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Abstract Background and Aims Decrease in pulmonary vascular resistance (PVR) during exercise confers favourable prognosis in biventricular physiology, but its role in Fontan circulation remains unknown. This study aimed to evaluate the prognostic value of PVR index (PVRI) response to exercise in adults post-Fontan palliation. Methods Retrospective cohort of 88 adults (age ≥18 years) post-Fontan undergoing exercise (supine cycling) cardiac catheterization. Patients were categorized into absence (n = 23) or presence (n = 65) of exercise-induced reduction in PVRI. The clinical endpoint was a composite of death or transplantation. Results Age at catheterization was 32.2 ± 8.8 years, and 45.5% were female. Resting and exercise PVRI were 1.9 ± 0.9 and 1.2 (interquartile range [IQR] 0.8–2.1) WU·m2, respectively. Clinical, biochemical and echocardiographic parameters were not associated with PVRI response to exercise. During a follow-up of 2.2 ± 1.4 (IQR 1.2–2.6) years, resting PVRI was not associated with the clinical endpoint (hazard ratio [HR] 0.95 per WU·m2, 95% confidence interval [CI] 0.52–1.74; P = 0.86), whereas exercise PVRI was (HR 2.15 per WU·m2, 95% CI 1.24–3.73; P = .007). Exercise PVRI remained predictive of outcomes after adjusting for exercise pulmonary artery wedge pressure (HR 2.08 per WU·m2, 95% CI 1.19–3.62; P = .01) or clinical risk factors individually. Two-year event-free survival was lower in the no PVRI reduction than in the reduction group (67% vs 95%; P < .001). Conclusions In adults post-Fontan, PVRI response to exercise is a robust predictor of clinical outcomes and offers additive prognostic information beyond resting invasive haemodynamic data and clinical risk factors, underscoring the importance of invasive exercise testing in this population.

Background Exercise cardiac catheterization is the gold standard for diagnosing diastolic dysfunction and impaired pulmonary reserve in patients with Fontan circulation. The diagnostic value of noninvasive parameters is unclear. Methods Patients who underwent simultaneous exercise hemodynamic evaluation and peripheral venous pressure (PVP) measurement were included. Echocardiographic surrogates for ventricular filling pressure were compared with invasive measures. Diastolic dysfunction was defined invasively as either resting pulmonary artery wedge pressure ≥12 mm Hg or exercise pulmonary artery wedge pressure >20 mm Hg. Results Twenty‐nine patients were included. Age at catheterization was 34±9 years. Atrioventricular valve systole‐to‐diastole duration ratio (S/D) and resting PVP were significant predictors of resting pulmonary artery wedge pressure (S/D: β=0.71 per 0.1 S/D [95% CI, 0.16–1.25]; P =0.01; PVP: β=0.68 per mm Hg [95% CI, 0.41–0.96]; P <0.001). By contrast, resting PVP was a predictor of diastolic dysfunction, whereas S/D was not. Based on these data, we proposed a 2‐tier assessment algorithm with the first tier considering resting PVP ≤15 mm Hg and S/D ≤1.1 and the second tier considering exercise PVP ≤25 mm Hg in those with 1 elevated resting parameter. This algorithm showed a positive predictive value of 88% (95% CI, 47%–100%), a negative predictive value of 90% (95% CI, 70%–99%), a sensitivity of 78% (95% CI, 40%–97%), and a specificity of 95% (95% CI, 75%–100%). Exercise PVP indexed to peak oxygen consumption also predicted invasively measured exercise pulmonary vascular resistance index (β=0.36 WU·m 2 per mm Hg/100 mL per min [95% CI, 0.08–0.64]; P =0.01). Conclusions This study presents a simple, noninvasive approach for evaluating diastolic function and pulmonary vascular reserve in patients with a Fontan circulation.

Background. Assessment tools in surgical education help identify improvement areas for trainees. We developed and present validity evidence for a novel Transplant Operative Assessment Tool to optimize technical feedback for surgical trainees in transplantation. Methods. The Transplant Operative Assessment Tool assesses learners on anatomy, technical skills, judgment, and communication. Performance is rated across 5 competency levels. Content validity evidence included a construct map using existing literature and expert cognitive interviews. Ratings were used to develop an item response theory calibration, which was then used to evaluate the tool and provide validity evidence. Results. Eighty-two assessments for 28 trainees (16 residents, 12 fellows) were completed by 25 faculty surgeons across 4 programs. Fifty-six kidney transplants, 13 liver transplants, and 13 donor nephrectomies were assessed. The mean assessment completion time was 4.1 ± 4.3 min. Internal structure validity was evaluated by calculating item infit (range, 0.86–1.15), indicating a strong model fit and confirming a high quality of items. Internal consistency was also high (Cronbach’s alpha = 0.94). There was a positive correlation between ratings and training level ( P < 0.01), indicating strong discriminatory power. Warm ischemia time for transplant operations did not correlate with performance ( P = 0.16). Conclusions. These data provide validity evidence for a novel operative assessment tool. This instrument can measure performance, monitor progress, document competency, and has the potential to provide valuable feedback.

Background: The purpose of this study was to describe outcomes after heart transplantation in adults with congenital heart disease (CHD) based on the experience from a high volume transplant center. Method: Retrospective cohort study of adults with CHD who underwent heart transplantation at Mayo Clinic Rochester, MN (2003-2024). Results: Of 89 patients (age 40 [9;66], 52% males) who underwent heart transplantation, 67 (75%) had biventricular physiology while 22 (25%) had Fontan physiology. Fifty (56%) and 39 (44%) receives single organ versus multi-organ transplantation, respectively. The proportion of patients with Fontan palliation undergoing heart transplantation was higher in the late (after 12/31/2023) era 31% [21 /67] versus 5% [1/22], p=0.005.The 30-day, 1-year, and 5-year survival rates were 97%, 91%, and 87%, respectively, and these rates were higher than the estimates from national registries. Patients with Fontan physiology had lower post-transplant survival compared to biventricular physiology, but Fontan physiology was not an independent predictor of mortality. The predictors of post-transplant mortality were longer cardiopulmonary bypass time, mechanical ventilation duration and postoperative mechanical circulatory support. Conclusions: We observed a higher post-transplant survival compared to historical estimates. Post-transplant mortality was related to operative and postoperative factors, and not to CHD physiology. There was a high proportion of patients requiring multi-organ transplantation, and a rising proportion of patients with Fontan physiology who underwent transplant in the later part of the study. These findings highlight important demographic changes, importance of institutional expertise, and the need for improvements in risk stratification and referral patterns to align with these changes.

Introduction: Transthyretin (TTR) amyloid cardiomyopathy (ATTR-CM) arises from amyloidogenic aggregates of destabilized TTR protein in variant (ATTRv-CM) or acquired wild-type TTR (ATTRwt-CM). The p.V142I (V122I) variant is the most common pathogenic TTR allele in the USA and has higher mortality vs wild type. Acoramidis, an oral TTR stabilizer achieving ≥90% stabilization, is approved in USA, UK, Europe, and Japan for treating ATTR-CM in adults. In ATTRibute-CM (NCT03860935), acoramidis showed a reduction in all-cause mortality (ACM) or first cardiovascular-related hospitalization (CVH) vs placebo (PBO), with consistent benefit in ATTRwt-CM and ATTRv-CM (all variants). We report clinical outcomes in participants with p.V142I ATTRv-CM. Research Question: What was the efficacy of acoramidis for clinical outcomes (ACM, CVH) in participants with p.V142I ATTRv-CM in ATTRibute-CM? Methods: In ATTRibute-CM, 632 participants were randomized 2:1 to receive acoramidis HCl 800 mg or PBO twice daily for 30 months. All participants enrolled in open-label extension (OLE) received acoramidis only. Exploratory post hoc analyses were done in the p.V142I ATTRv-CM subgroup. Time-to-event analyses used a stratified Cox proportional hazards model using treatment group as an explanatory factor and baseline 6MWD as a covariate, stratified by randomization factors: serum NT-proBNP and eGFR. ACM was analyzed at Month 42 (ATTRibute-CM 30 months + 12 months OLE). Results: Of the 59 patients with ATTRv-CM reported at randomization, 35 (59.3%) had p.V142I (23 acoramidis, 12 PBO) with comparable baseline characteristics; 4 were homozygous for p.V142I (1 acoramidis, 3 PBO). Through Month 30, ACM/first CVH occurred in 43.5% (10/23) of acoramidis vs 83.3% (10/12) in PBO (HR 0.311; 95% CI 0.120–0.805; Figure 1 ). Through Month 42, ACM occurred in 26.1% (6/23) of continuous acoramidis vs 66.7% (8/12) in PBO to acoramidis (HR 0.307; 95% CI 0.097–0.973; Figure 2 ). Conclusions: In participants with p.V142I ATTRv-CM, acoramidis use was associated with 69% risk reduction in ACM/first CVH through Month 30 and ACM through Month 42 vs PBO. This is the first report of clinical benefit of this magnitude observed in this high-risk population. These findings have biologic plausibility and may reflect the near-complete stabilization observed experimentally with acoramidis in p.V142I ATTR fibrils. These observations require confirmation in larger cohort studies.

Background: Heart failure (HF) continues to be a major cause of morbidity and mortality worldwide, placing a significant burden on healthcare systems. Differences in the outcomes of HF hospitalizations for adults in teaching vs. non-teaching hospitals in urban settings are uncertain. Research Question: Do outcomes of HF hospitalizations differ between patients hospitalized in urban teaching vs. non-teaching hospitals in the United States? Methods: HF hospitalizations were abstracted from the 2016 through 2022 Nationwide Readmissions Database and stratified into urban teaching vs. urban non-teaching hospital settings. Propensity-score matching was used to control for baseline differences between teaching and non-teaching hospital cohorts. Logistic regression and lognormal models were estimated to assess differences in inpatient mortality, length of stay (LOS), total costs, complications, and 30-day and 90-day all-cause readmissions. Odds ratios (OR) with associated 95% Confidence intervals (CI) and p-values were reported. Analyses were conducted via SAS v. 9.4. Results: A total of 7,558,299 weighted HF hospitalizations were included in the analysis, of which 76.3% involved urban teaching hospitalizations. Compared to urban non-teaching, HF hospitalizations in urban teaching hospitals were associated with higher odds of in-hospital mortality (OR 1.24, 95% CI:1.21-1.27); had higher complications, including cardiogenic shock (OR 2.58, 95% CI, 2.46, 2.70), cardiac arrest (OR 1.31, 95% CI, 1.27, 1.36), CPR (OR 1.28, 95% CI, 1.22, 1.34), and use of extracorporeal membrane oxygenation (OR 20.13, 95% CI, 13.0, 31.2), intra-aortic balloon pump (OR 4.46, 95% CI, 3.90, 5.10) and mechanical ventilation (OR 1.27, 95% CI, 1.23, 1.33); higher hospitalization cost (Ratio 1.18, 95% CI: 1.17,1.20), longer length of stay (OR 1.16, 95% CI: 1.15, 1.17) and a greater palliative care consultation rate (Ratio 1.35 (95% CI 1.30, 1.40) (all p<0.001) ( Figure 1 ). 30-day (OR 1.03, 95% CI: 1.02, 1.04) and 90-day (OR 1.05, 95% CI: 1.02, 1.07) all-cause readmission rates were also statistically higher (p<0.001), though the difference was clinically non-significant ( Figure 2 ). The home discharge rate was similar for teaching and non-teaching hospitals ( Figure 2 ). Conclusion: HF hospitalizations in urban teaching hospitals were associated with higher inpatient mortality, complication rates, resource utilization, and palliative care consult rates than urban non-teaching hospitals.

Background: Heart failure (HF) is the leading cause of mortality in adults with congenital heart disease (CHD) after transcatheter pulmonary valve replacement (TPVR), likely due to preexisting myocardial dysfunction and suboptimal reverse remodeling. Left ventricular (LV) diastolic dysfunction, unmasked by an acute increase in preload post-TPVR, may elevate left-sided filling pressures and precipitate pulmonary edema. However, the prognostic implications of elevated left-sided filling pressures prior to TPVR are currently unknown. Objective: To evaluate the prognostic value of pre-TPVR pulmonary artery wedge pressure (PAWP) and the heart failure with preserved ejection fraction – Age, Body mass index (BMI), Atrial fibrillation (HFpEF-ABA) score in patients undergoing TPVR. Methods: Adults with congenital heart disease (CHD) undergoing TPVR were stratified by pre-implant PAWP (<15 vs ≥15 mmHg) and HFpEF-ABA score (low <25%, intermediate 25–75%, high >75%). The composite endpoint was all-cause mortality, heart transplantation, heart failure (HF) hospitalization, or sustained ventricular arrhythmia. Kaplan-Meier and Cox regression analyses assessed associations with clinical outcomes. Results: Out of 150 patients, 37 (24.7%) had PAWP ≥15 mmHg. Elevated PAWP was associated with older age (36 [31;53] vs. 26 [19; 37] years, p<0.01), BMI (27.9 [24.5; 35.1] vs. 24.2 [20.6; 29.7] kg/m 2 , p<0.01), and higher HFpEF-ABA score (42.8 [9.5;63.6] vs. 6.4 [2.5;18.1]%, p<0.001) compared to normal PAWP. Over a median follow-up of 38 [13; 83] months, 26 events (17.3%) occurred. Kaplan-Meier analysis demonstrated a significant difference in event-free survival based on pre-TPVR PAWP categories (log-rank p=0.002) and HFpEF-ABA score categories (log-rank p<0.001). Elevated PAWP was associated with adverse outcomes (hazard ratio [HR] 4.27, 95% CI 1.61–11.31, p=0.003) (Figure 1), but this was no longer significant after age adjustment. HFpEF-ABA ≥25% was associated with adverse outcomes (HR 10.6, 95% CI 3.8–30.0, p<0.001) (Figure 2), independent of N-terminal prohormone of brain natriuretic peptide levels and left ventricular ejection fraction. Conclusion: Albeit confounded by demographics, pre-TPVR PAWP correlated with adverse long-term outcomes, and patients with this hemodynamic profile may require closer post-procedural surveillance. HFpEF-ABA was independently associated with incident events, representing an inexpensive, novel prognostic tool in patients undergoing TPVR.

Background: Patients with systemic right ventricle (sRV), including congenitally corrected transposition of great arteries (cc-TGA) and dextro-transposition of great arteries (d-TGA) post-atrial switch procedure are at risk of sudden cardiac death due to ventricular arrhythmias (VA). While programmed ventricular stimulation (PVS) can help with risk stratification in certain patients with congenital heart disease, its role in sRV is unknown. Objective: To study the diagnostic value of electrophysiology study (EPS) in predicting VAs in patients with sRV. Methods: EPS was performed in 53 patients with sRV at Mayo Clinic from 1994 to 2021. Patients with a history of sustained VA or cardiac arrest were excluded (n=19). The incidence of sustained VA (sudden cardiac death, sustained ventricular tachycardia [VT] or appropriate implantable cardioverter-defibrillator [ICD] therapy) was evaluated in the remaining 34 patients. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of EPS in predicting VAs is reported. Results: The mean age at EPS was 36.2±11.6 years, 21 (61.8%) were male, 21 (61.8%) had d-TGA and mean sRV ejection fraction was 31.3±10.8%. Indication for EPS was supraventricular tachycardias (n=15, 44.1%), syncope/palpitations (n=9, 26.5%) and non-sustained VT (n=6, 17.6%). 13/34 (38.2%) patients had inducible sustained VA, (5 [38.5%] with monomorphic VT and 8 [61.5%] with polymorphic VT/VF). Treatments included ICD implantation in all 13 patients and ablation in one patient. During a mean follow-up of 8±5.4 years, one patient with a positive PVS (inducible polymorphic VT) experienced sustained VT secondary to atrial flutter with 1:1 conduction. The sensitivity of PVS was 100%, specificity was 63.6%, PPV 7.7%, and NPV 100%. Conclusion: In this retrospective cohort of patients with sRV, polymorphic VT was the most commonly observed VA during PVS. The predictive value of a positive PVS was low in this cohort, and larger studies are needed to better define the role of EPS in risk stratification. Patients with negative EPS did not have future VAs recognizing that the overall event rate is low. Further multicenter research with a larger sample is required to develop predictive models to identify those at risk of VAs.

Backround: Advances in surgical and medical care of children born with congenital heart disease (CHD) has improved survival into adulthood. However, cardiac and non-cardiac morbidity and mortality remain common in adults with CHD (ACHD). We present the causes and predictors of mortality in a large cohort of ACHD patients from the USA. Methods/Approach: We conducted a retrospective review of ACHD patients followed at Mayo Clinic between 1992 - 2024. Mortality was ascertained using the Accruint national data base. Clinical characteristics and primary cause of death were identified from the electronic record. Kaplan-Meier (KM) survival analysis was performed to compare overall survival stratified by CHD severity. Cox proportional hazards regression was used to identify independent predictors of mortality. Results/Data: Amongst 9160 ACHD patients (mean age 38±16y at first visit, 51% males, 23% simple, 59% moderate and 18% severe CHD), mortality occurred in 1430(16%) patients during a mean follow-up of 11±7y. The mean age at death was 68±17 y, 58±17y, and 45±15y in mild, moderate and severe ACHD. KM analysis of survival and cause of death stratified by CHD severity are presented in Figures 2 and 3 respectively. Cause of death could not be ascertained in 33%%. Amongst those with a known cause of death, the proportion of non-cardiac death increased with decreasing severity of CHD. HF death and sudden cardiac death occurred in 11% and 19%. Infection, malignancy and chronic respiratory failure were important non-cardiac causes of death. Significant risk factors for mortality included CHD severity, ventricular arrhythmia, heart failure, declining functional capacity, diabetes and chronic kidney disease as presented in the Fig 1. Conclusion(s): Mortality in ACHD patients is associated with CHD severity, heart failure, ventricular arrhythmia and cardiovascular comorbidities. Early recognition and management of these risk factors may improve long-term survival. As patients with ACHD age, management of cardiovascular and noncardiac risk factors will require development of systems of care specific to this vulnerable population.