Egbe, Alexander C.

Background: Left ventricular global longitudinal strain (LVGLS) can detect early phases of LV systolic dysfunction, but its application has not been studied in Ebstein anomaly. We hypothesized that LVGLS can detect early phases of LV systolic dysfunction and that patients with occult LV systolic dysfunction will have worse hemodynamics, end-organ dysfunction, and suboptimal postoperative LV reverse remodeling after tricuspid valve surgery in comparison to patients with normal LV systolic function. Methods: In this retrospective cohort study, 371 Ebstein patients that underwent tricuspid valve surgery were divided into 3 groups: normal LV systolic function (normal LVGLS and LV ejection fraction; n=244, 77%), occult LV systolic dysfunction (abnormal LVGLS with normal LV ejection fraction; n=44, 14%), and overt LV systolic dysfunction (abnormal LVGLS and LV ejection fraction; n=27, 9%). Results: Compared with the normal LV function group, the occult group had smaller LV volume and cardiac output (2.1±0.4 versus 2.9±0.6 L/min per m 2 , P <0.001), worse end-organ dysfunction (glomerular filtration rate, 78±14 versus 91±18 mL/min per 1.73 m 2 , P =0.01), and suboptimal postoperative LV reverse remodeling. Although both the occult and overt groups had a similar degree of end-organ dysfunction (glomerular filtration rate, 78±14 versus 82±16 mL/min per 1.73 m 2 , P =0.3), the occult group was less likely to be on heart failure therapy (48% versus 96%, P <0.001). Conclusions: Abnormal LVGLS was associated with suboptimal postoperative LV reverse remodeling. These data suggest that LVGLS can potentially be used for risk stratification and provides a foundation for further studies to determine whether optimal heart failure therapy or tricuspid valve intervention can improve outcomes for LV systolic dysfunction in patients with Ebstein anomaly.

Abstract Background Several coarctation of aorta (COA) severity indices are used for timing of COA intervention, and to define severity of residual coarctation post-intervention. However, it is unclear how many of these COA indices are required in order to recommend intervention, and what degree of residual coarctation results in suboptimal recovery of the left ventricle (LV). Our aim was to assess the correlation between different COA indices and effects of chronic LV pressure overload (LV hypertrophy, diastolic and systolic dysfunction), and to determine the effect of residual coarctation on LV reverse remodeling after COA intervention. Methods COA severity indices were defined as Doppler COA gradient, systolic blood pressure, upper-to-lower-extremity systolic blood pressure gradient, aortic isthmus ratio. LV remodeling indices were defined as LV mass index (LVMI), LV global longitudinal strain (LVGLS), e' and E/e'. LV reverse remodeling was defined as the difference between indices obtained pre-intervention and 5-years post-intervention (delta LVMI, e', E/e', LVGLS). Results Of the COA indices analyzed in 546 adult COA patients, aortic isthmus ratio had the strongest correlation with LVMI (β±standard error −28.3±14.1, p&lt;0.001), LVGLS (1.51±0.42, p=0.005), e' (3.11±1.10, p=0.014), and E/e' (−13.4±6.67, p=0.008). Residual aortic isthmus ratio also had the strongest correlation with LV reverse remodeling, and residual aortic isthmus ratio &lt;0.7 was predictive of suboptimal LV reverse remodeling post-intervention. Conclusion Considering the known prognostic implications of LV remodeling and reverse remodeling in response to pressure overload, these results support the use of aortic isthmus ratio for timing of COA intervention, and for prognostication post-intervention. Funding Acknowledgement Type of funding source: None

Abstract Background Left ventricular (LV) pressure overload and coronary artery disease, both of which are common in patients with coarctation of aorta (COA), are risk factors for LV diastolic dysfunction. Patients with COA may have aortic vasculopathy that can result in LV pressure overload even in the absence of hemodynamically significant COA. We therefore hypothesized that patients with COA (without hemodynamically significant COA) will have more LV diastolic dysfunction compared to controls. Methods Adult patients with COA (OA peak velocity &lt;2 m/s) were matched 1:1 to patients without structural heart disease using propensity score method based on age, sex, body mass index, hypertension and blood pressure. The objective was to compare LV diastolic dysfunction (defined as E/e&gt;2 standard deviations above age-specific normative values) between COA patients and controls. Results Of 204 COA and 204 control patients (age 35±12 years), COA patients had higher septal and lateral E/e' ratio (12±4 vs 9±4, p=0.009) and (10±3 vs 7±3, p&lt;0.001), respectively. Compared to controls, the prevalence of LV diastolic dysfunction was higher in COA patients for every age group: &lt;40 years (63% vs 13%, p&lt;0.001); 41–60 years (87% vs 33%, p&lt;0.001); age &gt;60 years (82% vs 56%, p=0.076). Left ventricular mass index (LVMI) was the strongest determinant of E/e' (β=2.71 per 10 g/m2, standard error = 1.25, p&lt;0.001). Conclusion LV diastolic dysfunction was common in COA patients, and the association with LVMI suggests that COA patients may have ongoing LV pressure overload in the absence of hemodynamically significant re-coarctation. Funding Acknowledgement Type of funding source: None

Abstract Background Transcatheter stent therapy is as effective as surgery in producing acute hemodynamic improvement in patients with coarctation of aorta (COA). However, left ventricular (LV) remodeling after transcatheter COA intervention has not been systematically investigated. The purpose of this study was to compare remodeling of LV structure and function after transcatheter stent therapy vs surgical therapy for COA. Methods LV remodeling was assessed at 1, 3 and 5-years post-intervention using: LV mass index (LVMI), LV end-diastolic dimension, LV ejection fraction, LV global longitudinal strain (LVGLS), LV e' and E/e'. Results There were 44 and 128 patients in the transcatheter and surgical groups respectively. Compared to the surgical group, the transcatheter group had less regression of LVMI (−4.6 [95% CI: −5.5 to −3.7] vs −7.3 [95% CI: −8.4 to −6.6] g/m2, p&lt;0.001), less improvement in LVGLS (2.1 [95% CI 1.8–2.4] vs 2.9 [95% CI: 2.6–3.2]%, p=0.024) and e' (1.0 [95% CI: 0.7–1.2] vs 1.5 [95% CI: 1.3–1.7] cm/s, p=0.009) at 5 years post-intervention. Exploratory analysis showed a correlation between change in LVMI and LVGLS, and between change in LVMI and e', and this correlations were independent of the type of intervention received. Conclusions Transcatheter stent therapy was associated with less remodeling of LV structure and function during mid-term follow-up. As transcatheter stent therapy become more widely used in the adult COA population, there is a need for ongoing clinical monitoring to determine if these observed differences in LV remodeling translates to differences in clinical outcomes. Funding Acknowledgement Type of funding source: None

Abstract Background Ambulatory blood pressure monitoring (ABPM) is more sensitive than resting BP assessment in detecting hypertension in patients with coarctation of aorta (COA). However, it is not known whether ABPM provides a better measure of left ventricular (LV) pressure load and LV remodeling as compared to resting BP. LV pressure overload is the lynchpin in the pathogenesis of cardiovascular mortality in COA patients, because it leads to LV remodeling, LV dysfunction and heart failure, which sets-the-stage for cardiovascular death. Therefore identifying a sensitive clinical metric that reflects LV pressure load and LV remodeling, is an important step towards optimizing antihypertensive therapy to prevent LV dysfunction and mortality. We hypothesized that ambulatory systolic BP (SBP) has better correlation with arterial load and LV remodeling indices as compared to resting SBP. Methods Our study cohort comprised of adults with isolated COA without significant residual coarctation (Doppler peak velocity ≤2.5 m/sec), aortic or mitral valve disease. All patients underwent BP measurement at rest, followed by ABPM. Arterial load (LV pressure load) was assessed using Doppler-derived effective arterial elastance index (EAI). LV remodeling was assessed using: LV mass index (LVMI), and E/e'. We divided the cohorts into 4 categories (normotensive, masked, white-coat, and overt hypertension). Results Of the 106 patients (male 69 [65%); age 39±11 years), 98 (93%) had prior COA intervention at 6±5 years. Resting SBP was 132±17, daytime ambulatory SBP was 142±16, and nighttime ambulatory SBP was 128±12 mmHg. The mean arterial load and LV remodeling indices were: EAI 3.4±0.8 mmHg/ml·m2, LVMI 106±21 g/m2, and E/e'11±4. Compared to resting SBP, ambulatory SBP had better correlation with EAI, LVMI, and E/e'. EAI, LVMI and E/e' were significantly different between hypertension categories (Figure 1). Conclusions In this study, we demonstrated that ambulatory SBP had better correlations with arterial load and LV remodeling indices as compared to resting SBP. This suggests that ambulatory SBP was a more robust metric of LV pressure overload and remodeling, and can improve detection of vascular stiffness, LV hypertrophy and elevated LV filling pressure as compared to resting SBP. The results of the current study have important clinical implications with regards to initiation and titration of antihypertensive therapy. If ABPM is used as the gold standard for diagnosis of hypertension, the masked hypertension group (who would have been misclassified as normotensive based on resting SBP alone) will qualify for antihypertensive therapy. Additionally, since ambulatory SBP had better correlation with LV remodeling indices, perhaps titration of antihypertensive therapy using ABPM will potentially reduce the risk of LV hypertrophy and dysfunction due to hypertension. Figure 1 Funding Acknowledgement Type of funding source: None

Abstract Background Ambulatory systolic blood pressure (SBP) is more sensitive than resting-SBP in detecting hypertension in patients with coarctation of aorta (COA) and patients with idiopathic hypertension. A recent study showed that compared to patients with idiopathic hypertension with similar resting-SBP, COA patients had lower arterial compliance, and hence experienced higher SBP per unit increase in stroke volume during exercise. The purpose of this study was to compare resting vs ambulatory-SBP relationship between COA patients and non-COA patients (with and without hypertension), and to determine if ambulatory-SBP had better correlation with left ventricular (LV) remodeling as compared to resting-SBP. Methods Case-control study of 106 COA patients and 106 patients with idiopathic hypertension (ControlHTN+ group) matched by age, sex, body mass index and resting-SBP. Resting/ambulatory BP relationship in COA patients and patients with idiopathic hypertension were also compared to that of 19 patients without hypertension (ControlHTN- group). LV remodeling was assessed using LV mass index, e', and E/e'. Results Although the COA and ControlHTN+ groups had similar resting-SBP (by design), the COA group had a higher ambulatory-SBP and a higher prevalence of masked hypertension (30% vs 12%, p&lt;0.001). There was a stronger correlation between ambulatory-SBP (as compared to resting-SBP) and LVMI (r=0.36 vs r=0.55, p=0.042), and average E/e' (r=0.42 vs r=0.59, p=0.046), in the COA group but not the ControlHTN+ group. There was no difference in the resting/ambulatory BP relationship between ControlHTN+ and ControlHTN- groups, but both groups were significantly different from the COA group. Conclusion These results highlight the unique differences in disease pathophysiology between hypertension in patients with COA and those with idiopathic hypertension, and also suggest that ambulatory-SBP may be a more accurate measure of LV pressure overload in COA patients. This underscores the potential limitations of relying on resting-SBP alone for clinical decision making. Funding Acknowledgement Type of funding source: None

Background Although tricuspid valve surgery improves functional capacity in patients with Ebstein anomaly, it is not always associated with improvement in aerobic capacity. The purpose of this study was to identify the determinants of improved aerobic capacity after tricuspid valve surgery in adults with Ebstein anomaly with severe tricuspid regurgitation. Methods Retrospective study of patients with severe tricuspid regurgitation due to Ebstein anomaly that had tricuspid valve surgery at Mayo Clinic Rochester (2000–2019) and had preoperative and postoperative cardiopulmonary exercise tests and echocardiograms. The patients were divided into aerobic capacity(+) and aerobic capacity(-) groups depending on whether they had postoperative improvement in %-predicted peak oxygen consumption (VO2). Results Of 76 patients with severe tricuspid regurgitation due to Ebstein anomaly, 28 (37%) and 48 (63%) were in aerobic capacity(+) and aerobic capacity(-) groups, respectively. The average improvement in peak VO2 was 2.1±1.4 mL/kg/min and −0.9±0.4 mL/kg/min in the in aerobic capacity(+) and aerobic capacity(-) groups, respectively. Although both groups had similar severity of residual tricuspid regurgitation, the aerobic capacity(+) group had more postoperative improvement in right atrial (RA) function, left atrial (LA) function and left ventricular preload and stroke volume. Of the preoperative variables analysed, RA reservoir strain (relative risk 1.12; 95% CI 1.06 to 1.18); LA reservoir strain (relative risk 1.09; 95% CI 1.04 to 1.14) and LV stroke volume index (OR 1.04; 95% CI 1.01 to 1.07) were predictors of postoperative improvement in peak VO2. Conclusions One-third of patients with severe tricuspid regurgitation due to Ebstein anomaly had postoperative improvement in aerobic capacity, and atrial function indices were the best predictors of postoperative improvement in aerobic capacity. These data provide new insight into the haemodynamic determinants of exercise capacity and lay the foundation for further studies to determine whether postoperative improvement in aerobic capacity translates to improved long-term survival, and whether timing of tricuspid valve surgery based on these echocardiographic indices will improve long-term outcomes.

Objective To assess the prevalence of elevated systemic right ventricular (sRV) end-diastolic pressure and pulmonary arterial hypertension in adults with transposition of the great arteries (TGA) who have undergone atrial switch operation. Methods Forty-two adults (aged ≥18 years) with complete TGA and atrial switch palliation undergoing cardiac catheterisation between 2004 and 2018 at Mayo Clinic, MN, were identified. Clinical, echocardiographic and invasive haemodynamic data were abstracted from the medical charts and procedure logs. Results Mean age was 37.6±7.9 years; 28 were male (67%). The Mustard operation was performed in 91% of individuals. Mean estimated sRV ejection fraction by echocardiography was 33.3%±10.9% and ≥moderate tricuspid (systemic atrioventricular valve) regurgitation was present in 15 patients (36%). Mean sRV end-diastolic pressure was 13.2±5.4 mm Hg. An sRV end-diastolic pressure >15 mm Hg was present in 35% of individuals whereas a pulmonary artery wedge pressure (PAWP) >15 mm Hg was seen in 59%. Mean pulmonary artery pressure ≥25 mm Hg was seen in 47.5% of patients with PAWP being >15 mm Hg in all but one patient. Conclusion In adults after atrial switch, elevated sRV end-diastolic pressure was present in only one-third of patients whereas increased PAWP was seen in almost 60%. These findings are most likely related to a combination of decreased pulmonary atrial (functional left atrium) compliance and, in a subset of patients, pulmonary venous baffle obstruction. Elevation in pulmonary pressures was highly prevalent with concomitant elevation in PAWP being present in essentially all patients.

Abstract Aims Several coarctation of aorta (COA) severity indices are used for timing of COA intervention, and to define severity of residual coarctation post-intervention. However, it is unclear how many of these COA indices are required in order to recommend intervention, and what degree of residual coarctation results in suboptimal recovery of the left ventricle (LV). Our aim was to assess the correlation between different COA indices and effects of chronic LV pressure overload (LV hypertrophy, diastolic, and systolic dysfunction), and to determine the effect of residual coarctation on LV reverse remodelling after COA intervention. Methods and results COA severity indices were defined as Doppler COA gradient, systolic blood pressure (SBP, upper-to-lower-extremity SBP gradient, aortic isthmus ratio. LV remodelling indices were defined as LV mass index (LVMI), LV global longitudinal strain (LVGLS), e′ and E/e′. LV reverse remodelling was defined as the difference between indices obtained pre-intervention and 5-year post-intervention (delta LVMI, e′, E/e′, LVGLS). Of the COA indices analysed in 546 adult COA patients, aortic isthmus ratio had the strongest correlation with LVMI (β ± standard error −28.3 ± 14.1, P &lt; 0.001), LVGLS (1.51 ± 0.42, P = 0.005), e′ (3.11 ± 1.10, P = 0.014), and E/e′ (−13.4 ± 6.67, P = 0.008). Residual aortic isthmus ratio also had the strongest correlation with LV reverse remodelling, and residual aortic isthmus ratio &lt;0.7 was predictive of suboptimal LV reverse remodelling post-intervention. Conclusion Considering the known prognostic implications of LV remodelling and reverse remodelling in response to pressure overload, these results support the use of aortic isthmus ratio for timing of COA intervention, and for prognostication post-intervention.