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Although heart transplantation remains the ultimate treatment for end-stage heart failure, its epidemiological impact is limited by donor organ availability. Surgical and device-based approaches have been introduced with the aim of increasing systemic perfusion and in some circumstances promoting left ventricular recovery by inducing reverse remodelling. Innovative counterpulsation devices based on the established principle of the intra-aortic balloon pump have been developed, and of these, the CardioVad and the C-Pulse System have been introduced in clinical practice with convincing evidence of haemodynamic efficacy. The evolution from pulsatile to continuous-flow left ventricular assist devices has been associated with improved survival rates during the first 2 years of support with the potential of matching heart transplantation outcomes. However, blood contact with the device remains a significant challenge despite the highly sophisticated technology currently available. Innovative extra-vascular counterpulsation devices have been shown to overcome the limitations of the intra-aortic balloon pump and rend the device suitable for prolonged support. Monitoring of the performance of these novel devices is essential, and carotid Doppler ultrasonography is of utility in assessing the haemodynamic performance of the devices in a clinical setting. Computational modelling has played a role in the simulation of these devices and should continue to assist with their optimisation and implementation in clinical practice.

Background: Heart transplantation (HTx), the gold standard therapy for advanced heart failure, is limited by donor availability; alternative therapies are now becoming available., Aim: We examined the outcome of HTx with current immunosuppressive and adjunctive therapy., Design and Methods: We analysed the outcome of 399 consecutive patients who underwent transplantation at our centre (1995-2007). Prior to HTx 23% (98) required inotropic support, 8.5% (34) an intra-aortic balloon pump and 11% (43) a ventricular assist device., Results: Actuarial patient survival was 86% at 30 days, 79% at 1 year and 62% at 10 years. Survival was similar regardless of the heart failure severity, P=0.22. The cumulative incidence of allograft vasculopathy, Costanzo grade≥2, was 7% at 5 years and 23% by 10 years with an 11% cumulative probability of requiring a percutaneous coronary intervention by 10 years. Allograft function was preserved with a mean±SD left ventricular ejection fraction of 73±7% at 1 year and 74±8% at 10 years. The cumulative incidence of malignancy by 10 years was 27% (skin malignancy 13% and post transplant lymphoproliferative diseases 10%). The cumulative incidence of developing chronic kidney disease (CKD) with an estimated glomerular filtration rate≤45 ml/min/1.73 m2 was 42% at 1 year, 62% at 5 years and 72% at 10 years and of requiring long-term renal replacement therapy was 10.6% at 10 years., Conclusion: HTx provided good medium-term survival for patients with advanced heart failure, independent of its severity. The incidence of allograft vasculopathy was lower than reported previously but malignancy and CKD remain cause for concern.

Acute heart failure and cardiogenic shock are medical emergencies requiring urgent medical intervention. This article defines each syndrome and reviews the latest evidence regarding their clinical presentation, management and prognosis.

Inotropes are some of the most commonly used drugs in intensive care. However, their value in treating patients with heart failure is limited and prolonged use is associated with an increased mortality. Nevertheless inotropic agents increase cardiac contractility and can improve the cardiac output of patients with heart failure.

Background: We examined waiting time for adult heart transplantation in the UK and sought to determine whether recipients with particular ABO blood groups were disadvantaged., Methods: Data were obtained from the National Transplant Database. Registration outcome data were analyzed for 622 new, non-urgent, adult, heart-only registrations from April 1, 1999 to March 31, 2003. Unadjusted waiting times of the 618 first registrations were summarized using Kaplan-Meier estimates., Results: Death rates were relatively low, with no significant difference in the proportions of patients among the different blood groups who died while waiting. A smaller proportion of blood group O patients were transplanted at 1 year after registration, with a significant difference in waiting time to transplant between blood groups (p < 0.0001). Blood group A and AB patients were generally transplanted sooner than O and B patients, with median waiting times of 81 days (95% CI: 67 to 114) and 76 days (95% CI: 52 to 178) vs 214 days (95% CI: 162 to 308) and 174 days (95% CI: 78 to 249), respectively., Conclusions: Although no particular blood group was disadvantaged in terms of mortality on the heart transplant list, blood group O and B patients waited significantly longer for transplantation. The difference was at least partly due to a large proportion of blood group O hearts being used for non-O patients. To address this imbalance, the UK Transplant Cardiothoracic Advisory Group (CTAG) changed the allocation protocol, so that "out-of-zone" offers of blood group O donors for non-urgent patients are now restricted to O and B recipients.

Background: Left ventricular assist device (LVAD) treatment is known to lead to structural and functional cellular modifications in the heart. The relevance of these changes for clinical recovery is unknown., Methods and Results: We compared properties of cardiomyocytes obtained from tissue taken at explantation of the LVAD in patients with clinical recovery with those obtained from hearts of patients who did not show clinical recovery, thus requiring transplantation. Compared with myocytes taken at implantation, both the recovery and nonrecovery groups showed approximately 50% reduction in cell capacitance, an index of cell size. However, action potential duration shortened, L-type Ca2+ current fast inactivation was more rapid, and sarcoplasmic reticulum Ca2+ content was increased in the recovery compared with the nonrecovery group., Conclusions: These results show that specific changes in excitation-contraction coupling, and not regression of cellular hypertrophy, are specifically associated with clinical recovery after LVAD and further identify sarcoplasmic reticulum Ca2+ handling as a key functional determinant in patients with heart failure.

Background: Molecular mechanisms underlying the deterioration of patients undergoing LV assist device (LVAD) implantation remain poorly understood. We studied the cytokines tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta and IL-6 and the terminal stage of the apoptotic pathway in patients with decompensating heart failure who required LVAD support and compared them with patients with less severe heart failure undergoing elective heart transplantation., Methods and Results: Myocardial and serum samples from 23 patients undergoing LVAD implantation were compared with those from 36 patients undergoing elective heart transplantation. Myocardial TNF-alpha mRNA (1.71-fold; P<0.05) and protein (3.43+/-0.19 versus 2.95+/-0.10 pg/mg protein; P<0.05) were elevated in the LVAD patients. Immunocytochemistry demonstrated TNF expression in the myocytes. Serum TNF-alpha was also elevated (12.5+/-1.9 versus 4.0+/-0.4 pg/mL; P<0.0001) in the LVAD patients. IL-6 mRNA (2.57-fold higher; P<0.005) and protein (27.83+/-9.35 versus 4.26+/-1.24 pg/mg protein; P<0.001) were higher in the LVAD candidates, as was serum IL-6 (79.3+/-23.6 versus 7.1+/-1.6 pg/mL; P<0.0001). Interleukin-1beta mRNA expression was 9.78-fold higher in the LVAD patients (P<0.001). iNOS mRNA expression was similar to that in advanced heart failure patients and was not further elevated in the LVAD patients. Levels of procaspase-9 (8.02+/-0.91 versus 6.16+/-0.43 oligodeoxynucleotide [OD] units; P<0.01), cleaved caspase-9 (10.02+/-1.0 versus 7.34+/-0.40 OD units; P<0.05), intact and spliced DFF-45 (4.58+/-0.75 versus 2.84+/-0.23 OD units; P<0.05) were raised in LVAD patients, but caspase-3 and human nuclease CPAN were not., Conclusions: Elevated TNF-alpha, IL-1beta, and IL-6 and alterations in the apoptotic pathway were found in the myocardium and elevated TNF-alpha and IL-6 in serum of deteriorating patients who required LVAD support. These occurrences may have therapeutic implications and influence the timing of LVAD insertion.

ABSTRACT Milrinone is a bipyridine phosphodiesterase inhibitor with positive inotropic and vasodilatory effects. As interest in longer term use of intravenous therapy increases, it becomes essential to monitor its plasma concentration owing to a narrow therapeutic range, an increased half-life in renal failure and toxicity associated with high levels. A high-performance liquid chromatography (HPLC) method with mass (MS) detection using a triple quadrupole mass spectrometer is presented. The method was compared with the UV/HPLC method and validated according to current international guidelines. Coefficients of variation of less than 7.5% were obtained across the therapeutic range and 18.3% at 2.4 ng/mL, the lower limit of quantitation. Plasma from 13 cardiac surgery patients receiving standard intravenous doses of milrinone were measured. Eight patients achieved therapeutic milrinone levels within 3-4 h post start of infusion, one was borderline sub-therapeutic and four patients achieved levels that were above the upper limit of the therapeutic range and potentially toxic. This method offers high sensitivity, is rapid, easy to use and requires minimal amount of sample. We believe this method could become the reference procedure for clinical monitoring of milrinone and help to improve the safety of the use of this drug in patients with cardiac failure. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The article presents a study which examines the long-term outcome of heart transplantation in patients with amyloid heart disease. The study evaluated records of all amyloid heart disease patients who underwent heart transplantation to determine the survival, course of the systemic amyloid disease, and the cause of death. Results show that heart transplantation remains controversial due to the scarcity of available hearts for transplantation.

This article focuses on a study related to incidence and clinical significance of left ventricular assist device (LVAD) failure. Management of life threatening LVAD mechanical failure is becoming increasingly important with increasing use of these devices for prolonged periods as a bridge to recovery, as destination therapy, or as a bridge to transplantation, with support lengthening due to shortage of donors. Life threatening mechanical pump failure can be successfully managed in the majority of patients, encouraging the longer term use of these devices.