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.

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.

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.

Donor hypo- and hypernatremia are predictors for increased 1-year mortality after cardiac transplantation.

Donor hypernatremia is known to be associated with initial graft dysfunction in liver transplantation. Controversial data exist regarding the impact of sodium dysregulation on patient survival after heart transplantation (HTX). The aim of this study was to investigate the influence of donor sodium levels on survival in a large cohort of heart transplant recipients from the Eurotransplant registry. From 1997 to 2005, all consecutive adult HTX performed in the Eurotransplant region were included into this study (n = 4641 patients). Multivariate analysis was applied to investigate possible clinical predictors for 1-year post-transplant survival after cardiac transplantation (donor sodium levels, donor age, donor cause of death, recipient age, primary disease, urgency status, cold ischemia time). In multivariate analysis, recipients receiving a donor heart with serum sodium level lower than 130 mmol/l or higher than 170 mmol/l had a 1.25-fold higher risk for 1-year post-transplant mortality than patients with normal donor sodium ranges (P = 0.007). Other independent risk factors for impaired 1-year survival were recipient age, the indication for transplantation and the urgency status of the recipient. Our study demonstrates that hyponatremia as well as hypernatremia show a strong U-shaped correlation with poor survival after cardiac transplantation. Accurate donor management to avoid electrolyte disorder seems to be crucial for ensuring good quality of donor hearts.

[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.

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.

Long-term results of high vs. normal impedance ventricular leads on actual (Real-Life) pacemaker generator longevity.

AIM: The long-term effects of high impedance vs. standard impedance pacing leads on actual generator longevity were studied. METHODS AND RESULTS: In 40 patients (21 females, age 73 +/- 13 years) with standard dual-chamber pacemaker indication, bipolar standard impedance ventricular leads and high-impedance leads were implanted in a randomized fashion. Identical pacemaker generators and atrial pacing leads were implanted in all patients. Patients were observed during a mean follow-up of 89.8 +/- 8.8 months before pacemaker replacement. Initially, the patients who received the high-impedance leads had a lower current drain as compared with standard pacing impedance leads, and the estimated pacemaker longevity was significantly prolonged, too. But this pattern disappeared after 6 years of follow-up, and finally the actual pacemaker generators' replacement time was 86.7 +/- 6.8 months in standard impedance lead group vs. 91.2 +/- 10.3 months in high-impedance lead group (P = 0.17). CONCLUSION: Implantation of high pacing impedance leads for ventricular stimulation does not result in a benefit with respect to pacemaker longevity as compared with standard impedance leads.

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.

Catheter-based edge-to-edge mitral valve repair for pulmonary pressure reduction and to postpone heart transplantation in a teenaged patient.

We report a case of catheter-based edge-to-edge mitral valve repair in a teenage male patient with non-ischaemic cardiomyopathy to improve pulmonary hypertension secondary to severe functional mitral regurgitation (FMR) to defer anticipated heart transplantation. A 19-year-old patient with previous history of fulminant myocarditis followed by markedly left ventricular dysfunction presented with severe mitral regurgitation 3 years after initial recovery. Slightly over time, deterioration of FMR was associated with gradual increase in pulmonary artery pressures despite optimal medical therapy. MitraClip implantation in this young patient was successfully performed with sustainable improvement of pulmonary hypertension.

Donor heart selection and outcomes: An analysis of over 2,000 cases.

BACKGROUND: Decision-making when offered a donor heart for transplantation is complex, and supportive data describing outcomes according to acceptance or non-acceptance choices are sparse. Our aim was to analyze donor heart acceptance decisions and associated outcomes at a single center, and after subsequent acceptance elsewhere. METHODS: This investigation was a retrospective analysis of data obtained from the University of Vienna Medical Center and Eurotransplant centers for the period 2001 to 2015. RESULTS: Our center accepted 31.8% (699 of 2,199) of donor hearts offered. Unlike other centers, the acceptance rate, with or without transplantation, did not increase over time. Of the donor hearts rejected by our center, 38.1% (572 of 1,500) were later accepted elsewhere. Acceptance rates were twice as high for donor hearts initially rejected for non-quality reasons (339 of 601, 56.4%) compared with initial rejection for quality reasons (233 of 899, 25.9%). Three-year patient survival rate was 79% at Vienna; for donor hearts initially rejected by Vienna for non-quality reasons or quality reasons, it was 73% and 63%, respectively (p < 0.001). Outcomes at other centers after transplantation of grafts rejected by Vienna varied according to the reason for rejection, with good 3-year survival rates for rejection due to positive virology (77%), high catecholamines (68%), long ischemic time (71%), or low ejection fraction (68%), but poor survival was observed for hearts rejected for hypernatremia (46%), cardiac arrest (21%), or valve pathology (50%). CONCLUSIONS: A less restrictive policy for accepting donor hearts at our center, particularly regarding rejection for non-quality reasons or for positive virology, high catecholamine levels, longer ischemic time, or low ejection fraction, could expand our donor pool while maintaining good outcomes.

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.

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.

[Use of ECMO in adult patients with cardiogenic shock: a position paper of the Austrian Society of Cardiology]. / Positionspapier der Österreichischen Kardiologischen Gesellschaft zum Einsatz der extrakorporalen Membranoxygenation (ECMO) bei Erwachsenen kardiologischen Patienten.

The use of ECMO to stabilize critically ill patients with severely depressed cardiac function and hemodynamics increased in the last years due to broader availability, better performance and easier implantation of the devices. The present guidelines of the Austrian Society of Cardiology focus on the use of ECMO in adult non-operated patients with cardiac diseases. Not only indications and contraindications are highlighted, but also the equally important issues of monitoring, complication management, measures during implantation and operation, and weaning of the devices are treated in detail. Thereby the present guidelines aim to optimize the use of ECMO in the individual centers, and aim to help current non-ECMO centers in developing a local ECMO-program or to contact ECMO-centers for discussion of individual patients.

[Use of ECMO in adult patients with cardiogenic shock: a position paper of the Austrian Society of Cardiology]. / Positionspapier der Österreichischen Kardiologischen Gesellschaft zum Einsatz der extrakorporalen Membranoxygenation (ECMO) bei Erwachsenen kardiologischen Patienten.

The use of ECMO to stabilize critically ill patients with severely depressed cardiac function and hemodynamics increased in the last years due to broader availability, better performance and easier implantation of the devices. The present guidelines of the Austrian Society of Cardiology focus on the use of ECMO in adult non-operated patients with cardiac diseases. Not only indications and contraindications are highlighted, but also the equally important issues of monitoring, complication management, measures during implantation and operation, and weaning of the devices are treated in detail. Thereby the present guidelines aim to optimize the use of ECMO in the individual centers, and aim to help current non-ECMO centers in developing a local ECMO-program or to contact ECMO-centers for discussion of individual patients.

Successful transfer of a cardiac allograft from a heterotopic to an orthotopic position 16 years after transplantation.

The ever-increasing donor shortage sometimes demands unusual solutions. This article reports the first successful reuse of a heterotopically implanted heart, which was transferred to an orthotopic position 16 years after transplantation following definitive failure and removal of the native heart. The surgically demanding procedure succeeded without complications, and, 16 weeks later, the patient is classified as New York Heart Association I.

Effects of intracoronary shunts on coronary endothelial coating in the human beating heart.

BACKGROUND: Local occlusion of coronary arteries during beating heart revascularization leads to injury of the arterial wall especially disturbing the integrity of the endothelium. The aim of this study was to elucidate the effects of intracoronary shunts versus local occlusion with elastic silicone loops on the beating heart in human coronary arteries by scanning electron microscopy. METHODS: Coronary arteries of patients with dilated cardiomyopathy (n = 4) or ischemic heart disease (n = 8) undergoing heart transplantation were locally occluded either with a silicone loop or with a shunt inserted after arteriotomy. Unmanipulated segments of the coronary arteries served as controls. Integrity of the endothelial lining was observed with scanning electron microscopy. RESULTS: Scanning electron microscopy revealed a statistically significant higher injury after shunting compared with controls (p < 0.001) and vessel loop occlusion (p < 0.001). There was no difference between both patient groups according to control specimens or after manipulation. CONCLUSIONS: From this investigation we conclude that insertion of intracoronary shunts during beating heart surgery leads to severe endothelial denudation in human coronary arteries. Therefore, at present we recommend using intracoronary shunts selectively in cases in which critical ischemia or technical difficulties as a result of anatomic conditions are expected during anastomosis and avoiding routine shunt insertion into coronary arteries during beating heart revascularization.

Coagulation monitoring and management of anticoagulation during cardiac assist device support.

BACKGROUND: The incidence of clinically significant thromboembolic events due to the use of cardiac assist device systems remains high. Despite the considerable advances in cardiac assist device technology, the monitoring and management of the hypercoagulable coagulation status, resulting from foreign surfaces of the assist device system, altered rheologic conditions, and blood stasis in the recipient heart remain a challenge. Moreover septic complications and insufficient anticoagulation are responsible for thromboembolic events. METHODS: In addition to standard coagulation analysis, functional coagulation tests were performed including the use of a thrombelastographic monitoring system (ROTEG) and a platelet function analyzer (PFA-100). RESULTS: Severe biventricular ischemic heart failure developed in a 58-year-old man with acute myocardial infarction and he needed a biventricular assist device for a bridge to cardiac transplantation. Although the patient received acenocoumarol (Sintrom; Novartis Pharma, Vienna, Austria) and acetylsalicylic acid (Aspisol; Bayer AG, Leverkusen, Germany) as usual, ROTEG and the PFA-100 detected hypercoagulability while routine coagulation screening tests showed hypocoagulability. Moreover thrombus formation surrounding the canula of the left ventricular assist device was detected. Antithrombotic therapy with clopidogrel (Plavix) was initiated. Coagulation was closely monitored with modified thrombelastography and the PFA-100 to achieve sufficient but not overwhelming anticoagulation therapy. Three months after biventricular assist device implantation the patient underwent successful transplantation with no major blood loss. CONCLUSIONS: Thrombelastography should be the standard form of monitoring in such patients to decrease the risk of thromboembolic events and prevent bleeding complications.

Revisiting the cardiac versus thoracic pump mechanism during cardiopulmonary resuscitation.

The mechanism of forward blood flow due to external chest compressions during cardiopulmonary resuscitation (CPR) remains controversial, with the main theories being based on either a cardiac, or thoracic pump mechanism. Both potential mechanisms are well investigated by echocardiographic assessment. In the present case, a postoperative complication of cardiac tamponade that was detected by a thoracoabdominal CT-scan, led to cardiac arrest with subsequent successful CPR over 15 min until definitive surgical management was performed. This observation suggests that the thoracic pump mechanism may have been the predominant mechanism of forward blood flow in the present case of a pericardial tamponade.