Citations

Background: Patients with Fontan palliation have reduced aerobic capacity because of impaired cardiac, pulmonary, and skeletal muscle function. However, the assessment of aerobic capacity in this population still relies on comparisons with people without cardiovascular disease, rather than comparison with the expected aerobic capacity of other Fontan patients. The purpose of this study was to determine the expected aerobic capacity of adults with Fontan palliation. Method: Adults with Fontan palliation who underwent cardiopulmonary exercise test at Mayo Clinic (2003-2023) were stratified into quartiles based on the predicted peak VO 2 . We assessed the correlates of predicted peak VO 2 , and the relationship between predicted peak VO 2 quartiles and cardiovascular outcomes (death/transplant). Results: Of 323 patients (age 29±9 years; 177 [55%] men), the median peak VO2 was 19.1 (15.2 - 23.9) ml/kg/min, and this corresponds to a predicted peak VO 2 of 51% (range 19 -88; interquartile range 41 - 62). The correlates of higher predicted peak VO 2 were smaller body mass index, higher systemic saturation, and lower Fontan pressures. The top, 2 nd ,3 rd , and bottom quartile of predicted peak VO 2 corresponds to predicted peak VO 2 of 63-88%, 51-62%, 41-50%, and 19-40%, respectively. Using the top quartile as the reference, the 3 rd quartile (HR 1.13, 95% CI 1.03-1.28, p=0.02), and 4 th quartile were associated with a higher risk of death/transplant (HR 1.32, 95% CI 1.16-1.69, p<0.001). Conclusions: The results of the current study would help calibrate the interpretation of exercise test data in adults with Fontan palliation and improve risk stratification in this population.

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.

Abstract Funding Acknowledgements Type of funding sources: None. Background The impact of capacitance and blood volume redistribution on outcomes of patients with chronic heart failure is incompletely understood. Quantitative plasma volume (PV) measurements together with echocardiographic evaluation allow a comprehensive assessment of the interplay between volumetric overload, cardiac chamber remodelling and myocardial function. Purpose We hypothesize that PV expansion is associated with myocardial and renal dysfunction, right ventricular-pulmonary arterial uncoupling and unfavorable outcomes in HF patients with reduced ejection fraction (HFrEF). Methods Patients hospitalized at Mayo Clinic with decompensated HF and who had PV by the indicator-dilution nuclear methodology (Daxor BVA100) were included. Patients were considered hypervolemic if BV was ≥25% over expected. The primary endpoint was the composite of all-cause mortality or heart transplantation. The closest TTE to the time of PV was used to measure various indexes of myocardial performance (standard echo parameters and global chamber-specific strain parameters). Event-free survival was estimated using the Kaplan-Meier method. The relationship between PV and various parameters was evaluated with correlation coefficient (r²). Results A total of 65 patients were enrolled in the study. Reduced LVEF was present in 53 (81.6%) patients. There were 44 events (32 deaths, 12 heart transplants) after a median follow-up of 43 months (IQR 14–65). Results in patients with HFrEF are presented in the Table. Our main findings were: 1) PV expansion was associated with an increased risk of adverse events (Figure 1); 2) Volume redistribution correlated with various indexes of cardiac chamber function, suggesting that volume overload and associated cardiac remodeling may be responsible for altered myocardial mechanics in patients with HFrEF (Figure 2); 3) right ventricular-pulmonary arterial uncoupling was triggered by the plasma volume expansion, that causes postcapillary pulmonary hypertension; 4) PV redistribution was also associated with renal dysfunction and increasing the level of the protein catabolism (Table 1). Conclusion Expansion of plasma volume in HFrEF patients is associated with left atrium dilatation, abnormal filling of both atria and right ventricular dilatation / dysfunction. Plasma volume redistributions apparently became a trigger of right ventricular-pulmonary arterial uncoupling and stimulated postcapillary pulmonary hypertension, renal dysfunction with increasing the level of protein catabolism and unfavorable outcomes.

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: Left atrial (LA) reservoir strain <18% and booster strain <8% have been proposed as the optimal threshold to detect increased left ventricular (LV) filling pressure in patients with acquired heart disease. This study aimed to determine whether these LA strain cut-off points can detect increased LV filling pressure in adults with coarctation of aorta (COA). Methods: Retrospective study of adults with COA (n=126; age 36±16 years), that underwent non-simultaneous cardiac catheterization and echocardiography. Increased LV filling pressure was defined as pulmonary artery wedge pressure (PAWP) >12 mmHg or LV end-diastolic pressure (LVEDP) >16 mmHg. Results: The median PAWP was 13 (11-18) mmHg, and had a good correlation with LA reservoir strain (r=-0.69, p<0.001) and LA booster strain (r=-0.61, p<0.001). LA reservoir strain <18% had superior diagnostic power to detect PAWP >12 mmHg as compared to LA volume index >34 ml/m2, septal E/e’ >15, lateral E/e’ >13, and tricuspid regurgitation velocity >2.8 m/s (p<0.05 for all). The median LVEDP was 17 (14-20) mmHg, and LVEDP had a modest correlation with LA reservoir strain (r=-0.39, p<0.001) and LA booster strain (r=-0.33, p=0.002). LA reservoir strain <18% had superior diagnostic power to detect LVEDP >16 mmHg as compared to LA volume index >34 ml/m2, septal E/e’ >15, lateral E/e’ >13 and tricuspid regurgitation >2.8 m/s (p<0.05 for all). Conclusions: These data suggest that LA strain could be used to identify patients with increased LV filling pressure thereby improving patient selection for cardiac catheterization and interventions.

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.

Abstract Funding Acknowledgements Type of funding sources: None. Background Right heart and renal dysfunction occurring due to volume fluid redistribution remain a front-line issue in the development of the syndrome of congestion in chronic heart failure (HF). Quantitative total blood volume (TBV) measurements and Speckle-tracking Echo (STE) provide complementary information on the myocardial function which allows for providing a more integrated assessment of clinical status and outcomes. Purpose We hypothesize adverse outcomes in patients with heart failure (HF) who have expansion of TBV, right ventricular (RV) and renal dysfunction. Methods This is a prospective study and a total of 66 participants NYHA class III&IV with chronic HF are enrolled from 2014-2022. TBV, right heart catheterization, TTE, TEE, and kidney function tests is performed. STE is calculated using TomTec software for all heart chambers. Patients is divided into 1-st group of the total participants, 2-nd group is patients adverse outcomes which are heart transplant (HT) or death, 3rd group is of alive patients. Simple, multivariable linear regression analyses is used to evaluate associations between TBV, cardiac and renal function. Statistical analyses is performed using JMP, BlueSky, and two-sided with P-values &lt;0.05 considered to be statistically. Results Of 66 patients, the 1-st group has 66 patients, the 2nd group has 44 patients out of which deceased are 32 patients (48.4%), HT has 12 patients (18.1%), and the 3rd group has 22 patients (33.3%). In the 2nd group, out of the 44 patients, 35 (79.5%) patients have HFrEF, and 9 (20.4%) patients presented HFpEF. In the 3rd group out of 22 patients, 15 (68.2%) have HFrEF, and 7 (31.8%) patients have HFpEF. RV dimensions are significantly related to TBV in all groups of participants (Table 1). In the total patients, TBV is directly correlated to a moderate degree with EDSRV (r = 0.51, P &lt; 0.001), ESSRV (r = 0.44, P &lt; 0.001) and FAC (r = 0.40, P &lt; 0.001). More significant moderate and strong relationships are observed in patients with adverse outcome between TVB and EDSRV (r = 0.54, P &lt; 0.001), ESSRV (r = 0.65, P &lt; 0.001) and FAC (r = 0.48, P &lt; 0.001). In group 1, weak and direct association of TBV and RV GLS, FW LS, FW LSR, and RA reservoir strain. In the 2nd group, TBV directly correlated to a moderate degree with FW LS (r = 0.41, P = 0.005) and FW LSR (r = 0.43, P = 0.002). Similar relationships in the 2nd group are observed between TBV and renal function parameters (TBV and eGFR (r = 0.53, P &lt; 0.001)). The direct and weak correlation obtained between TBV and BUN in both 1st and 2nd groups. In patients with adverse outcomes, TBV is directly proportional to LV Diastolic BP. Conclusion The association among intravascular volume and parameters of RV dilatation, myocardial and renal dysfunction in patients with chronic HF is associated with adverse outcomes. Understanding the impact of all these variables guide optimal and effective individualized HF management and 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.