PCSK9 Inhibition in Patients After Heart Transplantation: a Retrospective Review and Literature Analysis.

PURPOSE OF REVIEW: Following cardiac transplantation, patients have an increased risk of developing cardiac allograft vasculopathy and atherosclerotic cardiovascular disease. Therefore, aggressive lipid management is indicated. Some patients do not achieve optimal lipid profiles with statin monotherapy, however, or discontinue statins due to intolerance. In this review, we investigated the use of PCSK9 inhibitors as an alternative treatment for hyperlipidemia following cardiac transplantation. RECENT FINDINGS: Nine published articles were identified that included 110 patients treated with alirocumab or evolocumab after cardiac transplantation. PCSK9 inhibitors were tolerated by all patients, and each study demonstrated an effective reduction of low-density lipoprotein ranging from 40 to 87% decrease from baseline. In our study, the 110 patients from literature review were added to a cohort of 7 similar patients from our institution for combined analysis. This report supports that PCSK9 inhibitors should be considered following cardiac transplantation when conventional medial therapy is not tolerated or ineffective.

Subjective and Objective Impact of Angiotensin Receptor-Neprilysin Inhibitors on Systemic Right Ventricle Patients.

INTRODUCTION: Patients with adult congenital heart disease (ACHD) who have an anatomic right ventricle supporting the systemic circulation have increased mortality and morbidity from heart failure (HF). Angiotensin receptor-neprilysin inhibitors (ARNI) have emerged as a standard of therapy for adults with HF. However, the effects of this therapy have not been extensively studied in ACHD patients, especially those with systemic right ventricle (SRV). HYPOTHESIS: ARNIs are associated with subjective and objective improvement in SRV patients. METHODS: Eighteen (18) SRV patients were prescribed ARNI at our institution in the last 5 years. Data before and during treatment, including demographics, medical history, New York Heart Association functional class (NYHA FC), labs, cardiac computed tomography (CT) or magnetic resonance imaging (MRI), echocardiographic measurements, cardiopulmonary stress test (CPET), and hospitalisation for HF were obtained by review of the electronic medical record. Statistical analysis was performed using paired t and Wilcoxon rank sum tests. RESULTS: Eighteen (18) SRV patients (mean age 40 yrs, 72% male) were treated with ARNI (median duration 13 mo) in addition to other HF medications. All patients tolerated ARNI without symptomatic or asymptomatic hypotension or worsening kidney function. High ARNI dose (97/103 mg) was achieved in three (17%) patients, and moderate (49/51 mg) in three (17%). At baseline, nine patients were NYHA FC 2, seven FC 3, and two FC 4. Mean baseline cardiopulmonary exercise testing (CPET) and echocardiographic data were: oxygen uptake (VO2) 18 mL/kg/min, minute ventilation/carbon dioxide (VE/VCO2) 38, right ventricular ejection fraction (RVEF) 32%, fractional area change (FAC) 21%. Significant tricuspid regurgitation was present in 33% (28% moderate, and 5% severe) and mean tricuspid annular plane systolic excursion (TAPSE) was 9.4 mm. With treatment, there was no statistically significant difference in blood pressure, labs, testing, or imaging. There was a statistically significant improvement in median NYHA FC (2 vs 2.5, p=0.005). When compared to an equal pre-ARNI median timeframe, there was a noted decrease in cardiac hospitalisation (4 vs 9) that did not reach statistical significance (p=0.313). CONCLUSION: In adult patients with failing systemic right ventricle, ARNI is safe and well tolerated. Their use is associated with improvement in functional status. Prospective studies on a larger group of patients are warranted to better understand the causes of this improvement.

Graduate medical education scholarly activities initiatives: a systematic review and meta-analysis.

BACKGROUND: According to the Accreditation Council for Graduate Medical Education residents "should participate in scholarly activity." The development of a sustainable, successful resident scholarship program is a difficult task faced by graduate medical education leadership. METHODS: A medical librarian conducted a systematic literature search for English language articles published on scholarly activities initiatives in Graduate Medical Education (GME) between January 2003 and March 31 2017. Inclusion criteria included implementing a graduate medical education research curriculum or initiative designed to enhance intern, resident, or fellow scholarly activities using a control or comparison group. We defined major outcomes as increases in publications or presentations. Random effects meta-analysis was used to compare the rate of publications before and after implementation of curriculum or initiative. RESULTS: We identified 32 relevant articles. Twenty-nine (91%) reported on resident publications, with 35% (10/29) reporting statistically significant increases. Fifteen articles (47%) reported on regional, national, or international presentations, with only 13% (2/15) reporting a statistically significant increase in productivity. Nineteen studies were eligible for inclusion in the meta-analysis; for these studies, the post-initiative publication rate was estimated to be 2.6 times the pre-intervention rate (95% CI: 1.6 to 4.3; p < 0.001). CONCLUSIONS: Our systematic review identified 32 articles describing curricula and initiatives used by GME programs to increase scholarly activity. The three most frequently reported initiatives were mentors (88%), curriculum (59%), and protected time (59%). Although no specific strategy was identified as paramount to improved productivity, meta-analysis revealed that the publication rate was significantly higher following the implementation of an initiative. Thus, we conclude that a culture of emphasis on resident scholarship is the most important step. We call for well-designed research studies with control or comparison groups and a power analysis focused on identifying best practices for future scholarly activities curricula and initiatives.