Andrew Lenneman

Treatment Strategies for Myocardial Recovery in Heart Failure

Opinion statementHeart failure is a progressive disorder characterized by adverse left ventricular remodeling. Until recently, this has been thought to be an irreversible process. Mechanical unloading with a left ventricular assist device (LVAD), particularly if combined with neurohormonal blockade with heart failure medications, can lead to a reversal of the heart failure phenotype, a process called “reverse remodeling.” Reverse remodeling refers to the regression of pathologic myocardial hypertrophy and improvement in LV chamber size that can occur in response to treatment. Myocardial recovery is the sustained normalization of structural, molecular, and hemodynamic changes sufficient to allow explant of the LVAD. Despite the fact that reverse remodeling is commonly seen in LVAD patients in clinical practice, myocardial recovery sufficient to allow device explantation is still rare. Previous experience suggests that young patients with short duration of heart failure and less myocardial fibrosis may be more likely to recover. Alternatively, it may just be that clinicians make a greater effort to recover these subgroups. A combined approach of mechanical unloading with LVADs and pharmacological management, together with regular testing of underlying myocardial function with the pump reduced to a speed at which it is not contributing, can increase the frequency of sustained recovery from heart failure. The goal is to achieve optimal unloading of the myocardium, combined with pharmacologic therapy aimed at promoting reverse remodeling. Myocardial recovery must be considered as a therapeutic target. Clinical variables such as pump speed and blood pressure must be optimized to promote maximal unloading, leading to reverse remodeling and myocardial recovery. Frequent echocardiographic and hemodynamic evaluation of underlying myocardial function must be performed. The combination of LVAD therapy with optimal neurohormonal blockade appears promising as an approach to myocardial recovery. In addition, there is a growing body of translational research which, when combined with LVADs, may further promote more durable recovery. Strategies to thicken the myocardium to enhance the durability of recovery prior to explantation, such as clenbuterol (which induces “physiological hypertrophy”), or intermittently reducing the pump speed to increase myocardial load may be beneficial. Emergence of cardiac stem cells and alternative biologic agents, when added to current therapies, may have a complementary role in promoting and maintaining myocardial recovery. This review will summarize both current strategies and emerging therapies.

Heart Transplant Survival Based on Recipient and Donor Risk Scoring: A UNOS Database Analysis.

Unlike the lung allocation score, currently, there is no quantitative scoring system available for patients on heart transplant waiting list. By using United Network for Organ Sharing (UNOS) data, we aim to generate a scoring system based on the recipient and donor risk factors to predict posttransplant survival. Available UNOS data were queried between 2005 and 2013 for heart transplant recipients aged ≥18 years to create separate cox-proportional hazard models for recipient and donor risk scoring. On the basis of risk scores, recipients were divided into five groups and donors into three groups. Kaplan–Meier curves were used for survival. Total 17,131 patients had heart transplant within specified time period. Major factors within high-risk groups were body mass index > 30 kg/m2 (46%), mean pulmonary artery pressure >30 mmHg (65%), creatinine > 1.5 mg% (63%), bilirubin > 1.5 mg% (54%), noncontinuous-flow left ventricular assist devices (45%) for recipients and gender mismatch (81%) and ischemia time >4 hours (88%) for donors. Survival in recipient groups 1, 2, 3, 4, and 5 at 5 years was 81, 80, 77, 74, and 62%, respectively, and in donor groups 1, 2, and 3 at 5 years was 79, 77, and 70%, respectively (p < 0.001). Combining donor and recipient groups based on scoring showed acceptable survival in low-risk recipients with high-risk donor (75% at 5 years). A higher recipient and donor risk score are associated with worse long-term survival. A low-risk recipient transplanted with high-risk donor has acceptable survival at 5 years, but high-risk recipient combined with a high-risk donor has marginal results. Using an objective scoring system could help get the best results when utilizing high-risk donors.

The Use of Eptifibatide Alone or in Combination With Heparin or Argatroban for Suspected Thrombosis in Patients With Left Ventricular Assist Devices

Pump thrombosis and hemolysis in patients with left ventricular assist devices (LVADs) are associated with significant morbidity and mortality. Intensification of anticoagulation has been suggested as potential therapy, with mixed results. The aim of this study is to assess the safety and efficacy of adding eptifibatide with or without an anticoagulation agent in managing patients with LVAD presenting with hemolysis and suspected pump thrombosis. This retrospective single center study included all patients who presented with their first episode of suspected pump thrombosis and were treated with eptifibatide with or without an anticoagulant between March 1, 2011 and July 30, 2015. A total of 27 patients (23 HeartMate II, 4 HeartWare) were identified. The average age was 55 years (range 19-75) and time from implant to event averaged 513 days (range 35-1760). The average lactate dehydrogenase on presentation was 1111 and 63% of patients had power elevations. The average international normalized ratio (INR) on admission was 2.4, with INR of ≥2 in 21/27 patients. All patients received eptifibatide: 10 received eptifibatide only, 9 received eptifibatide and argatroban, and 8 received eptifibatide and heparin. Warfarin was continued in 25/27 patients. Overall, 21 patients (77.8%) were successfully treated medically, 5 (18.5%) underwent pump exchange, and 1 (3.7%) died. There were no differences in outcomes or complications between the three treatment groups. Despite initial success, 12/21 patients developed repeat episodes of hemolysis at 1 year. The 1-year survival in the patients treated medically was 90% and surgically was 60%. Our experience indicates that medical therapy for hemolysis and suspected LVAD thrombosis with warfarin and eptifibatide alone or in combination with argatroban or heparin appears safe and may be effective, although the episodes of recurrent hemolysis after medical management remain high.

Effects of Beta Blockers and ACE Inhibitors after Left Ventricular Assist Device Implantation

While Beta blockers (BB) and Angiotensin converting enzyme inhibitors/Angiotensin receptor blockers (ACEinh/ARB) are important components in advanced heart failure (HF) therapy, their use after left ventricular assist device (LVAD) implantation remains controversial. Concern has been raised about possible adverse effects of BB on right ventricular (RV) function while tolerance and efficacy/outcome data for ACEinh are lacking. This study aimed to characterize the use of medical therapy post-LVAD implantation and to evaluate its safety and efficacy.

Posterior Reversible Encephalopathy Syndrome after Heart Transplantation: Diagnosis and Immunosuppressive Therapy

Posterior reversible encephalopathy syndrome, an infrequent neurotoxicity associated with the use of tacrolimus, was first described in 1996, as a reversible syndrome manifested by headache, altered mental function, seizures, and visual disturbances. We describe the case of a 37-year-old woman who developed neurologic symptoms consistent with encephalopathy after treatment with tacrolimus, which was prescribed to maintain immunosuppression after orthotopic heart transplantation. This report also discusses the imaging methods used in the diagnosis of posterior reversible encephalopathy and highlights the difficulty of maintaining immunosuppression and managing medication-related adverse effects, while taking into account the risk of acute rejection after transplantation.

Donor Oversizing Results in Improved Survival in Patients with Left Ventricular Assist Device.

Donor to recipient undersizing can result in diminished graft survival. The United Network for Organ Sharing database was retrospectively queried from January 2008 to December 2013 to identify adult patients who underwent heart transplantation. This population was divided into those without and with a left ventricular assist device (LVAD) at the time of transplant. Both groups were further subdivided into three groups: donor:recipient body mass index (BMI) ratio <0.8 (undersized), ≥0.8 and ⩽1.2 (matched), and >1.2 (oversized). Kaplan–Meier analysis was used to compare graft survival. Cox regression analysis was used to identify factors affecting graft survival time. There was no difference in mean graft survival between undersized, matched, and oversized groups in patients without an LVAD (p = 0.634). Mean graft survival was significantly worse for undersized patients with an LVAD when compared with matched and oversized patients (p = 0.032). Cox regression revealed age, creatinine, waitlist time, United Network for Organ Sharing status, BMI ratio, and total bilirubin as significant factors affecting graft survival time. A donor to recipient BMI ratio of ≥1.2 results in significantly improved long-term graft survival for patients with an LVAD at the time of heart transplantation compared with patients with a BMI ratio of <1.2. An oversized organ should be considered for patients supported with an LVAD.