Rationale and Design of a Multicenter Trial on Exploratory Analysis of the Effects of Advance Care Planning Guided by the Prediction Program of Heart Failure Prognosis on Quality of Life in Patients With Heart Failure　- ACQUAINT-Trial.

Background: Preplanning of care is necessary for patients with endstage heart failure (HF), but advance care planning (ACP) before the loss of a patient's comprehensive capacity is not yet routine for the public or the medical community. The challenge in accurately predicting a patient's prognosis is a strong barrier to implementing ACP. To address this problem, several models for risk stratification have been proposed and are available in clinical settings. Methods and Results: We randomized the procedure to provide estimated patient survival information to attending physicians and then assessed whether there was a change in (1) the frequency of ACP initiation occurred (physician-side evaluation), and/or (2) the patients' quality of life, including mental state (patient-side evaluation). Conclusions: This multicenter, open-label, single-blinded randomized clinical trial aims to assess the hypothesis that providing information on the estimated survival of a patient to the attending physicians will improve the frequency of ACP initiation and quality of life in patients with HF.

The interface between ice and alcohols analyzed by atomic force microscopy.

This study investigates the interface between ice and organic solvents using atomic force microscopy (AFM). Atomically flat ice surfaces were prepared and observed by AFM in 1-octanol, 1-hexanol, and 1-butanol. The results show differences in surface roughness influenced by the interaction of ice and alcohols. Young's modulus of ice was analyzed by force curve measurements, providing valuable insights into the properties of ice in liquid environments. The results showed the characteristics of the ice surface in different solvents, suggesting potential applications in understanding surface and interface phenomena associated with ice under realistic conditions.

Preoperative higher right ventricular stroke work index increases the risk of de novo aortic insufficiency after continuous-flow left ventricular assist device implantation.

During continuous-flow left ventricular assist device (CF-LVAD) support, hemodynamic shear stress causes a burden on aortic valve (AV) leaflets, leading to de novo aortic insufficiency (AI). This study investigated the influence of preoperative hemodynamic parameters on de novo AI in CF-LVAD recipients. We reviewed 125 patients who underwent CF-LVAD implantation without concomitant AV surgery between 2005 and 2018. De novo AI was defined as moderate or severe AI in those with none or trivial preoperative AI. During mean 30 ± 16 months of CF-LVAD support, de novo AI-free rate was 86% and 67% at 1 and 2 years, respectively. Multivariable analysis showed that higher right ventricular stroke work index (RVSWI) (hazard ratio, 1.12 /g/m2/beat; 95% confidence interval, 1.00-1.20; p = 0.047) and trivial grade AI (hazard ratio, 2.8; 95% confidence interval, 1.2-6.4; p = 0.020) were independent preoperative risk factors for de novo AI. The longitudinal analysis using generalized mixed effects model showed that higher RVSWI was associated with continuous AV closure after LVAD implantation (Odd ratio, 1.20/g/m2/beat; 95% confidence interval, 1.00-1.43 /g/m2/beat; p = 0.047). Right heart catheterization revealed that preoperative RVSWI was positively correlated with postoperative pump flow index in patients with continuously closed AV (r = 0.44, p = 0.04, n = 22). Preoperative higher RVSWI was a significant risk factor for de novo AI following CF-LVAD implantation. In patients with preserved right ventricular function, postoperative higher pump flow may affect AI development via hemodynamic stress on the AV.

End-stage Hypertrophic Cardiomyopathy with Advanced Heart Failure in Patients Carrying MYH7 R453 Variants: A Case Series.

The MYH7 R453 variant has been identified in inherited hypertrophic cardiomyopathy (HCM) and is associated with sudden death and a poor prognosis. The detailed clinical course of HCM with the MYH7 R453 variant, from a preserved to a reduced left ventricular ejection fraction, has not been reported. We identified the MYH7 R453C and R453H variants in three patients who progressively developed advanced heart failure requiring circulatory support and summarized the clinical course and echocardiographic parameters of these patients over the years. Because of the rapid disease progression, we consider genetic screening for patients with HCM imperative for future prognosis stratification.

Less Invasive Left Ventricular Unloading With Impella May Improve the Clinical Outcomes of Fulminant Myocarditis.

Fulminant myocarditis (FM) requiring temporary mechanical circulatory support (t-MCS) has a high mortality rate. Peripheral veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and intra-aortic balloon pump (IABP) are sometimes insufficient to induce cardiac recovery. For patients with FM refractory to VA-ECMO with IABP, we have applied a biventricular assist device (BIVAD) or Impella to unload the left ventricle and to fully support the systemic circulation. In the last 10 years, 37 refractory FM patients histologically diagnosed with myocarditis and who did not recover with VA-ECMO were treated with BIVAD (n = 19) or Impella (n = 18). No significant difference was found between the Impella and BIVAD groups in preoperative findings other than serum creatinine level. Seventeen of 18 patients in the Impella group were successfully weaned from t-MCS in 9 (6-12) days. Conversely, the temporary BIVAD was removed in 21 (11-38) days in 10 of 19 patients. Six patients died while on temporary BIVAD because of multiple organ failure and cerebral bleeding, and three patients required conversion to implantable VAD. Compared with BIVAD, left ventricular unloading with Impella could be less invasive and could promote cardiac recovery in refractory FM patients. The Impella has the potential to provide effective temporary MCS for FM patients.

Pathophysiological evaluations of initial plaque development after heart transplantation via serial multimodality imaging and cytokine assessments.

BACKGROUND: Detailed morphological characteristics of de novo and donor-transmitted plaques and the association of serum T-lymphocyte cytokine levels with plaque progression of coronary allograft vasculopathy within 1 year after heart transplantation are unknown. METHODS: In this retrospective analysis of data in a prospectively maintained database, 40 heart transplant recipients were included. We performed serial 3 vessel optical coherence tomography and intravascular ultrasound analyses, at the 8 week (baseline) and 12 month post-transplantation follow-ups, and serum cytokine measurements (n = 23). The correlation between serum cytokines and Δplaque burden (between baseline and follow-up) was evaluated depending on plaque morphology. RESULTS: Thirteen de novo plaques (maximum intimal thickness ≥0.5 mm at the 12 month follow-up without plaques at baseline) were identified in 8 recipients, and 31 donor-transmitted plaques (maximum intimal thickness ≥0.5 mm at baseline) were detected in 17 recipients. Compared with donor-transmitted plaques, the Δplaque burden in the de novo plaques, with mainly fibrous morphology, was high (38.8% [29.6%-41.2%] vs 8.7% [1.33%-13.6%], p < 0.001). Stratification of the morphology of donor-transmitted plaques revealed that the Δplaque burden in fibrous plaques (10.6% [7.0%-18.0%]) was similar to that in fibroatheroma (10.3% [8.7%-23.8%]). Serum interleukin-31 levels at baseline correlated with fibrous plaque proliferation (r = 0.73, p = 0.007) even under immunosuppressive conditions, whereas other cytokines (interleukin-1ß, interleukin-17, and interferon-gamma) were mostly undetectable. CONCLUSIONS: Intimal fibrous proliferation contributed to the progression of donor-transmitted and de novo plaques. Serum interleukin-31 levels at baseline may contribute to intimal fibrous proliferation within 1 year after heart transplantation.

Impella 5.0 support as a bridge to the exchange of an infected left ventricular assist device.

A pump infection is a fatal complication specific to left ventricular assist devices. Infection recurrence is a major concern when device exchange is indicated for pump infection. In the present case, we used the Impella 5.0 to maintain proper hemodynamics and to treat the infection in the absence of an implantable device. We demonstrate that the Impella 5.0 can serve as an effective bridge for device exchange by controlling infection and minimizing organ dysfunction, despite prolonged management.

Early Detection of Worsening Heart Failure in Patients at Home Using a New Telemonitoring System of Respiratory Stability.

BACKGROUND: Early detection of worsening heart failure (HF) with a telemonitoring system crucially depends on monitoring parameters. The present study aimed to examine whether a serial follow up of all-night respiratory stability time (RST) built into a telemonitoring system could faithfully reflect ongoing deterioration in HF patients at home and detect early signs of worsening HF in a multicenter, prospective study.Methods and Results: Seventeen subjects with New York Heart Association class II or III were followed up for a mean of 9 months using a newly developed telemonitoring system equipped with non-attached sensor technologies and automatic RST analysis. Signals from the home sensor were transferred to a cloud server, where all-night RSTs were calculated every morning and traced by the monitoring center. During the follow up, 9 episodes of admission due to worsening HF and 1 episode of sudden death were preceded by progressive declines of RST. The receiver operating characteristic curve demonstrated that the progressive or sustained reduction of RST below 20 s during 28 days before hospital admission achieved the highest sensitivity of 90.0% and specificity of 81.7% to subsequent hospitalization, with an area under the curve of 0.85. CONCLUSIONS: RST could serve as a sensitive and specific indicator of worsening HF and allow the detection of an early sign of clinical deterioration in the telemedical management of HF.

Renoprotection by long-term low-dose tolvaptan in patients with heart failure and hyponatremia.

AIMS: In previous randomized controlled trials, the use of tolvaptan (TLV) at a fixed dose of 30 mg/day for 1 year did not provide renal benefits in patients with heart failure (HF). This retrospective, cohort study examined the renoprotective effects of long-term, flexible-dose, and lower-dose TLV use. METHODS AND RESULTS: Tolvaptan users were defined as patients receiving TLV for at least 180 consecutive days or those who continued it until death, any cardiac events, or renal replacement therapy even if it was taken for <180 days. Of a total of 584 HF patients, 78 TLV users were identified. The median age, baseline B-type natriuretic peptide, and estimated glomerular filtration rate (eGFR) were 71 years, 243 pg/mL, and 54 mL/min/1.73 m2 , respectively. During follow-up (median, 461 days), TLV use (median average dose, 7.5 mg/day) was associated with frequent dose reductions of loop diuretics (incidence rate ratio [IRR], 1.5; 95% confidence interval [CI], 1.1-2.2), particularly in patients with serum sodium ≤135 mEq/L (IRR, 2.9; 95% CI, 1.5-5.7) (Pinteraction  = 0.04). In a mixed effects model, propensity score (PS)-matched TLV users had higher eGFRs over time than PS-matched never-users (P < 0.01). The entire cohort analyses (N = 584) yielded similar results. The renal benefit of TLV in terms of annualized eGFR slope was more pronounced in patients with lower sodium levels (Pinteraction  = 0.03). This effect modification was extinguished when patients who underwent a loop diuretic dose reduction during the follow-up period were excluded from the analysis. CONCLUSIONS: Long-term, flexible-dose, and low-dose TLV use was associated with better renal function, particularly in hyponatremic HF, possibly due to its loop diuretic dose-sparing effect in the long term.

Variability in estimated glomerular filtration rate and patients' outcomes in a real-world heart failure population.

AIMS: The prognostic significance of renal function variability has not been fully elucidated in heart failure (HF). This multicentre, prospective cohort study aimed to evaluate the usefulness of visit-to-visit variability in estimated glomerular filtration rate (eGFR) for predicting patients' outcomes in a real-world HF population. METHODS: A total of 564 patients who had survived HF hospitalization were randomly assigned with a 2:1 ratio to derivation and validation cohorts, and they were then followed after discharge. Using the data for 6 months after discharge, each patient's visit-to-visit eGFR variability (EGV) was estimated. In the derivation cohort, Cox regression analyses were performed to assess the association of EGV with a subsequent composite event (death and HF hospitalization). In the validation cohort, the predictive performance was compared among Cox regression models with EGV, those with B-type natriuretic peptide (BNP) and those with eGFR. RESULTS: In the derivation cohort (376 patients), median age, left ventricular ejection fraction (LVEF), BNP and eGFR at discharge were 72 years, 53.3%, 134.8 pg/mL and 58.7 mL/min/1.73 m2 , respectively. During a median follow-up of 2.2 years, higher EGV was associated with an increased risk of the composite event (adjusted hazard ratio [per standard deviation increase in log-transformed EGV], 1.5; 95% confidence interval, 1.1-2.0). A similar finding was observed in a stratified analysis by LVEF. In the validation cohort (188 patients), better model fit, discrimination, reclassification and calibration were observed for EGV than for 6-month averaged BNP or eGFR for predicting the composite event when added to HF risk prediction models. Adding EGV to models with BNP or eGFR improved model discrimination and reclassification. CONCLUSIONS: EGV predicts HF outcomes regardless of LVEF. Risk prediction models with EGV have good performance in real-world HF patients. The study findings highlight the clinical importance of observing visit-to-visit fluctuations in renal function in this population.

Focal severe decrease in myocardial technetium-99 m sestamibi uptake indicates ventricular irreversibility in patients with dilated cardiomyopathy.

OBJECTIVE: Technetium-99 m sestamibi (99mTc-MIBI) scintigraphy can identify non-viable left ventricular (LV) myocardium. However, the optimal cut-off value and the details of decreased 99mTc-MIBI uptake of the non-viable LV myocardium in patients with dilated cardiomyopathy (DCM) have not been well established. This study aimed to evaluate the decrease in 99mTc-MIBI uptake in each segment and in the whole LV myocardium, and to determine cut-off values for identifying non-viable LV myocardium in DCM patients. METHODS: Overall, 53 DCM patients with reduced LV ejection fraction (LVEF ≤ 40%) who underwent 99mTc-MIBI scintigraphy and any optimization of heart failure treatments were evaluated. LV myocardium was classified as viable or non-viable based on the absolute increase in LVEF of ≥ 10% unit leading to an LVEF of > 40% at follow-up, respectively. The decrease in myocardial 99mTc-MIBI uptake in each of the 17 segments was evaluated using three indices determined by different thresholds or standard references: segmental %uptake, rest score, and defect extent. Changes in the whole LV myocardium were evaluated by the minimum %uptake, and the summed rest score (SRS) and extent of LV defect were obtained using summed data of 17 segments. RESULTS: Segmental evaluation indicated a mild decrease in 99mTc-MIBI uptake in 18 patients with viable LV myocardium, whereas focal severe decrease in uptake was observed in patients with non-viable LV myocardium. In the receiver-operating characteristic curve analysis, the cut-off values of minimum %uptake, SRS, and LV defect extent for predicting non-viable LV were 39% (p < 0.01, area under the curve [AUC]: 0.87), 10 (p < 0.01, AUC: 0.91), and 23% (p < 0.01, AUC: 0.92), respectively. CONCLUSIONS: In DCM patients, myocardial 99mTc-MIBI %uptake of < 40% indicated non-viable myocardium. The focal and severe decrease in uptake in approximately more than a quarter of the LV myocardium may indicate non-viable LV.

Impella Support as a Bridge to Surgery for Severe Mitral Regurgitation With Cardiogenic Shock.

Background: Cardiogenic shock due to acute severe mitral regurgitation is characterized by multiple organ failure and acute pulmonary edema, leading to a high risk of mortality. Methods and Results: We report on a patient with acute, severe mitral regurgitation complicated by cardiogenic shock, refractory to both inotrope treatment and intra-aortic balloon pump support. The patient was successfully bridged to surgery with an Impella CP, a percutaneous left ventricular assist device. Conclusions: Mechanical support using an Impella CP can stabilize hemodynamics and may be used as a bridge to elective surgery for patients with mitral regurgitation with cardiogenic shock.

Feasibility of home-based cardiac rehabilitation using an integrated telerehabilitation platform in elderly patients with heart failure: A pilot study.

BACKGROUND: Cardiac rehabilitation (CR) is a widely recommended evidence-based intervention for patients with cardiovascular disease. However, the participation rate in CR has been reported to be low globally, mainly due to barriers in access to the CR center. We evaluated the feasibility and safety of a new remote real-time monitoring system for supervising home-based CR among elderly patients with heart failure (HF). METHODS: Hospitalized patients or outpatients followed for HF were enrolled. Patients received 12-week home-based CR under remote supervision using an integrated platform for telerehabilitation. Feasibility was evaluated by the participation and completion rates of the home-based CR sessions. Safety was assessed by adverse events during the sessions. All patients underwent baseline and 12-week assessment of exercise tolerance and lower extremity muscle strength. RESULTS: All 10 patients (mean age 76 ± 7 years; 60% male) who participated in the study completed the program without withdrawal during the study period. Median participation rate in the exercise sessions was 94.4% (interquartile range: 88.9-97.9%). While fatigue, common cold, and palpitation were observed, no serious cardiovascular events were reported. Six-minute walk distance significantly improved from 383 ± 94 m to 432 ± 83 m (p=0.003). CONCLUSIONS: Home-based CR under real-time supervision was feasible and safe among elderly HF patients. Our study suggests that home-based CR using an integrated telerehabilitation platform may be a potential option for patients who are unable to participate in center-based CR due to geographic or social accessibility and physical barrier issues.

Long-term outcomes of autologous skeletal myoblast cell-sheet transplantation for end-stage ischemic cardiomyopathy.

We evaluated the cardiac function recovery following skeletal myoblast cell-sheet transplantation and the long-term outcomes after applying this treatment in 23 patients with ischemic cardiomyopathy. We defined patients as "responders" when their left ventricular ejection fraction remained unchanged or improved at 6 months after treatment. At 6 months, 16 (69.6%) patients were defined as responders, and the average increase in left ventricular ejection fraction was 4.9%. The responders achieved greater improvement degrees in left ventricular and hemodynamic function parameters, and they presented improved exercise capacity. During the follow-up period (56 ± 28 months), there were four deaths and the overall 5-year survival rate was 95%. Although the responders showed higher freedom from mortality and/or heart failure admission (5-year, 81% versus 0%; p = 0.0002), both groups presented an excellent 5-year survival rate (5-year, 93% versus 100%; p = 0.297) that was higher than that predicted using the Seattle Heart Failure Model. The stepwise logistic regression analysis showed that the preoperative estimated glomerular filtration rate and the left ventricular end-systolic volume index were independently associated with the recovery progress. Approximately 70% of patients with "no-option" ischemic cardiomyopathy responded well to the cell-sheet transplantation. Preoperative renal and left ventricular function might predict the patients' response to this treatment.

Total percutaneous biventricular assist device implantation for fulminant myocarditis.

We report an effective therapeutic approach of mechanical circulatory support for a patient with cardiogenic shock and respiratory insufficiency due to fulminant myocarditis. An Impella® 5.0 was utilized as a left ventricular assist device (VAD) and percutaneous veno-pulmonary extracorporeal membrane oxygenation (ECMO) as a right VAD. These devices were implanted without sternotomy or thoracotomy. Although a combination of Impella and veno-arterial ECMO has been reported as percutaneous biventricular support, there are concerns that this combination is not beneficial for myocardial recovery in patients with respiratory insufficiency, because Impella expels insufficiently oxygenated blood from the left ventricle to the coronary arteries. Our approach took advantage of percutaneous implantation of ECMO and temporary VAD, eliminating the drawbacks of both devices, thus providing a more effective and less invasive form of temporary biventricular support.

A Case of Lymphocytic Myocarditis with Eosinophilic Degranulation Successfully Treated with Steroid Therapy.

A 49-year-old woman was admitted with suspicion of acute myocarditis. On the next day after admission, her serum troponin I level continued to rise, indicating progression of myocardial damage. Moreover, her symptoms persisted, and left ventricular ejection fraction did not improve. Because of a predominant infiltration of lymphocytes in the myocardial specimens, lymphocytic myocarditis was diagnosed. However, a close observation of the specimens revealed eosinophil degranulation. Based on this finding, intravenous steroid therapy was initiated. High-dose methylprednisolone led to rapid and appreciable improvements in symptoms and left ventricular function within 12 hours after the first administration, which was followed by normalization of serum troponin I level. Steroid therapy was switched to oral administration and tapered carefully. There was no recurrence of left ventricular dysfunction or elevation of serum troponin I level. In eosinophilic myocarditis, eosinophil degranulation has been recognized as an important finding associated with progression of inflammation and myocardial damage. However, no attention has been paid to the presence and clinical implications of eosinophil degranulation in lymphocytic myocarditis. This case indicates that eosinophil degranulation in lymphocytic myocarditis may be an important finding associated with a high therapeutic response to steroid therapy.

Recovery From Exhaustion of the Frank-Starling Mechanism by Mechanical Unloading With a Continuous-Flow Ventricular Assist Device.

BACKGROUND: We describe our original left ventricular assist device (LVAD) speed ramp and volume loading test designed to evaluate native heart function under continuous-flow LVAD support.Methods and Results:LVAD speed was decreased in 4 stages from the patient's optimal speed to the minimum setting for each device. Under minimal LVAD support, patients were subjected to saline loading (body weight [kg]×10 mL in 15 min). Echocardiographic and hemodynamic data were obtained at each stage of the LVAD speed ramp and every 3 min during saline loading. Patients were divided into Recovery (with successful LVAD removal; n=8) and Non-recovery (others; n=31) groups. During testing, increased pulmonary capillary wedge pressure caused by volume loading was milder in the Recovery than Non-recovery group (repeated measures analysis of variance; group effect, P=0.0069; time effect, P<0.0001; interaction effect, P=0.0173). Increased cardiac output from volume loading was significantly higher in the Recovery than Non-recovery group (group effect, P=0.0124; time effect, P<0.0001; interaction effect, P=0.0091). Therefore, the Frank-Starling curve of the Recovery group was located upward and to the left of that of the Non-recovery group. CONCLUSIONS: The LVAD speed ramp and volume loading test facilitates the precise evaluation of native heart function during continuous-flow LVAD support.

Jarvik 2000 with postauricular cable as destination therapy: first clinical case in Japan.

Currently in Japan, a left ventricular assist device powered by an abdominal driveline is the only type of left ventricular assist device available. The driveline is vulnerable to infection secondary to inappropriate fixation and the traditional Japanese custom of bathing is prohibited in patients with an abdominal driveline. The Jarvik 2000 with postauricular cable is a left ventricular assist device in which the driveline exits the body behind the ear (postauricular) instead of exiting through an abdominal site. This case report is the first to describe the implantation of Jarvik 2000 with postauricular cable as destination therapy in a Japanese patient. This device enables patients to take a bath and may reduce the incidence of driveline infection.