Background: Glucocorticoid treatment remains the cornerstone of therapy for immune checkpoint inhibitor (ICI) myocarditis, but data supporting the use of additional immunotherapy for steroid refractory cases remains limited. We investigate the safety and efficacy of infliximab in patients with ICI myocarditis who are refractory to corticosteroids. Additionally, we highlight the importance of a multi-disciplinary approach in the care for these complex patients. Methods: We retrospectively identified consecutive patients who developed ICI myocarditis at our institution between January 2017 and January 2020. Baseline characteristics, laboratory data and clinical outcomes were compared between patients who received infliximab and those who did not. Results: Of a total of 11 patients who developed ICI myocarditis, 4 were treated with infliximab. Aside from age, there were no significant differences in baseline patient characteristics between the two groups including total number of ICI doses received and duration from initial ICI dose to onset of symptoms. The time to troponin normalization was 58 vs. 151.5 days (p = 0.25). The duration of prednisone taper was longer in the infliximab group (90 vs. 150 days p = 0.32). All patients survived initial hospital admission. Over a median follow-up period of 287 days, two of the 4 patients died from sepsis 2 and 3 months after initial treatment of their myocarditis; one of these patients was on a steroid taper and the other patient had just completed a steroid taper. Conclusions: Infliximab, despite its black box warning in patients with heart failure, may be a safe and effective treatment for ICI myocarditis.

Purpose: We report on the clinical course and management of patients supported with durable implantable LVADs who developed outflow graft obstructions at a large academic center. Methods: We performed a retrospective review of patients receiving LVAD support from 2012 through 2020. Patients who developed an outflow graft obstruction diagnosed by computed tomography angiography (CTA) or angiogram were identified, and patient characteristics and outcomes were reported. Results: Of the 324 patients supported by LVAD at our institution, 11 patients (3.4%) were diagnosed with outflow graft obstructions. The most common presentation was low flow alarms, which was present in 10/11 patients, and the remaining patient presented with lightheadedness. Patients had minimal LDH elevation with 8/11 presenting with less than 2-fold the upper limit of normal. Transthoracic echocardiograms were not diagnostic, but CTA enabled non-invasive diagnoses in 8/11 of the patients. Three patients with extrinsic compression of the outflow graft successfully underwent endovascular stent placement, and three patients with outflow cannula kinks received supportive care. Of the five patients diagnosed with intraluminal thromboses, one received a heart transplant, one underwent an outflow graft revision, and three received supportive care due to comorbidities. Conclusion: Outflow graft obstructions remain a rare, but serious complication. The true prevalence of this entity is likely underestimated due to the non-specific clinical presentation. CTA is a pivotal non-invasive diagnostic step. Patients with external compression were successfully treated with endovascular stenting.

BACKGROUND: Patients undergoing first-time atrial fibrillation (AF) ablation can benefit from targeting non-pulmonary vein (PV) triggers. Preprocedural identification of high-risk individuals can guide planning of ablation strategy. This study aimed to create a preprocedural screening tool to identify patients at risk of non-PV triggers during first-time AF ablation. METHODS: All patients who underwent first-time AF ablation at the Hospital of the University of Pennsylvania between 2018 and 2022 were identified. Those who underwent non-PV trigger provocative maneuvers or had spontaneous non-PV trigger firing were included. Non-PV triggers were defined as non-PV ectopic beats triggering AF or sustained focal atrial tachycardia that occurred spontaneously, after AF cardioversion, or after standard provocative maneuvers. The provocative maneuvers included incremental isoproterenol infusion (3, 6, 12, and 20–30 µg/min) and an atrial burst pacing protocol. Risk factors associated with non-PV triggers in a stepwise multivariable logistic regression model with backward elimination were used to create a risk score. RESULTS: A total of 163 (8.0%) of 2038 patients had non-PV triggers during first-time AF ablation. Based on the multivariable model, we created a risk score using female sex (1 point; odds ratio [OR], 1.90 [95% CI, 1.36–2.67]), sinus node dysfunction (1 point; OR, 1.84 [95% CI, 1.04–3.24]), prior cardiac surgery (1 point; OR, 2.26 [95% CI, 1.45–3.53]), moderate to severe left atrial enlargement (2 points; OR, 3.43 [95% CI, 2.46–4.79]), and cardiac sarcoidosis/amyloidosis (4 points; OR, 7.24 [95% CI, 3.03–17.33]). Internal validation using bootstrap resampling showed an optimism-adjusted C statistic of 0.715 (95% CI, 0.678–0.751). Among all first-time AF ablations, 68.1% of procedures were low-risk for non-PV triggers (scores 0–1, 4.3% risk), 17.8% were intermediate-risk (score 2, 10.5% risk), and 14.1% were high-risk (score ≥3, 22.6% risk). CONCLUSIONS: A preprocedural screening tool can classify patients based on their risk of non-PV triggers during first-time AF ablation. This risk score can guide operators to identify patients who would benefit most from adjunctive non-PV trigger testing. However, further validation is needed to confirm these findings.

Introduction: The contribution of chronotropic incompetence to reduced exercise tolerance after a heart transplant is well known, but its role as a prognostic marker of post-transplant mortality is unclear. The aim of this study is to examine the relationship between post-transplant heart rate response (HRR) and survival. Methods: We performed a retrospective analysis of all adult heart transplant recipients at the University of Pennsylvania between the years 2000 and 2011 who underwent a cardiopulmonary exercise test (CPET) within a year of transplant. Follow-up time and survival status were observed through October 2019, using data merged from the Penn Transplant Institute. HRR was calculated by subtracting the resting HR from the peak exercise HR. The association between HRR and mortality was analyzed using Cox proportional hazard models and Kaplan–Meier analysis. The optimal cut-off point for HRR was generated by Harrell’s C statistic. Patients with submaximal exercise tests were excluded, defined by a respiratory exchange ratio (RER) cut-off of 1.05. Results: Of 277 patients with CPETs performed within a year post-transplant, 67 were excluded for submaximal exercise. In the 210 included patients, the mean follow-up time was 10.9 years (Interquartile range (IQR) 7.8–14). Resting HR and peak HR did not significantly impact mortality after adjusting for covariates. In a multivariable linear regression analysis, each 10-beat increase in heart rate response was associated with a 1.3 mL/kg/min increase in peak VO₂ and a 48 s increase in the total exercise time. Each beat/min increase in HRR was associated with a 3% reduction in the hazard of mortality (HR 0.97; 95% CI 0.96–0.99, p = 0.002). Using the optimal cut-off point generated by Harrell’s C statistic, survival was significantly higher in patients with an HRR > 35 beats/min compared to those with an HRR < 35 beats/min (log rank p = 0.0012). Conclusion: In heart transplant patients, a low HRR is associated with increased all-cause mortality and decreased exercise capacity. Additional studies are needed to validate whether targeting HRR in cardiac rehabilitation may improve outcomes.

Aims: While it is common practice to use intravenous (IV) iron in patients with left ventricular assist devices (LVADs) and iron deficiency, there is insufficient evidence regarding outcomes in this patient population. We evaluated the safety and effectiveness of IV iron therapy in patients supported by LVADs with iron deficiency. Methods: We performed a retrospective analysis of iron deficient patients on continuous LVAD support at a large academic center between 2008 and 2019. Patients were divided into two cohorts based on IV iron sucrose treatment. The primary endpoint was hemoglobin at 12 weeks. Secondary endpoints were mean corpuscular volume (MCV) and New York Heart Association (NYHA) class at 12 weeks. Safety endpoints included hospitalization, infection, pump thrombosis, arrhythmia, and gastrointestinal bleed. Models were weighted by the inverse probability of receiving IV iron using a propensity score, and endpoints were adjusted for their corresponding baseline values. Results: Among 213 patients, 70 patients received IV iron and 143 patients did not. Hemoglobin at 12 weeks was significantly greater among those treated (intergroup difference: 0.6 g/dL; 95% CI, 0.1 to 1.1; p = 0.01), while MCV was similar in both groups (intergroup difference: 0.7 μm³; 95% CI, −1.3 to 2.7; p = 0.50). NYHA class distribution at 12 weeks was significantly different (odds ratio for improvement: 2.84; 95% CI, 1.42 to 4.68; p = 0.003). The hazards of adverse events in each group were similar. Conclusions: In patients with LVADs and iron deficiency, treatment with IV iron sucrose was safe and associated with improvements in functional status and hemoglobin.