Alkali-treated titanium dioxide promotes formation of proteoglycan layer and altered calcification and immunotolerance capacity in bone marrow stem cell.

Introduction: In this study, we report that a proteoglycans (PGs)-layer between the bone and titanium dioxide (TiO2) surface after osseointegration improved the calcification capacity and immunotolerance of human bone marrow mesenchymal stem cells (hBMSCs) on TiO2. Alkaline treatment of TiO2 is a method for promoting osteogenesis in hBMSCs. We hypothesized that promotion of osteogenesis due to alkaline treatment was caused by changing PGs-layer on TiO2. Objective: This study aimed to analyze whether alkaline treatment of TiO2 affects PGs-layer formation and immunotolerance in hBMSCs. Methods: The topology and wettability of the alkaline-treated titanium (Ti-Al) and unprocessed titanium (Ti-MS) surfaces were characterized. Initial cell attachment, cell proliferation, calcification capacity, alkaline phosphatase activity, PGs-layer formation, PGs function, and the expression of osteogenic and immunotolerance-related genes were analyzed. The conditioned medium (CM) from hBMSCs grown on Ti-Al and Ti-MS was added to macrophages (hMps) and Jurkat cells, and immunotolerance gene expression in these cells was analyzed. Results: hBMSCs cultured on Ti-Al showed increased initial cell attachment, cell proliferation, PG-layer formation, and osteogenic capacity compared with hBMSCs on Ti-MS. Gene expression of indoleamine 2,3-dioxygenase (IDO) in the hBMSCs cultured on Ti-Al was higher than that in the hBMSCs on Ti-MS. CM from hBMSCs did not affect markers of M1 and M2 macrophages in hMps. CM from hBMSCs cultured on Ti-Al altered the gene expression of Foxp3 in Jurkat cells compared to that of CM from hBMSCs on Ti-MS. Significance: These results suggest that alkaline treatment of TiO2 altered PGs-layer formation, and changed the osteogenesis and immunotolerance of hBMSCs.

Pulmonary Vascular Reverse Remodeling After Left Ventricular Assist Device Implantation in Patients With Pulmonary Hypertension.

Prevalence of combined pre- and post-capillary (Cpc) pulmonary hypertension (PH) in patients with PH due to left heart disease (PH-LHD) and the long-term impact of left ventricular assist device (LVAD) implantation in patients with Cpc-PH are not fully elucidated. Eighty-nine patients with PH-LHD who underwent LVAD implantation were retrospectively analyzed. Patients were divided into two groups according to their preoperative pulmonary vascular resistance (PVR) and diastolic pressure gradient (DPG) values (Cpc-PH group, PVR >3 wood units [WU], or DPG ≥7 mmHg; isolated postcapillary [Ipc]-PH group, PVR ≤3 WU, and DPG <7 mmHg). There were 50 patients with Cpc-PH (PVR >3 WU [group A, n = 41]; PVR >3 WU and DPG ≥7 mmHg [group B, n = 8]; DPG ≥7 mmHg [group C, n = 1]), and 39 patients with Ipc-PH. Despite a successful LVAD implantation in all participants, 13 and two patients remained in groups A and B, respectively, early after LVAD implantation, whereas two patients each remained in groups A and B 1 year postoperatively. Values of PVR and DPG in the Cpc-PH group returned to normal levels by 3 years postoperatively. Over 50% of patients with PH-LHD had Cpc-PH, and PVR and DPG normalized in all participants within 3 years after LVAD implantation.

Impact of sleep-disordered breathing on ventricular tachyarrhythmias after left ventricular assist device implantation.

Sleep-disordered breathing (SDB) is associated with an increased risk of adverse events in patients with heart failure (HF); however, its impact in patients implanted with a left ventricular assist device (LVAD) remains unclear. We aimed to investigate the prevalence of SDB in patients with LVAD and its impact on their clinical outcomes. Fifty consecutive patients with LVAD who underwent portable sleep monitoring between September 2017 and April 2018 were prospectively enrolled, and they were followed up for 170 ± 36 days. According to their respiratory disturbance indexes (RDIs), they were categorized into the SDB group (RDI ≥ 15, n = 12) and the non-SDB group (RDI < 15, n = 38). The incidence of adverse events during the follow-up period was investigated after enrollment. Multivariate logistic regression analysis revealed significant differences in SDB in LVAD-implanted patients in terms of the logarithmic transformation brain natriuretic peptide (BNP) values (p = 0.005). The optimal BNP cut-off value for SDB prediction in LVAD-implanted patients was 300 pg/mL (sensitivity: 58.3%, specificity: 94.7%). During follow-up, ventricular tachyarrhythmias (VTas) occurred significantly more frequently in the SDB group (4 [33%] vs. 2 [5%] patients, p = 0.02); Atrial tachyarrhythmia (ATa) also tended to occur more frequently in the SDB group (2 [25%] vs. 2 [2%] patients, p = 0.07). SBD was prevalent in 24% of the LVAD-implanted patients with advanced HF. Furthermore, SDB was significantly associated with high BNP levels and was also potentially associated with subsequent incidence of VTa in patients with LVAD.

Implantation of ventricular assist devices in hypertrophic cardiomyopathy with left ventricular systolic dysfunction.

AIMS: The outcomes of patients with hypertrophic cardiomyopathy with left ventricular systolic dysfunction (HCM-LVSD) undergoing left ventricular assist device (LVAD) implantation remain unclear. We retrospectively evaluated the clinical impact of LVAD implantation on clinical outcomes, including haemodynamics and brain natriuretic peptide (BNP) levels, in patients with HCM-LVSD, in comparison with those with dilated cardiomyopathy (DCM). METHODS AND RESULTS: In this retrospective, single-centre, observational study conducted in Japan, the medical records of patients who underwent LVAD implantation in the National Cerebral and Cardiovascular Center between 2011 and 2020 were reviewed. We enrolled 96 patients with DCM (average age: 43.5 years; 73 men) and 24 patients with HCM-LVSD (average age: 48.3 years; 16 men). The HCM-LVSD group had smaller left ventricles with thicker ventricular walls than the DCM group, which became more prominent after LVAD implantation. Preoperatively, BNP values were comparable between both groups; however, 3 months post-implantation, they were significantly higher in the HCM-LVSD group. Pulmonary artery pulsatility index, right ventricular stroke work index, and cardiac index were lower, and right atrial pressure was higher, in the HCM-LVSD group, suggesting subclinical impairment of right ventricular function. The HCM-LVSD group demonstrated equivalent outcomes, including overall survival, cerebrovascular accidents, right ventricular failure, LVAD-related infections, arrhythmia, and aortic insufficiency, post-implantation. CONCLUSIONS: Despite a decreased right ventricular function with higher BNP values, patients with HCM-LVSD and DCM showed comparable outcomes post-LVAD implantation.

Efficacy of central extracorporeal life support for patients with fulminant myocarditis and cardiogenic shock.

OBJECTIVES: Fulminant myocarditis with cardiogenic shock requires extracorporeal life support (ECLS) and has poor outcomes. To improve outcomes, we have converted patients with severely impaired cardiac and multiorgan function from peripheral to central ECLS. In this study, we reviewed these patients' clinical outcomes and investigated associated factors. METHODS: We retrospectively studied 70 consecutive patients with fulminant myocarditis under peripheral support from 2006 to 2020. Forty-eight patients underwent surgical conversion to central support, and the remaining patients continued peripheral support. The end point was survival and ventricular assist device-free survival. RESULTS: More severe pulmonary congestion and multiorgan failure were present in patients with central than peripheral support. Weaning from ECLS was achieved in 95% and 62% of patients with peripheral and central support, respectively. Five-year survival was not significantly different between patients with central and peripheral support (71.2% vs 87.5%, respectively; P = 0.15). However, the ventricular assist device-free survival rate was significantly higher in patients with central than peripheral support (82.2% vs 52.0%, respectively; P = 0.017). A peak creatine kinase-MB level of >180 IU/l, rhythm disturbance and aortic valve closure were detrimental to functional recovery in patients with central support. CONCLUSIONS: Conversion to central ECLS is feasible and safe in patients with fulminant myocarditis. Patients with severe myocardial injury as shown by a high creatine kinase-MB level, rhythm disturbance and aortic valve closure should be converted to a durable left ventricular assist device.

The Predictive Value of Changes in Body Mass Index for the Incidence of Device-Specific Infections in Patients With Implantable Left Ventricular Assist Devices.

BACKGROUND: Implantable left ventricular assist devices (LVAD) have improved quality of life and survival in patients with advanced heart failure. However, LVAD-specific infections and predicting which patients will develop infections remain challenging. This study investigated whether changes in body mass index (BMI) during hospitalization following LVAD implantation are associated with LVAD-specific infections within 1 year of implantation.Methods and Results:Patients (n=135) undergoing LVAD implantation were retrospectively divided into 2 groups based on changes in BMI from LVAD implantation to discharge: those with and without decreases in BMI. Each group was further subdivided according to baseline albumin concentrations (high [>3.7 g/dL] and low [≤3.7 g/dL]). Twenty patients developed LVAD-specific infections within 1 year. Receiver operating characteristic curve analysis resulted in a ∆BMI cut-off of less than -0.128 kg/m2. In multivariate analysis, younger patients and those with decreases in BMI had significantly higher rates of LVAD-specific infection (P=0.010 and P=0.035, respectively). LVAD-specific infection rates were significantly higher for patients with low albumin and decreases in BMI than for patients with low albumin but no decrease in BMI. CONCLUSIONS: Decreases in BMI during hospitalization after LVAD implantation and younger age were independently associated with LVAD-specific infection within 1 year. Strict patient management may be needed to avoid decreases in BMI during hospitalization after LVAD implantation, particularly in patients with low baseline albumin concentrations.

Clinical potential of hemodynamic ramp test by simultaneous echocardiography and right heart catheterization for aortic insufficiency in a patient with continuous-flow left ventricular assist device.

Aortic insufficiency (AI) is an important adverse event in patients with continuous-flow (CF) left ventricular assist device (LVAD) support. AI is often progressive, resulting in elevated 2-year morbidity and mortality. The effectiveness of echocardiographic ramp studies in patients with AI has been unclear. Here, we describe a patient with a CF-LVAD implant who underwent aortic valve replacement (AVR), following assessment of AI using a hemodynamic ramp test with simultaneous echocardiography and right heart catheterization (RHC). The patient was a 21-year-old man with cardiogenic shock due to acute myocarditis, who underwent HeartWare CF-LVAD (HVAD) implantation. Heart failure persisted despite increased doses of diuretics and inotrope, as well as an increased HVAD pump rate. HVAD monitoring revealed a correlation between increased HVAD pump rate and flow at each speed step. A hemodynamic ramp test with simultaneous transthoracic echocardiography and RHC revealed a significant discrepancy between HVAD pump flow and cardiac output (CO) at each speed step; moreover, pulmonary capillary wedge pressure remained high. Therefore, the patient underwent AVR. Subsequently, his low CO symptoms disappeared and inotropes were successfully discontinued. A postoperative hemodynamic ramp test revealed that AVR had successfully closed the loop of blood flow and reduced the discrepancy between HVAD pump flow and CO, thereby increasing CO. The patient was then discharged uneventfully. In conclusion, a hemodynamic ramp test with simultaneous echocardiography and RHC was useful for the evaluation of the causal relationship between AI and low CO, and for selection of surgical treatment for AI in a patient with CF-LVAD.

Reversible left ventricular dysfunction due to severe stenosis of the elephant trunk graft: A case report.

Acquired coarctation of the aorta (CoA) following total aortic arch replacement (TAR) is a rare complication inducing left ventricular (LV) dysfunction probably due to increased LV afterload and secondary hypertension caused by increased upper body and decreased renal blood flow. We describe a case of a 35-year-old male who developed atypical CoA with severe LV dysfunction with LV ejection fraction of 10%, but without secondary hypertension after TAR using conventional elephant trunk (ET) technique for acute aortic dissection. Computed tomography revealed near-occlusive CoA due to narrowed distal ET. Because the myocardial histological findings were mild, and he had no cardiac failure history, we determined that LV function might be reversible. He underwent thoracic endovascular aortic repair (TEVAR), resulting in restored LV function. However, as the descending aortic false lumen distally to the end of ET was rapidly dilated, probably due to increased cardiac output and lower body blood flow, he underwent descending aortic replacement 3 months after TEVAR. In conclusion, a narrowed distal ET may cause LV dysfunction early after TAR, even without secondary hypertension. TEVAR may be a useful therapeutic option for a narrowed distant ET but can induce distal aortic dilatation. .

Impact of bridge-to-bridge strategies from paracorporeal to implantable left ventricular assist devices on the pre-heart transplant outcome: A single-center analysis of 134 cases.

BACKGROUND: In Japan, patients with heart failure who have a paracorporeal left ventricular assist device (pLVAD) and cannot be weaned from the VAD may undergo conversion to implantable continuous-flow LVAD (iLVAD) via a bridge-to-bridge (BTB) strategy for bridge-to-transplantation (BTT). This study aimed to evaluate the real-world clinical status of BTB strategies. METHODS: Among 134 patients who underwent iLVAD implantation for BTT, 34 patients underwent conversion from pLVAD to iLVAD (BTB group) and 100 patients underwent iLVAD implantation primarily (primary iLVAD group). The clinical characteristics and outcomes were compared between the two groups. RESULTS: No significant difference was found in the overall survival between the two groups (p = 0.26; log-rank test). However, the 1-year survival rate and the 1-year freedom from the composite events of death, stroke, systemic infection, and bleeding rate were lower in the BTB group than in the primary iLVAD group (survival rate, 88.2% vs. 99.0%, p = 0.0040; composite event-free survival rate, 26.1% vs. 49.8%, p = 0.030; log-rank test). Multivariate analysis indicated that the BTB strategy [hazard ratio (HR) 1.70, 95% confidence intervals (CI) 1.03-2.72; p=0.036] and serum total bilirubin levels at iLVAD implantation [HR 1.31, 95% CI 1.00-1.65; p=0.043] were independent predictors of 1-year composite events. CONCLUSIONS: The BTB strategy is useful in providing long-term survival in patients with acute critical diseases. However, the early mortality rate after conversion is higher in patients who underwent the BTB strategy.

Influence of Induction Therapy Using Basiliximab With Delayed Tacrolimus Administration in Heart Transplant Recipients　- Comparison With Standard Tacrolimus-Based Triple Immunosuppression.

BACKGROUND: Appropriate indications and protocols for induction therapy using basiliximab have not been fully established in heart transplant (HTx) recipients. This study elucidated the influence of induction therapy using basiliximab along with delayed tacrolimus (Tac) initiation on the outcomes of high-risk HTx recipients.Methods and Results:A total of 86 HTx recipients treated with Tac-based immunosuppression were retrospectively reviewed. Induction therapy was administered to 46 recipients (53.5%) with impaired renal function, pre-transplant sensitization, and recipient- and donor-related risk factors (Induction group). Tac administration was delayed in the Induction group. Induction group subjects showed a lower cumulative incidence of acute cellular rejection grade ≥1R after propensity score adjustment, but this was not significantly different (hazard ratio [HR]: 0.63, 95% confidence interval [CI]: 0.37-1.08, P=0.093). Renal dysfunction in the Induction group significantly improved 6 months post-transplantation (P=0.029). The cumulative incidence of bacterial or fungal infections was significantly higher in the Induction group (HR: 10.6, 95% CI: 1.28-88.2, P=0.029). CONCLUSIONS: These results suggest that basiliximab-based induction therapy with delayed Tac initiation may suppress mild acute cellular rejection and improve renal function in recipients with renal dysfunction, resulting in its non-inferior outcome, even in high-risk patients, when applied to the appropriate recipients. However, it should be carefully considered in recipients at a high risk of bacterial and fungal infections.

Incidence, Factors, and Prognostic Impact of Re-Exploration for Bleeding After Continuous-Flow Left Ventricular Assist Device Implantation　- A Japanese Single-Center Study.

BACKGROUND: Continuous-flow left ventricular assist device (CF-LVAD) substantially improves survival in endstage heart failure patients. However, bleeding complications are common after CF-LVAD implantation and in some cases, re-exploration for bleeding is needed. We aimed to investigate the incidence, timing, and risk factors of bleeding requiring re-exploration after CF-LVAD implantation.Methods and Results:We retrospectively reviewed 162 consecutive patients (age 43±13 years, 71% men) who underwent CF-LVAD implantation (HeartMateII 119, Jarvik2000 15, HVAD 13, EVAHEART 10, DuraHeart 5) from January 2012 to June 2019. During follow-up [median 662 days, interquartile range (IQR) 364-1,116 days], 35 (21.6%) experienced re-exploration for bleeding. The median timing of re-exploration was 6 (IQR 1-10) days. In the multivariate logistic regression analysis, postoperative platelet count was an independent predictor for re-exploration for bleeding after CF-LVAD implantation (per 104/µL: odds ratio 0.83, 95% confidence interval 0.74-0.93, P=0.002). Patients who experienced re-exploration for bleeding had a significantly worse survival rate than patients who did not (at 4 years, 73.6% vs. 90.1%, P=0.039). CONCLUSIONS: Re-exploration for bleeding is prevalent after CF-LVAD implantation, especially in patients with low postoperative platelet counts. As bleeding requiring re-exploration is associated with poor prognosis, risk stratification using the postoperative platelet count may be beneficial for these patients.

Chondroitin-4-sulfate transferase-1 depletion inhibits formation of a proteoglycan-rich layer and alters immunotolerance of bone marrow mesenchymal stem cells on titanium oxide surfaces.

Successful osseointegration is essential for dental implants. However, the complete molecular mechanism of osseointegration remains to be elucidated. In this study, we focused on the proteoglycan (PG)-rich layer between titanium oxides (TiOx) and bone, and chondroitin-4-sulfate transferase-1 (C4ST-1), which forms the sugar chain in PGs. Human bone marrow mesenchymal stem cells (hBMSCs) depleted of C4ST-1 were cultured on titanium (Ti) plates, and the interface between hBMSCs and TiOx was analyzed using transmission electron microscopy. Immunotolerance, proliferation, initial adhesion, and calcification of the cells were analyzed in vitro. At 14 days of cultivation, a PG-rich layer was observed between hBMSCs and TiOx. However, the PG-rich layer was reduced in C4ST-1-depleted hBMSCs on TiOx. Real-time RT-PCR showed that conditioned media increased the levels of expression of M1-macrophage markers in human macrophages. However, depletion of C4ST-1 did not affect calcification, cell proliferation, or initial cell adhesion on Ti plates. These results suggested that C4ST-1 in hBMSCs affects their immunotolerance and alters the formation of PG-rich layer formation on TiOx.

The effect of macrophages on an atmospheric pressure plasma-treated titanium membrane with bone marrow stem cells in a model of guided bone regeneration.

Guided bone regeneration (GBR) is an established treatment. However, the mechanisms of GBR are not fully understood. Recently, a GBR membrane was identified that acts as a passive barrier to regenerate bone via activation and migration of macrophages (Mps) and bone marrow stem cells (BMSCs). Atmospheric pressure plasma treatment of the titanium membrane (APP-Ti) activated macrophages. The purpose of this study was to analyze whether macrophages attached to an APP-Ti membrane affected differentiation of BMSCs in a GBR model. Human THP-1 macrophages (hMps) were cultured on non-treated Ti (N-Ti) and APP-Ti membrane. Macrophage polarization was analyzed by RT-PCR and immunocytochemistry. Secreted proteins from hMps on N-Ti and APP-Ti were detected by LC/MS/MS. hBMSCs were co-cultured with hMps on N-Ti or APP-Ti and analyzed by osteogenic differentiation, Alizarin red S staining, and alkaline phosphatase (ALP) activity. N-Ti and APP-Ti membrane were also implanted into bone defects of rat calvaria. hMps on APP-Ti were polarized M2-like macrophages. hMps on N-Ti secreted plasminogen activator inhibitor-1 and syndecan-2, but hMps on APP-Ti did not. hBMSCs co-cultured with hMps on APP-Ti increased cell migration and gene expression of osteogenic markers, but suppressed mineralization, while ALP activity was similar to that of hMps on N-Ti in vitro. The volume of newly formed bone was not significantly different between N-Ti and APP-Ti membrane in vivo. M2 polarized hMps on APP-Ti suppressed osteogenic induction of hBMSCs in vitro. The indirect role of hMps on APP-Ti in newly formed bone was limited.

A Novel Extracorporeal Continuous-Flow Ventricular Assist System for Patients With Advanced Heart Failure　- Initial Clinical Experience.

BACKGROUND: Bridge-to-decision (BTD) devices providing temporary mechanical circulatory support should be introduced to patients with advanced heart failure. This study evaluated the effectiveness and safety of a BTD device comprising an innovative extracorporeal continuous-flow temporary ventricular assist device (VAD) driven by a novel hydrodynamically levitated centrifugal flow blood pump.Methods and Results:Nine patients, comprising 3 with dilated cardiomyopathy, 3 with fulminant myocarditis, and 3 with ischemic heart disease, and 6 males, whose mean age was 47.7±8.1 years, were enrolled into the study. Six patients had Interagency Registry for Mechanically Assisted Circulatory Support profile 1, and 3 were profile 2. The primary endpoint was a composite of survival free from device-related serious adverse events and complications during circulatory support. Eight patients received left ventricular support, of whom 3 received concomitant right ventricular support using extracorporeal membrane oxygenation circuits, as a consequence of severe respiratory failure. One patient with fulminant myocarditis received biventricular support using the novel VAD system. After 19.0±13.5 days, 3 patients were weaned from circulatory support, because their native cardiac function recovered, and 6 patients required conversion to a durable device as a bridge-to-transplantation. One patient had non-disabling ischemic stroke episodes, and no patients died. CONCLUSIONS: This novel extracorporeal VAD system with a hydrodynamically levitated centrifugal pump can safely and successfully bridge patients with advanced heart failure to subsequent therapeutic stages.

Effect of Therapeutic Modification on Outcomes in Heart Transplantation Over the Past Two Decades　- A Single-Center Experience in Japan.

BACKGROUND: During these 2 decades (1999-2019), many therapeutic strategies have been developed in the field of heart transplant (HTx) to improve post-HTx outcomes. In the present study, 116 consecutive HTx adults between 1999 and 2019 were retrospectively reviewed to evaluate the influences of a therapeutic modification on post HTx outcomes.Methods and Results:Patient survival, functional status and hemodynamics after HTx and modification of therapeutic strategies were reviewed. The overall cumulative survival rate at 10 and 20 years post-HTx was 96.4 and 76.7%, respectively. There were no significant differences in survival rate or exercise tolerance after HTx between extracorporeal and implantable continuous flow-LVAD. Post-HTx patient survival in patients, irrespective of the donor risk factors such as donor age, low LVEF, history of cardiac arrest, was equivalent across cohorts, while longer TIT and higher inotrope dosage prior to procurement surgery were significant risk factors for survival. In 21 patients given everolimus (EVL) due to renal dysfunction, serum creatinine significantly decreased 1 year after initiation. In 22 patients given EVL due to transplant coronary vasculopathy (TCAV), maximum intimal thickness significantly decreased 3 years after initiation. CONCLUSIONS: The analysis of a 20-year single-center experience with HTx in Japan shows encouraging improved results when several therapeutic modifications were made; for example, proactive use of donor hearts declined by other centers and the use of EVL in patients with renal dysfunction and TCAV.

Effect of the Creatinine Excretion Rate Index, a Marker of Sarcopenia, on Prediction of Intracranial Hemorrhage in Patients With Advanced Heart Failure and a Continuous-Flow Left Ventricular Assist Device.

BACKGROUND: Sarcopenia is characterized by progressive loss of skeletal muscle and has frequently been associated with poor clinical outcomes in patients with advanced heart failure (HF). The urinary creatinine excretion rate (CER) index is an easily measured marker of muscle mass, but its predictive capacity for mortality and cerebrovascular events has not been investigated in patients with a continuous-flow implantable left ventricular assist device (CF-iLVAD).Methods and Results:We retrospectively reviewed 147 patients (mean [±SD] age 43.7±12.5 years, 106 male) who underwent CF-iLVAD implantation between April 2011 and June 2019. CER indices in 24-h urine samples before CF-iLVAD implantation were determined. Over a median follow-up of 2.3 years, there were 10 (6.8%) deaths and 43 (29.3%) cerebrovascular events. Patients were divided into 2 groups (low and high CER index) according to the median CER index in men and women (i.e., 13.71 and 12.06 mg·kg-1·day-1, respectively). Mortality and intracranial hemorrhage rates after CF-iLVAD implantation were significantly higher in the low than high CER index group (mortality 12.3% vs. 1.4% [P<0.01]; intracranial hemorrhage 23.3% vs. 8.1% [P=0.01]). Multivariate Cox proportional hazard models revealed that a low CER index was an independent predictor of intracranial hemorrhage in patients receiving a CF-iLVAD (hazard ratio 3.63; 95% confidence interval 1.43-9.24; P<0.01). CONCLUSIONS: A low preoperative CER index is an independent, non-invasive predictor of intracranial hemorrhage after CF-iLVAD implantation.

Mechanical Circulatory Support Combined With Immunosuppression for the Treatment of Giant Cell Myocarditis　- A Single-Center Experience in Japan.

BACKGROUND: The therapeutic strategy for giant cell myocarditis (GCM) remains controversial, so we reviewed the clinical status of Japanese patients with GCM.Methods and Results:We retrospectively reviewed 6 consecutive patients with GCM requiring percutaneous mechanical circulatory support (p-MCS), with 3 further requiring ventricular assist devices. One patient died during p-MCS. Cardiac function improved in the other 5 with immunosuppressive therapy, but only 3 patients treated with dual immunosuppressants, including cyclosporine (CyA), achieved >1-year survival. CONCLUSIONS: The prognosis of patients with fulminant GCM is poor, but a treatment that combines MCS and early administration of CyA-based immunosuppressants will be useful.

Experience of morphine therapy for refractory dyspnea as palliative care in advanced heart failure patients.

BACKGROUND: In the field of palliative care, morphine is known to be effective for alleviating dyspnea in cancer patients. However, little is known regarding the safety and efficacy of morphine therapy for refractory dyspnea as palliative care in advanced heart failure (HF) patients. METHODS: We retrospectively reviewed consecutive advanced HF patients who were referred to the Palliative Care Team at our institution and administered morphine for refractory dyspnea during hospitalization between September 2013 and December 2018. We investigated the details of morphine usage, vital signs, an 11-point quantitative symptom scale, and adverse events at baseline, 24 h, and 72 h after the start of treatment. RESULTS: Morphine was administered for refractory dyspnea in 43 advanced HF patients [mean age: 73.5 years, male: 28 (65%), New York Heart Association functional class IV: 43 (100%), median left ventricular ejection fraction: 25%, median B-type natriuretic peptide level: 927 pg/ml, concurrent intravenous inotrope: 33 (77%)]. Median initial dose of morphine was 5 mg/day in both oral and intravenous administration and median duration of administration was 5 days. Significant decreases in an 11-point quantitative symptom scale [7 (5, 9) vs. 2 (1, 6); p < 0.01, (data available in 8 patients)] and respiratory rate (22.2 ± 6.1 vs. 19.7 ± 5.2 breaths per minute; p < 0.01) were observed 24 h after the start of morphine administration. Meanwhile, oxygen saturation, blood pressure, and heart rate were not significantly altered after treatment (NS). Common adverse events were delirium (18%) and constipation (8%); however, no lethal adverse event definitely related to morphine therapy occurred during treatment. CONCLUSIONS: This single-center retrospective study revealed the clinical practice of morphine therapy and suggested that morphine therapy might be feasible for refractory dyspnea as palliative care in advanced HF patients.

Central conversion from peripheral extracorporeal life support for patients with refractory congestive heart failure.

Conversion from peripheral extracorporeal life support (ECLS) to the central one can improve and stabilize hemodynamics in patients with refractory congestive heart failure-related multiorgan failure, whereas indication and selection of the type of the central ECLS have not been fully established. Institutional outcome of the conversion therapy was herein reviewed to verify indication and selection of three types of central ECLS. This study enrolled an institutional consecutive surgical series of 24 patients with refractory congestive heart failure under peripheral ECLS, related to fulminant myocarditis (n = 15), dilated cardiomyopathy (n = 5), or acute myocardial infarction (n = 4). They were converted to central Y-extracorporeal membrane oxygenation (ECMO, n = 6), extracorporeal ventricular assist device (EC-VAD, n = 12), or pump catheter (n = 6), dependent upon the degree of multiorgan failure. Despite the different degree of multiorgan failure prior to the conversion, improvement in end-organ perfusion and reduction in right atrial and pulmonary artery pressure were promptly achieved regardless of the type of the central ECLS. There were five in-hospital mortalities (21%) during the central ECLS, whereas mechanical support was weaned-off in 11 cases (46%) and durable LVAD was subsequently implanted for bridge to transplantation in eight cases (33%). Conversion from the peripheral ECLS to the central ones, such as central Y-ECMO, EC-VAD or pump catheter, promptly established a sufficient support with heart and lung unloading in patients with refractory congestive heart failure.