Shelley A. Hall

Utilization of high donor sequence number grafts in cardiac transplantation

Donor sequence number (DSN) represents the number of candidates to whom a graft was offered and declined prior to acceptance for transplantation. We sought to investigate the outcomes of patients receiving high DSN grafts. Consecutive isolated adult cardiac transplantations performed at a single‐center were reviewed. Recipients were grouped into standard (≤75th percentile) DSN and high (>75th percentile) DSN. A previously validated donor risk index was used to quantify the risk associated with donor grafts, and recipient outcomes were assessed. Overall, 254 patients were included: 194 standard DSN (range 1‐79) and 60 high DSN (range 82‐1723). High DSN grafts were harvested at greater distance (P < .001) with increased ischemia time (P < .001), resulting in a modest increase in donor risk index (1 point median difference, P = .014). High DSN recipients were less frequently listed as UNOS status 1A (P < .001). Despite a nonsignificant trend toward increased in‐hospital/30‐day mortality in high DSN recipients, there were no differences in primary graft dysfunction or 1‐year survival (high DSN 89% vs standard DSN 88%, P = .82). After adjustment for risk factors, high DSN was not associated with increased 1‐year mortality (hazard ratio 1.18, 95%‐CI 0.54‐2.58, P = .68).

Determinants and Outcomes of Vasoplegia Following Left Ventricular Assist Device Implantation

Background Vasoplegia is associated with adverse outcomes following cardiac surgery; however, its impact following left ventricular assist device implantation is largely unexplored. Methods and Results In 252 consecutive patients receiving a left ventricular assist device, vasoplegia was defined as the occurrence of normal cardiac function and index but with the need for intravenous vasopressors within 48 hours following surgery for >24 hours to maintain a mean arterial pressure >70 mm Hg. We further categorized vasoplegia as none; mild, requiring 1 vasopressor (vasopressin, norepinephrine, or high‐dose epinephrine [>5 μg/min]); or moderate to severe, requiring ≥2 vasopressors. Predictors of vasoplegia severity were determined using a cumulative logit (ordinal logistic regression) model, and 1‐year mortality was evaluated using competing‐risks survival analysis. In total, 67 (26.6%) patients developed mild vasoplegia and 57 (22.6%) developed moderate to severe vasoplegia. The multivariable model for vasoplegia severity utilized preoperative Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile, central venous pressure, systolic blood pressure, and intraoperative cardiopulmonary bypass time, which yielded an area under the curve of 0.76. Although no significant differences were noted in stroke or pump thrombosis rates (P=0.87 and P=0.66, respectively), respiratory failure and major bleeding increased with vasoplegia severity (P<0.01). Those with moderate to severe vasoplegia had a significantly higher risk of mortality than those without vasoplegia (adjusted hazard ratio: 2.12; 95% confidence interval, 1.08–4.18; P=0.03). Conclusions Vasoplegia is predictive of unfavorable outcomes, including mortality. Risk factors for future research include preoperative INTERMACS profile, central venous pressure, systolic blood pressure, and intraoperative cardiopulmonary bypass time.

Donor predicted heart mass as predictor of primary graft dysfunction

BACKGROUNDnConcern over the hazards associated with undersized donor hearts has impeded the utilization of otherwise viable allografts for transplantation. Previous studies have indicated predicted heart mass (PHM) may provide better size matching in cardiac transplantation than total body weight (TBW). We investigated whether size-matching donor hearts by PHM is a better predictor of primary graft dysfunction (PGD) than matching by TBW.nnnMETHODSnRecords of consecutive adult cardiac transplants performed between 2012 and 2016 at a single-center academic hospital were reviewed. We compared patients implanted with hearts undersized by ≥30% with those implanted with donor hearts matched for size (within 30%), and performed the analysis both for undersizing by PHM and for undersizing by TBW. The primary outcome was moderate/severe PGD within 24 hours, according to the 2014 International Society for Heart and Lung Transplantation consensus. Secondary outcome was 1-year survival.nnnRESULTSnOf 253 patients, 21 (8%) and 30 (12%) received hearts undersized by TBW and PHM, respectively. The overall rate of moderate/severe PGD was 13% (33 patients). PGD was associated with undersizing if performed by PHM (p = 0.007), but not if performed by TBW (p = 0.49). One-year survival was not different between groups (log-rank, p > 0.8). Multivariate analysis confirmed that undersizing donor hearts by PHM, but not by TBW, was predictive of moderate/severe PGD (OR 3.3, 95% CI 1.3 to 8.6).nnnCONCLUSIONSnUndersized donor hearts by ≥30% by PHM may increase rates of PGD after transplantation, confirming that PHM provides more clinically appropriate size matching than TBW. Better size matching may ultimately allow for expanding the donor pool.

Reoperative sternotomy is associated with primary graft dysfunction following heart transplantation

OBJECTIVESnPrior sternotomy is associated with increased morbidity and mortality following heart transplantation. However, its effect on primary graft dysfunction (PGD), a major contributor to early mortality, is unknown. Herein, this effect is studied using the International Society for Heart and Lung Transplantation consensus definition for PGD.nnnMETHODSnMedical records of consecutive adult cardiac transplants between 2012 and 2016 were reviewed. Baseline characteristics, postoperative findings and 1-year survival were compared between patients with and without prior sternotomy.nnnRESULTSnAmong 255 total patients included, 139 (55%) had undergone prior sternotomy; these recipients were older, more often male, had higher body mass index, higher frequencies of united network for organ sharing (UNOS) 1A status and ischaemic cardiomyopathy and experienced longer waitlist times when compared with those without prior sternotomy (all Pu2009<u20090.018). Postoperatively, the prior sternotomy group exhibited higher rates of mild to severe PGD (32% vs 18%; Pu2009=u20090.015) and higher short-term mortality (Pu2009=u20090.017) and 1-year mortality (Pu2009=u20090.047). They required more blood transfusions, had more postoperative pneumonia, wound infection and longer hospital stays. A stepwise multivariable regression model identified prior sternotomy as a predictor of PGD (odds ratio 2.7). Multiple prior sternotomies was associated with even more UNOS 1A status, ischaemic cardiomyopathy and pneumonia. However, logistic modelling did not show a difference in the rate of PGD between those with 1 or ≥2 prior sternotomies.nnnCONCLUSIONSnOur data suggest that prior sternotomy is a risk factor for PGD. Consistent with previous reports, prior sternotomy is associated with increased morbidity, blood product utilization and 1-year mortality following cardiac transplantation.

Patient activation with respect to advanced heart failure therapy in patients over age 65 years

Background: Clinical and ethical issues persist in determining candidacy for advanced heart failure (HF) therapies in elderly patients. Selection takes many factors into account, including “activation” (engagement and ability to self‐manage). Objective: To investigate effects of age, activation, and depression/anxiety on selection and 6‐month survival of participants considered for therapy. Methods: Consecutive people referred for advanced HF therapy completed the Patient Activation Measure and Hospital Anxiety and Depression Scale. We analyzed data from participants by age (≥65 vs. <65 years), stratified by approval for therapy. Results: Among 168 referred, 109 were approved, with no difference in activation between age groups (88% highly activated). Similarly, activation was not associated with age among those not approved. Activation was related to anxiety in older, approved participants, but not to depression. Conclusions: Concerns regarding reduced self‐management in the elderly may not be valid. Age alone should not disqualify a candidate for advanced HF therapy.

The New Direct Antiviral Agents and Hepatitis C in Thoracic Transplantation: Impact on Donors and Recipients

Purpose of ReviewThe landscape of abdominal organ transplantation has been altered by the emergence of curative direct-acting antiviral agents for hepatitis C. Expansion of the thoracic donor pool to include the hearts and the lungs from hepatitis C-positive donors holds promise to increase available donor organs.Recent FindingsCase reports have documented separate lung and heart transplant patients who acquired, and then were cured of, donor-derived hepatitis C using these newer, more effective therapies. Single sites and national consortia are underway to help make this approach part of the standard-of-care. Pangenotypic therapies may simplify the paradigm.SummaryOrgans from donors with active hepatitis C viremia are likely suitable for transplant as long as the organ is otherwise acceptable. Best-practices for “informed-risk” transplant include a team-based approach and a selection of the antiviral regimen based on insurer’s formulary, potential drug interactions, and genotype.

Targeting Other Modifiable Risk Factors for the Prevention of Heart Failure: Diabetes, Smoking, Obesity, and Inactivity

Purpose of ReviewPrevention and reduction of risk factors is imperative in the battle against the heart failure epidemic. In this report, we update prior reviews with a focus on the modifiable risk factors of diabetes, smoking, obesity, and inactivity with regard to epidemiology, pathophysiology, management, and therapeutic options.Recent FindingsWhile the incidence of diabetes is rising, recent trials suggest options for diabetic patients to prevent cardiovascular morbidity, mortality, and heart failure, with several more trials underway. We highlight several novel agents including sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor antagonists. Tobacco smoking significantly increases the risk for heart failure, and recent data show early cessation may be beneficial. Education, support mechanisms, and weaning tools are useful, but some patients may benefit from behavioral counseling and even pharmacotherapy. Obesity is well recognized for its role in the development of heart failure and contributes to standard cardiovascular risk factors, left ventricular hypertrophy, sleep apnea, and metabolic syndrome. Lifestyle changes are vital to impacting this condition and thus rely heavily on patient motivation and compliance. Newer medications for assistance with weight loss have been approved, while bariatric surgery may be necessary for some. Specific effects of physical activity on heart failure prevention are not well delineated and may differ for patients with diabetes.SummaryExtensive efforts in patient education on self-management of their health, prevention and control of risk factors will be the ultimate solution to decreasing the incidence of heart failure in the future.

Salvage of severe primary graft dysfunction following heart transplantation using extracorporeal life support

Abstract Primary graft dysfunction (PGD) is the leading cause of early mortality after heart transplantation. Typically, mechanical circulatory support is necessary to provide hemodynamic support and to enable graft recovery. However, both the reported incidence of PGD and the reported salvage rates with extracorporeal membrane oxygenation (ECMO) vary widely. This may partly be due to variations in the definition of PGD and its levels of severity. We analyzed a prospectively maintained database of 255 transplant recipients at our institution to determine the effectiveness of ECMO support in those who develop severe PGD as defined by the International Society for Heart and Lung Transplantation consensus guidelines. Nineteen (7.5%) patients (aged 32–69 years) developed severe PGD and were treated with veno-arterial (VA) ECMO, which was initiated in the operating room at the time of transplant in most patients. The majority received VA ECMO through femoral cannulation. Two patients required veno-venous ECMO for respiratory support after VA ECMO separation. The 30-day in-hospital survival rate following transplantation was 63% (nu2009=u200912). In conclusion, ECMO proved to be a viable option for early hemodynamic support in patients with severe PGD and has become our preferred modality for mechanical circulatory support in these patients.