Mauricio Velez

Management of allosensitized cardiac transplant candidates

Cardiac transplantation remains the best treatment in patients with advanced heart failure with a high risk of death. However, an inadequate supply of donor hearts decreases the likelihood of transplantation for many patients. Ventricular assist devices (VADs) are being increasingly used as a bridge to transplantation in patients who may not survive long enough to receive a heart. This expansion in VAD use has been associated with increasing rates of allosensitization in cardiac transplant candidates. Anti-HLA antibodies can be detected before transplantation using different techniques. Complement-dependent lymphocytotoxicity assays are widely used for measurement of panel-reactive antibody (PRA) and for crossmatch purposes. Newer assays using solid-phase flow techniques feature improved specificity and offer detailed information concerning antibody specificities, which may lead to improvements in donor-recipient matching. Allosensitization prolongs the wait time for transplantation and increases the risk of post-transplantation complications and death; therefore, decreasing anti-HLA antibodies in sensitized transplant candidates is of vital importance. Plasmapheresis, intravenous immunoglobulin, and rituximab have been used to decrease the PRA before transplantation, with varying degrees of success. The most significant post-transplantation complications seen in allosensitized recipients are antibody-mediated rejection (AMR) and cardiac allograft vasculopathy (CAV). Often, AMR manifests with severe allograft dysfunction and hemodynamic compromise. The underlying pathophysiology is not fully understood but appears to involve complement-mediated activation of endothelial cells resulting in ischemic injury. The treatment of AMR in cardiac recipients is largely empirical and includes high-dose corticosteroids, plasmapheresis, intravenous immunoglobulin, and rituximab. Diffuse concentric stenosis of allograft coronary arteries due to intimal expansion is a characteristic of CAV. Its pathophysiology is unclear but may involve chronic complement-mediated endothelial injury. Sirolimus and everolimus can delay the progression of CAV. In some nonsensitized cardiac transplant recipients, the de novo formation of anti-HLA antibodies after transplantation may increase the likelihood of adverse clinical outcomes. Serial post-transplantation PRAs may be advisable in patients at high risk of de novo allosensitization.

Improved survival in patients with ventricular assist device therapy: the University of Wisconsin experience

OBJECTIVE Ventricular assist devices (VADs) have been implanted since 1990 in our institution, becoming an increasingly common treatment for end-stage heart failure. Beginning in 1997, VAD patients were discharged home when feasible. In August 2003, a dedicated multidisciplinary VAD team (cardiac surgeons, cardiologists, VAD coordinators, nurses, rehabilitation specialists, nutrition experts, psychologists, pharmacists, social workers, and administrators) was created to optimize the management of VAD patients. The purpose of this study is to analyze the impact of these changes in care at our center over the last 17 years. METHODS We retrospectively studied 107 consecutive VAD recipients between June 1990 and August 2006. VADs were implanted as bridge to recovery, bridge to transplant and destination therapy. The cohort was divided by care plans into early (n=37, June 1990-1996), mid (n=32, 1997-July 2003), and late groups (n=38, August 2003-August 2006). Demographic profile, survival and complications were assessed. RESULTS Patient demographics tended to show an increased severity of illness over time. Post-VAD survival rate significantly improved in the late group (post-VAD 1- and 3-year survival rates; early: 54.1% and 40.5%; mid: 51.6% and 41.9%; late: 86.8% and 82.5%, p<0.001, respectively). The incidence of complications including re-operation, major bleeding and major infection, significantly decreased in the late group (p<0.05). CONCLUSIONS Outcomes have improved dramatically in recent VAD patients, despite an increasingly high-risk patient population. These data suggest that advances in device technology and medical therapies, as well as a multidisciplinary approach, have improved survival on VAD therapy.

Improved Survival After Heart Transplantation in Patients With Bridge to Transplant in the Recent Era: A 17-year Single-center Experience

BACKGROUND Ventricular assist device (VAD) implantation as a bridge to transplant (BTT) has become an important approach for heart transplant candidates. In this study we document our institutional long-term results and recent improvements in BTT therapy. METHODS We retrospectively studied 531 consecutive heart transplant recipients between January 1990 and August 2007. The cohort was divided into old orthotopic heart transplant (OHT) without device (oOHT; n = 399, January 1990 to July 2003), old BTT (oBTT; n = 41, January 1990 to July 2003), new OHT without device (nOHT; n = 58, August 2003 to August 2007) and new BTT (nBTT; n = 33, August 2003 to August 2007) groups. Demographics and post-transplant outcomes were assessed. RESULTS Post-transplant survival in the nBTT group improved significantly compared with the oBTT group (log-rank test, p = 0.01) and survival in the nOHT group tended to be higher than in the oOHT group (p = 0.19). Survival in the oBTT group was significantly worse than in the oOHT group (p < 0.01). However, there was no difference between the nBTT and nOHT groups. The mean period of BTT support was 113 (range 5 to 524) days in the oBTT group and 148 (range 38 to 503) days in the nBTT group. Multivariate analysis revealed diabetes (p < 0.01) and biventricular support (p = 0.04) as significant independent predictors of post-transplant mortality. CONCLUSIONS Post-transplant survival has improved in recent BTT patients. Indeed, recent outcome for OHT after BTT has become equivalent to that for OHT without VAD. These data suggest that advances in device technology and our institutional multidisciplinary program have improved survival and allow BTT candidates to have an outcome equivalent to that of non-VAD patients in the recent era.

Why it Pays for Hospitals to Initiate a Heart Failure Disease Management Program

Heart failure is a clinical syndrome usually caused by structural changes in the heart. These changes result in varying degrees of symptomatic functional limitation, typically shortness of breath and fatigue. Heart failure is common, with a lifetime risk for its occurrence in a healthy 40-year-old of 20%. In the US, the cost of heart failure care is now estimated at over

Pathophysiology of Heart Failure

US30 billion annually (year 2007 values).Several forms of treatment have been devised for heart failure: medical, device based, and surgical. These are best individualized to each patient and used in stepped progression to goals that are based on current expert guidelines. When goal-directed treatment is accomplished, three major outcomes are expected: (i) symptom relief and improved quality of life; (ii) a slowing or partial reversal of cardiac structural abnormalities; and (iii) a reduction in mortality.Attempts to deliver care for this complex syndrome have led to the development of heart failure-specific disease management programs. These programs can take different forms. Some involve multi-disciplinary teams that comprise a wide array of specialized physicians, cardiac surgeons, nurses, and other allied health workers, all with specific tasks. Others have a more narrow focus and are nurse-led programs. These programs, when fully implemented, help the patient manage his/her disease more effectively through education about heart failure, the purpose and correct use of medication, and the full utilization of nutritional interventions. These programs are also ideally suited to deliver care for patients with end-stage disease, particularly those needing implantation of left ventricular assist devices or transplantation.When effectively implemented, these programs have been shown to improve quality of life, decrease rate of heart failure hospitalizations, and improve survival compared with usual care. Cost analyses of these programs are challenging, and in the most favorable circumstances the greater up-front cost of more intense care is paid back by a lower rate of utilization of inpatient resources. The details of the University of Wisconsin Program are discussed as an example of a comprehensive management program.

Left ventricular responses to acute changes in late systolic pressure augmentation in older adults.

Heart failure (HF) is a clinical syndrome resulting from structural or functional disorders that impair the heart’s ability to fill with or eject blood. The pathophysiologic mechanisms leading to HF are complex and encompass hemodynamic alterations and neurohormonal changes that contribute to the chronic, progressive nature of the disease. This chapter reviews the pathophysiologic mechanisms that underlie the clinical manifestations of the HF syndrome, primarily focusing on HF due to left ventricular systolic dysfunction. Cardiac compensatory mechanisms, hemodynamic adjustments, neurohormonal activation, ventricular remodeling, and arrhythmogenesis will be reviewed.