Faculty Bibliography

BACKGROUND:Belatacept (BTC), a fusion protein, selectively inhibits T-cell co-stimulation by binding to the CD80 and CD86 receptors on antigen-presenting cells (APCs) and has been used as immunosuppression in adult renal transplant recipients. However, data regarding its use in heart transplant (HT) recipients are limited. This retrospective cohort study aimed to delineate BTC's application in HT, focusing on efficacy, safety, and associated complications at a high-volume HT center. METHODS:A retrospective cohort study was conducted of patients who underwent HT between January 2017 and December 2021 and subsequently received BTC as part of their immunosuppressive regimen. Twenty-one HT recipients were identified. Baseline characteristics, history of rejection, and indication for BTC use were collected. Outcomes included renal function, graft function, allograft rejection and mortality. Follow-up data were collected through December 2023. RESULTS:Among 776 patients monitored from January 2017 to December 2021 21 (2.7%) received BTC treatment. Average age at transplantation was 53 years (± 12 years), and 38% were women. BTC administration began, on average, 689 [483, 1830] days post-HT. The primary indications for BTC were elevated pre-formed donor-specific antibodies in highly sensitized patients (66.6%) and renal sparing (23.8%), in conjunction with reduced calcineurin inhibitor dosage. Only one (4.8%) patient encountered rejection within a year of starting BTC. Graft function by echocardiography remained stable at 6 and 12 months posttreatment. An improvement was observed in serum creatinine levels (76.2% of patients), decreasing from a median of 1.58 to 1.45 (IQR [1.0-2.1] to [1.1-1.9]) over 12 months (p = .054). eGFR improved at 3 and 6 months compared with 3 months pre- BTC levels; however, this was not statistically significant (p = .24). Treatment discontinuation occurred in seven patients (33.3%) of whom four (19%) were switched back to full dose CNI. Infections occurred in 11 patients (52.4%), leading to BTC discontinuation in 4 patients (19%). CONCLUSION/CONCLUSIONS:In this cohort, BTC therapy was used as alternative immunosuppression for management of highly sensitized patients or for renal sparing. BTC therapy when combined with CNI dose reduction resulted in stabilization in renal function as measured through renal surrogate markers, which did not, however, reach statistical significance. Patients on BTC maintained a low rejection rate and preserved graft function. Infections were common during BTC therapy and were associated with medication pause/discontinuation in 19% of patients. Further randomized studies are needed to assess the efficacy and safety of BTC in HT recipients.

INTRODUCTION/UNASSIGNED:Right heart failure (RHF) is a well-known complication after left ventricular assist device (LVAD) implantation and portends increased morbidity and mortality. Understanding the mechanisms and predictors of RHF in this clinical setting may offer ideas for early identification and aggressive management to minimize poor outcomes. A variety of medical therapies and mechanical circulatory support options are currently available for the management of post-LVAD RHF. AREAS COVERED/UNASSIGNED:We reviewed the existing definitions of RHF including its potential mechanisms in the context of durable LVAD implantation and currently available medical and device therapies. We performed a literature search using PubMed (from 2010 to 2023). EXPERT OPINION/UNASSIGNED:RHF remains a common complication after LVAD implantation. However, existing knowledge gaps limit clinicians' ability to adequately address its consequences. Early identification and management are crucial to reducing the risk of poor outcomes, but existing risk stratification tools perform poorly and have limited clinical applicability. This is an area ripe for investigation with the potential for major improvements in identification and targeted therapy in an effort to improve outcomes.

INTRODUCTION/BACKGROUND:Monitoring for graft rejection is a fundamental tenet of post-transplant follow-up. In heart transplantation (HT) in particular, rejection has been traditionally assessed with endomyocardial biopsy (EMB). EMB has potential complications and noted limitations, including interobserver variability in interpretation. Additional tests, such as basic cardiac biomarkers, cardiac imaging, gene expression profiling (GEP) scores, donor-derived cell-free DNA (dd-cfDNA) and the novel molecular microscope diagnostic system (MMDx) have become critical tools in rejection surveillance beyond standard EMB. METHODS:This paper describes an illustrative case followed by a review of MMDx within the context of other noninvasive screening modalities for rejection. CONCLUSIONS:We suggest MMDx be used to assist with early detection of rejection in cases of discordance between EMB and other noninvasive studies.

BACKGROUND:Heart failure is a prevailing diagnosis of hospitalization and readmission within 6 months, and nearly a quarter of these patients die within a year. Guideline-directed medication therapies reduce risk of mortality by 73% over 2 years; however, the implementation of these therapies to their target dose in clinical practice continues to be challenging. In 2020, the Veterans Affairs (VA) Health Care System developed a HF dashboard to monitor and improve outpatient HF management. The DASH-HF (Dashboard Activated Services and Telehealth for Heart Failure) study is a randomized, pragmatic clinical trial to evaluate proactive dashboard-directed telehealth clinics to improve the use and dosing of guideline-directed medication therapy for patients with heart failure with reduced ejection fraction not on optimal guideline-directed medication therapy within the VA. METHODS:Three hundred veterans with heart failure with reduced ejection fraction met inclusion criteria with an optimization potential score (OPS) of 5 or less out of 10, representing nonoptimal guideline-directed medication therapy. The primary outcome was a composite score of guideline-directed medical therapy, the OPS, 6 months after the end of the intervention. Secondary outcomes included active prescriptions for each individual guideline-directed medical therapy class, HF-related hospitalizations, deaths, and clinician time per patient during the intervention clinics. RESULTS:There was no significant difference between the intervention arm and usual care group in the primary outcome (OPS, 2.9; SD=2.1 versus OPS, 2.6, SD=2.1); adjusted mean difference 0.3 (95% CI, -0.1 to 0.7) or in the prespecified secondary outcomes for hospitalization and all-cause mortality for the intervention of proactive dashboard-based clinics. CONCLUSIONS:A dashboard-based clinic intervention did not improve the OPS or secondary outcomes of hospitalization and all-cause mortality. There remains a larger opportunity to better target patients and provide more intensive follow-up to further evaluate the utility of proactive dashboard-based clinics for HF management and quality improvement. REGISTRATION:URL: https://www. CLINICALTRIALS:gov; Unique identifier: NCT05001165.

BACKGROUND:Gaps in the receipt and dosing of guideline-directed medical therapy (GDMT) persist for patients with heart failure with reduced ejection fraction (HFrEF) [1]. In 2020, the Veterans Affairs (VA) developed a heart failure (HF) specific population dashboard to monitor care quality and performance on standard HFrEF performance measures [2]. METHODS:The Dashboard Activated Services and Telehealth for HF (DASH-HF) study is a pragmatic randomized quality improvement study designed to evaluate the utility of proactive population management clinics using the VA's HF dashboard to optimize GDMT for patients with HFrEF. Panel management telemedicine clinics incorporated multidisciplinary clinicians to perform chart review and impromptu telephone encounters to evaluate current HFrEF management and opportunities to optimize GDMT. The study will evaluate the efficacy of proactive panel management to usual care at 6 months as quantified by the GDMT optimization potential score. Secondary outcomes include hospitalizations, mortality, and clinician time per intervention. The study completed enrollment and randomization of 300 participants. The intervention was performed from September to December 2021. CONCLUSION:DASH-HF will contribute to the literature by evaluating use of the existing VA dashboard to identify HF patients with the lowest adherence to GDMT and proactively target this group for the intervention. REGISTRATION:https://clinicaltrials.gov/. Unique identifier: NCT05001165.

BACKGROUND:This meta-analysis assessed the relationship between obstructive sleep apnea (OSA) and echocardiographic parameters of diastolic dysfunction (DD), which are used in the assessment of heart failure with preserved ejection fraction. METHODS:We searched the databases including Ovid MEDLINE, Ovid Embase, Scopus, Web of Science, Google Scholar, and EBSCO CINAHL from inception up to December 26, 2020. The search was not restricted to time, publication status, or language. Two independent investigators screened the identified studies and extracted the data in duplicate. We conducted a meta-analysis using RevMan v.5. The risk of bias was assessed using Cochrane collaboration tools. Comparisons were made between patients with OSA, diagnosed in-laboratory polysomnography or home sleep apnea testing, and patients without OSA in relation to established markers of DD. RESULTS:Primary search identified 2,512 studies. A total of 18 studies including 2,509 participants were included. The two groups were free of conventional cardiovascular risk factors. Significant structural changes were observed between the two groups. Patients with OSA exhibited greater left atrial volume index (LAVI) (3.94 95% CI [0.8, 7.07]; p = 0.000) and left ventricular mass index (11.10 95% CI [2.56, 19.65]; p = 0.000) as compared to control group. The presence of OSA was also associated with more prolonged deceleration time (10.44 ms 95% CI [0.71, 20.16]; p = 0.04), isovolumic relaxation time (IVRT) (7.85 ms 95% CI [4.48, 11.22]; p = 0.000), and a lower ratio of early to late mitral inflow velocities (E/A) ratio (-0.62 95% CI [-1, -0.24]; p = 0.001) suggestive of early DD. The early mitral inflow velocity to mitral annular early diastolic velocity (E/e') ratio (0.94 95% CI [0.44, 1.45]; p = 0.000) was increased. Linear correlation between severity of OSA and LAVI and IVRT parameters was observed but this association did not sustain for the E/A and E/e'. The ejection fraction was not significantly different between patients with OSA and healthy controls (-0.48 95% CI [-1.18, 0.23]; p = 0.18). CONCLUSION:An association between OSA and echocardiographic parameters of DD was detected that was independent of conventional cardiovascular risk factors. OSA may be independently associated with DD perhaps due to higher LV mass. Investigating the role of continuous positive airway pressure therapy in reversing or ameliorating DD is recommended.

Few randomized controlled trials (RCTs) and observational studies had shown acceptable short-term efficacy and safety of percutaneous coronary intervention (PCI) with drug-eluting stents (DES) compared with coronary artery bypass grafting (CABG) in selected patients with left main coronary artery disease (LMCAD). We aimed to evaluate long-term outcomes of PCI using DES compared with CABG in patients with LMCAD. On November 1, 2016, we searched available databases for published RCTs directly comparing DES PCI with CABG in patients with LMCAD. Odds ratios (ORs) were used as the metric of choice for treatment effects using a random-effects model. I-squared index was used to assess heterogeneity across trials. Prespecified end points were all-cause mortality, cardiovascular mortality, myocardial infarction (MI), stroke, and repeat revascularization at maximal available follow-up. We identified 5 RCTs including a total of 4,595 patients, with a median follow-up of 60 months. The risk of all-cause mortality (OR 1.01; 95% confidence interval [CI] 0.76 to 1.34) and cardiovascular mortality (OR 1.02; 95% CI 0.73 to 1.42) were comparable between PCI with DES and CABG. Similarly, there were no statistically significant differences between PCI with DES and CABG for MI (OR 1.45; 95% CI 0.87 to 2.40) and stroke (OR 0.87; 95% CI 0.38 to 1.98). Conversely, repeat revascularization was significantly higher with PCI compared with CABG (OR 1.82; 95% CI 1.51 to 2.21). In conclusion, in patients with LMCAD, PCI with DES appears to be a viable alternative to CABG at long-term follow-up, with similar risks of ischemic adverse events (mortality, MI, and stroke) but a higher risk of repeat revascularization.

OBJECTIVE:Obstructive Sleep Apnea (OSA) has been associated with both subclinical and accelerated atherosclerosis; however, it still remains unknown whether this association is unique or is mediated by the higher burden of co-existing cardio-metabolic disorders frequently seen in patients with OSA. PATIENTS AND METHODS:A total of 40 subjects without clinically diagnosed cardiovascular disease (CVD) referred for polysomnography test were included in the study. Subjects with apnea/hypopnea index (AHI > 15/h) were classified as moderate/severe OSA. Subclinical changes in carotid atherosclerosis were assessed using mean carotid intima-media thickness (cIMT) and presence of atheromatic plaques on both carotid arteries. The measurement was performed using B-mode ultrasonogram. Framingham risk score was used in the approximation of cardiovascular risk. RESULTS:The mean age of our cohort was 56.8 years, 70% (n = 28) of whom were males. Moderate/severe OSA was diagnosed in 21 subjects. Both groups were well matched in terms of clinical and demographic characteristics, and cardiovascular risk profile, as shown in their respective Framingham risk scores (10.4 ± 6.6 vs. 11.8 ± 8.8, p = NS). Patients with moderate/severe OSA had a higher mean AHI, 3% oxygen desaturation index, and lower minimum nocturnal oxygen saturation than controls. No significant differences were detected in terms of C-reactive protein levels. The two groups had similar cIMT (0.66 ± 0.17 vs. 0.75 ± 0.20 p = 0.33) and presence of atheromatic plaque (50% vs. 45%, p = 1.00). CONCLUSIONS:Our study suggests that among patients with similar cardiovascular risk profile and free of overt CVD, the severity of newly diagnosed OSA was not correlated with increased inflammation or subclinical carotid atherosclerosis.

AIMS/OBJECTIVE:Patients with human immunodeficiency virus (HIV) infection have an increased risk of acute myocardial infarction (MI), and 6.5-15% of mortality in this population is attributable to cardiovascular disease. However, the angiographic pattern of coronary artery disease (CAD) in patients with HIV undergoing percutaneous coronary intervention (PCI) remains unknown. We sought to assess and describe the angiographic features and burden of CAD in patients with HIV as compared to those without HIV infection. METHODS AND RESULTS/RESULTS:This is a retrospective, single-centre study comparing 93 patients with HIV infection who underwent PCI between 2003 and 2011 with 93 control patients without HIV infection matched for age (±3 years), gender, diabetes, and year of PCI (±2 years). Quantitative coronary angiography (QCA) was performed for all treated lesions at baseline and following PCI in both groups. One-year clinical outcomes post PCI were also analysed and compared. The mean age for both study populations was 57 years; patients with HIV were more likely to present with ST-segment elevation myocardial infarction (STEMI). Patients had a similar extent of CAD as measured by the presence of multivessel disease as well as SYNTAX score; however, patients with HIV were more likely to have lesions in the proximal segment of the respective coronary artery. While both groups mostly displayed none/mild calcified lesions, HIV+ patients had longer and fewer stenotic lesions. Clinical outcomes at one year were similar. CONCLUSIONS:While HIV+ patients were more likely to present with STEMI, detailed coronary angiographic analysis revealed less complex lesions and favourable anatomy. This paradox may suggest alterations in genesis and progression of atherosclerosis in this clinical setting.