Early acute kidney injury after tacrolimus administration in heart transplant recipients receiving basiliximab induction therapy.

OBJECTIVE: In this study, we aimed to analyze the association among the timing of tacrolimus initiation, time required to reach the target blood concentration, and early acute kidney injury (AKI) after tacrolimus administration in heart transplant recipients who received basiliximab induction therapy. MATERIALS AND METHODS: 88 patients treated with tacrolimus-based immunosuppressive therapy were retrospectively reviewed. Induction therapy was administered to 52 patients. AKI was evaluated within 7 days of tacrolimus administration. RESULTS: The rate of increase in tacrolimus trough concentration to the target trough concentration of 10 µg/mL early after its administration was set to be similar in the basiliximab induction and non-induction group; 8 and 2 patients developed AKI in the induction and non-induction group, respectively. In the induction group, there was no significant difference in the timing of tacrolimus initiation and the time required to reach the target concentration between patients who developed and did not develop AKI. In contrast, the cumulative incidence of AKI was significantly different between patients with an estimated glomerular filtration rate below and those with an estimated glomerular filtration rate above 43 mL/min/1.73m2 at the start of tacrolimus administration (37.5% and 11.4%, respectively; p = 0.045). CONCLUSION: In patients receiving basiliximab induction therapy, the timing of tacrolimus initiation and the time to reach the target concentration are unlikely to be associated with early AKI after tacrolimus administration. However, the recovery of sufficient renal function after heart transplantation is important for determining the start time of tacrolimus.

Case series: successful salvage from refractory cardiogenic shock caused by COVID-19-associated myocardial injury with temporary ventricular assist devices.

Background: Coronavirus disease 2019 (COVID-19) is predominantly known to cause respiratory injury; however, the present case series highlights four instances in which the infection resulted in significant cardiac complications. Among such cases, some represent severe cardiogenic shock, which necessitates the immediate introduction of mechanical circulatory support (MCS) for salvage. Case summary: This case series involved patients with COVID-19-associated myocardial injury leading to fulminant cardiogenic shock. These patients required immediate implementation of peripheral MCS, followed by an instant upgrade to a central MCS system due to anatomical limitations and severe biventricular dysfunction. Central MCS provided effective ventricular unloading, resulting in a significant and prompt improvement in ventricular function. The treatment timeline showed rapid deterioration followed by remarkable recovery within 2 weeks of MCS initiation, demonstrating the effectiveness of aggressive and tailored MCS strategies in managing severe COVID-19-related cardiac complications. Discussion: This study provides significant insights into the cardiovascular implications of COVID-19, particularly in the context of severe myocardial injury that leads to cardiogenic shock. The report underscores the importance of early recognition and intervention in such cases, focusing on the use of MCS as a life-saving modality. The findings also revealed unique pathological features of COVID-19-associated myocardial injury, including macrophage-predominant infiltration and microthrombosis, which are distinct from the features of conventional myocarditis. These findings highlight the need for further research on the pathophysiology of COVID-19-related cardiac injuries and the development of targeted therapeutic strategies.

Giant cell myocarditis attributable to myositis: therapeutic management under the guidance of serial endomyocardial biopsy-a case report.

Background: Giant cell myocarditis is a fatal disease that could be rapidly progressive if not properly managed. However, the role of immunosuppressive therapy, especially in refractory cases, remains unclear. Case summary: A 76-year-old man presented with back pain with elevated cardiac enzymes. Skeletal muscle and endomyocardial biopsies revealed giant cell myositis and giant cell myocarditis. Despite the initial immunosuppressive therapy, cardiac enzymes continued to rise. Serial endomyocardial biopsies enabled combination treatment of prednisolone, cyclosporine, and mycophenolate mofetil according to histological inflammatory activity. Discussion: We presented a case of refractory giant cell myocarditis preceded by giant cell myositis. While endomyocardial biopsy is an approach with risk of procedural complications, it can guide giant cell myocarditis management when the initial immunosuppressive therapy is ineffective.

Can right ventricular endomyocardial biopsy predict left ventricular fibrosis beforehand in dilated cardiomyopathy?

AIMS: Myocardial fibrosis of the left ventricle (LV) is a prognostic factor in dilated cardiomyopathy (DCM). This study aims to evaluate whether fibrosis of right ventricular (RV) endomyocardial biopsy (EMB) can predict the degree of LV fibrosis beforehand in DCM. METHODS AND RESULTS: Fibrosis extent in 70 RV-EMB specimens of DCM diagnosis was compared with that in the whole cross-sectional LV of excised hearts in the same patients (52 explanted hearts for transplant and 18 autopsied hearts). The median interval between biopsy and excision was 4.1 (0.13-19.3) years. The fibrosis area ratio of the EMBs and excised hearts were evaluated via image analysis. The distribution of cardiovascular magnetic resonance-late gadolinium enhancement (LGE) in the intraventricular septum was classified into four quartile categories. The fibrosis area ratio in RV-EMB correlated significantly with that in the short-axis cut of the LV of excised hearts (r = 0.82, P < 0.0001) and with a diffuse pattern of LGE (r = 0.71, P = 0.003). In a multivariate model, after adjusting for the interval between biopsy performance and heart excision, the fibrosis area ratio in RV-EMB was associated with that in LV-excised heart (regression coefficient, 0.82; 95% confidence interval, 0.68-0.95; P < 0.0001). CONCLUSIONS: The fibrosis observed in RV-EMB positively correlated with the extent of fibrosis in the LV of excised hearts in patients with DCM. The study findings may help predict LV fibrosis, considered a prognostic factor of DCM through relatively accessible biopsy techniques.

Depressive symptoms, right ventricular function, and muscular strength are associated with peak oxygen uptake in patients with implantable left ventricular assist devices.

BACKGROUND: Left ventricular assist device (LVAD) implantation is among the most effective treatment options for patients with severe heart failure. Although previous studies have examined the factors related to peak oxygen uptake (peak VO2 ), they were limited by the few patients involved and their focus on medical and physical functions. Therefore, this study comprehensively examined the factors associated with peak VO2 , which is an important prognostic factor in patients with implantable LVADs. METHODS: Eighty-nine patients who underwent initial LVAD implantation and were eligible for cardiopulmonary exercise testing (CPX) between May 2014 and September 2021 were included. The patients' mean age was 48 ± 12 years, and 70% were males. Based on previous studies, the cut-off was set at 12 and 14 mL/kg/min for patients taking ß-blocker and those not taking ß-blockers, respectively. Furthermore, factors associated with peak VO2 were examined using multivariate logistic regression analysis. RESULTS: The mean time from surgery to CPX administration was 73 ± 40 days. The high group had a higher cardiac index, right ventricular stroke work index (RVSWI), and isometric knee extensor muscular strength and lower Patient Health Questionnaire-9 (PHQ-9) and B-type natriuretic peptide values than the low group. Multivariate logistic regression analysis showed that RVSWI and KEMS were positively correlated, whereas PHQ-9 was negatively associated with peak VO2 . CONCLUSION: Right ventricular function, depressive symptoms, and lower limb muscular strength were associated with exercise capacity in patients with implantable LVADs.

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.

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.

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.

A unique cuff-sewing method to implant heartmate3 LVAD for arrhythmogenic right ventricular cardiomyopathy, facilitated by 3D-printing heart model.

Implantation of left ventricular assist device (LVAD) for arrhythmogenic right ventricular (RV) cardiomyopathy is challenging associated with small LV cavity, laterally dislocated LV apex, thin and fragile RV free wall. A 43-year-old male with more than 10 years of medical treatment developed congestive heart failure related to biventricular failure. Durable LVAD was indicated to prevent further deterioration of the RV function, which would be exacerbated by progression of LV dysfunction. To simulate surgery, we printed-out a 3D heart model based on enhanced CT scanning study to identify the optimal coring position in the LV apex, by which the inflow directs the mitral valve. We then found that the mini-cuff of the HeartMate3 should be fixed in the paper-thin RV free wall by the usual cuff-sewing method. In the surgery, after the coring as planned, 5 pairs of interrupted sutures on the medial side were passed from the luminal side of the LV and then to the mini-cuff, and the lateral side of the mini-cuff was fixed with a continuous sutures, not to sew into the RV wall. The surgery was completed without complications with a good hemodynamics. The 3D heart model facilitated this unique method, indicating a usefulness of printed-out heart model for cases with unusual cardiac anatomy, which needs implantation of durable LVAD.

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.

Status of adult outpatients with congenital heart disease in Japan: The Japanese Network of Cardiovascular Departments for Adult Congenital Heart Disease Registry.

BACKGROUND: The Japanese Network of Cardiovascular Departments for Adult Congenital Heart Disease (JNCVD-ACHD) was founded in 2011 for the lifelong care of adult patients with congenital heart disease (ACHD patients). This network maintains the first Japanese ACHD registry. METHODS AND RESULTS: From 2011 to 2019, the JNCVD-ACHD registered 54 institutions providing specialized care for ACHD patients in 32 of the 47 prefectures in Japan. The registry collected data on the disease profile for 24,048 patients from 50 institutions and the patient characteristics for 9743 patients from 24 institutions. The most common ACHDs were atrial septal defect (20.5 %), ventricular septal defect (20.5 %), tetralogy of Fallot (12.9 %), and univentricular heart (UVH)/single ventricle (SV; 6.6 %). ACHD patients without biventricular repair accounted for 37.0 % of the population. Also examined were the serious anatomical and/or pathophysiological disorders such as pulmonary arterial hypertension (3.0 %) including Eisenmenger syndrome (1.2 %), systemic right ventricle under biventricular circulation (sRV-2VC; 2.8 %), and Fontan physiology (6.0 %). The sRV-2VC cases comprised congenitally corrected transposition of the great arteries without anatomical repair (61.9 %) and transposition of the great arteries with atrial switching surgery (38.1 %). The primary etiology (86.4 %) for Fontan physiology was UVH/SV. In addition, developmental/chromosomal/genetic disorders were heterotaxy syndromes (asplenia, 0.9 %; polysplenia, 0.7 %), trisomy 21 (4.0 %), 22q11.2 deletion (0.9 %), Turner syndrome (0.2 %), and Marfan syndrome (1.1 %). CONCLUSIONS: Although the specific management of ACHD has systematically progressed in Japan, this approach is still evolving. For ideal ACHD care, the prospective goals for the JNCVD-ACHD are to create local networks and provide a resource for multicenter clinical trials to support evidence-based practice.

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.

Impact of the HeartMate 3 continuous-flow left ventricular assist device in patients with small body size.

OBJECTIVES: Limited data are available for use of the HeartMate 3 (HM 3) left ventricular assist device in patients with a small body surface area (BSA). Because the HM 3 is currently the sole device available worldwide, we conducted a single-centre retrospective study of patients with a small BSA (<1.5 m2) who underwent HM 3 implantation to better understand the operative and postoperative management. METHODS: This study enrolled 64 consecutive patients who had undergone HM 3 implantation from August 2018 to July 2021. The patients were divided into 2 groups based on their BSA before the operation: BSA of <1.5 m2 (small BSA group, n = 18) and BSA of ≥1.5 m2 (regular BSA group, n = 46). The primary study endpoint was survival free of events such as disabling stroke and pump failure. The secondary endpoint was the frequency of adverse events. RESULTS: The average BSA was 1.38 m2 in the small BSA group. The overall event-free survival rate at 12 months was 100% and 86.7% in the small BSA group and regular BSA group, respectively, and no significant difference was found between the 2 groups (log-rank P = 0.2). The number of cumulative adverse events of death, stroke of any severity, driveline infection, pump infection, ventricular arrhythmia, gastrointestinal Haemorrhage and pump failure was similar between the 2 groups. CONCLUSIONS: The HM 3 was safely implanted in patients with a small BSA, and postoperative outcomes were acceptable regardless of BSA. However, further research is needed to confirm the indications for HM 3 implantation in even smaller patients.

Bridge from central extracorporeal life support is a risk factor of cerebrovascular accidents after durable left ventricular assist device implantation.

A bridging strategy from extracorporeal life support (ECLS) is effective in salvage and a bridge to recovery or to a durable left ventricular assist device (LVAD) for acute refractory heart failure. However, the correlation of this strategy with adverse events after durable LVAD implantation has not been fully investigated. This study enrolled 158 consecutive patients who had either the HeartMate II or HeartMate 3 and were implanted for bridge-to-transplantation. These devices were implanted as the primary mechanical support device in 115 patients, whereas the remaining 43 underwent LVAD implantation as the bridge from central ECLS. The primary study endpoint was all-cause mortality and cerebrovascular accidents (CVAs) after durable LVAD implantation, and the secondary endpoints were adverse events. Overall survival was not significantly different between the two groups. In contrast, the probability of CVAs was significantly greater in the bridge group than in the primary group (probability of CVAs, P = 0.002; log-rank test). In Cox multivariate logistic regression analysis, a bridge from central ECLS was an independent predictive factor of CVAs (hazard ratio 4.27, 95% confidence interval 1.43-12.8; P = 0.0095). Patients who are bridged from central ECLS are more frequently complicated by CVAs compared with those who undergo primary implantation of a durable LVAD, but survival is not significantly different between the two groups. A bridge from central ECLS is an independent predictive factor of CVAs post-implantation of an LVAD.