Downregulation of PGRMC1 accelerates differentiation and fusion of a human trophoblast cell line.

Mononuclear cytotrophoblasts (CTs) differentiate and fuse to form multinuclear syncytiotrophoblasts (STs), which produce human chorionic gonadotropin (hCG) and progesterone to maintain pregnancy. Impaired differentiation and fusion of CTs to form STs are associated with hypertensive disorders of pregnancy and fetal growth restriction. Progesterone receptor membrane component 1 (PGRMC1) is a multifunctional single transmembrane heme-binding protein. We previously demonstrated that downregulation of PGRMC1 promotes endometrial stromal cell differentiation (decidualization). Here, we explored the role of PGRMC1 in trophoblast differentiation and fusion. PGRMC1 expression was lower in STs than in CTs of first-trimester placental tissues. PGRMC1 expression in BeWo cells (a trophoblast-derived choriocarcinoma cell line) decreased upon dibutyryl-cAMP (db-cAMP)-induced differentiation. Both inhibition and knockdown of PGRMC1 stimulated hCG production in the presence of db-cAMP. Furthermore, a quantitative cell fusion assay we developed revealed that inhibition and knockdown of PGRMC1 enhanced db-cAMP-stimulated cell fusion. Peroxisome proliferator-activated receptor γ (PPARγ) agonists decreased PGRMC1 expression and stimulated the cell fusion in BeWo cells. These findings suggest that downregulation of PGRMC1 expression in part through activation of PPARγ during trophoblast differentiation promotes hCG production and cell fusion for formation and maintenance of placental villi during pregnancy.

Successful echocardiography-guided medical management of severe early post-implant right ventricular failure in a patient with left ventricular assist device support: a case report.

BACKGROUND: Post-implant right heart failure (RHF) has been recognized as a crucial prognostic factor in patients receiving left ventricular assist devices (LVADs), and its management has long attracted attention from cardiologists and surgeons. CASE PRESENTATION: This report described an 18-year-old female with acutely deteriorating heart failure due to dilated cardiomyopathy who underwent paracorporeal pulsatile-flow LVAD and developed early post-implant RHF. At postoperative day (POD) six, she was almost asymptomatic at rest on 2.5 mg/kg/min of dobutamine; however, the echocardiogram, performed as part of the daily postoperative care, revealed a severely enlarged right ventricle with a decompressed left ventricle, implying the development of post-implant RHF. Bolus infusion of saline and reduction of pump flow (6.0 L/min to 3.0 L/min) led to normalization of both ventricular shapes in 30 s, suggesting that RHF could be managed without surgical interventions. Milrinone was started on POD six, followed by sildenafil administration on POD seven. Fluid balance was strictly adjusted under the close observation of daily echocardiograms. Milrinone and dobutamine were discontinued on PODs 18 and 21, respectively. The patient was listed for a heart transplant on POD 40. Despite reduced right ventricular function (right ventricular stroke work index of 182.34 mmHg*ml/m- 2, body surface area 1.5 m2), she was successfully converted to implantable LVAD on POD 44 with no recurrence of post-implant RHF thereafter for four years. CONCLUSIONS: In post-implant RHF management, early detection, together with proper and prompt medical management, is crucial to avoiding any surgical intervention. Close observation of daily echocardiograms might be helpful in detecting subclinical RHF and is useful for post-implant medical management.

A case report of cardiac allograft vasculopathy complicated with coronary vasospasm: insights from near-infrared spectroscopy, intravascular ultrasound, and optical coherence tomography.

Background: Cardiac allograft vasculopathy (CAV) remains a major complication after heart transplantation. Although coronary vasospasm after heart transplantation has occasionally been reported, the association between CAV and coronary vasospasm remains unclear. Case summary: A 68-year-old male with a history of heart transplantation 21 years ago presented with atypical angina. Coronary angiography demonstrated intermediate stenoses in the proximal and mid left anterior descending artery (LAD) and right posterolateral artery. Intracoronary acetylcholine provocation testing resulted in subtotal occlusion of the coronary arteries bilaterally, which was resolved by nitroglycerine administration, but the intermediate stenoses remained. The stenosis in the proximal LAD was physiologically significant based on fractional flow reserve. The patient was diagnosed with a developed CAV and concomitant coronary vasospasm and treated with percutaneous coronary intervention and nifedipine. Near-infrared spectroscopy and intravascular ultrasound showed a large isoechoic plaque with a low lipidic burden, suggesting a non-atherosclerotic plaque. Optical coherence tomography revealed a layered homogenous plaque, an intravascular imaging finding common in both CAV and coronary vasospasm. A drug-eluting stent dilated the stenosis, and follow-up angiography at 4 months showed no CAV progression. Discussion: This case highlights the potential association between CAV and coronary vasospasm. Intravascular imaging detected similarities in plaque morphology between CAV and coronary vasospasm, suggesting that coronary vasospasm might contribute to the development of CAV. Although coronary vasospasm may be underdiagnosed in heart transplant recipients due to the lack of symptoms involving the denervated heart, this case showed that appropriate provocation testing may be beneficial for evaluating the cause of CAV.

Efficacy of catheter cleaning methods using intravenous indwelling catheter, 10% silver nitrate solution and a monofilament nylon thread for deeply progressed superficial driveline infections: case series.

Driveline infection (DLI) is treated by local irrigation via driveline exit site (DLES) and surgical debridement is considered in patients with deep DLI. We describe three cases of deeply progressed superficial DLI that were considered to require surgical debridement but could be treated with a unique catheter cleaning method using intravenous indwelling catheter, a cotton swab with 10% silver nitrate solution and a monofilament nylon thread. Case 1 was a 60-y-old man with ischemic cardiomyopathy with left ventricular assist device implantation 2 y before. Daily bedside debridement with 10% silver nitrate solution was performed via the DLES. Case 2 was a 43-y-old man with ischemic cardiomyopathy who had recurrent DLI with methicillin-resistant Staphylococcus aureus, and case 3 was a 49-y-old woman with hypertrophic cardiomyopathy, who also showed improvement in their DLI with Pseudomonas aeruginosa. These cleaning methods may be useful for the deeply progressed superficial DLI.

Prognostic impact of lung computed tomography density in cardiogenic shock patients with veno-arterial extracorporeal membrane oxygenation.

BACKGROUND: Pulmonary complications often occur in patients receiving veno-arterial extracorporeal membrane oxygenation (VA ECMO). However, the prognostic impact of lung damage has not been fully elucidated. METHODS: This single-center retrospective observational study targeted patients with cardiogenic shock who received VA ECMO between 2012 and 2021. This study included 65 patients who underwent chest computed tomography (CT) on VA ECMO, followed by escalation to central mechanical circulatory support (MCS) with left ventricular venting. The average density of lung CT images was measured using region-of-interest methods, and the primary endpoint was 180-day all-cause death after escalation to the central MCS. RESULTS: Twenty-two patients (34%) developed 180-day all-cause death. According to the Cox regression analysis, age (hazard ratio [HR], 1.08; 95% confidence interval [CI], 1.03-1.14; p = 0.001), ischemic etiology (HR, 5.53; 95% CI, 2.09-14.62; p < 0.001), duration of VA ECMO support (HR, 1.19; 95% CI, 1.00-1.40; p = 0.045), and lung CT density (≥ -481 Hounsfield unit [HU]) (HR, 6.33; 95% CI, 2.26-17.72; p < 0.001) were independently associated with all-cause death. Receiver operating characteristic curve analysis determined that lung CT density ≥ -481 HU is an optimal cutoff value for predicting all-cause death (area under the curve [AUC], 0.72). The 180-day overall survival rate for patients with high lung CT density (≥ -481 HU) was significantly lower than that for those with low lung CT density (< -481 HU) (44.4% vs. 81.6%, respectively, p = 0.002). CONCLUSIONS: Higher lung CT density could be a useful predictor of death in patients with VA ECMO requiring central MCS escalation.

Impact of hypoalbuminemia on in-hospital mortality in patients with takotsubo syndrome: A multicenter registry of the Tokyo Cardiovascular Care Unit Network.

BACKGROUND: Hypoalbuminemia is common in critically ill patients and is associated with poor outcomes. However, the relationship between serum albumin levels and clinical outcomes in patients with takotsubo syndrome remains unclear. We examined the impact of hypoalbuminemia on in-hospital mortality in patients with takotsubo syndrome. METHODS: Using the multicenter registry of the Tokyo Cardiovascular Care Unit Network between January 2017 and December 2020, we identified 631 eligible patients with takotsubo syndrome (median age, 78 years; male proportion, 22 %) and documented serum albumin levels at admission, which were used to allocate patients to hypoalbuminemia (serum albumin <3.5 g/dL) or normal albumin (serum albumin ≥3.5 g/dL) groups. Patient characteristics and in-hospital mortality were compared between the groups. RESULTS: Hypoalbuminemia was detected in 200 (32 %) patients at admission. The hypoalbuminemia group was older and had a higher proportion of men and preceding physical triggers than the normal albumin group. In-hospital all-cause mortality was greater in the hypoalbuminemia group than in the normal albumin group (9.5 % vs. 1.9 %, p < 0.001). Both cardiac (3.0 % vs. 0.5 %, p = 0.015) and non-cardiac (6.5 % vs. 1.4 %, p = 0.002) mortality was greater in the hypoalbuminemia group. In multivariable logistic regression analysis, hypoalbuminemia was independently associated with increased in-hospital mortality, even after adjusting for confounders, including age, sex, and triggering events (odds ratio, 3.23; 95 % confidence interval, 1.31-7.95; p = 0.011). CONCLUSIONS: In patients with takotsubo syndrome, hypoalbuminemia is a common comorbidity and is associated with a substantial risk of in-hospital death. Close monitoring and comprehensive critical care are required in these patients.

A study of takotsubo syndrome over 9 years at the Tokyo Cardiovascular Care Unit Network Registry.

BACKGROUND: Takotsubo syndrome (TTS) is an acute cardiovascular disease with clinical manifestations similar to those of acute myocardial infarction (AMI), and TTS sometimes occurs just after catastrophes. Large-scale studies of TTS in Japan are scarce, so we examined data over 9 years from Tokyo metropolitan acute cardiovascular care hospital network registry. METHODS: A total of 1626 patients were diagnosed with TTS between 2010 and 2018 at Tokyo Cardiovascular Care Unit Network facilities, and data from all these patients were analyzed. We investigated annual and monthly captured incidence of TTS, temporal trend of the captured incidence proportion of TTS versus AMI, the occurrence of TTS on the day of the great earthquake, and we elucidated the prognostic factors for in-hospital death. RESULTS: The annual incidence proportion of TTS versus AMI increased from 2.3 % to 4.5 % (p < 0.001) over 9 years. The mean TTS patient age was 74.4 years: the peak incidence of TTS was at 80 to 84 years of age for both male and female; females accounted for 78.5 % of patients. The monthly variation of the incidence of TTS was found (p = 0.009). In 2011, a total of 137 cases of TTS occurred, with as many as 6 occurring on March 11, the day of the Great East Japan Earthquake. There was a definable trigger for TTS in 64 % (physical: 36 %; emotional: 27 %; others: 2 %). All-cause in-hospital mortality was 5.3 % and was higher in males than in females (10.3 % vs 3.9 %; p < 0.001). Non-cardiac causes accounted for 62 % of in-hospital mortality. Factors at presentation that were associated with in-hospital all-cause mortality were male sex, low body mass index, and a high C-reactive protein level. CONCLUSIONS: This study elucidated the clinical features, in-hospital outcomes, and their attributed factors in patients with TTS in real-world clinical practice in Japan.

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.

Acute Calcineurin Inhibitor Nephrotoxicity Diagnosed Using Kidney Doppler Ultrasonography After Heart Transplant: A Case Report.

BACKGROUND: Acute calcineurin inhibitor (CNI) nephrotoxicity is a common complication associated with CNI exposure. However, it can be difficult to diagnose. Herein, we report a case of acute CNI nephrotoxicity after heart transplant that was visualized using kidney Doppler ultrasonography. CASE REPORT: A 38-year-old female patient underwent heart transplant 5 years after the use of left ventricular assist device support because of advanced heart failure due to ischemic cardiomyopathy. Corticosteroids, tacrolimus, and mycophenolate mofetil were administered as immunosuppressive regimens postoperatively. The patient gradually developed kidney dysfunction despite a favorable perioperative clinical course and hemodynamics. Serum creatinine increased to 1.89 mg/dL on postoperative day (POD) 9, and the kidney Doppler ultrasonography examination showed severely reduced blood flow in the renal and renal segmental arteries, indicating acute CNI nephrotoxicity due to vasoconstriction of the renal arterioles. After the cessation of tacrolimus, kidney function returned to baseline levels within 2 days, and the kidney Doppler ultrasonography examination on POD 19 revealed a significant increase in blood flow in the renal and renal segmental arteries. Basiliximab followed by everolimus were administered as alternative immunosuppressants. No organic stenosis of the renal artery was detected on the kidney magnetic resonance angiography, and the patient was discharged on POD 51, without any other adverse events, including rejection. CONCLUSIONS: Although CNIs are widely used after heart transplant, acute nephrotoxicity should always be considered. After heart transplant, a kidney Doppler ultrasonography should be performed routinely and promptly if there are any clinical manifestations related to kidney function.

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.

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.

Leadless pacemaker implantation in a patient with a fully magnetically levitated left ventricular assist device.

Left ventricular assist device (LVAD) therapy is increasingly used in patients with end-stage heart failure. However, LVADs are associated with challenges, especially in the presence of a cardiac implantable electronic device. Although a leadless pacemaker (PM), the Micra™ Transcatheter Pacing System, can be used with LVADs, data regarding HeartMate 3™ LVAD are limited. In this report, we present a patient with a HeartMate 3™ LVAD who underwent successful leadless PM implantation after the removal of an infected cardiac resynchronization therapy defibrillator.

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.

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.