. Patients with low PWR (cut-off median 1.38 [W/kg], n = 257) were older and more anemic than those with high PWR (n = 257). In CPET, patients with low PWR displayed reduced peak oxygen consumption and impaired ventilatory efficiency compared with those with high PWR, whereas the peak respiratory exchange ratio was not significantly different between the 2 groups. There were 89 patients with events over a median follow-up period of 3.3 (interquartile range 0.8 to 5.5) years. The incidence of composite events was significantly higher in patients with low PWR than in those with high PWR (log-rank p <0.0001). In the multivariable Cox regression, lower PWR was associated with adverse events (hazard ratio 0.31, 95% confidence interval 0.13 to 0.73, p = 0.008). Low hemoglobin concentration was strongly related to impaired PWR (β coefficient = 0.43, per 1 g/100 ml increased, p <0.0001). In conclusion, PWR was associated with worse clinical outcomes, where blood hemoglobin was strongly related to PWR. Further study is required to identify therapies targeting peak workload achievements in exercise stress tests to improve the outcome in patients with CHF., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

A 64-year-old female without symptoms of heart failure was diagnosed with a two-chambered right ventricle (TCRV) during examination of a heart murmur and cardiac enlargement, for which surgery was performed. Under cardiopulmonary bypass and cardiac arrest, we first performed a right atrium and pulmonary artery incision and observed the right ventricle through the tricuspid and pulmonary valves, although we could not obtain a sufficient view of the right ventricular outflow tract. After subsequently incising the right ventricular outflow tract and the anomalous muscle bundle, the right ventricular outflow tract was patch-enlarged using a bovine cardiovascular membrane. After weaning from cardiopulmonary bypass, disappearance of the pressure gradient in the right ventricular outflow tract was confirmed. The patient's postoperative course was uneventful without any complications including arrhythmia.

Objectives: Evaluation of liver stiffness (LS) by magnetic resonance elastography (MRE) is useful for estimating right atrial pressure (RAP) in patients with heart failure (HF). However, its prognostic implications are unclear. We sought to investigate whether LS measured by MRE (LS-MRE) could predict clinical outcomes in patients with HF., Methods: We prospectively examined 207 consecutive HF patients between April 2018 and May 2021 after excluding those with organic liver disease. All patients underwent 3.0-T MRE. The primary outcome of interest was the composite of all-cause death and hospitalisation for HF., Results: During a median follow-up period of 720 (interquartile range [IQR] 434-1013) days, the primary outcome occurred in 44 patients (21%), including 15 (7%) all-cause deaths and 29 (14%) hospitalisations for HF. The patients were divided into two groups according to median LS-MRE of 2.54 (IQR 2.34-2.82) kPa. Patients with higher LS-MRE showed a higher incidence of the primary outcome compared to those with lower LS-MRE (p < 0.001). Multivariable Cox regression analyses revealed that LS-MRE value was independently associated with the risk of adverse events (hazard ratio 2.49, 95% confidence interval 1.46-4.24). In multivariable linear regression, RAP showed a stronger correlation with LS-MRE (β coefficient = 0.31, p < 0.001) compared to markers related to liver fibrosis., Conclusions: In patients without chronic liver disease and presenting with HF, elevated LS-MRE was independently associated with worse clinical outcomes. Elevated LS-MRE may be useful for risk stratification in patients with HF and without chronic liver disease., Key Points: • Magnetic resonance elastography (MRE) is an emerging non-invasive imaging technique for evaluating liver stiffness (LS) which can estimate right atrial pressure. • Elevated LS-MRE, which mainly reflects liver congestion, was independently associated with worse clinical outcomes in patients with heart failure. • The assessment of LS-MRE would be useful for stratifying the risk of adverse events in heart failure patients without chronic liver disease., (© 2022. The Author(s), under exclusive licence to European Society of Radiology.)

Although measuring right ventricular (RV) function during exercise is more informative than assessing it at rest, the relationship between RV reserve function, exercise capacity, and health-related quality of life (HRQoL) in patients with left ventricular assist devices (LVAD) remains unresolved. We aimed to investigate whether RV reserve assessed by the change in RV stroke work index (RVSWI) during exercise is correlated with exercise capacity and HRQoL in patients with LVAD. We prospectively assessed 24 consecutive patients with LVAD who underwent invasive right heart catheterization in the supine position. Exercise capacity and HRQoL were assessed using the 6-min walk distance (6 MWD) and peak oxygen consumption (V̇o 2 ) in cardiopulmonary exercise testing, and the EuroQol visual analog scale (EQ-VAS), respectively. The patients were divided into two groups according to the median ΔRVSWI (change from rest to peak exercise). Patients with lower ΔRVSWI had significantly lower changes in cardiac index and absolute value of RV dP/d t than those with higher ΔRVSWI. The ΔRVSWI was positively correlated with 6 MWD ( r = 0.59, P = 0.003) and peak V̇o 2 ( r = 0.56, P = 0.006). In addition, ΔRVSWI was positively correlated with the EQ-VAS ( r = 0.44, P = 0.030). In contrast, there was no significant correlation between RVSWI at rest and 6 MWD ( r = -0.34, P = 0.88), peak V̇o 2 ( r = 0.074, P = 0.74), or EQ-VAS ( r = 0.127, P = 0.56). Our findings suggest that the assessment of RV reserve function is useful for risk stratification in patients with LVAD. NEW & NOTEWORTHY The change in right ventricular stroke work index (RVSWI) during exercise, not RVSWI at rest, was associated with exercise capacity and HRQoL. Our findings suggest that the assessment of change in RVSWI during exercise as a surrogate of RV reserve function may aid in risk stratification of patients with LVAD.

A novel pump, the left atrial assist device (LAAD), is a device specifically for the treatment of heart failure with preserved ejection fraction (HFpEF). The LAAD is a mixed-flow pump that is implanted in the mitral position and delivers blood from the left atrium to the left ventricle. During the development process, we aimed to explore whether device activation in torque control (TC) mode would improve the function of the LAAD. The TC mode causes adjustment of the pump speed automatically during each cardiac cycle in order to maintain a specified torque. In this study, we tested four different TC settings (TC modes 0.9, 1.0, 1.25, and 1.5) using an in vitro mock circulatory loop. Mild, moderate, and severe diastolic heart failure (DHF) conditions, as well as normal heart condition, were simulated with the four TC modes. Also, we evaluated the LAAD in vivo with three calves. The LAAD was implanted at the mitral position with four TC settings (TC modes 0.9, 1.0, 1.1, 1.2). With LAAD support, the in vitro cardiac output and aortic pressure recovered to normal heart levels at TC 1.25 and 1.5 even under severe DHF conditions with little pump regurgitation. The TC mode tested in vivo with three calves, and it also showed favorable result without elevating the left ventricular end-diastolic pressure. These initial in vitro and in vivo results suggest that the TC mode could be potentially effective, and the LAAD could be a treatment option for HFpEF patients., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Few interventions have shown improved prognosis in patients with heart failure and preserved ejection fraction (HFpEF). Serum chloride levels, which are affected by serum renin secretion, are associated with the prognosis of HFpEF patients. However, the relationship between serum chloride levels and the effects of renin-angiotensin system inhibitors (RASi) in HFpEF patients remains unclear. We investigated whether the prognostic benefit of RASi depends on baseline serum chloride levels in HFpEF patients., Methods: This observational study included 506 hospitalized patients with HFpEF (ejection fraction ≥50%) who were discharged. They were divided into two categories based on serum chloride levels at admission (cutoff level: 101 mEq/L) according to previous reports. In each chloride category, all-cause mortality, the primary endpoint, was compared between patients who received RASi and those who did not., Results: Patients who received RASi had a significantly lower mortality rate after discharge than those who did not, but only in the lower chloride category (log-rank, P = 0.001). Multivariable Cox regression analysis confirmed the effect of risk reduction by RASi on all-cause mortality in the lower chloride category (adjusted hazard ratio: 0.31, 95% confidence interval: 0.11-0.84). The prognostic advantages of RASi were evident in the lower chloride category, but not in the higher chloride category, at admission (P for interaction = 0.027)., Conclusion: RASi administration was associated with an improved prognosis only in HFpEF patients with a low baseline serum chloride level. Clinicians should consider RASi administration if patients' serum chloride levels are low, to improve the long-term prognosis of HFpEF patients., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022. Published by Elsevier B.V.)

Background: Determinants of exercise intolerance in a phenotype of heart failure with preserved ejection fraction (HFpEF) with normal left ventricular (LV) structure have not been fully elucidated., Methods: Cardiopulmonary exercise testing and exercise-stress echocardiography were performed in 44 HFpEF patients without LV hypertrophy. Exercise capacity was determined by peak oxygen consumption (peak VO 2 ). Doppler-derived cardiac output (CO), transmitral E velocity, systolic (LV-s') and early diastolic mitral annular velocities (e'), systolic pulmonary artery (PA) pressure (SPAP), tricuspid annular plane systolic excursion (TAPSE), and peak systolic right ventricular (RV) free wall velocity (RV-s') were measured at rest and exercise. E/e' and TAPSE/SPAP were used as an LV filling pressure parameter and RV-PA coupling, respectively., Results: During exercise, CO, LV-s', RV-s', e', and SPAP were significantly increased (p < 0.05 for all), whereas E/e' remained unchanged and TAPSE/SPAP was significantly reduced (p < 0.001). SPAP was higher and TAPSE/SPAP was lower at peak exercise in patients showing lower-half peak VO 2 . In univariable analyses, LV-s' (R = 0.35, p = 0.022), SPAP (R = -0.40, p = 0.008), RV-s' (R = 0.47, p = 0.002), and TAPSE/SPAP (R = 0.42, p = 0.005) were significantly correlated with peak VO 2 . In multivariable analyses, not only SPAP, but also TAPSE/SPAP independently determined peak VO 2 even after the adjustment for clinically relevant parameters., Conclusions: In HFpEF patients without LV hypertrophy, altered RV-PA coupling by exercise could be associated with exercise intolerance, which might not be caused by elevated LV filling pressure., Competing Interests: Declaration of competing interest There is no conflict of interest to disclose relating to the present study., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Renin-angiotensin system inhibitor (RASi) and β-blocker provide prognostic benefits as guideline-directed medical therapy (GDMT) in patients with heart failure and reduced ejection fraction (HFrEF). However, there is limited data for the favorable effects in such patients receiving regular hemodialysis. We aimed to evaluate the prognostic impact of RASi and β-blocker in patients with HFrEF who receive regular hemodialysis., Methods: In this retrospective, single-center, observational study, from 2110 consecutive patients hospitalized for HF and who survived to discharge, 97 with HFrEF who received regular hemodialysis were included for analysis. They were classified into three groups according to prescribed medication at discharge following index hospitalization: both RASi and β-blocker (Dual-GDMT group: n = 55), either RASi or β-blocker (Mono-GDMT group: n = 34), and neither RASi nor β-blocker (No-GDMT group: n = 8). The primary endpoint was a composite of all-cause death and rehospitalization for heart failure., Results: The mean age was 66 years and 79% of the patients were men. During the median follow-up of 501 days, the primary endpoint occurred in 43 patients (44%). Kaplan-Meier analysis revealed that the Dual-GDMT group had the lowest rates of the primary endpoint (log-rank test for trend: p < 0.001). Even after adjustment for diverse covariates (multivariate Cox regression), the Dual-GDMT (hazard ratio [HR]: 0.04, 95% confidence interval (CI): 0.005-0.32) and Mono-GDMT (HR: 0.08, 95% CI: 0.01-0.50) groups had better prognoses than the No-GDMT group., Conclusions: The prescription of RASi and/or β-blocker was associated with a lower adverse-event rate after discharge in patients with HFrEF who were on regular hemodialysis., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: The left atrial assist device (LAAD) is a novel pump that was developed specifically for the treatment of heart failure with preserved ejection fraction. The device is surgically implanted in the mitral position. This study aimed to characterize the various device-fitting configurations in the mitral annular position., Methods: Rapidly prototyped LAAD models (n = 5) were fabricated with five different driveline configurations: (A) annulus level/intra-cuff running; (B) supra-cuff/below coronary sinus (CS); (C) infra-cuff; (D) supra-annulus/supra-CS; (E) left ventricular free wall level. The 3D-printed models were implanted in extracted fresh porcine hearts (80-100 kg, adult, healthy porcine) and the proximity of anatomical structures between the driveline and CS and coronary artery (CA) were measured., Results: All five device configurations were evaluated for fitting. For the purpose of preventing blood clot formation around the driveline, the mitral annulus (MA) as a driveline pass-way (configuration A) has been considered advantageous with the current device, in that the driveline exposure to blood has been avoided. The CS does not exist at exactly the same level as the MA, and there is less risk of injuring it than using the left atrial free wall. However, there is an inevitable risk of damaging the CA, so careful visual inspection before inserting the driveline is needed., Conclusions: Several options of driveline exteriorization were demonstrated, and the safety of each configuration was evaluated. Using the MA as a pathway for the driveline exit is considered to be a reasonable and safe method., (© 2022 The Authors. Artificial Organs published by International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

There is disparity between the sexes in cardiovascular diseases including heart failure (HF). This study aimed to investigate the effect of periodontal disease (PD) on plasma B-type natriuretic peptide (BNP) concentration across sex, age, and menopausal status, as well as the interaction effect of PD and diabetes mellitus (DM) on BNP. This large-scale prospective cohort study enrolled 7539 individuals with no myocardial infarctions or angina pectoris at baseline from the general Japanese population. The association between baseline number of missing teeth (MT) and the longitudinal changes in BNP over 5 years (ΔBNP) was evaluated according to sex and menopausal status. Among 7539 participants, 3190 were postmenopausal women with a mean age ± standard deviation of 61.1 ± 7.6 at baseline. Multivariate analysis revealed a positive association between MT and ΔBNP among postmenopausal women even after adjusting for covariates, including traditional HF risk factors (coefficient, 0.210; 95% confidence interval [CI], 0.107 to 0.312; P < 0.001), but not in men aged > 50. Including an interaction term (MT × DM) in the multivariate model revealed a positive interaction between MT and DM in ΔBNP among postmenopausal women (coefficient for interaction, 1.365; 95% CI, 0.902 to 1.827; P for interaction < 0.001). In conclusion, our study showed a positive association between MT and ΔBNP, as well as a positive effect of the interactive association between MT and DM, among postmenopausal women. Our results suggest a sex difference of an adverse effect of PD on initial myocardial wall stress in the ventricles., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Despite the advances in the left ventricular assist device (LVAD), there are still situations that require a biventricular assist device (BVAD) system. The purpose of this study was to explore and compare the system performance interactions with the HeartMate3 (HM3) and HeartWare (HVAD) in a BVAD configuration using the virtual mock loop (VML) simulation tool., Methods: The VML simulation tool is an in silico implementation of a lumped parameter model of the cardiovascular system with mechanical circulatory support. Patients with ejection fractions of 60%, 20%, and 15% were simulated in VML, and the HVAD and HM3 in a BVAD with ventricular cannulation were applied to simulated conditions. Pump speeds that restored baseline normal hemodynamics were determined. To determine the optimal speeds for BVAD, the left and right arterial pressures (LAP, RAP) were plotted., Results: In the HVAD, LAP and RAP are balanced at 11 mm Hg with LVAD 3500 rpm, right ventricular assist device (RVAD) 2200 rpm; at 13 mm Hg with LVAD 3000 rpm, RVAD 1700 rpm; and at 14 mm Hg with LVAD 2500 rpm, RVAD 1300 rpm. For the HM3, at 8 mm Hg with LVAD 7000 rpm, RVAD 5000 rpm; at 9 mm Hg with LVAD 6000 rpm, RVAD 4300 rpm; and at 9.5 mm Hg with LVAD 5000 rpm, RVAD 3500 rpm., Conclusion: The RVAD/LVAD speed ratios required for atrial balance were approximately 0.6 for the HVAD and 0.7 for the HM3. However, the HVAD required RVAD speeds below its range of operation., (© 2022 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Background: Under the revised heart allocation system in the United States, bridge to transplant (BTT) patients with left ventricular assist device (LVAD) have a longer waitlist period, as they are now lowly prioritized. However, little is known regarding the long-term trajectory of functional capacity (FC) and health-related quality of life (HR-QOL) among BTT-LVAD patients., Methods: We retrospectively analyzed 442 consecutive patients with BTT-LVAD between April 2013 and May 2019 from a Japanese nationwide registry. FC (New York Heart Association [NYHA] functional class, peak oxygen uptake [VO 2 ], and 6-min walk test [6MWT]) and HR-QOL (European Quality of Life [EQ-5D index] and Visual Analogue Scale [EQ-VAS]) were assessed at baseline and for up to 60 months after LVAD implantation., Results: During the follow-up period of 30 months (IQR 18-42 months), 100 (22.6%) patients underwent transplantation, 37 (8.3%) died, and 14 (3.1%) underwent explantation for recovery. Mean peak VO 2 , 6MWT distance, EQ-5D index, and EQ-VAS significantly improved 3 months after LVAD implantation (p = 0.0012, p = 0.0037, p < 0.001, p < 0.001, respectively). Furthermore, these improvements were sustained for up to 60 months following LVAD implantation. Major adverse events including device failure, infection, stroke, and bleeding, which occurred within the first 3 months after LVAD implantation may have not affected FC or HR-QOL for up to 60 months (p = 0.15, p = 0.22, respectively)., Conclusions: BTT patients showed long-term preservation of FC and HR-QOL, suggesting that BTT remains an option despite the long waiting time to HTx., (Copyright © 2022 Elsevier B.V. All rights reserved.)

There is limited data on whether diastolic dysfunction in patients with heart failure (HF) and recovered ejection fraction (HFrecEF) is associated with worse prognosis. We retrospectively assessed 96 patients diagnosed with HFrecEF and created ROC curve of their diastolic function at the 1-year follow-up for the composite endpoint of cardiovascular death and HF readmission after the follow-up. Eligible patients were divided into two groups according to the cutoff value of E/e' ratio (12.1) with the highest AUC (0.70). Kaplan-Meier analysis showed that HFrecEF with high E/e' group had a significantly poorer prognosis than the low E/e' group (log-rank, p = 0.01). Multivariate Cox regression analysis revealed that the high E/e' group was significantly related to the composite endpoint (hazard ratio 5.45, 95% confidence interval [CI] 1.23-24.1). The independent predictors at discharge for high E/e' ratio at the 1-year follow-up were older age and female sex after adjustment for covariates (odds ratio [OR] 1.07, 95% CI 1.01-1.13 and OR 4.70, 95% CI 1.08-20.5). In conclusion, HFrecEF with high E/e' ratio might be associated with a poor prognosis. Older age and female sex were independent predictors for a sustained high E/e' ratio in patients with HFrecEF., (© 2022. The Author(s).)

Background: We are developing a left atrial assist device (LAAD) that is implanted at the mitral position to treat diastolic heart failure (DHF) represented by heart failure with preserved ejection fraction., Methods: The LAAD was tested at 3 pump speeds on a pulsatile mock loop with a pneumatic pump that simulated DHF conditions by adjusting the diastolic drive. The LAAD was implanted in 6 calves, and the hemodynamics were assessed. In 3 cases, DHF conditions were induced by using a balloon inserted into the left ventricle, and in 2 cases, mitral valve replacement was also performed after the second aortic cross-clamp., Results: DHF conditions were successfully induced in the in vitro study. With LAAD support, cardiac output, aortic pressure and left atrial pressure recovered to normal values, whereas pulsatility was maintained for both in vivo and in vitro studies. Echocardiography showed no left ventricular outflow tract obstruction, and the LAAD was successfully replaced by a mechanical prosthetic valve., Conclusions: These initial in vitro and in vivo results support our hypothesis that use of the LAAD increases cardiac output and aortic pressure and decreases left atrial pressure, while maintaining arterial pulsatility., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: Constrictive pericarditis (CP) is a rare disease, and the diagnosis and surgical treatment of CP remain challenging. The aim of this study was to evaluate our Japanese single-center experience with isolated pericardiectomy for CP to elucidate the factors associated with improved outcomes., Methods: Over a 20-year period, 44 consecutive patients underwent isolated pericardiectomy at our institution. The cause of CP was: idiopathic (59%), postsurgical (32%), tuberculosis (7%), and postradiation (2%) of the patients. All patients were diagnosed with CP using multiple modalities, including echocardiography, cardiac catheterization, computed tomography, or magnetic resonance imaging (MRI). Median sternotomy was performed in 42 (95%) patients. Twenty-eight (68%) patients underwent radical pericardiectomy., Results: The postoperative diagnosis in all patients was CP. Among the multiple modalities, cardiac MRI had the greatest diagnostic sensitivity (97.2%). There were no operative or hospital deaths; late mortality occurred in seven (15.9%) patients in the series. Multivariable analysis showed that preoperative low LVEF was a risk factor for long-term mortality. Seven patients were readmitted for heart failure postoperatively. Multivariable analysis showed incomplete pericardiectomy and use of a preoperative inotrope were risk factors for readmission for heart failure., Conclusions: The diagnosis using multimodality imaging for CP was effective in our institution and tagged cine MRI had the greatest sensitivity in diagnosing CP. Preoperative condition, including preoperative low LVEF or inotrope use, was correlated with long-term outcome after pericardiectomy. Pericardiectomy should be performed early and as radically as possible to prevent recurrent heart failure., (© 2022. The Author(s), under exclusive licence to The Japanese Association for Thoracic Surgery.)

Background: Autophagy is a cellular process that degrades a cell's own cytoplasmic components for energy provision and to maintain a proper intracellular environment. Left ventricular reverse remodeling (LVRR) promises a better prognosis for patients with dilated cardiomyopathy (DCM)., Objectives: The authors tested the hypothesis that autophagy is involved in LVRR and has prognostic value in the human failing heart., Methods: Using left ventricular endomyocardial biopsy specimens from 42 patients with DCM (21 LVRR-positive and 21 LVRR-negative) and 7 patients with normal cardiac function (control), the authors performed immunohistochemistry and immunofluorescent labeling of LC3 and cathepsin D and electron microscopic observation in addition to general morphometry under light microscopy., Results: The clinical characteristics of LVRR-positive patients were similar to those of the LVRR-negative patients, except for pulmonary artery pressure and left atrial dimension. Morphometry under light microscopy did not differ among specimens from DCM patients, regardless of their LVRR status. Electron microscopy revealed that autophagic vacuoles (autophagosomes and autolysosomes) and lysosomes were abundant within cardiomyocytes from DCM patients. Moreover, cardiomyocytes from LVRR-positive patients contained significantly more autophagic vacuoles with higher autolysosome ratios and cathepsin D expression levels than cardiomyocytes from LVRR-negative patients. Logistic regression analysis adjusted for age showed that increases in autophagic vacuole number and cathepsin D expression were predictive of LVRR. DCM patients who achieved LVRR experienced fewer cardiovascular events during the follow-up period., Conclusions: The authors show that autophagy is a useful marker predictive of LVRR in DCM patients. This provides novel pathologic insight into a strategy for treating the failing DCM heart., Competing Interests: Funding Support and Author Disclosures This study was supported in part by JSPS KAKENHI grant no. JP21K08077 from the Japan Society for the Promotion of Science and a research grant from Gifu University School of Medicine. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Heart failure with preserved ejection fraction (HFpEF) is characterized by diastolic dysfunction and multiple comorbidities. The number of patients is continuously increasing, with no improvement in its unfavorable prognosis, and there is a strong need for novel treatments. New devices and drugs are difficult to assess at the translational preclinical step due to the lack of high-fidelity large animal models of HFpEF. In this review, we describe the summary of historical and evolving techniques for developing large animal models. The representative methods are pressure overload models, including (1) aortic banding, (2) aortic stent, (3) renal hypertension, and (4) mineralocorticoid-induced hypertension. Diet-induced metabolic syndromes are also used. A new technique with an inflatable balloon inside the left ventricle can be used during acute/chronic in vivo surgeries to simulate HFpEF-like hemodynamics for pump-based therapies. Canines and porcine are most widely used, but other non-rodent animals (sheep, non-human primates, felines, or calves) have been used. Feline models present the most well-simulated HFpEF pathology, but small size is a concern, and the information is still very limited. The rapid and reliable establishment of large animal models for HFpEF, and novel methodology based on the past experimental attempts with large animals, are needed., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: G protein-coupled receptors (GPCRs) regulate the pathological and physiological functions of the heart. GPCR antagonists are widely used in the treatment of chronic heart failure. Despite therapeutic advances in the treatments for cardiovascular diseases, heart failure is a major clinical health problem, with significant mortality and morbidity. Corticotropin releasing hormone receptor 2 (CRHR2) is highly expressed in cardiomyocytes, and cardiomyocyte-specific deletion of the genes encoding CRHR2 suppresses pressure overload-induced cardiac dysfunction. This suggests that the negative modulation of CRHR2 may prevent the progression of heart failure. However, there are no systemic drugs against CRHR2., Findings: We developed a novel, oral, small molecule antagonist of CRHR2, RQ-00490721, to investigate the inhibition of CRHR2 as a potential therapeutic approach for the treatment of heart failure. In vitro, RQ-00490721 decreased CRHR2 agonist-induced 3', 5'-cyclic adenosine monophosphate (cAMP) production. In vivo, RQ-00490721 showed sufficient oral absorption and better distribution to peripheral organs than to the central nervous system. Oral administration of RQ-00490721 inhibited the CRHR2 agonist-induced phosphorylation of cAMP-response element binding protein (CREB) in the heart, which regulates a transcription activator involved in heart failure. RQ-00490721 administration was not found to affect basal heart function in mice but protected them from pressure overload-induced cardiac dysfunction., Interpretation: Our results suggest that RQ-00490721 is a promising agent for use in the treatment of chronic heart failure., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Aims: Little is known about the long-term outcomes of β-blockers use in patients with coronary artery disease (CAD) without myocardial infarction (MI) and reduced ejection fraction (rEF). However, more attention should be paid to the oral administration of β-blockers in elderly patients who are susceptible to heart failure (HF), sinus node dysfunction, or rate response insufficiency. We aimed to evaluate the long-term impact of β-blockers in elderly patients with CAD without MI or systolic HF who have undergone percutaneous coronary intervention., Methods and Results: A total of 1018 consecutive elderly patients with CAD (mean age, 72 ± 7 years; 77% men) who underwent their first intervention between 2010 and 2018 were included in this study. According to the presence or absence of the use of β-blockers, 514 patients (50.5%) were allocated to the β-blocker group, and 504 (49.5%) to the non-β-blocker group. We evaluated the incidence of 4-point major adverse cardiovascular events (4P-MACE), including cardiovascular death, non-fatal MI, non-fatal stroke, admission for HF, target vessel revascularization (TVR), and all-cause death. We focused on the association between chronotropic incompetence of β-blockers and incidence of a new HF and analysed the results using an exercise electrocardiogram regularly performed in the outpatient department after percutaneous coronary intervention. During a median follow-up duration of 5.1 years, 83 patients (8.3%) developed 4P-MACE, including cardiovascular death in 17, non-fatal MI in 13, non-fatal stroke in 25, and admission for HF in 39 patients. Additionally, 124 patients (12.2%) had a TVR and 104 (10.2%) died of other causes. Kaplan-Meier analysis showed that the cumulative incidence rate of 4P-MACE in the β-blocker group was significantly higher than that in the non-β-blocker group (15.4% vs. 10.0%, log-rank test, P = 0.015). Above all, the cumulative incidence rate of admission for HF in the β-blocker group was significantly higher (8.8% vs. 3.2%, log-rank test, P < 0.001). The β-blocker group had significantly lower resting heart rate, stress heart rate, and stress-rest Δ heart rate on exercise electrocardiogram. Multivariate Cox hazard analysis revealed that EF, β-blocker use, stress-rest Δ heart rate, and CKD were strong independent predictors of admission for HF., Conclusions: Long-term β-blocker use was significantly associated with an increased risk of adverse cardiovascular events in elderly patients with CAD without MI or systolic HF. In particular, the chronotropic incompetence action of β-blockers could increase the risk of admission for HF in elderly patients with CAD without MI and systolic HF, and the present findings warrant further investigation., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Objectives: Stroke is a substantial complication of left ventricular assist device (LVAD) implantation. The relationship between stroke and the anatomical position of the inflow cannula of patients who underwent LVAD implantation was investigated., Methods: We enrolled 15 patients with advanced-stage heart failure who underwent implantation of continuous-flow-LVAD. Data of patients who suffered a stroke within 6 months after LVAD implantation were retrospectively compared to those who remained free of stroke. The distance between the inflow duct and left ventricular (LV) septum (duct-sep distance) and its ratio to LV diastolic diameter (LVDd) were measured from echocardiography at 1 month after LVAD implantation. Receiver operating characteristic curves for the endpoint of stroke using the duct-sep distance to LVDd ratio was created and the cut-off value was calculated. The incidence of stroke during the 6 months after LVAD implantation according to this ratio was estimated using the Kaplan-Meier method., Results: At 1 month after LVAD implantation, there were no significant differences in baseline characteristics and echocardiography parameters between the stroke and stroke-free groups. Receiver operating characteristic curve analysis for the endpoint of stroke using the duct-sep distance to LVDd ratio revealed 0.217 as a cut-off value (sensitivity: 80%, specificity: 80%, area under the curve: 0.72). Stroke was more frequent in patients with a duct-sep distance to LVDd ratio ⩾0.217 at 1 month than in those with a lower ratio., Conclusion: The duct-sep distance to LVDd ratio was associated with the occurrence of stroke, suggesting that inflow cannula position influences the incidence of stroke.

Syndecan-1 is found in the endothelial glycocalyx and is released into the bloodstream during stressed conditions, including severe diseases such as acute kidney injury, chronic kidney disease, and cardiovascular disease. This study investigated the prognostic value of serum syndecan-1 concentration in patients with heart failure upon admission. Serum syndecan-1 concentration was analyzed in 152 patients who were hospitalized for worsening heart failure from September 2017 to June 2018. The primary outcome of the study was readmission-free survival, defined as the time from the first admission to readmission for worsened heart failure or death from any cause, which was assessed at 30 months after discharge from the hospital. The secondary outcome of the study was survival time. Blood samples and echocardiogram data were analyzed. Univariate and multivariable time-dependent Cox regression analyses adjusted for age, creatinine levels, and use of antibiotics were conducted. The serum syndecan-1 concentration was significantly associated with readmission-free survival. Subsequently, the syndecan-1 concentration may have gradually decreased with treatment. The administration of human atrial natriuretic peptide and antibiotics may have modified the relationship between readmission-free survival and serum syndecan-1 concentration (p = 0.01 and 0.008, respectively). Serum syndecan-1 concentrations, which may indicate injury to the endothelial glycocalyx, predict readmission-free survival in patients with heart failure., Competing Interests: The authors declare no conflict of interest relevant to the content of this manuscript.

Aims: The CONtrolling NUTritional status (CONUT) score represents the nutritional status of patients with heart failure (HF). Although high CONUT scores on admission are associated with increased risks of cardiovascular (CV) events in patients with HF, the impact of CONUT changes during hospitalization on their long-term prognosis is unclear. This study aimed to investigate the impact of CONUT score changes on the clinical outcomes of patients with HF after discharge., Methods and Results: This observational study included 1705 patients hospitalized with HF who were discharged alive. The patients were categorized depending on their CONUT scores at admission and discharge into persistently high, high at admission and normal at discharge, normal at admission and high at discharge, and persistently normal CONUT groups. The primary endpoint was a composite of CV death and readmission for HF after discharge. The primary endpoint occurred in 652 patients (38%) during the median 525 day follow-up period. Patients with persistently high CONUT scores had the highest composite endpoint rate (log-rank trend test: P < 0.001). After adjusting for covariates, the hazard ratio for the composite outcome was significantly lower for the patients with high CONUT scores at admission and normal CONUT scores at discharge than that for those with persistently high CONUT scores (hazard ratio: 0.69; 95% confidence interval: 0.49-0.98)., Conclusions: Nutritional status changes in patients with HF that occurred during hospitalization were associated with CV events after discharge. Improving the nutritional status of patients may improve their clinical outcomes., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Background: Diagnosing heart failure with preserved ejection fraction (HFpEF) is challenging. Although the H 2 FPEF score and HFA-PEFF algorithm have been proposed for diagnosing HFpEF, previous validation studies were conducted in stable chronic heart failure (HF). Moreover, information on their applicability in the Asian population is limited. We sought to investigate these scores' diagnostic performance for HFpEF in Japanese patients recently hospitalized due to acute decompensated HF., Methods: We examined patients with HFpEF recently hospitalized with acute decompensated HF from a nationwide HFpEF-specific multicenter registry (HFpEF group) and control patients who underwent echocardiography to investigate the cause of dyspnea in our hospital (Non-HFpEF group)., Results: The studied population included 372 patients (194 HFpEF group and 178 Non-HFpEF group; HFpEF prevalence, 52%). A high H 2 FPEF score (6-9 points) could diagnose HFpEF with a high specificity of 97% and a positive predictive value (PPV) of 94%, and a low H 2 FPEF score (0-1 point) could rule out HFpEF with a high sensitivity of 97% and a negative predictive value (NPV) of 93%. HFpEF could be diagnosed with a high HFA-PEFF score (5-6 points) (specificity, 84%; PPV, 82%) or ruled out with a low HFA-PEFF score (0-1 point) (sensitivity, 99%; NPV, 89%). The H 2 FPEF score was significantly superior to the HFA-PEFF score in diagnostic accuracy (area under the curve: 0.89 vs. 0.82, respectively, p = 0.004)., Conclusions: The H 2 FPEF and the HFA-PEFF scores had acceptable diagnostic accuracy in diagnosing HFpEF in Japanese patients., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: There are a lot of reports of the renal failure and heart failure due to coarctation of the aorta. However, there are no case reports in which revascularization dramatically improved left ventricular function in patients with progressive decline in left ventricular function. Herein, we present a rare case in which the left ventricular function was dramatically improved by surgical treatment for progressive left ventricular dysfunction due to atypical coarctation of the aorta., Case Presentation: A 58-year-old man underwent left axillary artery-bilateral femoral artery bypass at another hospital for atypical coarctation of the aorta due to Takayasu's arteritis. Approximately 10 years later, he was re-hospitalized for heart failure, and the left ventricular ejection fraction gradually decreased to 28%. Computed tomography showed severe calcification and stenosis at the same site from the peripheral thoracic descending aorta to the lower abdominal aorta of the renal artery, and aortography showed delayed bilateral renal artery blood flow. An increase in plasma renin activity was also observed. Despite the administration of multiple antihypertensive drugs, blood pressure control was insufficient. We decided to perform surgical treatment to improve progressive cardiac dysfunction due to increased afterload and activated plasma renin activity. Descending thoracic aorta-abdominal aorta bypass and revascularization of the bilateral renal arteries via the great saphenous vein grafts were performed. Postoperative blood pressure control was improved, and the dose of antihypertensive drugs could be reduced. Plasma renin activity decreased, and transthoracic echocardiography 1.5 years later showed an improvement in contractility with a left ventricular ejection fraction of 58%., Conclusion: In atypical coarctation of the aorta in patients with decreased bilateral renal blood flow, heart failure due to renal hypertension, and progressive decrease in left ventricular contractility, descending thoracic aorta-abdominal aortic bypass and bilateral renal artery recirculation can be extremely effective., (© 2021. The Author(s).)

Heart failure with preserved ejection fraction (HFpEF) is a syndrome with an unfavorable prognosis, and the number of the patients continues to grow. Because there is no effective therapy established as a standard, including pharmacological treatments, a movement to develop and evaluate device-based therapies is an important emerging area in the treatment of HFpEF patients. Many devices have set their target to reduce the left atrial pressure or pulmonary capillary wedge pressure because they are strongly related to the symptoms and prognosis of HFpEF, but the methodology to achieve it varies based on the devices. In this review, we summarize and categorize these devices into the following: (1) interatrial shunt devices, (2) left ventricle expander, (3) electrical therapy, (4) left ventricular assist devices, and (5) mechanical circulatory support devices under development. Here, we describe the features and specifications of device-based therapies currently under development and those at more advanced stages of preclinical testing. Advantages and limitations of these technologies, with insights on their safety and feasibility for HFpEF patients, are described.

We are developing a new left atrial assist device (LAAD) for patients who have heart failure with preserved ejection fraction (HFpEF). This study aimed to assess the hemodynamic effects of the LAAD under both normal heart conditions and various diastolic heart failure (DHF) conditions using a mock circulatory loop. A continuous-flow pump that simulates LAAD, was placed between the left atrial (LA) reservoir and a pneumatic ventricle that simulated a native left ventricle on a pulsatile mock loop. Normal heart (NH) and mild, moderate, and severe DHF conditions were simulated by adjusting the diastolic drive pressures of the pneumatic ventricle. With the LAAD running at 3200 rpm, data were collected at 60, 80, and 120 bpm of the pneumatic ventricle. Cardiac output (CO), mean aortic pressure (AoP), and mean LA pressure (LAP) were compared to evaluate the LAAD performance. With LAAD support, the CO and AoP rose to a sufficient level at all heart rates and DHF conditions (CO; 3.4-3.8 L/min, AoP; 90-105 mm Hg). Each difference in the CO and the AoP among various heart rates was minuscule compared with non-pump support. The LAP decreased from 21-23 to 17-19 mm Hg in all DHF conditions (difference not significant). Furthermore, hemodynamic parameters improved for all DHF conditions, independent of heart rate. The LAAD can provide adequate flow to maintain the circulation status at various heart rates in an in vitro mock circulatory loop.

Objectives: Many patients with heart failure have preserved ejection fraction but also diastolic dysfunction, with no effective therapy. We are developing a new pump (left atrial assist device, LAAD) for implantation at the mitral position to pump blood from the left atrium to sufficiently fill the left ventricle. The purpose of the initial in vitro study was to demonstrate that the LAAD can reduce left atrial pressure (LAP) and increase cardiac output (CO) while maintaining arterial pulsatility and normal aortic valve function using a proof-of-concept device., Methods: The LAAD concept was tested at 3 pump speeds on a pulsatile mock loop with a pneumatic pump that simulated the normal function of the native ventricle as well as 3 levels of diastolic heart failure (DHF 1, 2, and 3) by adjusting the diastolic drive pressure to limit diastolic filling of the ventricle., Results: Without the LAAD, CO and aortic pressure (AoP) decreased dramatically from 3.8 L/min and 100 mm Hg at normal heart condition to 1.2 L/min and 35 mm Hg at DHF 3, respectively. With LAAD support, both CO and AoP recovered to normal heart values at 3200 rpm and surpassed normal heart values at 3800 rpm. Furthermore, with LAAD support, LAP recovered to almost that of the normal heart condition at 3800 rpm., Conclusions: These initial in vitro results support our hypothesis that use of the LAAD increases CO and AoP and decreases LAP under DHF conditions while maintaining arterial pulsatility and full function of the aortic valve., (Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

L-carnitine (LC) supplementation improves cardiac function in hemodialysis (HD) patients. However, whether reducing LC supplementation affects carnitine kinetics and cardiac function in HD patients treated with LC remains unclear. Fifty-nine HD patients previously treated with intravenous LC 1000 mg per HD session (three times weekly) were allocated to three groups: LC injection three times weekly, once weekly, and placebo, and prospectively followed up for six months. Carnitine fractions were assessed by enzyme cycling methods. Plasma and red blood cell (RBC) acylcarnitines were profiled using tandem mass spectrometry. Cardiac function was evaluated using echocardiography and plasma B-type natriuretic peptide (BNP) levels. Reducing LC administration to once weekly significantly decreased plasma carnitine fractions and RBC-free carnitine levels during the study period, which were further decreased in the placebo group ( p < 0.001). Plasma BNP levels were significantly elevated in the placebo group ( p = 0.03). Furthermore, changes in RBC (C16 + C18:1)/C2 acylcarnitine ratio were positively correlated with changes in plasma BNP levels (β = 0.389, p = 0.005). Reducing LC administration for six months significantly decreased both plasma and RBC carnitine levels, while the full termination of LC increased plasma BNP levels; however, it did not influence cardiac function in HD patients.

We are developing a left atrial assist device (LAAD) to pump blood from the left atrium to the left ventricle for patients who have heart failure with preserved ejection fraction (HFpEF). This study aimed to assess the hemodynamics with the LAAD implanted at two different levels: the mitral valve (MV) level, after removing the MV; and the supravalvular level, preserving MV function conditions using an in vitro mock circulatory loop. Normal heart and mild, moderate, and severe diastolic heart failure conditions were simulated, and the LAAD was set at three different speeds. Without the LAAD support, cardiac output (CO) decreased from 3.7 to 1.1 L/min, aortic pressure (AoP) decreased from 100 to 33 mm Hg, and left atrial pressure (LAP) increased from 16 to 23 mm Hg as the diastolic function became impaired. With high pump support after removing the MV, CO and AoP readings were comparable with those for preserved MV function (CO reached 3.9-4.1 L/min, AoP reached more than 110 mm Hg, and LAP dropped to 16-17 mm Hg under both conditions at high pump speeds). In the mock circulatory loop, our LAAD appeared to have sufficient ability to maintain the hemodynamic status at both positions., Competing Interests: Disclosure: K.F., D.J.H., J.H.K., and R.C.S. are co-inventors of the LAAD. The other authors have no conflicts of interest to report., (Copyright © ASAIO 2020.)

Background: Delirium is a common adverse event observed in patients admitted to the intensive care unit (ICU). However, the prognostic value of delirium and its determinants have not been thoroughly investigated in patients with acute heart failure (AHF)., Methods: We investigated 408 consecutive patients with AHF admitted to the ICU. Delirium was diagnosed by means of the Confusion Assessment Method for ICU tool and evaluated every 8 hours during the patients' ICU stays., Results: Delirium occurred in 109 patients (26.7%), and the in-hospital mortality rate was significantly higher in patients with delirium (13.8% vs 2.3%; P < 0.001). Multivariate logistic regression analysis showed that delirium independently predicted in-hospital mortality (odds ratio [OR] 4.33, confidence interval [CI] 1.62-11.52; P = 0.003). Kaplan-Meier analysis showed that the 12-month mortality rate was significantly higher in patients with delirium compared with those without (log-rank test: P < 0.001), and Cox proportional hazards analysis showed that delirium remained an independent predictor of 12-month mortality (hazard ratio 2.19, 95% CI 1.49-3.25; P < 0.001). The incidence of delirium correlated with severity of heart failure as assessed by means of the Get With The Guidelines-Heart Failure risk score (chi-square test: P = 0.003). Age (OR 1.05, 95% CI 1.02-1.09; P = 0.003), nursing home residential status (OR 3.32, 95% CI 1.59-6.94; P = 0.001), and dementia (OR 5.32, 95% CI 2.83-10.00; P < 0.001) were independently associated with the development of delirium., Conclusions: Development of delirium during ICU stay is associated with short- and long-term mortality and is predicted by the severity of heart failure, nursing home residential, and dementia status., (Copyright © 2020 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

An advanced ventricular assist device (VAD), which is under development in our institution, has specific features that allow changes in the axial rotor position and pump performance by intrapump pressure difference. However, performance could be influenced by the pump orientation because of the effect of gravity on the rotor position. The purpose of this study was to evaluate the effects of pump orientation on the pump performance, including pulse pressure and regurgitant flow through the pump when the pump was stopped. Bench testing of the VAD was performed on a static or pulsatile mock loop with a pneumatic device to simulate the native ventricle. The pump performance, including pressure-flow curve, pulsatility, and regurgitant flow, was evaluated at several angles, ranging from -90° (inlet pointed upward) to +90° (inlet pointed downward) at pump speeds of 2000, 2500, 3000, and 3500 rpm. The pump performance was slightly lower at +90° at all rotational speeds, compared with -90°. The pulse pressure on the pulsatile mock loop (80 bpm) was 50 mm Hg without pump support, remained at 50 mm Hg during pump support, and was not changed by orientation (-90°, 0°, and +90°). When the pump was stopped, the regurgitant flow was near 0 L/min at all angles. Pump orientation had a minor effect on pump performance, with no effect on pulse pressure or regurgitant flow when the pump was stopped. This indicates that the effect of gravity on the rotor assembly is insignificant., (© 2020 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

We are developing a novel type of miniaturized left ventricular assist device that is configured for transapical insertion. The aim of this study was to assess the performance and function of a new pump by using a Virtual Mock Loop system for device characterization and mapping. The results, such as pressure-flow performance curves, from pump testing in a physical mock circulatory loop were used to analyze its function as a left ventricular assist device. The Virtual Mock Loop system was programmed to mimic the normal heart condition, systolic heart failure, diastolic heart failure, and both systolic and diastolic heart failure, and to provide hemodynamic pressure values before and after the activation of several left ventricular assist device pump speeds (12,000, 14,000, and 16,000 r/min). With pump support, systemic flow and mean aortic pressure increased, and mean left atrial pressure and pulmonary artery pressure decreased for all heart conditions. Regarding high pump-speed support, the systemic flow, aortic pressure, left atrial pressure, and pulmonary artery pressure returned to the level of the normal heart condition. Based on the test results from the Virtual Mock Loop system, the new left ventricular assist device for transapical insertion may be able to ease the symptoms of patients with various types of heart failure. The Virtual Mock Loop system could be helpful to assess pump performance before in vitro bench testing.

Epirubicin-based chemotherapy carries a risk of inducing heart failure, although the frequency is rare. Bevacizumab, an anti-vascular endothelial growth factor monoclonal antibody, has recently been widely used in patients with recurrent breast cancer as a first-line chemotherapeutic agent. Heart failure or arterial thromboembolism has been reported as a rare cardiovascular complication of bevacizumab. We herein report a breast cancer patient with reversible cancer therapeutics-related cardiac dysfunction associated with bevacizumab and epirubicin complicating intracardiac thrombi in the left atrium and left ventricle. This case underscores the importance of tailored medical planning according to the individual status in patients receiving anti-cancer therapies.

Biventricular assist device (BVAD) implantation is the treatment of choice in patients with severe biventricular heart failure and cardiogenic shock. Our team has developed a miniaturized continuous flow, double-ended centrifugal pump intended for total artificial heart implant (CFTAH). The purpose of this initial in vivo study was to demonstrate that the scaled-down CFTAH (P-CFTAH) can be appropriate for BVAD support. The P-CFTAH was implanted in 4 acute lambs (average weight, 41.5 ± 2.8 kg) through a median sternotomy. The cannulation was performed through the left and right atria, and cannulae length adjustment was performed for atrial and ventricular cannulation. The BVAD system was tested at 3 pump speeds (3000, 4500, and 6000 rpm). The BVAD performed very well for both atrial and ventricular cannulation within the 3000-6000 rpm range. Stable hemodynamics were maintained after implantation of the P-CFTAH. The self-regulating performance of the system in vivo was demonstrated by the left (LAP) and right (RAP) pressure difference (LAP-RAP) falling predominantly within the range of -5 to 10 mm Hg with variation, in addition to in vitro assessment of left and right heart failure conditions. Left and right pump flows and total flow increased as the BVAD speed was increased. This initial in vivo testing of the BVAD system demonstrated satisfactory device performance and self-regulation for biventricular heart failure support over a wide range of conditions. The BVAD system keeps the atrial pressure difference within bounds and maintains acceptable cardiac output over a wide range of hemodynamic conditions., (Copyright © 2020 Elsevier Inc. All rights reserved.)

This study aimed to evaluate a newly designed circulatory mock loop intended to model cardiac and circulatory hemodynamics for mechanical circulatory support device testing. The mock loop was built with dedicated ports suitable for attaching assist devices in various configurations. This biventricular mock loop uses two pneumatic pumps (Abiomed AB5000 ™ , Danvers, MA, USA) driven by a dual-output driver (Thoratec Model 2600, Pleasanton, CA, USA). The drive pressures can be individually modified to simulate a healthy heart and left and/or right heart failure conditions, and variable compliance and fluid volume allow for additional customization. The loop output for a healthy heart was tested at 4.2 L/min with left and right atrial pressures of 1 and 5 mm Hg, respectively; a mean aortic pressure of 93 mm Hg; and pulmonary artery pressure of 17 mm Hg. Under conditions of left heart failure, these values were reduced to 2.1 L/min output, left atrial pressure = 28 mm Hg, right atrial pressure = 3 mm Hg, aortic pressure = 58 mm Hg, and pulmonary artery pressure = 35 mm Hg. Right heart failure resulted in the reverse balance: left atrial pressure = 0 mm Hg, right atrial pressure = 30 mm Hg, aortic pressure = 100 mm Hg, and pulmonary artery pressure = 13 mm Hg with a flow of 3.9 L/min. For biventricular heart failure, flow was decreased to 1.6 L/min, left atrial pressure = 13 mm Hg, right atrial pressure = 13 mm Hg, aortic pressure = 52 mm Hg, and pulmonary artery pressure = 18 mm Hg. This mock loop could become a reliable bench tool to simulate a range of heart failure conditions.

We have created a simulation model to investigate the interactions between a variety of mechanical circulatory support (MCS) devices and the circulatory system with various simulated patient conditions and disease states. The present simulation accommodates a family of continuous-flow MCS devices under various stages of consideration or development at our institution. This article describes the mathematical core of the in silico simulation system and shows examples of simulation output imitating various disease states and of selected in vitro and clinical data from the literature.

Background: The safety and efficacy of angiotensin converting enzyme inhibition (ACEI) after heart transplantation (HT) is unknown. This study examined long-term clinical outcomes after ACEI in HT recipients., Methods: The ACEI after HT study was a prospective, randomized trial that tested the efficacy of ACEI with ramipril after HT. In this study, long-term clinical outcomes were assessed in 91 patients randomized to either ramipril or placebo (median, 5.8 years). The primary endpoint was a composite of death, retransplantation, hospitalization for rejection or heart failure, and coronary revascularization., Results: The primary endpoint occurred in 10 of 45 patients (22.2%) in the ramipril group and in 14 of 46 patients (30.4%) in the placebo group (Hazard ratio (HR), 0.68; 95% CI, 0.29-1.51; P = .34). When the analysis was restricted to comparing patients who remained on a renin-angiotensin system inhibitor beyond 1 year with those who did not, there was a trend to improved outcomes (HR, 0.54; 95% CI, 0.22-1.28, P = .16). There was no significant difference in creatinine, blood urea nitrogen, and potassium at 3 years after randomization. The cumulative incidence of the primary endpoint was significantly higher in patients in whom the index of microcirculatory resistance increased from baseline to 1 year compared with those in whom it did not (39.1 vs 17.4%, HR: 3.36; 95% CI, 1.07-12.7; P = .037)., Conclusion: The use of ramipril after HT safely lowers blood pressure and is associated with favorable long-term clinical outcomes. Clinical Trial Registration-URL: https://www.clinicaltrials.gov. Unique identifier: NCT01078363., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Elevated serum uric acid (UA) is associated with an increased risk of cardiovascular disease and worse clinical outcome in patients with cardiovascular disease. Nevertheless, the prognostic value of serum UA level in hospitalized heart failure patients with preserved ejection fraction (HFpEF) has not been fully elucidated. The aim of this study was to investigate whether serum UA level on admission could be associated with subsequent mortality in hospitalized patients with HFpEF. We examined 516 consecutive hospitalized HFpEF (left ventricular ejection fraction ≥50%) patients with decompensated heart failure from our HFpEF-specific multicenter registry who had serum UA data on admission. The primary outcome of interest was all-cause death. During a median follow-up period of 749 (interquartile range 540 to 831) days, 90 (17%) patients died. Higher serum UA level was significantly related to increased incidence of all-cause death (p = 0.016). In addition, patients with higher serum UA (≥6.6 mg/dl, median) and plasma B-type natriuretic peptide (≥401.2 pg/ml, median) levels had the highest incidence of all-cause death in the groups (p = 0.002). In multivariable Cox regression analysis, serum UA was an independent determinant of mortality (hazards ratio 1.23, 95% confidence interval 1.10 to 1.39) even after adjustment for prespecified confounders, renal function and the use of diuretics before admission. In conclusions, higher admission serum UA was an independent determinant of mortality in hospitalized HFpEF patients. Our findings indicate the importance of assessing admission serum UA level for further risk stratification in hospitalized patients with HFpEF., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Aims: The prognostic implication of left ventricular outflow tract velocity time integral (LVOT-VTI) on admission in hospitalized heart failure with preserved ejection fraction (HFpEF) patients has not been determined. We sought to investigate whether LVOT-VTI on admission is associated with worse clinical outcomes in hospitalized patients with HFpEF., Methods and Results: We studied consecutive 214 hospitalized HFpEF patients who had accessible LVOT-VTI data on admission, from a prospective HFpEF-specific multicentre registry. The primary outcome of interest was the composite of all-cause death and readmission due to heart failure. During a median follow-up period of 688 (interquartile range 162-810) days, the primary outcome occurred in 83 patients (39%). The optimal cut-off value of LVOT-VTI for the primary outcome estimated by receiver operating characteristic analysis was 15.8 cm. Lower LVOT-VTI was significantly associated with the primary outcome compared with higher LVOT-VTI (P = 0.005). Multivariable Cox regression analyses revealed that lower LVOT-VTI was an independent determinant of the primary outcome (hazard ratio 0.94, 95% confidence interval 0.91-0.98). In multivariable linear regression, haemoglobin level was the strongest independent determinant of LVOT-VTI among clinical parameters (β coefficient = -0.61, P = 0.007). Furthermore, patients with lower LVOT-VTI and anaemia had the worst clinical outcomes among the groups (P < 0.001)., Conclusions: Lower admission LVOT-VTI was an independent determinant of worse clinical outcomes in hospitalized HFpEF patients, indicating that LVOT-VTI on admission might be useful for categorizing a low-flow HFpEF phenotype and risk stratification in hospitalized HFpEF patients., (© 2019 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)