The mid-term outcomes of aortic root replacement after surgical repair for CHD.

OBJECTIVE: The purpose of this study is to assess the mid-term outcomes of aortic root replacement after repair of CHDs. METHOD: This is a single-institutional retrospective, cohort study with consecutive patients undergoing aortic root replacement after surgical repair of CHDs between 1999 and 2022. Operative indications included aortic root dilatation with/without aortic insufficiency, sinus of Valsalva rupture, or aortic dissection involving the root. RESULTS: Forty-four patients (36 male and 8 female) were enrolled. Mean age at the root replacement was 36.6 ± 11.9 years. The most frequent primary diagnosis was congenital aortic stenosis (n = 10) and ventricular septal defect (n = 10). Mean time from the surgical repair to aortic root replacement was 26.6 ± 13.0 years. Operative indications were aortic root enlargement with or without aortic valve aetiology (n = 40), sinus of Valsalva rupture (n = 2), and aortic dissection (n = 2). Forty-two patients underwent valve-replacing aortic root replacement, and two patients underwent valve-sparing, with 40 concomitant procedures. The median follow-up was 3.5 (1.3-7.6) years. There were one early and five late mortalities and five cardiovascular-related reoperations. Actuarial survival at 5-10 years after root replacement was 81.0 ± 6.6%. The cumulative incidence of cardiovascular-related reoperation and aortic root or valve-related reoperation at 5 years after root replacement was 11.9% and 5.6%, respectively. CONCLUSION: The early and mid-term outcomes of aortic root replacement for patients with a history of repair of CHDs were favourable in terms of survival and aortic root or valve-related reoperation.

Sick sinus syndrome concomitant with myopathy associated with anti-mitochondrial antibodies: a case report.

Background: Anti-mitochondrial antibody (AMA)-associated myopathy is known to be concomitant with primary biliary cirrhosis and to cause both skeletal muscle disorders and arrhythmias, myocardium disorders, and respiratory muscle disorders. We report a case of AMA-associated myopathy in which the bradycardia-related symptoms preceded the skeletal muscle symptoms. Case summary: A 59-year-old woman visited the emergency room in our hospital following a syncopal event. The patient was bradycardiac (45 b.p.m.) with a junctional rhythm resulting from sick sinus syndrome (SSS) and was suffering from heart failure. Blood tests revealed elevated creatine kinase (CK) and hepatic enzymes. She underwent permanent pacemaker implantation. However, it proved difficult to detect the electrical potential in the right atrium. Although successful atrial pacing was achieved at the lower right atrial septum, the atrial threshold was markedly high and she depended on ventricular pacing. One year later, neurological examination and muscle biopsy confirmed the diagnosis of AMA-associated myopathy. Following this diagnosis, steroid pulse therapy was initiated. Steroid administration relieved her symptoms and lowered the CK levels but the atrial standstill persisted. The patient takes low-dose prednisolone and has had an uneventful course for 3 years. Discussion: To the best of our knowledge, this is the first case of AMA-associated myopathy diagnosed by the first symptom related to bradycardia due to SSS. Patients with AMA-associated myopathy can experience a variety of cardiac symptoms, including arrhythmias, and initially complain of cardiac symptoms without symptoms of skeletal myopathy. This disease should be considered when diagnosing patients with arrhythmia and elevated CK.

Smooth muscle differentiation of coronary intima in autopsy tissues after sirolimus-eluting stent implantation.

BACKGROUND: In coronary atherosclerotic disease, the proliferation of intimal smooth muscle cells (SMCs) is regarded as beneficial with respect to stable and unstable plaques, but is thought detrimental in discussions on coronary stent restenosis. To resolve this discrepancy, we focused on the quality, not quantity, of intimal SMCs in coronary atherosclerotic disease. METHODS: Autopsied coronary artery specimens from seven patients implanted with bare metal stents (BMS), three with paclitaxel-eluting stents (PES), and 10 with sirolimus (rapamycin)-eluting stents (SES) were immunostained for SMC markers. Cultured human coronary artery SMCs were also treated with sirolimus and paclitaxel. RESULTS: Intimal SMC differentiation, estimated by the ratio of h-caldesmon+ cells to α-smooth muscle actin+ (α-SMA+) cells, was significantly increased whereas dedifferentiation, estimated from the ratio of fibroblast activation protein alpha (FAPα)+ cells to α-SMA+ cells, was significantly decreased, in tissues of SES compared with BMS cases. No difference in the degree of differentiation was found between PES and BMS cases or between the three groups in nonstented arteries used as controls. Correlation analyses for each field of view revealed a significant positive correlation between h-caldesmon and calponin staining but significant negative correlations with FAPα staining in α-SMA+ cells. Cultured SMCs were shorter (dedifferentiated) and showed an increased FAPα/α-SMA protein when treated with paclitaxel, whereas they became elongated (differentiated) and showed increased calponin/α-SMA proteins with sirolimus. CONCLUSIONS: The SMCs of the coronary intima may differentiate after SES implantation. SMC differentiation may explain both the plaque stabilization and reduced risk of reintervention associated with SES.

A case of neuroendocrine carcinoma with massive invasion to the liver and multiorgan causing acute liver failure.

INTRODUCTION: Acute liver failure (ALF) due to a malignant neoplasm is rare. Here, we present a case of neuroendocrine carcinoma (NEC) with massive invasion to the liver and multi-organ causing ALF that resulted in a poor outcome. A 56-year-old man was referred to our hospital for ALF of unknown cause. Abdominal imaging studies revealed hepatomegaly with multiple intrahepatic lesions. The patient also showed disseminated intravascular coagulation. Despite administration of prednisolone for the ALF, he died suddenly of respiratory failure on day 3 after admission. Autopsy showed a markedly enlarged liver weighing 4,600 g with diffuse nodular lesions. The tumors had metastasized to the lungs, spleen, adrenal glands, and bone marrow. Severe pulmonary hemorrhage was also noted. Histologically, the tumors were poorly differentiated and composed of small-sized and uniform neoplastic cells, positive for chromogranin A, synaptophysin, CD56, and p53 with a Ki-67 labeling index of over 50%. As there was no primary lesion in the gastrointestinal tract, pancreas, or other organs, primary hepatic neuroendocrine carcinoma (PHNEC) was suspected. CONCLUSION: We experienced a case of NEC causing ALF and multi-organ invasion with a rapidly deteriorating course. Liver metastasis from a neuroendocrine tumor/neoplasm is common, while a primary hepatic neuroendocrine tumor/neoplasm is extremely rare. We could not determine PHNEC; however, it was highly suspected. Further studies are needed to elucidate the pathogenesis of this rare disease.

Clinical Validation of a Neointima-Inducing Inflow Cannula in a Continuous Flow Left Ventricular Assist Device.

Wedge thrombus formation around the inflow cannula of a continuous left ventricular assist device (LVAD) is a source of systemic thromboemboli. We previously reported the potential advantages of a new inflow cannula wrapped with titanium mesh (GU30) over the standard smooth surface oblique cut cannula (GU10). The objective of the present study was to clinically validate this new cannula. A retrospective cohort analysis of patients with implanted LVAD (EVAHEART) comparing the GU10 to the GU30 was conducted. Clinical outcomes, including survival, the incidence of thromboembolism, and bleeding events, were compared. Gross and histopathological analyses of explanted GU30 cannula were conducted following transplant or patient death. No significant differences in the survival rate, severe emboli, or cerebral bleeding were observed during the LVAD implantation. However, severe emboli occurred earlier after LVAD implantation when using the GU30 cannula compared with the GU10. In cases of long LVAD support, the neointima fully covered the inflow of the GU30 cannulae without wedge thrombus formation. The titanium mesh-wrapped inflow cannulae did not reduce the overall incidence of neurological events significantly. However, the titanium mesh-wrapped inflow cannula induced autologous neointimal growth over the cannula and prevented wedge thrombus formation in late-phase LVAD implantation.

Inhibition of extracellular matrix integrity attenuates the early phase of aortic medial calcification in a rodent model.

BACKGROUND AND AIMS: The mechanism of vascular calcification (VC) resembles that of bone metabolism, and a correlation has frequently been reported between calcification and vascular extracellular matrix (ECM) regulating its integrity; however, the detailed mechanisms remain unclear. In this study, we examined how the vascular ECM, especially collagen metabolism, is involved in the process of VC. METHODS: VC was modeled using 5-week-old male Sprague-Dawley rats fed a diet containing warfarin and vitamin K1 (WVK). Additionally, ß-aminopropionitrile (BAPN) was administered to inhibit lysyl oxidase (LOX), which is an enzyme that mediates collagen cross-linking. Harvested aortic samples were analyzed by staining with alizarin red (AR), immunohistochemistry (IHC), transmission electron microscopy (TEM), and ex vivo microcomputed tomography (µCT). RESULTS: Rats fed WVK developed increasing numbers of aortic medial calcifications (AMCs) over time. TEM images indicated punctate calcification within collagen fibers in the early phase of AMC. AR staining of translucent samples revealed the distribution and severity of calcification, and these lesions were significantly decreased in the BAPN group. Three-dimensional reconstructed µCT images that allowed the quantification of calcified volumes revealed that BAPN significantly reduced the bulk of calcification. Moreover, IHC showed that both LOX and collagen I were present around the sites of AMC, and thus the IHC-positive area was reduced in the BAPN group compared to the WVK group. CONCLUSIONS: The results indicated that inhibition of LOX by BAPN attenuated AMC, and that collagen metabolism plays a significant role in the early pathogenesis of VC.

Histological features of endomyocardial biopsies in patients undergoing hemodialysis: Comparison with dilated cardiomyopathy and hypertensive heart disease.

BACKGROUND: Heart failure is a frequently occurring complication in patients on maintenance hemodialysis (HD). However, the histological features of right ventricular endomyocardial biopsy (RVEMB) samples remain unclear. METHODS: The clinical characteristics and histological findings of consecutive patients undergoing HD with available RVEMB samples (HD group; n=28) were retrospectively compared with those of patients with dilated cardiomyopathy (n=56) and hypertensive heart disease (n=15). RESULTS: The mean myocyte diameter was significantly larger in the HD group than in the other groups (P<.001), whereas the mean percent area of fibrosis did not differ among the three groups. Immunohistochemical analysis revealed that the capillary density was significantly lower in the HD group compared with the other groups (P<.001), and it was positively associated with left ventricular ejection fraction (P=.014). The number of CD68-positive macrophages, which was significantly higher in the HD group compared with the other two groups (P<.001), was associated with cardiovascular mortality (P=.020; log-rank test). CONCLUSIONS: Myocyte hypertrophy, macrophage infiltration, and reduced capillary density were characteristic histological features of the RVEMB samples in patients undergoing HD, which may be related to the pathogenesis of cardiac dysfunction.

Characteristics of patients with advanced heart failure having eosinophilic infiltration of the myocardium in the recent era.

Eosinophilic infiltration of the myocardium is occasionally observed as an incidental histological finding in endomyocardial biopsy specimens before heart transplantation (HTx) as well as in explanted heart obtained at the time of HTx. However, the indications for HTx in these patients have not yet been fully established. We investigated the pre-HTx characteristics of the recipients with myocardial eosinophilic infiltration in the explanted heart and diagnosed as hypersensitivity myocarditis (HSM) (21 among 761 recipients, 2.8%). Dobutamine, a common cause of HSM, was administered to 12 patients (57%). Ten patients (47.6%) were on milrinone and 4 (19.0%) were on ventricular assist devices. Post-transplant survival of HSM patients was comparable to that of patients transplanted for active myocarditis or other cause of heart failure. In conclusion, myocardial eosinophilic infiltration is associated with multiple medications in patients with advanced heart failure; however, it does not affect the post-transplant prognosis.

Outcome of patients having heart transplantation for lymphocytic myocarditis.

Heart transplantation (HT) for myocarditis has been controversial because of earlier reports of a poor prognosis after the procedure. We sought to determine whether lymphocytic myocarditis (LM) at the time of HT affects cardiac allograft rejection and survival after HT compared with other patients without LM in the current era of HT. We retrospectively reviewed 759 consecutive patients who underwent de novo HT at Columbia University Medical Center between 2000 and 2010 and compared prognosis after HT of the patients with pathologically proven LM in their explanted hearts with that of age- and gender-matched patients with idiopathic dilated cardiomyopathy (IDC group; n = 96) and with ischemic cardiomyopathy (IC group; n = 64). Thirty-two patients (4.2%) had LM in the explanted hearts pathologically. Among the 3 groups, no statistically significant difference was observed in the number of biopsy-diagnosed acute cellular rejection (ACR; International Society for Heart & Lung Transportation grade ≥2R) events during the first year after HT. In contrast, the frequency of biopsy-diagnosed ACR in subsequent years was greater in the LM group (n = 8, 3.8%) than in IC group (n = 3, 0.5%, p = 0.006), although no different from that of patients with IDC. The frequency of antibody-mediated rejection and posttransplant survival did not differ among the 3 groups. In conclusion, patients with pre-HT LM have an increased frequency of late ACR after HT compared with patients with IC. Nevertheless, survival of LM patients after HT is comparable to that of patients transplanted for IDC or IC.

Hypersensitivity myocarditis and outcome after heart transplantation.

BACKGROUND: Hypersensitivity myocarditis (HSM) is associated with the use of multiple drugs and has been occasionally observed in patients awaiting heart transplantation (HTx). However, whether HSM at the time of HTx affects long-term prognosis, including acute cellular rejection (ACR) and antibody-mediated rejection (AMR), after HTx remains unclear. METHODS: Between 2000 and 2010, 759 consecutive patients underwent de novo HTx at Columbia University Medical Center and were retrospectively reviewed. Clinical characteristics and pathologic findings of patients with a pre-HTx HSM diagnosed by histologic evaluation of the explanted heart were analyzed. Prognosis after HTx was compared between patients with and without pre-HTx HSM. RESULTS: HSM was observed in 21 patients (2.7%), but in no case was HSM clinically diagnosed. Twelve patients (57%) had received dobutamine infusions. HSM patients had varying degrees of perivascular or interstitial eosinophilic infiltrates with rare necrosis in the explanted heart. The number of biopsy specimens diagnosed with ACR (International Society for Heart and Lung Transplantation Grade ≥2R) was 11 (3.9%) in HSM patients and 197 (2.2%) in patients without HSM (p = 0.06) during the first year post-HTx, and 11 (3.8%) in HSM patients and 78 (1.5%) in patients without HSM (p = 0.006) after the second year post-HTx. Post-HTx survival did not differ in patients with or without pre-HTx HSM. CONCLUSIONS: HSM at the time of HTx is associated with an increased frequency of late ACR after HTx. Post-HTx survival is not influenced by pre-HTx HSM.

Cardiac transplantation in patients with hypertrophic cardiomyopathy.

Cardiac transplantation is a treatment option for patients with hypertrophic cardiomyopathy (HC) who developed refractory heart failure and/or intractable arrhythmia. However, the pretransplant characteristics and post-transplant prognosis for patients with nondilated idiopathic HC has not yet fully elucidated. Therefore, we retrospectively reviewed 813 consecutive transplant recipients undergoing cardiac transplantation at Columbia University Medical Center from 1999 to 2010 and compared the clinical course of 41 patients with idiopathic HC with that of 373 patients with ischemic heart disease and 398 patients with other heart disease. The patients with HC were younger than those with ischemic heart disease (47.8 ± 14.0 vs 57.1 ± 9.4 years; p <0.0001). The proportion of patients undergoing ventricular assist devise surgery for bridge-to-transplant was lower in patients with HC than in those with ischemic heart disease or other heart disease (14.6% vs 31.1% vs 35.7%, all p <0.01). The post-transplant survival of those with HC was better than that for those with ischemic heart disease (90.1% vs 85.8% and 83.9% vs 67.1% at 1 and 5 years, respectively; p = 0.0359), although it was not significantly different from those with other heart disease. Proportional hazards analysis revealed that the subjects with HC had reduced post-transplant mortality (hazard ratio 0.4760, 95% confidential interval 0.1889 to 0.9762; p = 0.042) on univariate, but not multivariate, analysis. Most patients with HC had nondilated left ventricles (left ventricular end-diastolic dimension ≤ 55 mm; n = 27), and post-transplant survival did not differ from that for those with dilated left ventricles (left ventricular end-diastolic dimension >55 mm; n = 14). In conclusion, the post-transplant survival of those with HC did not differ from those of the subjects who underwent transplant for other non-HC indications.

Primary omental pleomorphic liposarcoma identified at autopsy in a living donor kidney transplant recipient.

Metastatic and recurrent tumors of the omentum are common, but primary omental pleomorphic liposarcoma (POPL) is an extremely rare type of solid omental tumor. We describe the case of a patient with POPL who received a renal transplant from a living donor. Despite good allograft function, the volume of peritoneal fluid gradually increased. An exploratory laparotomy could not be performed because the patient was obese and developed hemodynamic instability. Therefore, a shunt was placed between the peritoneal cavity and the internal jugular vein using the Denver® shunt system; however, the patient died of respiratory insufficiency. On the basis of the autopsy results, we diagnosed the patient's condition as POPL. We speculated that the malignancy did not originate directly from the donor cells. We report POPL in a living donor renal transplant recipient.