The first case report of de novo Crohn's disease after heart transplantation successfully treated with ustekinumab.

Inflammatory bowel disease (IBD) is a complex chronic inflammatory intestinal disease. The development of de novo IBD after solid organ transplantation with immunosuppressive agents has been rarely reported. We present the case of a 65-year-old man with repeated colitis after heart transplantation (HTx) who was diagnosed with Crohn's disease (CD). The patient underwent HTx due to non-ischemic dilated cardiomyopathy. Six months after HTx, he developed serious diarrhea and a transient fever, which persisted for about 6 months. Valganciclovir or any antibiotic agents were not effective for his symptoms and longitudinal ulcers in colonoscopy aggravated during the course, so that we made a diagnosis of CD. We started 5-aminosalicylic acid and found improvement in his symptoms and colonoscopic findings. However, 7 months after improvement, CD worsened. We started ustekinumab by which his condition successfully went into remission again. While oral immunosuppressive drugs are thought to suppress autoimmune diseases in general, IBD should be included in the differential diagnoses for recurring enterocolitis after HTx. Poorly controlled CD can lead to serious and potentially fatal complications, but in this case, ustekinumab has been used safely and effectively for the treatment of CD. Learning objective: Colitis is a common complication after heart transplantation (HTx). Although cytomegalovirus colitis or posttransplant lymphoproliferative disorder are observed commonly, de novo inflammatory bowel disease (IBD) should be considered when serious refractory colitis occurs. Not only 5-aminosalicylic acid but also ustekinumab, which is a monoclonal antibody to the p40 subunit of interleukin (IL)-12 and IL-23, may be a safe and effective treatment for de novo IBD after HTx.

Right heart reserve function assessed with fluid loading predicts late right heart failure after left ventricular assist device implantation.

BACKGROUND: A left ventricular assist device (LVAD) is an effective therapeutic option for advanced heart failure. Late right heart failure (LRHF) is a complication after LVAD implantation associated with increasing morbidity and mortality; however, the assessment of right heart function, including right heart reserve function after LVAD implantation, has not been established. We focused on a fluid loading test with right heart catheterization (RHC) to evaluate right heart pre-load reserve function and investigate its impact on LRHF. METHODS: Patients aged > 18 who received continuous-flow LVAD between November 2007 and December 2022 at our institution and underwent RHC with saline loading (10ml/kg for 15 min) 1 month after LVAD implantation were included. RESULTS: Overall, 31 LRHF or deaths (RHF group) have occurred in 149 patients. Comparing the RHF and non-RHF groups, pulmonary artery pulsatility index (PAPi) at rest (1.8±0.89 vs. 2.5±1.4, p=0.02) and right ventricular stroke work index (RVSWi) change ratio with saline loading (0.96±0.32 vs. 1.1±0.20, p=0.03) was significantly different. The PAPi at rest and RVSWi change ratio with saline loading were identified as the postoperative risks for LRHF or death. The cohort was divided into three groups based on whether the PAPi at rest and RVSWi change ratio were low. The event-free curve significantly differed between the three groups (p<0.001). CONCLUSIONS: Hemodynamic assessment with saline loading can evaluate the right ventricular pre-load reserve function of patients with LVAD. The low RVSWi change with saline loading was a risk factor for LRHF following LVAD implantation.

Effect of renal function under left ventricular assist device support on the cardiac function and clinical events after heart transplantation.

AIM: We investigated the effects of pre-transplantation renal dysfunction under left ventricular assisted device (LVAD) support on post-transplantation cardiac function, and patient prognosis after heart transplantation (HTx). METHOD: All patients who were bridged by LVAD and underwent HTx at our hospital between 2007 and 2022 were included in this study. Patients were classified into two groups based on estimated glomerular filtration rate (eGFR) before HTx: renal dysfunction (RD) group (eGFR < 60 mL/min/1.73 m2 ) and non-renal dysfunction (NRD) group. RESULT: A total of 132 patients were analyzed, of whom 48 were classified into the RD group and 84 into the NRD group (RD group, 47.9 ± 10.1 years; NRD group, 38.4 ± 11.9 years, p < .0001). Under LVAD support before HTx, the RD group tended to have a history of right ventricular failure (RD group, nine (19%); NRD group, seven (8%); p = .098). After HTx, the echocardiographic parameters did not differ between the two groups in the long term. Furthermore, more concise hemodynamic parameters, exemplified by right heart catheterization, were not significantly different between the two groups. Regarding graft rejection, no significant differences were found in acute cellular rejection and cardiac allograft vasculopathy following HTx. In contrast, patients with RD before HTx had significantly increased mortality in the chronic phase after HTx and initiation of maintenance dialysis, without any overt changes in cardiac function. CONCLUSION: Pre-transplantation renal dysfunction under LVAD support significantly affected clinical course after HTx without any overt changes in graft cardiac function.

A new assessment method for right ventricular diastolic function using right heart catheterization by pressure-volume loop.

Diastolic stiffness coefficient (ß) and end-diastolic elastance (Eed) are ventricular-specific diastolic parameters. However, the diastolic function of right ventricle had not been investigated sufficiently due to the lack of established evaluation method. We evaluated the validity of these parameters calculated using only data of right heart catheterization (RHC) and assessed it in patients with restrictive cardiomyopathy (RCM) and cardiac amyloidosis. We retrospectively analyzed 46 patients with heart failure who underwent RHC within 10 days of cardiac magnetic resonance (CMR). Right ventricular end-diastolic volume and end-systolic volume were calculated using only RHC data, which were found to be finely correlated with those obtained from CMR. ß and Eed calculated by this method were also significantly correlated with those derived from conventional method using CMR. By this method, ß and Eed were significantly higher in RCM with amyloidosis group than dilated cardiomyopathy group. In addition, the ß and Eed calculated by our method were finely correlated with E/A ratio on echocardiography. We established an easy method to estimate ß and Eed of right ventricle from only RHC. The method finely demonstrated right ventricular diastolic dysfunction in patients with RCM and amyloidosis.

Successful Treatment with Letermovir in a Heart Transplant Recipient with UL97 Mutation Ganciclovir-Resistant Cytomegalovirus Colitis and Viremia.

Currently available anti-cytomegalovirus (CMV) agents are sometimes poorly tolerated, owing to their side effects. Letermovir is a novel anti-CMV drug that is only approved for CMV prophylaxis in hematopoietic stem cell transplant recipients, with fewer side effects. We report the case of a heart transplant recipient with UL97 mutation (L595F) ganciclovir-resistant cytomegalovirus colitis who was successfully treated with off-label use of letermovir. In treating CMV infection or disease with letermovir, a transient rise or lag in the clearance of CMV-DNA polymerase chain reaction levels has been observed. Our case suggests that CMV-pp65 antigenemia can be an additional marker of treatment efficacy.

Prophylactic negative pressure wound therapy is not effective for preventing driveline infection following left ventricular assist device implantation.

BACKGROUND: Driveline infection (DLI) following left ventricular assist device (LVAD) implantation remains an unresolved problem. Negative pressure wound therapy (NPWT) promotes wound healing by applying negative pressure on the surface of the wound. Recently, the prophylactic application of NPWT to closed surgical incisions has decreased surgical site infections in various postsurgical settings. Therefore, we evaluated the efficacy and safety of prophylactic NPWT for preventing DLI in patients with LVAD implantation. METHODS: Prophylactic NPWT was provided to 50 patients who received continuous-flow LVADs as bridge-to-transplant therapy at our institution between May 2018 and October 2020 (NPWT group). The negative pressure dressing was applied immediately after surgery and retained on the driveline exit site for 7 days with a continuous application of -125 mm Hg negative pressure. The primary outcome was DLI within 1 year of LVAD implantation. We compared the rate of DLI incidence in the NPWT group with that in the historical control cohort (50 patients) treated with the standard dressing (SD) who received LVAD implantation between July 2015 and April 2018 (SD group). RESULTS: No severe complications were associated with the NPWT. During the follow-up period, DLI was diagnosed in 16 participants (32%) in the NPWT group and 21 participants (42%) in the SD group. The rates of DLI incidence and freedom from DLI did not differ between groups (p = 0.30 and p = 0.63). CONCLUSIONS: Prophylactic NPWT at the driveline exit site was safe following LVAD implantation. However, it did not significantly reduce the risk of DLI.

Residual Pulmonary Vascular Resistance Increase Under Left Ventricular Assist Device Support Predicts Long-Term Cardiac Function After Heart Transplantation.

Aims: We compared hemodynamics and clinical events after heart transplantation (HTx) in patients stratified by the severity of residual pulmonary vascular resistance (PVR) after left ventricular assist device (LVAD) implantation for bridge to transplantation. Methods: We retrospectively analyzed patients who had undergone HTx at the University of Tokyo Hospital. We defined the high PVR group as patients with PVR of >3 Wood Units (WU) as measured by right heart catheterization performed 1 month after LVAD implantation. Results: We included 85 consecutive HTx recipients, 20 of whom were classified in the high PVR group and 65 in the low PVR group. The difference in PVR between the two groups became apparent at 2 years after HTx (the high PVR group: 1.77 ± 0.41 WU, the low PVR group: 1.24 ± 0.59 WU, p = 0.0009). The differences in mean pulmonary artery pressure (mPAP), mean right arterial pressure (mRAP), and mean pulmonary capillary wedge pressure (mPCWP) tended to increase from the first year after HTx, and were all significantly higher in the high PVR group at 3 years after HTx (mPAP: 22.7 ± 9.0 mm Hg vs. 15.4 ± 4.3 mm Hg, p = 0.0009, mRAP: 7.2 ± 3.6 mm Hg vs. 4.1 ± 2.1 mm Hg, p = 0.0042, and mPCWP: 13.4 ± 4.5 mm Hg, 8.8 ± 3.3 mm Hg, p = 0.0040). In addition, pulmonary artery pulsatility index was significantly lower in the high PVR group than in the low PVR group at 3 years after HTx (2.51 ± 1.00 vs. 5.21 ± 3.23, p = 0.0033). The composite event including hospitalization for heart failure, diuretic use, and elevated intracardiac pressure (mRAP ≥ 12 mm Hg or mPCWP ≥ 18 mm Hg) between the two groups was significantly more common in the high PVR group. Residual high PVR was still an important predictor (hazard ratio 6.5, 95% confidence interval 2.0-21.6, and p = 0.0023) after multivariate Cox regression analysis. Conclusion: Our study demonstrates that patients with residual high PVR under LVAD implantation showed the increase of right and left atrial pressure in the chronic phase after HTx.

Determining the factors for interhospital transfer in advanced heart failure cases.

Background: There are some patients with advanced heart failure (HF), for whom implantable left ventricular assist device (LVAD) or heart transplantation (HTx) should be considered. Some of them need to be transferred between hospitals. There are few reports on the interhospital transfer of patients with advanced HF and their subsequent clinical course.In this study, we investigated the characteristics and clinical course of patients transferred to a LVAD/HTx center, focusing on the distance between hospitals. Methods: We retrospectively examined 141 patients who were transferred to our hospital, considering the indications of LVAD implantation or HTx. We divided the patients into two groups: those referred <33 km (short-distance) and those referred more than 33 km (long-distance). The primary outcome was the composite outcome of increased catecholamine dose, mechanical support, or renal dysfunction within 1 week of transfer. Results: Continuous catecholamine infusion was significantly more common in patients in the long-distance group, whereas extracorporeal membrane oxygenation (ECMO) placement was significantly more common in short-distance group.Patients transferred via long distance had significantly higher rates of increased catecholamine doses, mechanical support including intra-aortic balloon pumping (IABP) and ECMO, and renal dysfunction within 1 week of transfer than patients transferred via short distance. Multivariate analysis showed that low body mass index (BMI) and long distance were independent predictive factors for the primary outcome. Conclusions: When patients with advanced HF are transferred from far distant hospitals or with low BMI, it may be necessary to devise various measures for interhospital transport.

A Cold-Blooded Tiptoer: Nonresolving Cellulitis in an Immunocompromised Patient.

Mycobacterium haemophilum is a nontuberculous mycobacteria (NTM) with a predilection for skin and soft tissue infection (SSTI) in the immunocompromised host. We report a case of disseminated M haemophilum infection initially presenting as a nonresolving subacute cellulitis of bilateral lower extremities. Genetic sequencing was used for final identification, while a commercially available polymerase chain reaction test returned a false-positive result for Mycobacterium intracellulare. Consequently, we highlight the importance of M haemophilum as a major differential diagnosis of SSTI in the immunocompromised host and the need for careful interpretation of rapid diagnostic tests.

Sarcopenia and risk of infection in adult heart transplant recipients in Japan.

AIMS: Heart transplantation (HT) is an effective therapeutic option for end-stage heart failure. Infection is a major cause of morbidity and mortality after HT. Sarcopenia, defined as the loss of muscle mass and strength, is a common comorbidity in HT candidates with end-stage heart failure. However, the effects of sarcopenia on the occurrence of post-HT infections are not well understood. Therefore, we explored the association between the skeletal muscle mass and post-transplant infections in adult HT recipients. METHODS AND RESULTS: We retrospectively examined the records of 135 patients who underwent HT between August 2007 and November 2019 at our institution. Pre-transplant computed tomography was used to calculate the skeletal muscle index (SMI) at the level of the third lumbar vertebra. Muscle wasting was defined as the SMI of the lowest sex-based tertiles. The primary endpoint was infections within 6 months of HT. The study included 109 patients (80 men, mean age: 41.6 ± 12.0 years): 37 patients in the muscle wasting group and 72 patients in the non-muscle wasting group. The mean SMI values in the muscle wasting and non-muscle wasting groups were 29.9 ± 4.8 cm2 /m2 and 40.7 ± 6.7 cm2 /m2 , respectively. Prior to HT, 108 (99.1%) patients were on left ventricular assist device support, and during that support, the rate of late right heart failure was significantly higher in the muscle wasting group than non-muscle wasting group (P = 0.012). Sixteen infections occurred within 6 months of HT. The most common infection sites included the respiratory tract (n = 5) and the upper gastrointestinal tract (n = 5), followed by the urinary tract (n = 4). Overall, 10 patients experienced infections in the muscle wasting group (27.0%) and 6 in the non-muscle wasting group (8.3%) (P = 0.009). Two patients in the muscle wasting group required intensive care unit admission, compared to none in the non-muscle wasting group. Low skeletal muscle mass was associated with infections in the univariate and multivariate logistic regression models (hazard ratio: 3.68, 95% confidence interval: 1.19-11.3; P = 0.023). However, the duration of all-cause mortality within 3 years did not differ between the groups (P = 0.56). CONCLUSIONS: Low skeletal muscle mass is a predictor of post-HT infections within 6 months of HT.

Late-onset right ventricular failure after continuous-flow left ventricular assist device implantation: case presentation and review of the literature.

With the widespread use of implantable left ventricular assist device (LVAD), right ventricular failure (RVF) has become a serious problem that becomes apparent several weeks or later after LVAD implantation. However, there are no marked preoperative signs of RVF. This is called late-onset RVF and is currently a major problem leading to long-term complications following implantable LVAD use. Pathogenically, this could be the result of left ventricular suction by LVAD that causes the septum shift to the left ventricular side. This causes a change in morphology of the right ventricle, resulting in impaired right ventricular function. Aortic insufficiency and ventricular arrhythmia, which are also important as long-term complications after LVAD implantation, are considered to be closely involved in the onset and progression of RVF. Once late-onset RVF develops, exercise capacity declines and inotrope administration may be required. Late-onset RVF was also reported to be significantly associated with increased mortality. Several predictors of RVF have been proposed such as preoperative left ventricular diastolic dimension <64 mm, tricuspid valve annulus diameter ≥41 mm, and so on. However, some reports identified no predictors. The basic treatment strategy for late-onset RVF is to optimize volume status by administering diuretics and ensuring inotrope as needed. ß-blockers and antiarrhythmic agents often need to be reduced in terms of dosage or even discontinued because these might reduce right ventricular function. Although their efficacy is unclear, pulmonary vasodilators may be used to reduce right ventricular afterload. It is better to decrease the rotation speed of LVAD to minimize the displacement of the septum; however, this is often difficult because the required flow rate cannot be secured. Progress in the prevention and management of late-onset RVF is required because the number of patients who require longer-term LVAD support will increase with the spread of LVAD use as destination therapy.

Long-Term renal function after implantation of continuous-flow left ventricular assist devices: A single center study.

BACKGROUND: Implantable continuous-flow left ventricular assist device (LVAD) improve renal function in advanced heart failure. However, the long-term effects of LVAD on renal function have not been investigated thoroughly. We aimed to assess long-term renal function in patients with LVAD support and to identify predictors for late deterioration in renal function (LDRF). METHODS: One hundred patients underwent LVAD implantation as a bridge to transplant at the University of Tokyo Hospital between May 2011 and December 2018. We assessed renal function at intervals (preoperative, 1, 6, 12, 18, 24 and 30 months after LVAD implantation). We divided patients into two groups: "with LDRF," whose renal function at 30 months had decreased by >25% compared with preoperatively (n = 14), and "without LDRF" (n = 55). RESULTS: Renal function improved at 1 month, returned to preoperative levels at 6 months, and remained there up to 30 months after LVAD implantation. However, renal function impairment became evident in patients with LDRF 18 months after LVAD implantation. A ratio of right atrial pressure/pulmonary artery wedge pressure > 0.57 and left ventricular dimension diastole ≤ 67 mm were preoperative independent risk factors for LDRF. In addition, the incidence of perioperative acute kidney injury, ventricular arrhythmia, aortic insufficiency, and late right ventricular failure was significantly higher in patients with LDRF. CONCLUSION: LDRF after LVAD implantation corresponded to several risk factors, including a small left ventricle and LVAD-related complications, such as right ventricular failure.

Case Report: A Case of Acute Cellular Rejection Due to Atopic Dermatitis Exacerbation 3 Years After Heart Transplantation.

Background: Little evidence has been presented about the association between previous atopic/allergic disease and graft rejection after solid organ transplantation. Thus, we present a case wherein acute cellular rejection (ACR) after heart transplantation (HTx) was noted along with exacerbation of atopic disease. Case Summary: A 32-year-old man was admitted at our hospital for regular monitoring of graft rejection. He had undergone heart transplant 3 years prior due to dilated cardiomyopathy. Echocardiogram revealed good biventricular function, and no abnormal findings were found in blood sampling tests. However, biopsy showed moderate ACR [Grade 2R(ISHLT 2004)/3A(ISHLT 1990)], which required twice-repeated steroid pulses with intensified immunosuppression. Meanwhile, his atopic dermatitis, which was diagnosed before having heart failure, was getting worse for the past 6 months. The exacerbation of atopic dermatitis was presumed to be related to the development of the intractable cellular rejection. Discussion: This case suggested the association of atopic disease and graft rejection after HTx. We examined 76 patients from a cohort of previous studies who underwent HTx at our hospital, which suggested that patients with atopic/allergic disorders such as atopic dermatitis and asthma tended to have a significantly higher frequency of moderate rejection than non-allergic patients. (p = 0.012; Fisher's exact test). Our case also suggests that exacerbation of atopic dermatitis might cause graft rejection of the transplanted organ, so that it is important to carefully evaluate the risk of graft rejection if there is a previous history of atopic/allergic disease.

Carbon Monoxide Diffusing Capacity Predicts Cardiac Readmission in Patients Undergoing Left Ventricular Assist Device Implantation in Japan.

Carbon monoxide diffusion capacity (DLCO) is impaired in heart failure patients; however, its clinical impact has not been well investigated in the left ventricular assist device (LVAD) population. We explored the predictive value of preoperative DLCO in the survival and cardiac readmission rates after LVAD implantation. Seventy-six patients who received continuous-flow LVAD as bridge-to-transplant therapy from November 2007 to September 2018 and underwent pulmonary function test before LVAD implantation were included. The primary study endpoints were death and readmission for heart failure or arrhythmia (cardiac readmission). Patients were stratified into two groups according to the percent of predicted DLCO (%DLCO). Pulmonary vascular resistance (PVR) was equivocal between the groups preoperatively, whereas the low DLCO group (%DLCO < 80%) showed significantly high PVR postoperatively. The mortality rate was not different between the groups. The 2 year cardiac readmission rate was 33.5% in the low DLCO group and 8.7% in the high DLCO group (%DLCO ≥ 80%) (P = 0.028). The %DLCO was associated with cardiac readmission in univariate and multivariate analyses (hazard ratio: 4.32; 95% CI: 1.50-15.9; P = 0.005). Low %DLCO was associated with high PVR postoperatively and was a risk factor for cardiac readmission after LVAD implantation.

Association between infectious event and de novo malignancy after heart transplantation.

The aim of the study was to investigate the incidence of and risk factors for de novo malignancy after heart transplantation (HTx) in a single center. We assessed 102 consecutive patients who received HTx and were followed-up in our center regularly for > 1 year from June 2006 to May 2018. We investigated the incidence of and risk factors for de novo malignancy. The cumulative incidence of each malignancy type during the follow-up period was one (0.98%) for skin cancer, four (3.92%) for nonskin solid organ cancer, and six (5.88%) for posttransplant lymphoproliferative disorder (PTLD). The percentage of patients with more than one infectious event ≤ 1 year after HTx was higher in the malignancy group than in the non-malignancy group. Furthermore, Kaplan-Meier analysis revealed that the incidence rate of infectious events was higher in patients with malignancies than in those without (log-rank P < 0.001). After dividing malignancies into a PTLD group and a solid organ malignancy group, we found that negative Epstein-Barr virus serostatus, cytomegalovirus-positive antigenemia, and the occurrence of any viral or gastrointestinal infectious event at ≤ 1 year were more frequent in patients with PTLD than in patients without it. The survival rate was significantly lower for patients with solid organ malignancy than for patients without malignancy. In conclusion, there was a correlation between infectious events and de novo malignancy, particularly in patients with PTLD. We should confirm this finding by conducting a larger cohort study.

Differences in the prognoses of patients referred to an advanced heart failure center from hospitals with different bed volumes.

Few reports have discussed appropriate strategies for patient referrals to advanced heart failure (HF) centers with available left ventricular assist devices (LVADs). We examined the association between the characteristics and prognoses of referred patients with advanced HF and the bed volume of the referring hospitals. This retrospective analysis evaluated 186 patients with advanced HF referred to our center for consultation about the indication of LVAD between January 1, 2015, and August 31, 2018. We divided the patients into two groups according to the bed volume of their referring hospital (high bed volume hospitals (HBHs): ≥ 500 beds in the hospital; low bed volume hospitals (LBHs): < 500 beds). We compared the primary outcome measure, a composite of LVAD implantation and all-cause death, between the patients referred from HBHs and patients referred from LBHs. The 186 patients with advanced HF referred to our hospital, who were referred from 130 hospitals (87 from LBHs and 99 from HBHs), had a mean age of 43.0 ± 12.6 years and a median left ventricular ejection fraction of 22% [15-33%]. The median follow-up duration of the patients was 583 days (119-965 days), and the primary outcome occurred during follow-up in 42 patients (43%) in the HBH group and 20 patients (23%) in the LBH group. Patients referred from HBHs tended to require catecholamine infusion on transfer more often than those referred from LBLs (36.5% (HBH), 20.2% (LBL), P = 0.021). Kaplan-Meier analysis indicates that the occurrence of the primary outcome was significantly higher in the HBH patients than in the LBH patients (log-rank P = 0.0022). Multivariate Cox proportional hazards analysis revealed that catecholamine support on transfer and long disease duration were statistically significant predictors of the primary outcome. Patients from HBHs had a greater risk of the primary outcome. However, the multivariate analysis did not indicate an association between referral from an HBH and the primary outcome. In contrast, catecholamine support on transfer, long duration of disease, and low blood pressure were independent predictors of the primary outcome. Therefore, these should be considered when determining the timing of a referral to an advanced HF center, irrespective of the bed volume of the referring hospital.

Takotsubo syndrome in the same heart before and after heart transplantation.

Heart transplantation is an effective therapy for patients with end-stage heart failure. In some cases, Takotsubo syndrome (TTS) was seen in the donor heart. We report a case of TTS in a 40-year-old woman with a history of epileptic seizures who underwent heart transplantation from a donor with TTS. The donor was brain-dead due to severe hypoxic encephalopathy during cardiac arrest with TTS. Fifteen months after heart transplantation, she was readmitted for epileptic seizures. Electrocardiogram showed T-wave inversion, and transthoracic echocardiography showed apical ballooning. Coronary angiography was normal, and endomyocardial biopsy was negative for rejection. Iodine-123 metaiodobenzylguanidine imaging demonstrated a low heart-to-mediastinum ratio and high washout rate. Eighteen days after admission, recovery of left ventricular dysfunction was confirmed, and she was diagnosed with TTS triggered by epileptic seizures. It is important to recognize the risk of recurrent TTS in heart transplantation patients from a donor with TTS.

Impact of tacrolimus versus cyclosporin A on renal function during the first year after heart transplant.

AIMS: Nephrotoxicity of calcineurin inhibitors (CNIs) is associated with adverse events in patients undergoing heart transplant (HTx), although studies directly comparing tacrolimus (TAC) versus cyclosporin A (CsA), especially in combination with everolimus and low-dose CNIs approach, are limited. Thus, we sought to investigate the associations of TAC and CsA with clinical outcomes in HTx recipients, with specific focus on renal function. METHODS AND RESULTS: From August 2007 to February 2017, 72 consecutive patients (39 treated with TAC vs. 33 with CsA) receiving de novo HTx in a single transplant centre were retrospectively evaluated. We used the instrumental variable method to account for unmeasured confounding. The study outcomes were percentage change in estimated glomerular filtration rates (eGFR) (safety endpoint) and biopsy-proven acute rejection (efficacy endpoint) within the first year after HTx. The enrolled patients (median age 40 years) were predominantly men (68%). There were no significant differences in baseline characteristics, including eGFR (64.8 [45.7-96.4] mL/min/1.73 m2 in TAC vs. 65.6 [57.9-83.0] mL/min/1.73 m2 for CsA; P = 0.48), other than sex (male, 49% for TAC vs. 91% for CsA; P < 0.001) between the two groups. Within the first year after HTx, 23 (59%) in the TAC group switched mycophenolate mofetil to everolimus, whereas 16 (48%) in the CsA group (P = 0.52). At 12 months, the rates of mortality and end-stage renal disease requiring renal replacement therapies were both 0%. In the instrumental variable analysis, no differences in renal function as well as graft rejection for 1 year after HTx existed between the TAC and CsA groups. These results were similar when taking into account of everolimus use. CONCLUSIONS: Irrespective of everolimus use with low-dose CNIs, our analysis using the instrumental variable method showed no differences in renal function as well as graft rejection during the first year after HTx between HTx recipients who received TAC or CsA.