Indications, Complications, and Outcomes of Cardiac Surgery After Heart Transplantation: Results From the Cash Study.

Background: Allograft pathologies, such as valvular, coronary artery, or aortic disease, may occur early and late after cardiac transplantation. Cardiac surgery after heart transplantation (CASH) may be an option to improve quality of life and allograft function and prolong survival. Experience with CASH, however, has been limited to single-center reports. Methods: We performed a retrospective, multicenter study of heart transplant recipients with CASH between January 1984 and December 2020. In this study, 60 high-volume cardiac transplant centers were invited to participate. Results: Data were available from 19 centers in North America (n = 7), South America (n = 1), and Europe (n = 11), with a total of 110 patients. A median of 3 (IQR 2-8.5) operations was reported by each center; five centers included ≥ 10 patients. Indications for CASH were valvular disease (n = 62), coronary artery disease (CAD) (n = 16), constrictive pericarditis (n = 17), aortic pathology (n = 13), and myxoma (n = 2). The median age at CASH was 57.7 (47.8-63.1) years, with a median time from transplant to CASH of 4.4 (1-9.6) years. Reoperation within the first year after transplantation was performed in 24.5%. In-hospital mortality was 9.1% (n = 10). 1-year survival was 86.2% and median follow-up was 8.2 (3.8-14.6) years. The most frequent perioperative complications were acute kidney injury and bleeding revision in 18 and 9.1%, respectively. Conclusion: Cardiac surgery after heart transplantation has low in-hospital mortality and postoperative complications in carefully selected patients. The incidence and type of CASH vary between international centers. Risk factors for the worse outcome are higher European System for Cardiac Operative Risk Evaluation (EuroSCORE II) and postoperative renal failure.

The European Registry for Patients with Mechanical Circulatory Support (EUROMACS): second EUROMACS Paediatric (Paedi-EUROMACS) report.

OBJECTIVES: A second paediatric report has been generated from the European Registry for Patients with Mechanical Circulatory Support (EUROMACS). The purpose of EUROMACS, which is operated by the European Association for Cardio-Thoracic Surgery, is to gather data related to durable mechanical circulatory support for scientific purposes and to publish reports with respect to the course of mechanical circulatory support therapy. Since the first report issued, efforts to increase compliance and participation have been extended. Additionally, the data provided the opportunity to analyse patients of younger age and lower weight. METHODS: Participating hospitals contributed pre-, peri- and long-term postoperative data on mechanical circulatory support implants to the registry. Data for all implants in paediatric patients (≤19 years of age) performed from 1 January 2000 to 1 July 2019 were analysed. This report includes updates of patient characteristics, implant frequency, outcome (including mortality rates, transplants and recovery rates) as well as adverse events including neurological dysfunction, device malfunction, major infection and bleeding. RESULTS: Twenty-nine hospitals contributed 398 registered implants in 353 patients (150 female, 203 male) to the registry. The most frequent aetiology of heart failure was any form of cardiomyopathy (61%), followed by congenital heart disease and myocarditis (16.4% and 16.1%, respectively). Competing outcomes analysis revealed that a total of 80% survived to transplant or recovery or are ongoing; at the 2-year follow-up examination, 20% died while on support. At 12 months, 46.7% received transplants, 8.7% were weaned from their device and 18.5% died. The 3-month adverse events rate was 1.69 per patient-year for device malfunction including pump exchange, 0.48 for major bleeding, 0.64 for major infection and 0.78 for neurological events. CONCLUSIONS: The overall survival rate was 81.5% at 12 months following ventricular assist device implant. The comparison of survival rates of the early and later eras shows no significant difference. A focus on specific subgroups showed that survival was less in patients of younger age (<1 year of age) (P = 0.01) and lower weight (<20 kg) (P = 0.015). Transplant rates at 6 months continue to be low (33.2%) The fact that the EUROMACS registry is embedded within the European Association for Cardio-Thoracic Surgery Quality Improvement Programme offers opportunities to focus on improving outcomes.

Results of primary biventricular support: an analysis of data from the EUROMACS registry.

OBJECTIVES: The purpose of this study was to describe pre- and postoperative data from the EUROMACS registry with regard to indications, for and survival and complication rates of patients with primary continuous flow and pulsatile biventricular long-term assist devices (BiVADs) versus total artificial hearts (TAHs) or left ventricular assist devices (LVADs) + short-term right ventricular assist device (RVAD) implants. METHODS: We investigated patients who received implants between 1 January 2011 and 21 October 2017. Clinical baseline information about comorbidities, laboratory results, medical and device therapies and echocardiographic, haemodynamic and right ventricle (RV) parameters were evaluated along with the rates of deaths and complications. RESULTS: A total of 413 of 3282 patients (12.5%) needed a biventricular pump. We investigated 37 long-term BiVADs, 342 LVAD + short-term RVAD implants and 34 TAHs. Minor differences were found in the baseline characteristics of our population, which had an overall high morbidity profile. The 1-year survival rate was 55% for patients with a continuous flow BiVAD; 52% for patients with an LVAD + short-term RVAD; 37% for patients with pulsatile BiVADs; and 36% for patients with a TAH. No statistical difference was observed among the groups. Over 50% of patients with BiVAD support were classified as INTERMACS profiles 1 and 2. The percent of patients with ambulatory heart failure (INTERMACS 4‒7) undergoing BiVAD implants was modest at <15%. No patients with a pulsatile BiVAD (n = 15) or a TAH (n = 34) were implanted as destination therapy, but 27% of the patients with continuous flow BiVADs (n = 6) and 23% of the patients with LVAD + short-term RVAD (n = 342) were implanted as 'destination'. The adverse events profile remained high, with no significant difference among pump types. The right ventricular stroke work index and right heart failure scores indicated poor RV function in all groups. After 3 months of LVAD + short-term RVAD support, 46.7% still required ongoing support, and only 18.5% were weaned from RVAD support; 33.1% died. CONCLUSIONS: The mortality rate after BiVAD support was high. Survival rates and adverse events were statistically not different among the investigated groups. In the future, composite study end points examining quality of life and adverse events beyond survival may help in shared decision-making prior to general mechanical circulatory support, particularly in patients with BiVAD implants.

MELAS Syndrome and Kidney Disease Without Fanconi Syndrome or Proteinuria: A Case Report.

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS syndrome) represents one of the most frequent mitochondrial disorders. The majority of MELAS cases are caused by m.3243A>G mutation in the mitochondrial MT-TL1 gene, which encodes the mitochondrial tRNALeu(UUR). Kidney involvement usually manifests as Fanconi syndrome or focal segmental glomerulosclerosis. We describe a patient with MELAS mutation, cardiomyopathy, and chronic kidney disease without Fanconi syndrome, proteinuria, or hematuria. While the patient was waitlisted for heart transplantation, her kidney function deteriorated from an estimated glomerular filtration rate of 33 to 20mL/min/1.73m2 within several months. Kidney biopsy was performed to distinguish decreased kidney perfusion from intrinsic kidney pathology. Histologic examination of the biopsy specimen showed only a moderate degree of tubular atrophy and interstitial fibrosis, but quantitative analysis of the m.3243A>G mitochondrial DNA mutation revealed high heteroplasmy levels of 89% in the kidney. Functional assessment showed reduced activity of mitochondrial enzymes in kidney tissue, which was confirmed by immunohistology. In conclusion, we describe an unusual case of MELAS syndrome with chronic kidney disease without apparent proteinuria or tubular disorders associated with Fanconi syndrome, but widespread interstitial fibrosis and a high degree of heteroplasmy of the MELAS specific mutation and low mitochondrial activity in the kidney.

Mediastinal liposarcoma.

A 64-year-old male underwent surgical resection of a large liposarcoma of the mediastinum. The management of this unusual tumor is the subject of this case report.

[Evaluation of the potential organ donor with special regards to heart donation]. / Der potentielle Organspender - Evaluierung unter besonderer Berücksichtigung der Herzentnahme.

Regarding limited availability of organ donors for heart transplantation, it is necessary to discuss optimal donor evaluation and donor management. In this manuscript general donor-related parameters as well as heart-specific parameters are discussed regarding international literature. In addition, "marginal" donors and in contrast "optimal" donors are defined. Donor management including optimal hemodynamic management and additional specific intensive care aspects are presented. Exact donor evaluation allows for matching the organ to the most suitable recipient and is therefore especially in the context of marginal donors a crucial step within transplantation process.

[Biomarker for diagnosis of rejection after heart transplantation]. / Biomarker zur Diagnose der zellulären Abstossung nach Herztransplantation.

Heart transplantation is an established therapeutic modality in patients with end-stage heart failure. In the 1st year after transplantation acute cellular rejection is still important. The diagnosis of acute cellular rejection is based on the histological evaluation of endomyocardial biopsy (EMB) specimens. EMB is an invasive procedure with a definite risk and poor tolerance in some patients. Imaging methods like echocardiography and magnetic resonance imaging as well as intracardiac ECG have been used for noninvasive diagnosis of acute cellular rejection. In addition, a large number of circulating biomarkers have been evaluated for noninvasive diagnosis of rejection. B-type natriuretic peptide, troponin and inflammatory markers are the most important biomarkers in this field. Although these parameters are useful, none of them has the potential to replace EMB as the gold standard for diagnosis of rejection. In the near future microarray technology might get important for diagnosis of acute cellular rejection. Using microarray technique gene expression profiles can be detected, which are associated with an increased risk for rejection. Ongoing studies will demonstrate, whether microarrays can at least reduce the number of EMBs.

Cardiac sarcoidosis mimicking arrhythmogenic right ventricular dysplasia.

Isolated manifestation of sarcoidosis in the heart is very rare. The present work describes the case of a 41-year-old woman with ventricular tachycardia and severe symptoms of heart failure in June 2006. Clinical, MRI and echocardiographic findings revealed the diagnosis of an arrhythmogenic right ventricular dysplasia. Due to the severe progression of the disease, cardiac transplantation was performed in August 2007. Histopathological examination of the explanted heart, however, revealed numerous non-necrotising granulomas with giant cells, lymphocytic infiltration and interstitial fibrosis, finally confirming the diagnosis of a myocardial sarcoidosis.

Shunt or snare: coronary endothelial damage due to hemostatic devices for beating heart coronary surgery.

BACKGROUND: Occlusion of coronary arteries during off-pump coronary bypass operations bears the potential for endothelial injury. The aim of this study was to elucidate the effects of hemostatic devices on the beating heart in human coronaries by means of scanning electron microscopy. METHODS: The coronary arteries of 9 patients with dilated cardiomyopathy and 13 with ischemic heart disease undergoing heart transplantation were handled with intracoronary shunts as well as external snaring techniques on a beating heart, after cannulation but before starting cardiopulmonary bypass. Adjacent noninstrumented coronary artery segments served as controls. Integrity of endothelial lining was observed with scanning electron microscopy. RESULTS: Nearly all coronary artery segments manipulated with a shunt exhibited a severe injury with extensive endothelial denudation. Endothelial injury was significantly higher after manipulation with intracoronary shunts compared with external occlusion devices (p < 0.001) or control specimens (p < 0.001). Plaque rupture was apparent in 3 samples. CONCLUSIONS: Manipulation of human coronary arteries during off-pump operations leads to endothelial denudation and plaque rupture. From this investigation we conclude that insertion of intracoronary shunts during beating heart operations leads to severe endothelial denudation in human coronary arteries. We therefore recommend using shunts selectively in cases where critical ischemia or technical difficulties due to anatomic conditions are expected during anastomosis. The clinical significance of these structural damages has to be further investigated with clinical trials.

Zygomycosis and other rare filamentous fungal infections in solid organ transplant recipients.

Fungi cause severe infections in solid organ transplant (SOT) recipients. Recently, a shift towards non-Aspergillus filamentous fungal infections (nAFFI) was noticed. In a series of 2878 SOTs (kidney, pancreas, islets, liver, heart, lung, and bowel) performed between January 1995 and December 2006 at the Innsbruck medical university, eleven cases of nAFFI were diagnosed. The encountered species included Zygomyzetes (n = 8), and Alternaria alternate, Pseudallescheria boydii, Trichoderma spp. (one each); there were three liver and three heart, one intestinal, pancreas, lung, bilateral forearm and renal recipient each. Five patients died from nAFFI (zygomycosis: 4, Pseudallerichia boydii: 1); four were diagnosed postmortem. In five cases infection was surgically treated in combination with antifungals. Risk factors for nAFFI were renal failure (73%) and intensified immunosuppression (73%); two cases were associated with post-transplant lymphoproliferative disorder, one with graft versus host disease. An increase in the incidence of nAFFI was observed parallel to introduction of caspofungin and voriconazole (three cases until 12/2003, seven cases thereafter). NAFFI are increasingly found in SOT recipients. If diagnosed in time, the outcome seems acceptable. Intensified immunosuppression and exposure to antifungals not active against zygomycetes may be risk factors. Surgical therapy may play an important role in these infections.

Prolonged extracorporeal membrane oxygenation-assisted support provides improved survival in hypothermic patients with cardiocirculatory arrest.

OBJECTIVE: Extracorporeal circulation is considered the gold standard in the treatment of hypothermic cardiocirculatory arrest; however, few centers use extracorporeal membrane oxygenation instead of standard extracorporeal circulation for this indication. The aim of this study was to evaluate whether extracorporeal membrane oxygenation-assisted resuscitation improves survival in patients with hypothermic cardiac arrest. METHODS: A consecutive series of 59 patients with accidental hypothermia in cardiocirculatory arrest between 1987 and 2006 were included. Thirty-four patients (57.6%) were resuscitated by standard extracorporeal circulation, and 25 patients (42.4%) were resuscitated by extracorporeal membrane oxygenation. Accidental hypothermia was caused by avalanche in 22 patients (37.3%), drowning in 22 patients (37.3%), exposure to cold in 8 patients (13.5%), and falling into a crevasse in 7 patients (11.9%). Multivariate logistic regression analysis was used to compare extracorporeal membrane oxygenation with extracorporeal circulation resuscitation, with adjustment for relevant parameters. RESULTS: Restoration of spontaneous circulation was achieved in 32 patients (54.2%). A total of 12 patients (20.3%) survived hypothermia. In the extracorporeal circulation group, 64% of the nonsurviving patients who underwent restoration of spontaneous circulation died of severe pulmonary edema, but none died in the extracorporeal membrane oxygenation group. In multivariate analysis, extracorporeal membrane oxygenation-assisted resuscitation showed a 6.6-fold higher chance for survival (relative risk: 6.6, 95% confidence interval: 1.2-49.3, P = .042). Asphyxia-related hypothermia (avalanche or drowning) was the most predictive adverse factor for survival (relative risk: 0.09, 95% confidence interval: 0.01-0.60, P = .013). Potassium and pH failed to show statistical significance in the multivariate analysis. CONCLUSIONS: Extracorporeal rewarming with an extracorporeal membrane oxygenation system allows prolonged cardiorespiratory support after initial resuscitation. Our data indicate that prolonged extracorporeal membrane oxygenation support reduces the risk of intractable cardiorespiratory failure commonly observed after rewarming.

Malignancies of the colorectum and anus in solid organ recipients.

Patients undergoing solid organ transplantation (SOT) are at increased risk for developing malignancies due to the long term immunosuppression. Data on malignancies of the large intestine after various types of SOT are rare. A total of 3595 SOTs were performed between 1986 and 2005 at our center and retrospectively analyzed with regard to the incidence and course of malignancies of the colon, rectum, and anus. Standard immunosuppression consisted of calcineurin inhibitors in combination with azathioprine or mycophenolate mofetil and steroids with or without antithymocyte globulin or IL-2 receptor antagonist induction. A total of 206 patients (5.7%) developed malignancies. Colorectal adenocarcinoma was diagnosed in nine patients (0.25%; mean age at diagnosis 65 years) at a mean of 5.3 years after transplantation. Five patients (55%) died 7.2 years post-transplant due to cardiovascular disease (n = 4) and tumor progression (n = 1). Four patients developed anal neoplasia (0.11%) 7 years post-transplant with 100% 1-year survival. Five patients showed post-transplant lymphoproliferative disorders (PTLD) with intestinal involvement. The incidence of anal but not of colorectal cancers in our transplant recipients differed from that of immunocompetent individuals of corresponding age (0.11% vs. 0.002% and 0.25% vs. 0.3%). PTLD may involve the colon.

Interventional and medical treatment of acute heart failure due to inflammation: four cases.

Four patients (aged 15-41 years, mean age 26.7 years) with fulminant myocarditis undergoing mechanical circulatory support are reported. All patients suffered from acute low-output syndrome refractory to inotropic support. Diagnosis was confirmed by histology and immunohistochemistry. RT-PCR (reverse transcription-polymerase chain reaction) from endomyocardial biopsy specimens revealed parvovirus B19 in two patients and a coinfection with Chlamydia pneumoniae and parvovirus B19 in one patient. Midterm support with the biventricular Thoratec system was preceded by implantation of an extracorporeal membrane oxygenation (ECMO) device in two patients. Two patients regained full cardiac function and were successfully weaned from the ventricular assist device (VAD) after 12 and 40 days. Heart transplantation was performed in another patient without evidence of myocardial recovery after 53 days. One patient died of cerebral hemorrhage on day 12 after VAD implantation. In summary, patients with life-threatening fulminant myocarditis can be successfully bridged to recovery or transplantation with mechanical circulatory support.

Outcome evaluation of the bridge-to-bridge concept in patients with cardiogenic shock.

BACKGROUND: Patients with cardiogenic shock can be stabilized by percutaneous implantation of extracorporeal membrane oxygenation (ECMO). If weaning from ECMO is impossible, the implantation of a ventricular assist device (VAD) is required. Patients either go for recovery of myocardial function (bridge to recovery) or for heart transplantation (bridge to transplant). METHODS: One hundred thirty-one patients were supported with ECMO between March 1995 and November 2005. Reasons for ECMO implantation were acute heart failure, acute or chronic heart failure, and postcardiotomy heart failure. In 28 patients, subsequent VAD implantation was necessary (bridge to bridge concept). RESULTS: Fourteen bridge to bridge patients (50%) became long-time survivors with a mean follow-up of 39 months. Risk factors for mortality were status post-cardiopulmonary resuscitation and elevated lactate and bilirubin levels before VAD implantation. Complications after ECMO and VAD implantation were bleeding and thromboembolic events. The most common cause of death was multiorgan failure. CONCLUSIONS: Bridge to bridge is a successful concept for selected patients with cardiogenic shock. During ECMO support, patients can be evaluated for comorbidities. For patients with a combination of risk factors (status post-cardiopulmonary resuscitation, elevated lactate levels, and impaired liver function), VAD implantation should be considered very carefully.

Endomyocardial biopsy - jugular/subclavian vein approach.

Endomyocardial biopsy (EMB) is a diagnostic procedure mainly to survey the sufficiency of immunosuppressive therapy after cardiac transplantation. Other indications for EMB remain controversial. After insertion of an introducer sheet in Seldinger's technique, four to six biopsies are taken from the right ventricle by fluoroscopic guidance. EMB is a very safe operation with a low complication rate which can be rapidly performed with little inconvenience for the patient if performed by a skilled surgeon.

Early detection and successful therapy of fulminant chlamydia pneumoniae myocarditis.

We report a case involving a young female patient with Chlamydia pneumoniae myocarditis who required assist device therapy for acute heart failure. Early diagnosis was provided by endomyocardial biopsy, and tailored antibiotic therapy facilitated quick recovery of myocardial function. This is the first case to report detecting C pneumoniae as the pathogen responsible for fulminant myocarditis while the patient was still alive and to report long-term follow-up data.

B-type natriuretic peptide as a marker of allograft rejection after heart transplantation.

B-type natriuretic peptide (BNP) concentrations, a cardiac hormone released upon cardiac stress, was monitored in patients after heart transplantation. Rejection was assessed by the International Society for Heart and Lung Transplantation (ISHLT) criteria. BNP was assessed by a cross-sectional approach. We found significantly (p = 0.024) increased concentrations during rejection episodes of ISHLT grade 2 and higher. BNP yielded only a moderate diagnostic accuracy (area under the receiving characteristic curve: mean = 0.76, 95% confidence interval 0.53-0.92) to detect clinically significant episodes of rejection, which was too low to replace endomyocardial biopsies. Acute rejection episodes were associated with marked BNP increases and a significant decrease in case of successful treatment in the individual long-term monitoring in the majority of patients. BNP monitoring seems to be a useful addition in the individual follow-up of heart transplant recipients to rule out significant rejection.

Cardiac transplantation complicated by acute thrombotic occlusion of the right coronary artery.

We report the case of a 63-year-old male patient undergoing cardiac transplantation due to fourth time aortic valve endocarditis. The postoperative course was complicated by thrombotic occlusion of the right coronary artery (RCA) causing acute right ventricular myocardial infarction, which required extracorporeal membrane oxygenation. The RCA could be reopened by catheter-based intervention and the patient stabilized. In order to avoid further immobilization, a right ventricular assist device was implanted and an aortocoronary bypass to the RCA was performed. After that, the patient stabilized progressively, could be weaned from the assist device, and was discharged home 6 weeks after transplantation. On coronary angiography, which is routinely performed 4 to 6 weeks after transplantation, a fistula from the RCA to the right ventricle was detected which was treated conservatively. Five months after transplantation, the patient is in good clinical condition without signs of recurrent endocarditis. This case shows that intense interdisciplinary cooperation of cardiac specialists allows the successful management of very complex patients in serious clinical conditions.

Severe endocarditis in transplant recipients--an epidemiologic study.

Infective endocarditis (IE) is reported with an incidence of 6/100,000 inhabitants in the general population. Even though immunosuppression predisposes to systemic infection, reports regarding IE after solid organ transplantation (SOT) are sparse. From 1989 to 2004, 2556 patients underwent SOT at the University Hospital Innsbruck. During this period, 27 transplant recipients were diagnosed IE. Nine patients (33.3%) were diagnosed at autopsy, eight patients (29.6%) were cured by antibiotic treatment and 10 patients (37.1%) underwent surgery. Overall mortality was 44.4% (12 patients). Staphylococcus was the predominant microorganism in 16 cases (59.3%), fungal infection was present in four patients (14.8%). Incidence of IE was 1% (95% CI: 0.67-1.49), indicating a 171-fold risk compared with the overall population. IE after SOT constitutes a significant problem and is associated with an excessive high mortality. Alertness to this condition is indicated, as we might diagnose more cases of IE in the future.