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.

De novo malignancy in heart transplant recipients: A single center experience in Japan.

BACKGROUND: Because of aggressive immunosuppression, heart transplant recipients have a high risk of de novo malignancy, which is a major cause of death and worse prognosis, regardless of the type. However, the impact of de novo malignancy on Japanese heart transplant recipients is unknown. METHODS: We analyzed 103 Japanese heart transplant recipients over 18-years-old at the time of transplantation between April 1999 and April 2017. Patient characteristics and prognosis were compared between heart transplant recipients with or without de novo malignancy after heart transplantation (HTx). Additionally, univariate and multivariate analyses for the risk factors of de novo malignancy after HTx were performed. RESULTS: De novo malignancy developed in 7 patients (6.8%; post-transplant lymphoproliferative disorders, n=3; Bowen's disease, n=1; colon cancer, n=2; bladder cancer, n=1). Follow-up time and previous antibody mediated rejection (AMR)≥grade 1 were risk factors of de novo malignancy after HTx in multivariate analysis (OR: 1.19, 95% CI: 1.00-1.42, p=0.043; and OR: 10.7, 95% CI: 1.37-83.68, p=0.038, respectively). History of malignancy was a potential risk factor, albeit not significant (OR: 23.05, 95% CI: 0.99-534.53, p=0.071). The survival rates in patients with de novo malignancy was significantly lower than in those without de novo malignancy (3-year survival rate: 100% versus 67%, p=0.0025). CONCLUSIONS: Long follow-up time and previous AMR≥grade 1 were risk factors of de novo malignancy after HTx. Japanese heart transplant recipients with de novo malignancy have worse prognosis; therefore, screening examinations are important for early diagnosis.

Clinical determinants of successful weaning from extracorporeal membrane oxygenation in patients with fulminant myocarditis.

AIMS: Patients with fulminant myocarditis (FM) often present with cardiogenic shock and require mechanical circulatory support, including extracorporeal membrane oxygenation (ECMO) and ventricular assist device (VAD) implantation. This study sought to clarify the determinants of successful weaning from ECMO in FM patients. METHODS AND RESULTS: We studied 37 consecutive FM patients supported by ECMO as the initial form of mechanical circulatory support between January 1995 and December 2014 in our hospital. Twenty-two (59%) patients were successfully weaned from ECMO, while 15 (41%) were not. There were significant differences in levels of peak creatine kinase and those of its MB isoform (CK-MB), left ventricular posterior wall thickness (LVPWT), and prevalence of cardiac rhythm disturbances. Receiver operating characteristic curve analysis revealed that a peak CK-MB level of 185 IU/L and LVPWT of 11 mm were the optimal cut-off values for predicting successful weaning from ECMO (areas under the curve, 0.89 and 0.85, respectively). During the follow-up [median 48 (interquartile range 8-147) months], 83% of FM patients who were weaned from ECMO survived, with preserved fractional shortening based on echocardiography. Of the 15 FM patients who were not weaned from ECMO, nine bridged to VAD, and only two were successfully weaned from VAD and survived. CONCLUSIONS: These results indicate that myocardial injury, as evidenced by CK-MB and LVPWT, and prolonged presence of cardiac rhythm disturbances are important clinical determinants of successful weaning from ECMO.

Impact of mitral valve intervention with left ventricular assist device implantation on postoperative outcomes and morphologic change.

Although mitral regurgitation (MR) is prevalent in patients with end-stage heart failure, the impact of mitral valve (MV) surgery on outcomes after left ventricular assist device (LVAD) implantation and morphologic changes of MV remains unclear. We retrospectively reviewed 74 patients who underwent LVAD implantation as a bridge to transplant. Of these, 11 (15%) underwent MV repair concomitant with or prior to LVAD implantation, while 27 patients with preoperative significant (moderate or greater) MR did not undergo concomitant MV surgery. The mean interval between LVAD implantation and the last echocardiographic examination was 913 days. Irrespective of MV surgery, significant LV reverse remodeling including decreased LV and left atrial dimension and improved MR severity was observed in all patients except for patients with prior MV surgery. Histopathological examination of explanted hearts removed at heart transplantation (n = 69) or autopsy (n = 5) revealed that the MV annulus was still dilated (mean perimeter 11.7 cm) in the patients with preoperative significant MR and no concomitant MV surgery. Concomitant MV surgery at the time of LVAD implantation for significant MR might not be always necessary for bridge to transplant or destination therapy cases. However, it might be required in patients having potential for cardiac recovery or patients with severe pulmonary hypertension and depressed right ventricle.

Detecting Cardiac Sarcoidosis with a Right Atrial Mass Using Transthoracic Echocardiography.

An asymptomatic 40-year-old woman with a first-degree atrioventricular block presented a right atrial mass in transthoracic echocardiograms. Transesophageal echocardiograms showed abnormally thickened tissue on the interatrial septum, which extended around the aortic annulus. Multimodality examinations demonstrated lesions in the heart, lungs, liver, and spleen, suggesting sarcoidosis. She was diagnosed with cardiac sarcoidosis after we detected granulomas in a lung specimen. A right atrial mass shrunk following steroid therapy. We should therefore consider the possibility of cardiac sarcoidosis when we see wall thickening and a mass echo in the atrium. These signs may point to an early-phase lesion of cardiac sarcoidosis.

Serum Brain Natriuretic Peptide Concentration 60 Days After Surgery as a Predictor of Long-Term Prognosis in Patients Implanted With a Left Ventricular Assist Device.

Mechanical circulatory support by a left ventricular assist device (LVAD) is used to bridge patients with advanced heart failure to transplant or as a definitive treatment. We retrospectively sought predictors of long-term outcome in a cohort of 83 patients who had undergone LVAD treatment. We subjected perioperative clinical data of patients to statistical analysis to establish parameters associated with all-cause mortality, and the cutoff values, sensitivity, and specificity of those that had a statistically significant relation with survival. Mean follow-up was 717 days (standard deviation, 334 days; range, 17-1,592 days). Fourteen patients (16.8%) died, but nine (10.8%) were weaned from support. Serum brain natriuretic peptide (BNP) concentration measured 60 days after implantation was significantly associated with all-cause mortality. The optimal BNP cutoff value to predict death during LVAD support was 322 pg/ml, with a sensitivity of 71.4% and specificity of 79.8%. Two-year survival was 92.0% in those with 60 days serum BNP concentration <322 pg/ml compared with 70.5% in those in whom it was ≥322 pg/ml (p = 0.003). The relation between BNP and survival likely reflects recovery of native myocardial function and improvements in global health and should assist clinicians in the on-going management of long-term LVAD therapy.

Left coronary artery occlusion caused by a large thrombus on the left coronary cusp in a patient with a continuous-flow ventricular assist device.

Despite continual improvements in ventricular assist device (VAD) therapy, various clinical issues are emerging. Importantly, various types of thromboembolic complications have been reported to date. Recently, we encountered a rare continuous-flow VAD-related thromboembolic event that resulted in acute myocardial infarction. A 26-year-old female who just underwent HeartMate II(®) VAD implantation suddenly developed widespread anterolateral myocardial infarction on postoperative day 16. Echocardiography and aortography revealed a large thrombus on the left coronary cusp of the aortic valve that almost completely occluded the left coronary ostium. After VAD implantation, her aortic valve did not open, even at relatively low pump speeds; this was thought to be one of the causes for thrombus formation. Continuous suction of blood from the left ventricle and non-pulsatile flow into the ascending aorta resulted in a continuously closed aortic valve and stagnation of blood in the coronary cusp. Furthermore, both small body size (body surface area <1.3 m(2)) and postoperative right ventricular failure may have exacerbated blood stagnation and thrombus formation in this patient. We should have adjusted the anticoagulation and antiplatelet therapy protocols based on the patient's condition. She underwent off-pump coronary artery bypass surgery and remained in clinically stable condition afterwards.

Progression of isolated tricuspid regurgitation late after left-sided valve surgery. Clinical features and mechanisms.

BACKGROUND: Severe tricuspid regurgitation (TR) sometimes develops late after left-sided valve surgery without left heart failure, pulmonary hypertension or rheumatic tricuspid valve. The purpose of the present study was to investigate clinical characteristics and mechanisms of severe isolated TR late after left-sided valve surgery. METHODS AND RESULTS: A total of 372 consecutive patients who underwent left-sided valve surgery between 1990 and 2003 and who were followed up with echocardiography for at least 5 years, were retrospectively investigated. The mean follow-up period was 9.4 years. Clinical background, preoperative and postoperative echocardiographic parameters were evaluated. Among the 372 patients, severe isolated TR was detected in 23 patients, which developed at a mean of 8.6 years after surgery. Twenty-two of 23 patients had undergone mitral valve surgery. Multivariate logistic regression analysis identified the presence of preoperative atrial fibrillation and preoperative ejection fraction as independent determinants for the development of severe isolated TR. In patients with severe isolated TR, the tricuspid annular diameter and the right atrial area were already enlarged early after surgery and both of these increased prior to TR progression. CONCLUSIONS: Severe isolated TR developing late after mitral valve surgery is not uncommon, thus it is important to recognize this disease entity. Annular dilatation was the main cause of isolated TR and serial echocardiographic data are important to detect progression of isolated TR and to assess its mechanisms.

Marked elevation of soluble fas ligand and cytokine secretion after splenectomy in aggressive natural killer cell leukemia/lymphoma.

We report a case of Epstein-Barr virus-associated aggressive natural killer cell leukemia/lymphoma with giant splenomegaly in which splenectomy resulted in progression of apoptosis and hemophagocytosis. The serum level of ferritin, triglycerides, interferon-gamma (IFN-gamma), interleukin 10 (IL-10), and soluble Fas ligand (sFasL) increased markedly, and liver damage progressed after splenectomy. The number of apoptotic cells in peripheral blood smears increased following splenectomy. In the present case, splenectomy caused disruption of the cytokine network, resulting in apoptosis of blood cells and hepatocytes, as well as phagocytosis.