Objectives: The aim of this study was to test the hypothesis that narrowing the landing zone using commercially available endografts would enable transcatheter pulmonary valve replacement (TPVR) using commercially available transcatheter heart valves. Background: TPVR is challenging in an outsized native or patch-repaired right ventricular outflow tract (RVOT). Downsizing the RVOT for TPVR is currently possible only using investigational devices. In patients ineligible because of excessive RVOT size, TPVR landing zones were created using commercially available endografts. Methods: Consecutive patients with native or patch-repaired RVOTs and high or prohibitive surgical risk were reviewed, and this report describes the authors’ experience with endograft-facilitated TPVR (EF-TPVR) offered to patients ineligible for investigational or commercial devices. All EF-TPVR patients were surgery ineligible, with symptomatic, severe pulmonary insufficiency, enlarged RVOTs, and severe right ventricular (RV) enlargement (>150 ml/m2). TPVR and surgical pulmonary valve replacement (SPVR) were compared in patients with less severe RV enlargement. Results: Fourteen patients had large RVOTs unsuitable for conventional TPVR; 6 patients (1 surgery ineligible) received investigational devices, and 8 otherwise ineligible patients underwent compassionate EF-TPVR (n = 5 with tetralogy of Fallot). Three strategies were applied on the basis of progressively larger RVOT size: single-barrel, in situ fenestrated, and double-barrel endografts as required to anchor 1 (single-barrel and fenestrated) or 2 (double-barrel) transcatheter heart valves. All were technically successful, without procedure-related, 30-day, or in-hospital deaths. Two late complications (stent obstruction and embolization) were treated percutaneously. One patient died of ventricular tachycardia 36 days after EF-TPVR. Compared with 48 SPVRs, RV enlargement was greater, but 30-day and 1-year mortality and readmission were no different. The mean transvalvular pressure gradient was lower after EF-TPVR (3.8 ± 0.8 mm Hg vs. 10.7 ± 4.1 mm Hg; p < 0.001; 30 days). More than mild pulmonary insufficiency was equivalent in both (EF-TPVR 0.0% [n = 0 of 8] vs. SPVR 4.3% [n = 1 of 43]; p = 1.00; 30 days). Conclusions: EF-TPVR may be an alternative for patients with pulmonic insufficiency and enlarged RVOTs ineligible for other therapies.

Loeys-Dietz syndrome (LDS) is a rare connective tissue disease associated with mutations in transforming growth factor (TGF) signaling leading to an increased risk of arterial calcification, aneurysms, and/or dissections. We report a case in which genetics evaluation revealed a rare variant E244K in the TGFB3 gene. The variant leads to the substitution of glutamic acid for lysine, two amino acids with dissimilar properties. Analysis from evolutionary data shows the glutamic acid is maintained across species. The clinical significance of the E244K variant in association with LDS was never previously reported as pathologic. This case report aims to report that the significance of the E244K variant in the TGFB3 gene is found to be pathologic in our case. A search on the Genome Aggregation Database (gnomAD) did not reveal any previously identified individuals with this variant, despite being a well-covered region. ClinVar has a few entries for E244K, where most of them are listed as unknown significance. Bringing together the genotype evidence with our patient's clinical picture, we consider the variant to be pathogenic for this family.

Advances in treatment and early revascularization have led to improved outcomes for patients with acute coronary syndrome (ACS). However, elderly ACS patients are less likely to receive evidence-based treatment, including revascularization therapy, due to uncertainty of the associated benefits and risks in this population. This article addresses key issues regarding medical and revascularization therapy in elderly ACS patients based on a review of the medical literature and in concordance with clinical practice guidelines from the American Heart Association (AHA) and the American College of Cardiology (ACC).

Objective: Risk factors for major adverse events late after Fontan palliation are unknown. Prior studies have suggested ventricular function and morphology as important risk factors. The aim of this study is to (1) characterize the late major adverse event profile in adult Fontan patients and (2) identify additional risk factors that may contribute to adverse outcomes. Design and Setting: A retrospective review of all adult patients >15 years post-Fontan seen at a tertiary academic center was conducted. Clinical, laboratory, cardiac data, and abdominal imaging were collected via chart review. Major adverse events (death, cardiac transplantation, or listing) were identified, and timing of events was plotted using Kaplan-Meier methods. Univariate and multivariate logistic regression was used to determine independent predictors of late-term events. Results: A total of 123 adult Fontan patients were identified (mean time post-Fontan 22.4 years [±4.4]). Major adverse events occurred in 19/123 patients (15%). In this 15-year survivor cohort, transplant-free survival rates were 94.6%, 82.9%, and 59.8% at 20, 25, and 30 years postoperation, respectively. Modes of death were Fontan failure with preserved function (4), congestive heart failure with decreased function (2), sudden death (2), thromboembolic event (1), post-Fontan conversion (2), and posttransplant (2). No differences in adverse outcomes were found based on morphology of the systemic ventricle, Fontan type, or systolic ventricular function. On the other hand, features of portal hypertension (OR 19.0, CI 4.7-77.3, P < .0001), presence of a pacemaker (OR 13.4, CI 2.6-69.8, P=.002), and systemic oxygen desaturation (OR 0.86, CI 0.75-0.98, P=.02) were risk factors for major adverse events in the multivariate analysis. Conclusions: In adult Fontan patients surviving >15 years post-Fontan, portal hypertension, oxygen desaturation, and need for pacemaker were predictive of adverse events. Traditional measures may not predict late-term outcomes in adult survivors; further study of the liver's role in late outcomes is warranted.

Background The association of antidepressant medication type with the risk of cardiovascular disease ( CVD ) is unclear. We hypothesized that selective serotonin reuptake inhibitors ( SSRI s) are associated with lower risks of CVD events relative to tricyclics and other non- SSRI antidepressants. Methods and Results We studied 2027 participants from the ARIC (Atherosclerosis Risk in Communities) study (mean age 63±10 years; 29% men; 78% white) treated with antidepressants at some time between 1987 and 2013. Antidepressant usage was confirmed by participants bringing pill bottles to study visits. CVD events in the study sample were identified, including atrial fibrillation, heart failure, myocardial infarction, and ischemic stroke. Hazard ratios were used to compare CVD events adjusted for sociodemographic and clinical risk factors in SSRI s users (47%) versus non- SSRI users. Participants were followed from antidepressant initiation up to 2016 for a median of 13.5 years. We identified 332 atrial fibrillation, 365 heart failure, 174 myocardial infarction and 119 ischemic stroke events. CVD risk was similar for SSRI s and non- SSRI antidepressant users (hazard ratio, 1.10; 95% CI , 0.86-1.41 for atrial fibrillation; hazard ratio, 0.98; 95% CI, 0.77-1.25 for heart failure; hazard ratio, 0.91; 95% CI , 0.64-1.29 for myocardial infarction; and hazard ratio, 1.07; 95% CI , 0.70-1.63 for ischemic stroke). Conclusions SSRI use was not associated with reduced risk of incident CVD compared with non- SSRI antidepressant use. These results do not provide evidence supporting the use of SSRI s compared with tricyclics and other non- SSRI antidepressants in relation to CVD risk.

Fontan failure can occur even with normal systolic ventricular function and often in the context of significant liver disease. We hypothesized that Fontan failure is hemodynamically distinct from traditional heart failure and characterized by low systemic vascular resistance (SVR) index and preserved cardiac index. Twenty-seven symptomatic adult Fontan (SAF) patients who underwent catheterization from 2001 to 2011 constituted our study group. Fifty-four predominantly asymptomatic pediatric Fontan (PF) patients who underwent catheterization during the same period were randomly selected to perform a control:case cohort analysis. Clinical comparisons were made between the 2 groups. The adults were more symptomatic than the PF cohort (New York Heart Association classes I and II or III and IV: 48% or 52% [SAF] vs 94% or 6% [PF], respectively, p <0.01). SAF versus PF mean catheterization findings were central venous pressure 18 ± 6 versus 14 ± 3 mm Hg (p <0.01), SVR index 1,680 ± 368 versus 1,960 ± 550 dyn s/cm 5/m2 (p = 0.02), and cardiac index 2.7 ± 0.8 versus 2.8 ± 0.7 L/min/m2 (p = 0.25). By imaging, the SAF cohort demonstrated a greater incidence of abnormal liver texture changes (96% vs 75%, p = 0.04) and nodularity (77% vs 42%, p = 0.02). In conclusion, adult patients with failing Fontan circulation had a lower SVR index and similar cardiac index compared with the pediatric cohort. Liver disease in the adults was more advanced. Our data suggest that Fontan failure is a distinct circulatory derangement with hemodynamic features similar to portal hypertension, albeit with limited ability to augment cardiac output.

Background Chronic congestive hepatopathy is known to cause hepatic fibrosis and portal hypertension in patients post-Fontan operation for single ventricle palliation. The clinical significance of these findings is not clear. We hypothesized that features of portal hypertension would be significantly related to major adverse events. Methods A retrospective review of 73 adult and pediatric post-Fontan patients referred for a liver evaluation from 2001 to 2011 was performed. The relationship between features of portal hypertension (VAST score ≥ 2, 1 point each for Varices, Ascites, Splenomegaly or Thrombocytopenia) and a major adverse event (death, need for transplant, or hepatocellular carcinoma) was examined using logistic regression. Results 73 post-Fontan patients (30% female, 73% Caucasian, 66% systemic left ventricle (SLV), mean age 24 ± 11 years, mean interval from Fontan 17 ± 6 years) were included in analysis. Features of portal hypertension (VAST score ≥ 2) were present in 26 (36%), and there were 19 major adverse events: death (n = 12), transplant (n = 6), and HCC (n = 1). A significant relationship was found between VAST score ≥ 2 and major adverse events (OR = 9.8, 95% CI [2.9-32.7]). After adjusting for time since Fontan, SLV, age, hemoglobin and type of failure, VAST score ≥ 2 remained significant (OR = 9.1, 95% CI [1.4-57.6]). Conclusion Fontan patients with features of portal hypertension have a 9-fold increased risk for a major adverse event. Therapies targeted to manage clinical manifestations of portal hypertension, and early referral to heart transplant may help delay major adverse events. Future prospective studies are needed to confirm these findings.