Dronavalli V.B.,University of Birmingham |
Banner N.R.,Harefield Hospital |
Bonser R.S.,University of Birmingham
Journal of the American College of Cardiology | Year: 2010
Demand for donor hearts exceeds supply, and a significant number of patients die while awaiting transplantation. Within the pool of currently unused potential donor hearts, a proportion may be suitable for transplantation but are declined due to anticipated poor function. Despite current assessment methods, in some donor hearts accepted for transplantation early graft failure develops in the recipient. Current methods of assessment are inadequate, and there is a potential for biomarkers to improve identification of satisfactory hearts for transplantation or hearts destined to fail in the recipient. Biomarkers are routinely used to diagnose and risk-stratify myocardial infarction, acute coronary syndromes, and heart failure. Some of these might facilitate donor heart assessment. Cardiac troponins, cytokines, inflammatory markers, natriuretic peptides, and intracellular proteins may each have discriminant value. This review details the current status of biomarkers in the assessment of donor hearts. © 2010 American College of Cardiology Foundation.
Strueber M.,Hannover Medical School |
O'Driscoll G.,Royal Perth Hospital |
Jansz P.,St Vincents Hospital |
Khaghani A.,Harefield Hospital |
And 2 more authors.
Journal of the American College of Cardiology | Year: 2011
Objectives: The aim of this study was to conduct an initial clinical evaluation of the new HeartWare Ventricular Assist System (HeartWare, Inc., Framingham, Massachusetts) in a multicenter, prospective, nonrandomized single-arm clinical trial. Background: Heart failure is a worldwide epidemic. The effectiveness of heart transplantation and medical therapy is limited, resulting in the emergence of mechanical circulatory support as a primary treatment for end-stage heart disease. Left ventricular assist devices that use rotary pumps are small and durable, which might reduce morbidity and mortality during support. Methods: Fifty heart transplant candidates with New York Heart Association functional class IV symptoms were supported at 5 international centers by the HeartWare System for 180 days, until heart transplant, myocardial recovery and device explant, or death. Patients who continue to be supported have been followed for a minimum of 2 years. Results: Of the 50 patients, 20 (40%) received transplants, 4 (8%) had the pump explanted after myocardial recovery, and 17 (34%) continue support at 2 years. Nine (18%) patients died during support from sepsis (n = 3), multiple organ failure (n = 3), or hemorrhagic stroke (n = 3). The actual survival at 6, 12, and 24 months was 90%, 84%, and 79%, respectively. In the survivors, measures of quality of life showed a significant improvement over baseline values. Significant improvements were found for recognition memory at 3 months after implant (p = 0.006). The most frequent adverse events were infection and bleeding. Conclusions: Patients with end-stage heart failure can be safely and effectively supported by the HeartWare Ventricular Assist System with improved quality of life and neurocognitive function. © 2011 by the American College of Cardiology Foundation.
Ibrahim M.,Harefield Hospital |
Yacoub M.H.,Harefield Hospital
Heart Failure Clinics | Year: 2014
The discovery of substantial myocardial improvement following the mechanical unloading afforded by left ventricular assist device (LVAD) therapy challenged the dogma of heart failure being irreversible. Since then, a significant experience with the use of LVAD therapy as a bridge to recovery has accumulated. The discovery of substantial structural and functional changes (reverse remodeling) in the myocardium has resulted in an intensive effort to define the biologic determinants of the reversibility of these changes. Herein the scientific foundations, clinical practice, and future of the use of LVADs as a bridge to recovery are reviewed. © 2014 Elsevier Inc.
Raja S.G.,Harefield Hospital
International Journal of Surgery | Year: 2012
Background: For the cardiac surgeon and patient the development of sternal wound infection is a serious post-operative complication associated with increased risk of death and also considerable morbidity. Methods: Nine publications were identified using the PubMed online database and search terms 'gentamicin-containing collagen implant' plus 'surgical site infection', 'wound infection' and 'cardiac surgery'. Results: Six out of eight studies demonstrated that prophylactic use of gentamicin-containing collagen implants (GCCI) significantly reduce the wound infection rate following cardiac surgery (via sternotomy) compared to standard treatment alone. The adjunctive use of GCCI is particularly beneficial in high-risk subjects e.g. diabetes and obese patients. GCCI significantly improve the morbidity associated with SSI following cardiac surgery by shortening the recovery phase and length of hospital stay; reducing the need for surgical revision and use of antibiotics. GCCI have been shown to be cost saving across a wide spectrum of patients. A further study has shown that GCCI may also have a therapeutic role to play in patients with deep sternal wounds. Conclusion: This review demonstrates that when used dry prior to insertion GCCI can be effective in reducing the rate of SSI following cardiac surgery. GCCI have also been shown to be cost saving as they reduce the substantial morbidity associated with deep SSI. The adjunctive use of GCCI is particularly beneficial in high-risk patients. GCCI may also have a role to play in the treatment of deep sternal wound infection. © 2012 Surgical Associates Ltd.
Raja S.G.,Harefield Hospital
Recent Patents on Cardiovascular Drug Discovery | Year: 2012
Multiple cell types in the vascular wall rely upon the rho-kinase (ROCK) signaling pathway for homeostatic function and response to injury. These cell types include endothelial and vascular smooth muscle cells, inflammatory cells, and fibroblasts. Rho is a guanosine triphosphate binding protein that activates its downstream target rho-kinase, in response to activation of a variety of G-protein coupled receptors. When activated, ROCK inhibits myosin phosphatase and conversely upregulates the ezrin-radixin-moesin family of kinases. In vitro activation of these signaling cascades results in modulation of multiple cellular processes, including enhanced vasoconstriction, proliferation, impaired endothelial response to vasodilators, chronic pulmonary remodeling, and upregulation of vasoactive cytokines via the NF-κB transcription pathway. ROCK activity has also been linked specifically to a number of known effectors of pulmonary arterial hypertension (PAH), including endothelin-1, serotonin, and endothelial nitric oxide synthase, among others. Recently, elevated ROCK activity has been demonstrated in various animal models of PAH with ROCK inhibitors associated with pulmonary vasodilatation and regression of PAH. ROCK inhibitors are a new class of agents which may be beneficial in the treatment of PAH. Fasudil (Daiichi Chemical and Pharmacological Company, Ibaragi, Japan), a first generation ROCK inhibitor, has been widely studied. Emerging evidence from both animal and human studies suggests that fasudil can promote vasodilation independent of the mechanism that induces vasoconstriction and will be useful in conditions in which endothelial function is impaired including PAH. Several recent patents have described fasudil as a potential therapeutic option in PAH. This article provides an overview of the role of ROCK in the pathogenesis of PAH and discusses the clinical efficacy of fasudil as a therapeutic option for treating PAH. © 2012 Bentham Science Publishers.
Burke M.M.,Harefield Hospital
American Journal of Transplantation | Year: 2016
In heart transplantation, semiquantitative scoring schemes of structural and infl ammatory components of coronary allograft vasculopathy (CAV) identify a subset of recipients with CAV who also show concurrent or previous subclinical antibody-mediated rejection, of potential importance in CAV pathogenesis. See the article from Loupy et al on page 111. Copyright © 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.
Hodges A.M.,Harefield Hospital |
Hodges A.M.,Imperial College London
Transplantation | Year: 2012
Background: Antibody-mediated rejection (AMR) is an important problem after heart transplantation. Most cases seem to occur in sensitized recipients with preformed donor-specific human leukocyte antigen antibody (DSA) early after transplantation. Few data exist on AMR in patients who form de novo DSA. We describe the clinical features and treatment outcome for late AMR secondary to de novo DSA. Methods: This was a retrospective, observational cohort study. All heart transplant patients treated for symptomatic AMR secondary to de novo DSA between November 2005 and August 2011. Results: Fifteen patients were treated for AMR giving an incidence of 3.1 cases per 1000 person years and a prevalence of 1.4%. All had evidence of heart failure on presentation and de novo DSA at diagnosis. There was a spectrum of histologic and immunohistochemical findings. Despite treatment with immunepheresis, intravenous immunoglobulin, and rituximab, and in some cases total lymph node irradiation (n=3) and bortezomib (n=2), clinical outcomes were poor. DSA antibody levels, measured using Labscreen single antigen kits, were reduced by a mean of 76% with a median of 77% and a range of 35% to 99%, but were not eliminated. Forty-six percent had persistent cardiac allograft dysfunction. Mean and median survival was 1.3 and 0.8 years after diagnosis of AMR. Only 40% were alive at the end of the study period. Conclusion: Late cardiac AMR caused by de novo DSA was an uncommon but serious problem. Despite treatment consistent with current best practice, 46% of patients developed persistent cardiac dysfunction and their medium-term survival was poor. Copyright © 2012 by Lippincott Williams & Wilkins.
Raja S.G.,Harefield Hospital
International Journal of Surgery | Year: 2015
Coronary artery disease (CAD) is a leading cause of mortality and morbidity in diabetics. Diabetics make up to 20%-35% of all patients undergoing coronary revascularization. Patients with diabetes represent a particularly difficult subset for revascularization due to increased short- and long-term mortality as well as a higher risk of repeat revascularization procedures. Potential factors contributing to the increased risk include co-morbid illnesses, small, diffusely diseased target vessels, progression of native CAD, hyperglycaemic endothelial dysfunction, and systemic inflammation. For diabetic patients with multi-vessel disease, revascularization by coronary artery bypass grafting (CABG) is regarded as the preferred option. There is increasing recognition that the use of arterial conduits for CABG is associated with improved outcomes compared to use of venous conduits. Amongst arterial conduits bilateral internal mammary arteries (BIMA) have emerged as the superior conduits due to better cardiac event-free survival. Consistent with its benefits in non-diabetic patients, BIMA grafting is presumed to offer similar benefits in diabetic patients. However, BIMA grafting remains underutilised in diabetics due to perceived increased risk of sternal wound infection. This review article provides an overview of BIMA grafting in diabetic patients focussing on outcomes, concerns, and controversies associated with BIMA usage in this high-risk group of patients. © 2014 IJS Publishing Group Limited.
Raja S.G.,Harefield Hospital
Current Cardiology Reviews | Year: 2012
The increase in life expectancy has confronted cardiac surgery with a rapidly growing population of elderly patients requiring surgical myocardial revascularization. Recent advances in surgical and anesthetic techniques and improvements in postoperative care have made coronary artery bypass grafting an established therapeutic option for the treatment of coronary artery disease in this group of patients. However, conventional coronary artery bypass grafting on cardiopulmonary bypass is associated with significant risk and related morbidity and mortality in the elderly. In recent years off-pump coronary artery bypass grafting has emerged as a safe and less invasive strategy for surgical myocardial revascularization. Off-pump coronary artery bypass grafting by avoiding the deleterious effects of cardiopulmonary bypass can offer potential benefits to elderly patients requiring surgical myocardial revascularization. This review article provides an overview of the age-related cardiovascular changes, epidemiology of coronary artery disease in the elderly and focuses on outcomes of surgical myocardial revascularization with special emphasis on the impact of off-pump coronary artery bypass surgery in the elderly. © 2012 Bentham Science Publishers.
Benedetto U.,Harefield Hospital |
Raja S.G.,Harefield Hospital
Journal of Thoracic and Cardiovascular Surgery | Year: 2014
Objectives The effectiveness of the routine retrosternal placement of a gentamicin-impregnated collagen sponge (GICS) implant before sternotomy closure is currently a matter of some controversy. We aimed to develop a scoring system to guide decision making for the use of GICS to prevent deep sternal wound infection.Methods Fast backward elimination on predictors, including GICS, was performed using the Lawless and Singhal method. The scoring system was reported as a partial nomogram that can be used to manually obtain predicted individual risk of deep sternal wound infection from the regression model. Bootstrapping validation of the regression models was performed.Results The final populations consisted of 8750 adult patients undergoing cardiac surgery through full sternotomy during the study period. A total of 329 patients (3.8%) received GICS implant. The overall incidence of deep sternal wound infection was lower among patients who received GICS implant (0.6%) than patients who did not (2.01%) (P =.02). A nomogram to predict the individual risk for deep sternal wound infection was developed that included the use of GICS. Bootstrapping validation confirmed a good discriminative power of the models.Conclusions The scoring system provides an impartial assessment of the decision-making process for clinicians to establish if GICS implant is effective in reducing the risk for deep sternal wound infection in individual patients undergoing cardiac surgery through full sternotomy. © 2014 by The American Association for Thoracic Surgery.