[Cardiac transplantation]. / Hjertetransplantation.

More than 100,000 heart transplants have been performed worldwide since 1967. Surgical and medical procedures have improved and median survival in many centres including those participating in Scandiatransplant now exceed 13 years. The article reviews current indications and contraindications for cardiac transplantation and highlights improvements in donor selection, organ preservation, surgical techniques, immunosuppression, and rejection surveillance.

Decreased mitochondrial oxidative phosphorylation capacity in the human heart with left ventricular systolic dysfunction.

AIMS: Heart failure (HF) with left ventricular systolic dysfunction (LVSD) is associated with a shift in substrate utilization and a compromised energetic state. Whether these changes are connected with mitochondrial dysfunction is not known. We hypothesized that the cardiac phenotype in LVSD could be caused by reduced mitochondrial oxidative phosphorylation (OXPHOS) capacity and reduced mitochondrial creatine kinase (miCK) capacity. The study aim was to test mitochondrial OXPHOS capacity in LVSD myocardium compared with OXPHOS capacity in a comparable patient group without LVSD. METHODS AND RESULTS: Myocardial biopsies were obtained from the left ventricle during cardiac valve or left ventricular assist device (LVAD) surgery. Patients were stratified according to left ventricular ejection fraction (LVEF) into LVSD (LVEF <45%, n = 14) or CONTROL (LVEF >45%, n = 15). Mitochondrial respiration was measured in muscle fibres with addition of non-fatty acid substrates or octanoyl-l-carnitine, a medium chain fatty acid (MCFA). The in situ enzyme capacity of miCK was determined from APD titrations in the presence or absence of creatine. Maximal OXPHOS capacity with non-fatty acid substrates was lower in the LVSD group compared with the CONTROL group (P ≤ 0.05). ADP sensitivity always increased significantly (P ≤ 0.05) with the addition of creatine, after which the sensitivity was highest (P ≤ 0.05) in LVSD compared with CONTROL. The stimulation of OXPHOS from octanoyl-l-carnitine titrations elicited ∼40% lower respiration in LVSD compared with CONTROL (P ≤ 0.05). CONCLUSION: Human LVSD is associated with markedly diminished OXPHOS capacity, particularly in MCFA oxidation. This offers a candidate mechanism for a compromised energetic state and decreased reliance on fatty acid utilization in HF.

Left ventricular assist device as bridge to recovery for anthracycline-induced terminal heart failure.

Anthracycline treatments are hampered by dose-related cardiotoxicity, frequently leading to heart failure (HF) with a very poor prognosis. The authors report a case of a 19-year-old man developing HF after anthracycline treatment for Ewing sarcoma. Despite medical treatment, his condition deteriorated to terminal HF, leading to implantation of a mechanical left ventricular assist device (LVAD). His heart function recovered, allowing explantation of the device 14 months after implantation. Heart transplantation is often contraindicated in the first years after treatment for cancers, and LVAD as "bridge to recovery" may be warranted in similar patients.

Central and peripheral blood flow during exercise with a continuous-flow left ventricular assist device: constant versus increasing pump speed: a pilot study.

BACKGROUND: End-stage heart failure is associated with impaired cardiac output (CO) and organ blood flow. We determined whether CO and peripheral perfusion are maintained during exercise in patients with an axial-flow left ventricular assist device (LVAD) and whether an increase in LVAD pump speed with work rate would increase organ blood flow. METHODS AND RESULTS: Invasively determined CO and leg blood flow and Doppler-determined cerebral perfusion were measured during 2 incremental cycle exercise tests on the same day in 8 patients provided with a HeartMate II LVAD. In random order, patients exercised both with a constant (≈9775 rpm) and with an increasing pump speed (+400 rpm per exercise stage). At 60 W, the elevation in CO was more pronounced with increased pump speed (8.7±0.6 versus 8.1±1.1 L · min(-1); mean±SD; P=0.05), but at maximal exercise increases in CO (from 7.0±0.9 to 13.6±2.5 L · min(-1); P<0.01) and leg blood flow [0.7 (0.5 to 0.8) to 4.4 (3.9 to 4.8) L · min(-1) per leg; median (range); P<0.001] were similar with both pumping modes. Normally, middle cerebral artery mean flow velocity increases from ≈50 to ≈65 cm · s(-1) during exercise, but in LVAD patients with a constant pump speed it was low at rest (39±14 cm · s(-1)) and remained unchanged during exercise, whereas in patients with increasing pump speed, it increased by 5.2±2.8 cm · s(-1) at 60 W (P<0.01). CONCLUSIONS: With maximal exercise, the axial-flow LVAD supports near-normal increments in cardiac output and leg perfusion, but cerebral perfusion is poor. Increased pump speed augments cerebral perfusion during exercise.

Primary cardiac tumors: a clinicopathologic evaluation of four cases.

INTRODUCTION: We report the clinical, pathological, and immunohistochemical features of four primary malignant cardiac tumors identified at the Department of Pathology, Rigshospitalet, Denmark. A panel of immunohistochemical markers for classification is proposed. METHODS: Between 2000 and 2008, four patients with malignant cardiac tumors were treated at our hospital. We retrospectively reviewed the medical records and evaluated the patient characteristics and treatment. RESULTS: Three patients presented with severe dyspnea; one patient presented with chest pain. Transthoracic echocardiography demonstrated, in all four cases, abnormal masses in the atria. The cases were, based on morphological features and immunoprofile, classified as myogenic sarcoma (two cases), undifferentiated pleomorphic sarcoma, and leiomyosarcoma. Three of the patients received orthotopic heart transplantation. One patient survived 6.5 years after the diagnosis, and two patients are still alive 2 and 3 years after being diagnosed, respectively. CONCLUSIONS: All four cases were sarcomas. A limited number of immunohistochemical markers can be used in order to define a specific line of differentiation. In this small study, three of the patients were offered orthotopic heart transplantation, and the survival times were generally longer than in most series.

[Normalisation of left ventricular function after 13 months of mechanical circulatory support]. / Normalisering af venstre ventrikel efter 13 måneders mekanisk cirkulationsstøtte.

We discuss the first Danish case in which a left ventricular assist device (HeartMate 2) could be explanted after 13 months of support due to cardiac recovery in a young patient who presented with severe dilated cardiomyopathy during pregnancy. Aggressive medical treatment with angiotensin converting enzyme inhibitor, beta blocker and aldosterone antagonist was used, and the patient remained stable without circulatory support several months after device removal.

Incidence of ventricular arrhythmias in patients on long-term support with a continuous-flow assist device (HeartMate II).

The incidence of ventricular tachycardia (VT) or ventricular fibrillation (VF) in patients supported with a continuous-flow left ventricular assist device (LVAD) has not been investigated in detail. In 23 consecutive recipients of a HeartMate II, we analyzed the incidence of VT/VF during a total of 266 months of follow-up. Sustained VT or VF occurred in 52% of the patients, with the majority of arrhythmias occurring in the first 4 weeks after LVAD implantation. VT/VF requiring implantable cardioverter-defibrillator (ICD) shock or external defibrillation occurred in 8 patients and significant hemodynamic instability ensued in 3 patients. There were no clear predictors of VT/VF, and it is argued that prophylactic ICD implantation should be considered in patients supported with a continuous-flow LVAD.

Severely impaired von Willebrand factor-dependent platelet aggregation in patients with a continuous-flow left ventricular assist device (HeartMate II).

OBJECTIVES: This study investigated the influence of the mechanical blood pump HeartMate II (HMII) (Thoratec Corporation, Pleasanton, California) on blood coagulation and platelet function. BACKGROUND: HMII is an implantable left ventricular assist device used for the treatment of heart failure. Patients treated with HMII have increased bleeding tendencies. METHODS: We measured agonist-induced platelet aggregation in 16 patients on HMII support. RESULTS: The von Willebrand factor (vWF)-dependent ristocetin-induced platelet aggregation was impaired in 11 of the 16 patients, of which 12 had experienced at least 1 minor or major bleeding episode. The impaired ristocetin-induced platelet aggregation was associated both with decreased specific activity of plasma vWF, presumably due to lack of high molecular weight vWF multimers, as well as with attenuated function of the platelets themselves. CONCLUSIONS: The results imply that HMII treatment is associated with impaired platelet aggregation, which may contribute to an increased tendency to bleed.

HeartMate II left ventricular assist device; early European experience.

OBJECTIVE: The novel axial flow left ventricular assist device HeartMate II was introduced into clinical practice in Europe as part of the pilot study and after CE approval in November 2005. In order to get an overview of the use and performance of the device in Europe a group of investigators was founded to compare the initial results. METHODS: In a retrospective analysis of the first 101 consecutive cases in Europe, data were collected with regard to postoperative outcome and severe adverse events and anticoagulation protocols. Results were stratified by intention to treat as a bridge to transplant or as chronic support therapy in heart failure (destination therapy). RESULTS: In 70% of patients, the HeartMate II was intended as a bridge to transplant therapy, in 30%, it was used as a destination therapy device. The perioperative mortality post implant was 20% in the bridge to transplant patients and 7% in the destination therapy arm. However, after 1 year a comparable survival was observed in both groups (69% destination therapy, 63% bridge to transplant). Main causes of death were multiple organ failure (n=12) and cerebrovascular accidents (n=5). All, but one cerebrovascular accident occurred in the first 9 days after surgery. Only one other death was reported thereafter and there was no mechanical failure of the device. CONCLUSIONS: Even in the early experience the HeartMate II was used as a chronic support device in a substantial number of patients in Europe. Although the total experience is still limited, the incidence of cerebrovascular accidents is very low and the survival beyond the perioperative period is excellent.

Comparable three months' outcome of total arterial revascularization versus conventional coronary surgery: Copenhagen Arterial Revascularization Randomized Patency and Outcome trial.

OBJECTIVE: The in-hospital safety of total arterial revascularization for coronary artery bypass surgery seems to be comparable to conventional revascularization, but randomized trials evaluating this are few and data on complications in the postoperative months are sparse. METHODS: In a randomized single-center trial, 331 patients underwent total arterial revascularization using single or bilateral internal thoracic and radial arteries versus conventional revascularization using the left internal thoracic artery and saphenous vein grafts. We report the results from 3 months' follow-up. RESULTS: The mean age of patients was 59 +/- 8 years, and 39 were women (12%). The median EuroSCORE was 2 (interquartile range 1-4). The arterial group comprised 161 patients, and the conventional group comprised 170 patients. The mean number of bypasses in the arterial group was 2.9 +/- 0.9 versus 3.2 +/- 0.9 in the conventional group (P = .004). Three months' follow-up for the arterial versus conventional groups showed the following: deaths: 1 (0.6%) versus 0; stroke: 3 (1.9%) versus 3 (1.8%); myocardial infarction: 6 (3.7%) versus 4 (2.4%); sternal wound reoperation: 4 (2.5%) versus 0 (P = .054); arm and leg wound complications requiring hospitalization: 3 (1.9%) versus 6 (3.5%) (P = .50), respectively. CONCLUSION: These results confirm previous reports that total arterial revascularization can be performed with low in-hospital morbidity and mortality. Further, in the 3 postoperative months, total arterial revascularization did not lead to more complications or admissions than conventional surgery. Arterial grafting was performed with significantly fewer bypasses, but no differences in anginal status were seen after 3 months. A tendency toward more sternal complications after arterial grafting was observed, but clinical outcomes were comparable to conventional grafting.

[Percutaneous assist device during acute heart failure]. / Perkutan cirkulationsstøtte ved akut hjertesvigt.

International guidelines recommend the intraaortic balloon pump (IABP) as an assist of the left ventricle. Assist devices other than the IABP have become available. To improve the overall treatment of patients with heart failure, basic knowledge of assist devices in referral department is crucial. The TandemHeart increases flow and decreases metabolic demands. Several complications have been reported. Technological advances during the last few years have produced a smaller assist device. The Impella Recover LP 2.5 has been proved safe and able to perform a flow increase of 2.5 l/min and decrease metabolic demands.

[The Mechanical Heart--HeartMate 1--Danish results]. / Det mekaniske hjerte--HeartMate 1--de danske resultater.

INTRODUCTION: In 1998 the Heart Centre at the Danish National University Hospital implemented a new programme with long-term mechanical circulatory assist to patients with terminal heart failure who could not wait for a donor heart. A so-called Mechanical Heart, HeartMate 1, was to replace a failing left ventricle so that the patient could be resuscitated and await heart transplantation. The aim of the present study is to describe the results of this new treatment in Denmark. MATERIALS AND METHODS: A total of 28 patients with a mean age of 41 years were treated with the HeartMate 1 system in the period 1998 to 2006. Two patients had the system changed to a new HeartMate 1 due to mechanical problems. Both patients were later successfully heart transplanted. A third patient had the system successfully changed to a HeartMate 2 and he is waiting for a donor heart. RESULTS: Hemodynamic observations reveal fast improvement after implantation of the HeartMate system. Patients who were later heart transplanted had the HeartMate system implanted for a mean of 220 days. About 90% of those that were transplanted later improved due to the system from New York Heart Associations class IV to class I-II and they could often be discharged to a normal social life with a well-functioning HeartMate. Calculated 1-year survival with the HeartMate system was 82%. CONCLUSION: Patients with terminal heart failure can be treated and improved by implantation of the HeartMate system and await successful heart transplantation. Permanent advanced assist systems do exist today and these can be applied as a final treatment in selected patients--so-called destination therapy with mechanical circulatory support. The present study shows that it is very likely that the Heart Centre at the Danish National University Hospital will be able to establish a well-functioning programme for destination therapy.

[Destination therapy in end-stage heart failure. A possible alternative to heart transplantation?]. / Destinationsterapi ved terminalt hjertesvigt. Et muligt alternativ til hjertetransplantation?

The incidence of heart failure continues to increase but the number of available heart donors is limited. Implantation of circulatory assist devices as a permanent alternative to heart transplantation has become a promising new alternative in patients not eligible for heart transplantation (destination therapy). New technical advances have increased the durability of the devices and reduced complications.New generations of rotator pumps are smaller and more durable and will expand the use of these devices for destination therapy. This review discusses the current state of knowledge and indications for destination therapy in end-stage heart failure.