Summary Dilated cardiomyopathy is defined by the presence of left ventricular dilatation and contractile dysfunction. Genetic mutations involving genes that encode cytoskeletal, sarcomere, and ...nuclear envelope proteins, among others, account for up to 35% of cases. Acquired causes include myocarditis and exposure to alcohol, drugs and toxins, and metabolic and endocrine disturbances. The most common presenting symptoms relate to congestive heart failure, but can also include circulatory collapse, arrhythmias, and thromboembolic events. Secondary neurohormonal changes contribute to reverse remodelling and ongoing myocyte damage. The prognosis is worst for individuals with the lowest ejection fractions or severe diastolic dysfunction. Treatment of chronic heart failure comprises medications that improve survival and reduce hospital admission—namely, angiotensin converting enzyme inhibitors and β blockers. Other interventions include enrolment in a multidisciplinary heart failure service, and device therapy for arrhythmia management and sudden death prevention. Patients who are refractory to medical therapy might benefit from mechanical circulatory support and heart transplantation. Treatment of preclinical disease and the potential role of stem-cell therapy are being investigated.
Heart transplantation from donation after circulatory death (DCD) donors is a rapidly expanding practice. In this review, we describe the history and challenges of DCD heart transplantation and ...overview the procurement protocols and methods of limiting ischemic injury, current outcomes, and future directions. There are now at least three protocols that permit resuscitation and viability assessment of the DCD heart either in situ or ex situ. While the retrieval protocol for hearts from DCD donors will depend on local regulations, the outcomes of DCD heart transplant recipients reported to date are excellent regardless of the retrieval protocol and are comparable to the outcomes of heart transplant recipients from donation after brain death (DBD) donors. In the two centers with the largest published experience, DCD heart transplantation now accounts for one third of their heart transplant activity. With international trends indicating that there is an increasing utilisation of the DCD pathway, it is expected that DCD donors will become a major source of heart donation worldwide.
The effects of two cationic peptides on phospholipid lateral diffusion in binary mixtures of POPC with various anionic phospholipids were measured via 31P CODEX NMR. Large unilamellar vesicles ...composed of POPC/POPG (70/30 mol/mol), or POPC/DOPS (70/30 mol/mol), or POPC/TOCL (85/15 mol/mol), or POPC/DOPA (50/50 mol/mol) were exposed to either polylysine (pLYS, N = 134 monomers) or KL-14 (KKLL KKAKK LLKKL), a model amphipathic helical peptide, in an amount corresponding to 80% neutralization of the anionic phospholipid charge by the cationic lysine residues. In the absence of added peptide, phospholipid lateral diffusion coefficients (all measured at 10 °C) increased with increasing reduced temperature (T-Tm). The POPC/DOPA mixture was an exception to this generalization, in that lateral diffusion for both components was far slower than any other mixture investigated, an effect attributed to intermolecular hydrogen bonding. The addition of pLYS or KL-14 decreased lateral diffusion in the POPC/DOPS LUV, but had minimal effects in the POPC/POPG LUV, indicating that ease of access of the cationic peptide residues to the anionic phospholipid groups was important. Both cationic peptides produced the opposite effect in the POPC/DOPA case, in that lateral diffusion increased significantly in their presence, with KL-14 being most effective. This latter observation was interpreted in terms of the electrostatic / H-bond model proposed by Kooijman et al. Journal of Biological Chemistry, 282:11356–11,364, 2007 to describe the mechanism of interaction between the phosphomonoester head group of PA and the tertiary amine of lysine.
Display omitted
•31P CODEX NMR measured phospholipid lateral diffusion coefficients DL in binary mixtures.•DL scaled with the reduced temperature T-Tm, except for POPC/DOPA which exhibited unusually slow diffusion.•PolyLysine slowed diffusion of DOPS and TOCL, but alleviated the “prior restraint” on DOPA,•KL-14, an amphipathic model antibacterial cationic peptide, behaved in a similar fashion,
Tricuspid regurgitation (TR) is common after cardiac transplantation and results in poorer outcomes. Transplant recipients are at high prohibitive risk for redo surgical procedures because of risks ...associated with a subsequent sternotomy, immunosuppression, and renal failure. Percutaneous therapies have recently become available and may be an option for transplant recipients. However, transplant recipients have complex geometry, and there is a myriad of causes of TR posttransplant. There is a need for careful patient selection for all percutaneous valve interventions, and this is particularly true in transplant recipients who suffer from right ventricular failure and rejection and may undergo repeated endomyocardial biopsies. Cognizant of the rapid developments in this space, this review article focuses on the causes of TR, treatments, and future therapies in heart transplantation recipients to the transplant cardiologist navigate this complex area.
Although primary graft dysfunction (PGD) is fairly common early after cardiac transplant, standardized schemes for diagnosis and treatment remain contentious. Most major cardiac transplant centers ...use different definitions and parameters of cardiac function. Thus, there is difficulty comparing published reports and no agreed protocol for management. A consensus conference was organized to better define, diagnose, and manage PGD. There were 71 participants (transplant cardiologists, surgeons, immunologists and pathologists), with vast clinical and published experience in PGD, representing 42 heart transplant centers worldwide. State-of-the-art PGD presentations occurred with subsequent breakout sessions planned in an attempt to reach consensus on various issues. Graft dysfunction will be classified into primary graft dysfunction (PGD) or secondary graft dysfunction where there is a discernible cause such as hyperacute rejection, pulmonary hypertension, or surgical complications. PGD must be diagnosed within 24 hours of completion of surgery. PGD is divided into PGD-left ventricle and PGD-right ventricle. PGD-left ventricle is categorized into mild, moderate, or severe grades depending on the level of cardiac function and the extent of inotrope and mechanical support required. Agreed risk factors for PGD include donor, recipient, and surgical procedural factors. Recommended management involves minimization of risk factors, gradual increase of inotropes, and use of mechanical circulatory support as needed. Retransplantation may be indicated if risk factors are minimal. With a standardized definition of PGD, there will be more consistent recognition of this phenomenon and treatment modalities will be more comparable. This should lead to better understanding of PGD and prevention/minimization of its adverse outcomes.
PDF
