Goda, Ahmed

Background: Pulmonary hypertension (PH) and secondary right ventricle dysfunction is present in 20% of adults with coarctation of aorta (COA) based on echocardiographic studies. There are limited data about invasive hemodynamic characterization of PH in COA. The purpose of this study was to delineate the clinical features, hemodynamics, and outcomes of PH in COA. Method: Retrospective cohort study of adults with repaired COA that underwent right heart catheterization (RHC). PH was defined as pulmonary artery (PA) mean pressure >20 mmHg, and PH was classified as isolated precapillary PH and combined pre/postcapillary PH. Results: Of 99 COA patients that underwent RHC, 57 (58%) had PH. Of the patients with PH, 14 (25%) had isolated precapillary PH while 43 (75%) had postcapillary PH with or without precapillary disease. The correlates of PH were PA compliance (adjusted OR 0.79, 95% CI 0.71-0.86 per 1 ml/mmHg), left atrial reservoir strain (adjusted OR 0.95, 95% CI 0921-0.98 per 1%), and atrial fibrillation (adjusted OR 2.18, 95% CI 1.20-13.5). Higher PA mean pressure was associated with risk of cardiovascular events (adjusted HR 1.04, 95% CI 1.02-1.06 per 1 mmHg) and all-cause mortality (adjusted HR 1.05, 95% CI 1.02-1.08 per 1 mmHg). Conclusions: PH was present in over half of adults with COA referred for RHC, and one-quarter of the patients with PH presented with isolated precapillary PH suggesting an underlying PA vascular dysfunction as a contributing mechanism. Further studies are required to determine optimal therapies and strategies for prevention and treatment of PH in this population.

Background: Chronic left ventricular (LV) pressure overload is common in adults with repaired coarctation of aorta (COA). However, there is no validated systematic approach for assessing cardiac remodeling and damage in this population. The purpose of this study was to evaluate the role of cardiac damage staging scheme (validated for calcific aortic stenosis) for prognostication in adults with repaired COA. Methods: Patients were classified using a modified cardiac damage scheme: stage 0 (no cardiac damage), stage 1 (LV damage), stage 2 (left atrial damage), stage 3 (pulmonary vascular/tricuspid valve damage), and stage 4 (right ventricular damage). Results: Of 795 patients (age 36±16 years), 270 (34%) had stage 0, 198 (25%) had stage 1, 225 (28%) had stage 2, 37 (5%) had stage 3, and 65 (8%) had stage 4 cardiac damage. The 795 patients were followed for 7.3 (2.8-9.6) years, and 94 (12%) died, of which 75 (9%) were cardiovascular deaths. Cardiac damage stage was independently associated with all-cause mortality (adjusted HR 1.31, 95% CI 1.22-1.40, per unit increase in stage), and cardiovascular mortality (adjusted HR 1.42, 95% CI 1.28-1.55, per unit increase in stage). The addition of the cardiac damage stage to the base model (clinical and echocardiographic variables) provided significant incremental improvement in the prediction of 5-year risk of all-cause mortality over the base model (net reclassification index 0.39, p<0.001). Hypertension was associated with cardiac damage and mortality. Conclusions: The cardiac damage scheme can be used for risk stratification, and potentially guide therapy in the COA population.

Background: Aortic regurgitation (AR) can develop in adults with repaired coarctation of aorta (COA), but there are limited data about left ventricular (LV) remodeling and clinical outcomes in this population. The purpose of the study was to compare LV remodeling (LV mass index [LVMI], LV ejection fraction [LVEF], and septal E/e’) and onset of symptoms before aortic valve replacement (AVR), and LV reverse remodeling (%-change in LVMI, LVEF and E/e’) after AVR in patients with versus without repaired COA presenting with AR. Methods:: Asymptomatic adults with repaired COA presenting with moderate/severe AR (AR-COA group) were matched 1:2 to asymptomatic adults without COA and similar severity of AR (control group). Results: Although both groups (AR-COA n=52, and control n=104) had similar age, sex, body mass index, aortic valve gradient, and AR severity, the AR-COA group had higher LVMI (124±28 versus 102±25 g/m2, p<0.001) and E/e’ (12.3±2.3 versus 9.5±2.1, p=0.02) but similar LVEF (63±9% versus 67±10%, p=0.4). COA diagnosis (adjusted HR 1.95, 95%CI 1.49-2.37, p<0.001), older age, E/e’, and LV hypertrophy wereassociated with onset of symptoms. Of 89 patients (AR-COA n=41, and control n=48) with echocardiographic data at 1-year post-AVR, the AR-COA group had less regression of LVMI (-8% [95%CI -5 to -11] versus -17% [95%CI -15 to -21], p<0.001) and E/e’ (-5% [95% CI -3 to -7] versus -16% [95% CI -13 to -19], p<0.001). Conclusions: Patients with COA and AR had a more aggressive clinical course, and perhaps may require a different threshold for surgical intervention.

Background: The prognostic implications of exercise induced hypertension (EIH) in adults with repaired coarctation of aorta (COA) and treated hypertension are unknown. The purpose of this study was to assess the relationship between EIH and cardiovascular events, and to determine whether exercise blood pressure (BP) improved risk stratification in this population. Methods: Retrospective study of patients with COA on antihypertensive therapy that underwent exercise testing (2003-2019). BP was measured at rest in 3 different clinical settings and averaged to determine the resting BP. EIH was defined as systolic BP (SBP) >210 (males) or >190 (females) at peak exercise. Cardiovascular event was defined as atrial fibrillation, ventricular tachycardia, heart failure hospitalization, heart transplant, and cardiovascular death. Results: Of 327 patients (age 35±13 years), 116 (35%) had EIH. Although the resting BP was similar between patients with versus without EIH, the EIH group had higher pulsatile arterial load, more advanced left ventricular remodeling, and were less likely to be on angiotensin converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB). EIH was associated with cardiovascular events (HR 1.06 [95%CI 1.02-1.08]) independent of resting SBP, and improved prognostic accuracy above resting SBP (C-statistic 0.671 [95%CI 0.645-0.694] to 0.727 [95%CI 0.709-0.750], p=0.01). ACEI/ARB was associated with a lower risk of cardiovascular events. Conclusions: EIH was associated with cardiovascular events independent of resting BP, and patients receiving ACEI/ARB had lower risk of EIH and cardiovascular events. These data suggest that exercise BP could be used to assess adequacy of antihypertensive therapy, and to guide titration of antihypertensive therapy.

Introduction: Chronic elevation of left heart filling pressure causes pulmonary vascular remodeling, pulmonary hypertension, and right heart dysfunction. Although diastolic dysfunction is relatively common in patients with coarctation of aorta (COA), there are limited data about the prevalence and prognostic implications of pulmonary hypertension and right heart dysfunction in this population. The purpose of the study was to assess right heart function and hemodynamics in patients with COA, and to determine the relationship between right heart indices and clinical outcomes. Methods: Right heart structure, function and hemodynamics were assessed with these indices: right atrial (RA) volume, RA pressure, RA reservoir strain, right ventricular (RV) global longitudinal strain, RV end-diastolic area, RV systolic pressure, and tricuspid regurgitation severity. These indices were used to generate a composite right heart hemodynamic score (RHHS), range 0-5. We then assessed the relationship between RHHS and primary outcome (death/transplant) and secondary outcomes (heart failure hospitalization and hepatorenal function). Results: Of 821 COA patients, RA dysfunction, RV dysfunction, and pulmonary hypertension were present in 16%, 14%, and 20% of patients respectively. RHHS was independently associated with primary and secondary outcomes (p<0.001). For every unit increase in RHHS, we observed 83% increase in death/transplant and 71% increase in heart failure hospitalization. Conclusions: The current study underscores an important point, which is that COA is not just a disease of the left heart but can result in right heart dysfunction, and that the onset of right heart dysfunction is associated with adverse outcomes.

Introduction: Valvuloarterial impedance (Zva) is used for assessment of left ventricular (LV) global pressure load in patients with aortic stenosis (AS) and impaired arterial compliance. Since patients with coarctation of aorta (COA) have impaired arterial compliance, we hypothesized that COA patients with ≥moderate AS (AS-COA group) will have higher Zva, symptomatic progression, and cardiovascular events, as compared to non-COA patients with similar AS severity (AS group). Methods: 1:1 propensity matching of 71 AS-COA and 71 AS patients based on age, sex, body mass index, and aortic valve mean gradient. Results: The AS-COA group had higher Zva (4.2±0.6 vs 3.5±0.4 mmHg/ml*m 2 , p<0.001), more advanced cardiac remodeling, and higher 5-year incidence of symptomatic progression (85% vs 51%, p<0.001). Pre-operative Zva was independently associated with cardiac remodeling (r=0.66, p<0.001) and symptomatic progression (HR 1.08, 1.05-1.12, per mmHg/ml*m 2 increase in Zva). Of 172 patients, 117 underwent aortic valve replacement (AVR). The AS-COA group had higher residual Zva(3.3±0.5 vs 2.4±0.4 mmHg/ml*m 2 , p<0.001), less robust LV mass index (LVMI) regression at 1-year post-AVR, and higher 5-year incidence of cardiovascular events. Post-operative Zva was independently associated with LVMI regression (r=-0.46, p<0.001) and cardiovascular events (HR 1.06, 1.02-1.10, per mmHg/ml*m 2 increase in Zva). Conclusions: Adults with repaired COA repair and moderate-severe AS had higher LV global pressure load, cardiac remodeling, symptomatic progression, and cardiovascular events as compared to non-COA patients with similar severity of AS. Zva can identify patients at risk for adverse outcomes, and perhaps should be used for risk stratification with regards to timing of AVR.