Primary graft dysfunction after heart transplantation: a thorn amongst the roses.

Primary graft dysfunction (PGD) remains the leading cause of early mortality post-heart transplantation. Despite improvements in mechanical circulatory support and critical care measures, the rate of PGD remains significant. A recent consensus statement by the International Society of Heart and Lung Transplantation (ISHLT) has formulated a definition for PGD. Five years on, we look at current concepts and future directions of PGD in the current era of transplantation.

Algorithms to guide ambulance clinicians in the management of emergencies in patients with implanted rotary left ventricular assist devices.

Advances in left ventricular assist device (LVAD) therapy have resulted in increasing numbers of adult LVAD recipients in the community. However, device failure, stroke, bleeding, LVAD thrombosis and systemic infection can be life-threatening emergencies. Currently, four LVAD systems are implanted in six UK transplant centres, each of which provides device-specific information to local emergency services. This has resulted in inconsistent availability and content of information with the risks of delayed or inappropriate decision-making. In order to improve patient safety, a consortium of UK healthcare professionals with expertise in LVADs developed universally applicable prehospital emergency algorithms. Guidance was framed as closely as possible on the standard ABCDE approach to the assessment of critically ill patients.

The Emerging Potential of the Apelin-APJ System in Heart Failure.

The apelin-APJ system is a novel neurohormonal pathway, with studies to date suggesting that it may be of pathophysiologic relevance in heart failure and may indeed be a viable therapeutic target in this syndrome. This interest is driven primarily by the demonstration of its vasodilator, inotropic, and aquaretic actions as well as its apparent antagonistic relationship with the renin-angiotensin system. However, its promise is heightened further by the observation that, unlike other and more established cardioprotective pathways, it appears to be down-regulated in heart failure, suggesting that augmentation of this axis may have a powerful effect on the heart failure syndrome. We review the literature regarding the apelin-APJ system in heart failure and suggest areas requiring further research.

British societies guideline on the management of emergencies in implantable left ventricular assist device recipients in transplant centres.

An implantable left ventricular assist device (LVAD) is indicated as a bridge to transplantation or recovery in the United Kingdom (UK). The mechanism of action of the LVAD results in a unique state of haemodynamic stability with diminished arterial pulsatility. The clinical assessment of an LVAD recipient can be challenging because non-invasive blood pressure, pulse and oxygen saturation measurements may be hard to obtain. As a result of this unusual situation and complex interplay between the device and the native circulation, resuscitation of LVAD recipients requires bespoke guidelines. Through collaboration with key UK stakeholders, we assessed the current evidence base and developed guidelines for the recognition of clinical deterioration, inadequate circulation and time-critical interventions. Such guidelines, intended for use in transplant centres, are designed to be deployed by those providing immediate care of LVAD patients under conditions of precipitous clinical deterioration. In summary, the Joint British Societies and Transplant Centres LVAD Working Group present the UK guideline on management of emergencies in implantable LVAD recipients for use in advanced heart failure centres. These recommendations have been made with a UK resuscitation focus but are widely applicable to professionals regularly managing patients with implantable LVADs.

The Glasgow Experience of Extended Myocardial Protection: A Novel Method of Implantation to Reduce Primary Graft Dysfunction After Heart Transplant.

OBJECTIVES: Around 2000 heart transplants are performed in Europe annually. The rates of primary graft dysfunction in Europe are among the highest in the world. With increasing demand for organs and the limited supply of donors, novel techniques such as ex vivo normothermic perfusion have garnered incre-asing interest. We present a series of patients who underwent heart transplant at our unit in which we used a novel implantation technique to reduce primary graft dysfunction. MATERIALS AND METHODS: We compared our experience with the novel method detailed in our article (Glasgow experience group) with a contemporary UK cohort (2015-2016) of patients (control group). We performed multivariable logistic regression to compare the Glasgow experience with the control group with primary graft dysfunction as the outcome measure. We adjusted for donor age, recipient diabetes mellitus, urgent listing status, bypass time, and total ischemic time. RESULTS: Among 194 patients in both cohorts, 140 patients (72.1%) were men and 36 (18.6%) had ischemic cardiomyopathy. The odds ratio of primary graft dysfunction in the control group was 2.99 (95% CI, 1.02- 8.75) compared with the Glasgow experience group. CONCLUSIONS: Our novel approach was associated with significant reductions in primary graft dysfunction, with a trend toward improved 1-year survival. Larger studies are needed to show differences after further adjustment for known confounders of primary graft dysfunction. We believe this novel technique is safe, cost-effective, and reproducible.

Primary Graft Dysfunction after Heart Transplantation - Unravelling the Enigma.

Primary graft dysfunction (PGD) remains the main cause of early mortality following heart transplantation despite several advances in donor preservation techniques and therapeutic strategies for PGD. With that aim of establishing the aetiopathogenesis of PGD and the preferred management strategies, the new consensus definition has paved the way for multiple contemporaneous studies to be undertaken and accurately compared. This review aims to provide a broad-based understanding of the pathophysiology, clinical presentation and management of PGD.

Plasma apelin concentration is depressed following acute myocardial infarction in man.

AIMS: Apelin, a novel peptide with a putative role in cardiovascular homeostasis, has gained interest as an endogenous inotrope, but has yet to be described following acute myocardial infarction (AMI) in man. We aimed to characterize plasma apelin concentrations following AMI and to examine its relationship with clinical and prognostic biomarkers. METHODS AND RESULTS: Plasma concentrations of apelin, N-terminal probrain natriuretic peptide (NT-proBNP), norepinephrine, and arginine vasopressin were measured in 100 patients [mean age 58.9 +/- 12 (SD) years, 77% male] admitted with AMI, with echocardiographic left ventricular (LV) ejection fraction <40%, at mean 46 h after admission and at 24 weeks. Cardiac magnetic resonance imaging was performed pre-discharge and at 24 weeks. Thirty-eight subjects with no cardiac history acted as controls. Apelin concentration was reduced early after AMI (0.54 +/- 0.25 vs. 3.22 +/- 3.01 ng/mL, P <0.001) and remained low at 24 weeks, although it did increase significantly from baseline to 0.62 +/- 0.36 ng/mL, P = 0.030. Apelin had no relationship with any parameter of LV function over time. A relationship was found between baseline apelin and norepinephrine (r = 0.26, P = 0.008). Both NT-proBNP and norepinephrine correlated with adverse ventricular function after AMI. CONCLUSION: Plasma apelin concentration is reduced early after AMI, increases significantly over time, but remains depressed at 24 weeks.

The spectrum of 5-fluorouracil cardiotoxicity.

Cardiotoxicity is a rare but serious complication of 5-fluorouracil therapy. Coronary vasospasm and, less frequently, acute myocarditis have been identified as underlying mechanisms. We report a case of severe toxicity in a relatively young and fit male patient being treated for metastatic colonic adenocarcinoma displaying characteristics that cannot be explained by either mechanism alone.

Recurrent myocardial infarction in a 50-year-old woman.

CLINICAL INTRODUCTION: A 50-year-old woman presented with an inferoposterior ST-elevation myocardial infarction (STEMI) and underwent emergency percutaneous coronary intervention (PCI). Angiography revealed acute occlusion of the circumflex and right coronary (RCA) arteries. PCI was uncomplicated. Her medical history included asthma, hypertension and chronic sinusitis.Three months later, she presented with a non-STEMI (NSTEMI), and angiogram showed a new focal stenosis in the left anterior descending artery. Pressure wire assessment induced severe coronary spasm. After liberal intracoronary nitrate, fractional flow reserve measured 0.71, so a further stent was implanted. Six days later, she was readmitted with another NSTEMI. Repeat angiogram revealed patent stents, with severe spasm of the distal RCA which improved following nitrate (figure 1A,B). Four days later, she was readmitted with further NSTEMI. Coronary angiography was not felt to be appropriate, and she was discharged with vasodilator therapy.heartjnl;105/12/960/F1F1F1Figure 1(A) Angiogram of RCA pre nitrates; (B) Angiogram of RCA post nitrates; (C) CT brain post cardiac arrest; (D) CMR post cardiac arrest.The following day, she had an out-of-hospital ventricular fibrillation (VF) arrest and was successfully resuscitated. CT brain showed no evidence of neurological injury (figure 1C). Cardiac magnetic resonance imaging (CMR) was performed prior to implantable cardioverter defibrillator (ICD) implantation (figure 1D). Eosinophils had been persistently elevated with a peak of 1.78×109 (normal: 0.02-0.5×109). Antinuclear antibodies and antineutrophil cytoplasmic antibodies (ANCA) were negative. QUESTION?: What is the diagnosis for her recurrent acute coronary syndrome and VF arrest?Aggressive atherosclerotic coronary artery disease.Prinzmetal's variant angina.Loeffler endocarditis.Coronary vasculitis.