Heart transplantation: current practice and outlook to the future.

QUESTIONS UNDER STUDY: The field of heart transplantation has seen substantial progress in the last 40 years. The breakthroughs in long-term survival were followed by a period of stagnation in the last decade. This review summarises current recommendations for the identification of candidates for heart transplantation and their immunological and non-immunological postoperative follow-up. RESULTS: The progress made in the treatment of patients with advanced heart failure has considerably changed the profile of candidates for heart transplantation. Patients are older, and the load of co-morbidities is more important requiring careful evaluation for candidacy. Long-standing research in the field of immunosuppression made available various drugs, which decrease the risk of acute allograft rejection and prolong survival after heart transplantation. Powerful new molecules are entering early phase clinical studies, suggesting further improvement in the near future. As a consequence, treatment of non-immunological co-morbidity after heart transplantation will gain in importance, however, the base of evidence guiding current recommendations is poor. CONCLUSIONS: The substantial progress in heart failure treatment and immunosuppression after heart transplantation has changed the profile of heart transplant recipients. The arrival of new molecules will provide additional alternatives for immunosuppressive treatment while studies have to address non-immunological treatment in order to improve long-term survival after heart transplantation

Mechanical circulatory support for destination therapy.

Patients with chronic heart failure who are not eligible for heart transplant and whose life expectancy depends mainly on the heart disease may benefit from mechanical circulatory support. Mechanical circulatory support restores adequate cardiac output and organ perfusion and eventually improves patients' clinical condition, quality of life and life expectancy. This treatment is called destination therapy (DT) and we estimate that in Switzerland more than 120 patients per year could benefit from it. In the last 10 years, design of the devices, implantation techniques and prognoses have changed dramatically. The key to successful therapy with a left ventricular assist device is appropriate patient selection, although we are still working on the definition of reliable inclusion and exclusion criteria and optimal timing for surgical implantation. Devices providing best long-term results are continuous flow, rotary or axial blood pumps implanted using minimally invasive techniques on a beating heart. These new devices (Thoratec HeartMate II and HeartWare HVAD) have only a single moving part, and have improved durability with virtually 10 years freedom from mechanical failure. In selected patients, the overall actuarial survival of DT patients is 75% at 1 year and 62% at 2 years, with a clear improvement in quality of life compared with medical management only. Complications include bleeding and infections; their overall incidence is significantly lower than with previous devices and their management is well defined. DT is evolving into an effective and reasonably cost-effective treatment option for a growing population of patients not eligible for heart transplant, showing encouraging survival rates at 2 years and providing clear improvement in quality of life. The future is bright for people suffering from chronic heart failure

Red cell distribution width and mortality in acute heart failure patients with preserved and reduced ejection fraction.

Elevated red blood cell distribution width (RDW) is a valid predictor of outcome in acute heart failure (AHF). It is unknown whether elevated RDW remains predictive in AHF patients with either preserved left ventricular ejection fraction (LVEF) ≥50% or reduced LVEF (<50%). Prospective local registry including 402 consecutive hospitalized AHF patients without acute coronary syndrome or need of intensive care. The primary outcome was all-cause mortality (ACM) at 1 year after admission. Demographic and clinical data derive from admission, echocardiographic examinations (n = 269; 67%) from hospitalization. The Cox proportional hazard model including all patients (P < 0.001) was adjusted for age, gender, and RDW quartiles. Independent predictors of 1-year ACM were cardiogenic shock (HR 2.86; CI: 1.3-6.4), male sex (HR 1.9; CI: 1.2-2.9), high RDW quartile (HR 1.66; CI: 1.02-2.8), chronic HF (HR 1.61; CI: 1.05-2.5), valvular heart disease (HR 1.61; CI: 1.09-2.4), increased diastolic blood pressure (HR 1.02 per mmHg; CI: 1.01-1.03), increasing age (HR 1.04 by year; CI: 1.02-1.07), platelet count (HR 1.002 per G/l; CI: 1.0-1.004), systolic blood pressure (HR 0.99 per mmHg; CI: 0.98-0.99), and weight (HR 0.98 per kg; CI: 0.97-0.99). A total of 114 patients (28.4%) died within the first year; ACM of all patients increased with quartiles of rising RDW (χ(2) 18; P < 0.001). ACM was not different between RDW quartiles of patients with reduced LVEF (n = 153; χ(2) 6.6; P = 0.084). In AHF with LVEF ≥50% the probability of ACM increased with rising RDW (n = 116; χ(2) 9.9; P = 0.0195). High RDW is associated with increased ACM in AHF patients with preserved but not with reduced LVEF in this study population

Three-Dimensional Self-Navigated T2 Mapping for the Detection of Acute Cellular Rejection After Orthotopic Heart Transplantation.

T2 mapping is a magnetic resonance imaging technique measuring T2 relaxation time, which increases with the myocardial tissue water content. Myocardial edema is a component of acute cellular rejection (ACR) after heart transplantation. This pilot study compares in heart transplantation recipients a novel high resolution 3-dimensional (3D) T2-mapping technique with standard 2-dimensional (2D) T2-mapping for ACR detection. Consecutive asymptomatic patients (n = 26) underwent both 3D T2 mapping and reference 2D T2 mapping magnetic resonance imaging on the day of endomyocardial biopsy (EMB). 3D T2 maps were obtained at an isotropic spatial resolution of 1.72 mm (voxel volume 5.1 mm(3)). 2D and 3D maps were matched anatomically, and maximum segmental T2 values were compared blinded to EMB results. In addition, all 3D T2 maps were rendered as 3D images and inspected for foci of T2 elevation. T2 values of segments from 2D and reformatted 3D T2 maps agreed (p > 0.5). The highest 2D segmental T2 values were 49.9 ± 4.0 ms (no ACR = 0R, n = 18), 48.9 ± 0.8 ms (mild ACR = 1R, n = 3), and 65.0 ms (moderate ACR = 2R). Rendered 3D T2 maps of cases with 1R showed foci with significantly elevated T2 signal (T2 = 58.2 ± 3.6 ms); 5 cases (28%) in the 0R group showed foci with increased T2 values (>2 SD above adjacent tissue) that were not visible on the 2D T2 maps. This pilot study in a small cohort suggests equivalency of standard segmental analysis between 3D and 2D T2-mapping. 3D T2 mapping provides a spatial resolution that permits detection of foci with elevated T2 in patients with mild ACR

Cardiac Surgery in Advanced Heart Failure.

Mechanical circulatory support and heart transplantation are established surgical options for treatment of advanced heart failure. Since the prevalence of advanced heart failure is progressively increasing, there is a clear need to treat more patients with mechanical circulatory support and to increase the number of heart transplantations. This narrative review summarizes recent progress in surgical treatment options of advanced heart failure and proposes an algorithm for treatment of the advanced heart failure patient at >65 years of age

Risk Estimation of Severe Primary Graft Dysfunction in Heart Transplant Recipients Using a Smartphone.

Currently, there are no standardized guidelines for graft allocation in heart transplants (HTxs), particularly when considering organs from marginal donors and donors after cardiocirculatory arrest. This complexity highlights the need for an effective risk analysis tool for primary graft dysfunction (PGD), a severe complication in HTx. Existing score systems for predicting PGD lack superior predictive capability and are often too complex for routine clinical use. This study sought to develop a user-friendly score integrating variables from these systems to enhance the efficacy of the organ allocation process. Severe PGD was defined as the need for mechanical circulatory support and/or death from an unknown etiology within the first 24 hours following HTx. We used a meta-analytical approach to create a derivation cohort to identify risk factors. We then applied a logistic regression analysis to generate an equation predicting severe PGD risk. We used our previous experience in HTx to create a validation cohort. Subsequently, we implemented the formula in a smartphone application. The meta-analysis comprising six studies revealed a 10.5% ( 95% confidence interval (CI): 5.3-12.4) incidence rate of severe PGD and related 30-day mortality of 38.6%. Eleven risk factors were identified: female donors, female donor to male recipient, undersized donor, donor age, recipient on ventricular assist device support, recipient on amiodarone treatment, recipient with diabetes and renal dysfunction, re-sternotomy, graft ischemic time, and bypass time. An equation to predict the risk, including the 11 parameters (GREF-11), was created using logistic regression models and validated based on our experience involving 116 patients. In our series, 29 recipients (25%) required extracorporeal membrane oxygenation support within 24 hours post-HTx. The overall 30-day mortality was 4.3%, 3.4%, and 6.8% in the non-PGD and severe PGD groups, respectively. The area under the receiver operating characteristic (AU-ROC) curve of the model in the validation cohort was 0.804. The GREF-11 application should offer HTx teams several benefits, including standardized risk assessment and bedside clinical decision support, thereby helping minimize the risk of severe PGD post-HTx