Emergency department evaluation of chest pain among adult congenital heart disease patients.

BACKGROUND: Data regarding emergency department (ED) assessment of acute chest pain (CP) and incidence of myocardial infarction (MI) among adult congenital heart disease (ACHD) patients, relative to the non-congenital population, is lacking. OBJECTIVES: To describe MI risk in ACHD patients presenting to the ED with chest pain and to compare clinical characteristics, diagnostic testing patterns, and outcomes to controls. METHODS: We retrospectively identified a cohort of ACHD patients presenting with acute CP and matched them with non-ACHD controls at a large tertiary-level ED during the period 1998-2018. RESULTS: The congenital and control cohorts comprised 297 patients respectively. While MI was less common among ACHD patients (5.2%) than controls (19.7%), P = .01, arrhythmia (14% vs 6%, P < .001) and acute heart failure (3% vs 0.3%, P = .02) were more often the cause of symptoms. Despite more often presenting with non-anginal CP (81% vs 66%, P < .001) and having fewer CAD risk factors (P = .03), ACHD patients underwent more frequent stress testing (22% vs 14%, P < .001) and underwent invasive coronary angiography with equal frequency (7% vs 8%, P = .99). The trend of greater diagnostic scrutiny for acute coronary disease, in the absence of increased risk, strongly correlated with degree of congenital complexity. Both CP character and HEART Score reliably predicted MI for ACHD patients and controls (both P < .001). CONCLUSION: MI is an uncommon cause of CP among ACHD patients presenting to the ED and occurs less frequently than seen in the general population. Established MI predictors, CP character and HEART Score, can reliably identify MI in ACHD patients.

Hospital Readmissions in Children with Pulmonary Hypertension: A Multi-Institutional Analysis.

OBJECTIVE: To assess the rate of and risk factors for 30-day hospital readmission in children with pulmonary hypertension. STUDY DESIGN: The Pediatric Health Information System database was analyzed for patients ≤18 years old with pulmonary hypertension (International Classification of Diseases, Ninth Revision, diagnosis codes of 416.0, 416.1, 416.8, or 416.9) admitted from 2005 through 2014. A generalized hierarchical regression model was used to determine significant ORs and 95% CIs associated with 30-day readmission. RESULTS: A total of 13580 patients met inclusion criteria (median age 1.7 years [IQR 0.3-8.7], 45.3% with congenital heart disease). Admissions increased 4-fold throughout the study period. Associated hospital charges increased from $119 million in 2004 to $929 million in 2014. During initial admission, 57.4% of patients required admission to the intensive care unit, and 48.2% required mechanical ventilation. The 30-day readmission rate was 26.3%. Mortality during readmission was 4.2%. Factors increasing odds of readmission included a lower hospital volume of pulmonary hypertension admissions (1.41 [1.23-1.57], P < .001) and having public insurance (1.26 [1.16-1.38], P < .001). Decreased odds of readmission were associated with older age and the presence of congenital heart disease (0.86 [0.79-0.93], P < .001). CONCLUSIONS: The pediatric pulmonary hypertension population carries significant morbidity, as reflected by a high use of intensive care unit resources and a high 30-day readmission rate. Younger patients and those with public insurance represent particularly at-risk groups.

Transcatheter thrombectomy of acute pulmonary embolism in an adult Fontan patient: a case report.

Background: The Fontan operation is a well-described palliative procedure for functional single-ventricle patients. This population has an increased risk of thrombo-embolic events. Adequate imaging, and therefore diagnosis, requires an understanding of the unique anatomy and physiology of a Fontan. Optimal strategies for the prevention and treatment of thrombo-embolic complications in the Fontan population are poorly defined. Case summary: A 28-year-old female with a history of Ebstein anomaly of the tricuspid valve status post-Fontan presented with chest pain and acute hypoxia. Computed tomographic angiography (CTA) reported a submassive pulmonary embolism (PE). She was initiated on a heparin drip. Catheterization demonstrated elevated Fontan pressures and a large thrombus in the right lower pulmonary artery that was removed with an aspiration device. The patient was transitioned to a direct oral anticoagulant (DOAC) following the procedure. Discussion: Thrombotic complications are common in the adult Fontan population. Given the morbidity and mortality associated with this complication, the use of proper imaging techniques is imperative. Traditional CTA imaging for PE in Fontan patients often has contrast filling defects related to their anatomy and physiology. Utilization of adequate imaging techniques helps decrease cost and additional radiation exposure. In addition, it avoids inappropriate hospitalization, need for anticoagulation, and potential need for catheterization toconfirm or exclude the presence of PE. For Fontan patients with a thrombus, prior event, and no contraindications, current guidelines recommend oral anticoagulation with a vitamin K antagonist; however, there are increasing data on the use of DOACs in this population.

Clinical Outcomes of Adult Fontan-Associated Liver Disease and Combined Heart-Liver Transplantation.

BACKGROUND: The impact of Fontan-associated liver disease (FALD) on post-transplant mortality and indications for combined heart-liver transplant (CHLT) in adult Fontan patients remains unknown. OBJECTIVES: The purpose of this study was to assess the impact of FALD on post-transplant outcomes and compare HT vs CHLT in adult Fontan patients. METHODS: We performed a retrospective-cohort study of adult Fontan patients who underwent HT or CHLT across 15 centers. Inclusion criteria were as follows: 1) Fontan; 2) HT/CHLT referral; and 3) age ≥16 years at referral. Pretransplant FALD score was calculated using the following: 1) cirrhosis; 2) varices; 3) splenomegaly; or 4) ≥2 paracenteses. RESULTS: A total of 131 patients (91 HT and 40 CHLT) were included. CHLT recipients were more likely to be older (P = 0.016), have a lower hemoglobin (P = 0.025), require ≥2 diuretic agents pretransplant (P = 0.051), or be transplanted in more recent decades (P = 0.001). Postmatching, CHLT demonstrated a trend toward improved survival at 1 year (93% vs 74%; P = 0.097) and improved survival at 5 years (86% vs 52%; P = 0.041) compared with HT alone. In patients with a FALD score ≥2, CHLT was associated with improved survival (1 year: 85% vs 62%; P = 0.044; 5 years: 77% vs 42%; P = 0.019). In a model with transplant decade and FALD score, CHLT was associated with improved survival (HR: 0.33; P = 0.044) and increasing FALD score was associated with worse survival (FALD score: 2 [HR: 14.6; P = 0.015], 3 [HR: 22.2; P = 0.007], and 4 [HR: 27.8; P = 0.011]). CONCLUSIONS: Higher FALD scores were associated with post-transplant mortality. Although prospective confirmation of our findings is necessary, compared with HT alone, CHLT recipients were older with higher FALD scores, but had similar survival overall and superior survival in patients with a FALD score ≥2.

Morbidity and Mortality in Adult Fontan Patients After Heart or Combined Heart-Liver Transplantation.

BACKGROUND: An increasing number of adult Fontan patients require heart transplantation (HT) or combined heart-liver transplant (CHLT); however, data regarding outcomes and optimal referral time remain limited. OBJECTIVES: The purpose of this study was to define survivorship post-HT/CHLT and predictors of post-transplant mortality, including timing of referral, in the adult Fontan population. METHODS: A retrospective cohort study of adult Fontan patients who underwent HT or CHLT across 15 centers in the United States and Canada was performed. Inclusion criteria included the following: 1) Fontan; 2) HT/CHLT referral; and 3) age ≥16 years at the time of referral. Date of "failing" Fontan was defined as the earliest of the following: worsening fluid retention, new ascites, refractory arrhythmia, "failing Fontan" diagnosis by treating cardiologist, or admission for heart failure. RESULTS: A total of 131 patients underwent transplant, including 40 CHLT, from 1995 to 2021 with a median post-transplant follow-up time of 1.6 years (Q1 0.35 years, Q3 4.3 years). Survival was 79% at 1 year and 66% at 5 years. Survival differed by decade of transplantation and was 87% at 1 year and 76% at 5 years after 2010. Time from Fontan failure to evaluation (HR/year: 1.23 [95% CI: 1.11-1.36]; P < 0.001) and markers of failure, including NYHA functional class IV (HR: 2.29 [95% CI: 1.10-5.28]; P = 0.050), lower extremity varicosities (HR: 3.92 [95% CI: 1.68-9.14]; P = 0.002), and venovenous collaterals (HR: 2.70 [95% CI: 1.17-6.20]; P = 0.019), were associated with decreased post-transplant survival at 1 year in a bivariate model that included transplant decade. CONCLUSIONS: In our multicenter cohort, post-transplant survival improved over time. Late referral after Fontan failure and markers of failing Fontan physiology, including worse functional status, lower extremity varicosities, and venovenous collaterals, were associated with post-transplant mortality.

Utility of Cardiac Magnetic Resonance Imaging in Predicting Atrial Arrhythmias in Repaired Tetralogy of Fallot.

Arrhythmias are the leading cause of morbidity and mortality in repaired tetralogy of Fallot (TOF), and over 20% of these patients will develop a sustained atrial arrhythmia during their lifetimes. Cardiac magnetic resonance imaging (cMRI) is frequently performed in TOF, although its ability to identify patients at risk of atrial arrhythmias is uncertain. Adult TOF patients (n = 175) with no history of atrial arrhythmia who underwent cMRI between 2003 and 2020 at a single tertiary care center were identified. Clinical characteristics and imaging findings were evaluated to identify a predilection for atrial arrhythmias using Kaplan-Meier survival analysis and log-rank testing. Multivariable Cox regression was used to determine independent predictors of atrial arrhythmias. Over a median follow-up of 3.6 years, 29 patients (17%) developed atrial arrhythmias. Independent predictors of atrial arrhythmia included age (hazard ratio [HR] 1.06 per 1-year increase, 95% confidence interval [CI] 1.02 to 1.09, p = 0.002), diabetes mellitus (HR 4.26, 95% CI 1.26 to 14.41, p = 0.020), indexed right ventricular end-diastolic volume (RVEDVi), (HR 1.20 per 10-ml/m2 increase, 95% CI 1.05 to 1.39, p = 0.010), and moderate or greater tricuspid regurgitation (TR) (HR 6.32, 95% CI 2.15 to 18.60, p = 0.001). Utilizing Kaplan-Meier analysis, patients with at least mild right ventricular dilation (RVEDVi >100 ml/m2, p = 0.047) and greater than or equal to moderate TR (p <0.001) were found to be significantly more likely to develop atrial arrhythmias. In conclusion, cMRI can help to identify TOF patients at increased risk for atrial arrhythmia beyond standard clinical and imaging data by better quantifying RVEDVi and degree of TR.

Impact of Pulmonary Hypertension on Survival Following Device Closure of Atrial Septal Defects.

Pulmonary hypertension (PH), defined as mean pulmonary arterial pressure ≥25 mm Hg, may be a complication of a secundum atrial septal defect (ASD). This study sought to evaluate the impact of PH at time of ASD device closure on patient survival. A prospectively collected database of ASD closures was utilized. Patients were stratified by age above and below the cohort median (48 years). Survival was analyzed by preprocedural PH status, age cohort, and echocardiographic resolution of PH at 3 months postdevice closure. PH was present in 48 of 228 patients (21.1%) and was more common in the older cohort (31.3% vs 10.6%, p <0.01). ASD size was unrelated to the presence of PH (p = 0.33). Older patients had more medical co-morbidities including diabetes (p = 0.02), hyperlipidemia (p <0.01), and systemic hypertension (p <0.01) compared with younger patients. PH did not impact survival in patients ≤48 years, but PH was associated with fivefold increased risk of death in patients >48 years (p < 0.01). Patients with preprocedural PH and RVSP ≥40 mm Hg at 3-month follow-up continued to have an increased risk of mortality (p <0.01), whereas those with resolution of PH had similar survival to those without PH at time of closure. In conclusion, PH is common in adults with unrepaired ASDs and appears unrelated to defect size. PH in older adults and its persistence closure are strong predictors of a worsened clinical outcome. These patients may benefit from additional risk assessment and advanced medical therapies to mitigate this risk.

Outcomes of lung disease-associated pulmonary hypertension and impact of elevated pulmonary vascular resistance.

BACKGROUND: The clinical characteristics, hemodynamic changes and outcomes of lung disease-associated pulmonary hypertension (LD-PH) are poorly defined. METHODS: A prospective cohort of PH patients undergoing initial hemodynamic assessment was collected, from which 51 patients with LD-PH were identified. Baseline characteristics and long-term survival were compared with 83 patients with idiopathic pulmonary arterial hypertension (iPAH). RESULTS: Mean age (±standard deviation) of LD-PH patients was 64 ±â€¯10 years, 30% were female and 78% were New York Heart Association class III-IV. The LD-PH group was older than the iPAH group (64 ±â€¯10 vs 56 ±â€¯18 years, respectively, P = 0.003) with a lower percentage of women (30% vs 70%, P = 0.007). LD-PH patients had smaller right ventricular sizes (P = 0.02) and less tricuspid regurgitation (P = 0.03) by echocardiogram, and lower mean pulmonary arterial pressures (mPAP) (P = 0.01) and pulmonary vascular resistance (PVR) (P = 0.001) at catheterization. Despite these findings, mortality was equally high in both groups (P = 0.16). 5-year survival was lower in patients with interstitial lung disease compared to those with obstructive pulmonary disease (P = 0.05). Among the LD-PH population, those with mild to moderately elevated mPAP and those with PVR <7 Wood units demonstrated significantly improved survival (P = 0.04 and P = 0.001, respectively). Vasoreactivity was not associated with improved survival (P = 0.64). A PVR ≥7 Wood units was associated with increased risk of mortality (hazard ratio (95% confidence interval), 3.59 (1.27-10.19), P = 0.02). CONCLUSIONS: Despite less severe PH and less right heart sequelae, LD-PH has an equally poor clinical outcome when compared to iPAH. A PVR ≥7 Wood units in LD-PH patients was associated with 3-fold higher mortality.

Effect of Patent Foramen Ovale in Patients With Pulmonary Hypertension.

Septostomy reduces right ventricular (RV) workload at the expense of hypoxemia in patients with advanced pulmonary hypertension (PH). A patent foramen ovale (PFO) may serve as a "natural" septostomy, but the incidence and impact of a PFO in PH remains uncertain. We prospectively examined echocardiograms in 404 PH patients referred for initial hemodynamic assessment. Patients included had saline bubble injection and if negative repeatinjection after Valsalva maneuver. Echocardiographic and hemodynamic data were examined. Survival was modeled using Kaplan-Meier method. Eisenmenger syndrome or known atrial shunts other than PFO were excluded: 292 patients met entry criteria. A PFO was identified in 16.8% of the entire cohort, 22.9% of pulmonary arterial hypertension (PAH) patients, and 8.6% of Dana Point group 2 PH patients. Right atrial to pulmonary capillary wedge pressure difference was lowest in the latter group (-7.9 ± 7.1 vs -1.7 ± 5.5 mm Hg for all others, p <0.01). Patients with a PFO were younger (53.9 vs 58.6 years, p = 0.02). A PFO was more often present with moderately or severely dilated (p = 0.01) or dysfunctional (p = 0.03) RVs. Six year survival was unchanged by PFO presence for all patients, including those with PAH. Proportional hazards analysis found only age and functional class independently predicted survival (p <0.01). A PFO is identified less often in Dana Point group 2 PH, likely due to inability of Valsalva maneuver to overcome right atrial to pulmonary capillary wedge pressure difference. In conclusion, the incidence of a PFO in the PH population increases with more dilated and dysfunctional RVs, suggesting that the PFO may be stretched open rather than congenital. The presence of a PFO does not impact survival in PH or PAH.

Coronary Disease and Modifying Cardiovascular Risk in Adult Congenital Heart Disease Patients: Should General Guidelines Apply?

There are >1.4 million adult congenital heart disease (CHD; ACHD) patients living in the United States. Coronary artery disease (CAD) is at least as prevalent in ACHD patients as in the general population and has become a leading cause of their mortality. In the majority of cases, CAD in the ACHD population is driven by the presence of traditional cardiovascular disease (CVD) risk factors. 80% of ACHD patients have at least one CVD risk factor. Hypertension (HTN), obesity and physical inactivity are frequently seen in both pediatric and adult patients with CHD. Many ACHD patients demonstrate abnormal glucose metabolism and are at an increased risk for developing diabetes. Current guidelines for CVD risk assessment and prevention do not specifically mention patients with CHD but are likely applicable to most of these patients. Specific CHD populations have "high-risk" lesions that are associated with an increased risk of CVD complications and may warrant intensified screening and treatment. These include patients with a history of coarctation of the aorta or with prior coronary artery ostial manipulation (patients with a history of d-transposition of the great arteries or anomalous aortic origin of a coronary artery). The physiology of single ventricle patients is also poorly suited for the effects of superimposed CVD; these patients may benefit from intensified treatment of CVD risk factors, particularly HTN and obesity.

Characteristics of pediatric pulmonary hypertension trials registered on ClinicalTrials.gov.

The investigation of pediatric pulmonary hypertension (PH) drugs has been identified as a high priority by the United States National Institutes of Health (NIH). Studying pediatric PH is challenging due to the rare and heterogeneous nature of the disease. We sought to define the pediatric PH clinical trials landscape, to evaluate areas of trial success or failure, and to identify potential obstacles to the study of pediatric PH drugs. Interventional pediatric (ages 0-17 years) PH trials registered on ClinicalTrials.gov from June 2005 through December 2014 were analyzed. There were 45 pediatric PH trials registered during the study period. Median (IQR) projected trial enrollment was 40 (24-63), with seven trials (16%) targeting > 100 participants. Industry was the most common trial sponsor (n = 23, 50%), with only two (4.4%) NIH-sponsored trials. Phosphodiesterase inhibitors were the most frequently studied drug (n = 18, 39%). Single group study designs were used in 44% (n = 20) with an active comparator (parallel, factorial, or cross-over designs) in 25 trials, including 22 with randomization and ten that were double-blinded. Study outcomes varied markedly with inconsistent use of known surrogate and composite endpoints. One-third of trials (n = 15, 33%) were terminated, predominantly due to poor participant enrollment. Of the 17 completed trials, 11 had published results and only three efficacy trials met their primary endpoint. There are unique challenges to drug development in pediatric PH, including enrolling patients, identifying appropriate study endpoints, and conducting randomized, controlled, double-blind trials where the likelihood of meeting the study endpoint is optimized.

Atrial ectopic tachycardia in a patient with marfan syndrome.

The fibrillin defect central to Marfan syndrome is believed to affect myocardial conduction and predispose affected patients to various arrhythmias, including ventricular tachycardia, atrial fibrillation, and atrioventricular nodal reentry tachycardia. Here we describe an adult Marfan patient with atrial ectopic tachycardia. To our knowledge, this is the first reported case of atrial ectopic tachycardia in the setting of Marfan syndrome.