Egbe, Alexander C.

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.

Background: The purpose of this study was to assess the role of echocardiography for a comprehensive assessment of cardiac remodeling, and the relationship between indices of cardiac remodeling and cardiovascular events (defined as the composite end point of heart failure hospitalization, heart transplant, or cardiovascular death) in adults with congenitally corrected transposition of great arteries (cc-TGA). Methods: This is a retrospective study of adults with cc-TGA who underwent echocardiogram (2003–2020). Offline image analysis was performed in all patients. Chamber (atrial and ventricular) function and size were assessed by strain imaging and 2-dimensional echocardiography. Results: Of 233 patients with cc-TGA (40±15 years), 123 (55%) had at least one cardiac procedure before baseline echocardiogram. Of 233 patients, 76% and 61% had left atrial dysfunction and systemic right ventricular dysfunction, respectively; while 43% and 11% had right atrial dysfunction and left ventricular dysfunction, respectively. During a median follow-up of 8.9 years, 114 (49%) underwent additional cardiac procedures, and 66 (28%) had cardiovascular events. Left atrial reservoir strain, right ventricular global longitudinal strain, right atrial reservoir strain, left ventricular systolic pressure, and left ventricular global longitudinal strain were independently associated with cardiovascular events. Conclusions: In addition to the clinical importance of right ventricular systolic dysfunction in cc-TGA that is already well described, the current study demonstrated, for the first time, that biatrial dysfunction was common and was associated with clinical outcomes. Since there are currently no effective therapies for atrial and ventricular dysfunction in patients with cc-TGA, there is a need for research to identify novel strategies to prevent atrial and ventricular dysfunction in this population.

Background: Valvulo-arterial impedance (Zva) is used for assessment of left ventricular (LV) global pressure load in patients with aortic stenosis (AS) and impaired arterial compliance. Because patients with repaired coarctation of aorta (COA) have impaired arterial compliance, we hypothesized that COA patients with greater than or equal to 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: Propensity matching (1:1) of 71 AS-COA and 71 AS patients based on age, sex, body mass index, and aortic valve mean gradient (cohort 1). Of 172 patients, 117 patients (AS-COA [n=62]; AS [n=55]) underwent aortic valve replacement, cohort 2. Cohort 1 was used to assess the relationship between preoperative Zva, cardiac remodeling, and symptomatic progression, while cohort 2 was used to assess the relationship between postoperative Zva, LV mass index regression (reduction in LV mass index after aortic valve replacement), and cardiovascular events. Results: The AS-COA group had higher Zva (4.2±0.6 versus 3.5±0.4 mm Hg/mL·m 2 , P <0.001), more advanced cardiac remodeling, and higher 5-year incidence of symptomatic progression (85% versus 51%, P <0.001). Preoperative Zva was independently associated with cardiac remodeling (r=0.66, P <0.001) and symptomatic progression (hazard ratio, 1.06 [1.02–1.10], per mm Hg/mL·m 2 increase in Zva). The AS-COA group had higher postoperative Zva (3.3±0.5 versus 2.4±0.4 mm Hg/mL·m 2 , P <0.001), less robust LV mass index regression at 1-year post–aortic valve replacement, and higher 5-year incidence of cardiovascular events. Postoperative Zva was independently associated with LV mass index regression (r=−0.46, P <0.001) and cardiovascular events (hazard ratio, 1.06 [1.02–1.10], per mm Hg/mL·m 2 increase in Zva). Conclusions: Adults with AS-COA 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 aortic valve replacement.

Abstract Aims Conotruncal anomalies share common embryogenic defects of the outflow tracts and great arteries, which result in a predisposition to aortic aneurysms. The purpose of this study was to describe the prevalence and risk of progressive aortic aneurysms in adults with conotruncal anomalies. Methods and results Retrospective study of adults with conotruncal anomalies that underwent cross-sectional imaging 2003–20. Aneurysm was defined as aortic root/mid-ascending aorta &gt;2.1 mm/m2/&gt;1.9 mm/m2, progressive aneurysm as increase by &gt;2 mm, and severe aneurysm as dimension &gt;50 mm. Of 2261 patients (38 ± 12 years; male 58%), 1167 (52%) had an aortic aneurysm, and 205 (14%) had a severe aortic aneurysm. Mean annual increase in aortic root/mid-ascending aorta was 0.3 ± 0.1 mm/0.2 ± 0.1 mm. The 3-, 5-, and 7-year cumulative incidence of the progressive aortic aneurysm was 4%, 7%, and 9%, respectively. The rate of aneurysm growth decreased with age, with no significant growth after age 40 years. There was an excellent correlation between aortic indices from cross-sectional imaging and echocardiography. Of 950 females, 184 had ≥1 pregnancy, and 81 (44%) of the 184 patients had aortic aneurysm prior to pregnancy. There was no aortic dissection or progression of the aortic aneurysm during pregnancy. Overall, there was no aortic dissection during 7984 patient-years of follow-up. Conclusions Aortic aneurysm was common in patients with conotruncal anomalies. However, the risk of progressive aneurysm or dissection was low. Collectively, these data suggest a benign natural history and perhaps a less frequent need for cross-sectional imaging. Further studies are required to determine the optimal timing for surgical intervention in this population.

Background: 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, 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 coarctation of aorta and to determine the relationship between right heart indices and cardiovascular events defined as heart failure hospitalization, heart transplant, or cardiovascular death. Methods: Right heart structure, function, and hemodynamics were assessed with these indices: right atrial volume, right atrial pressure, right atrial reservoir strain, right ventricular global longitudinal strain, right ventricular end-diastolic area, right ventricular systolic pressure, and tricuspid regurgitation severity. Right heart hemodynamic score, range 0 to 5, was generated based on the correlation between the right heart indices and cardiovascular events, using half of the cohort (derivation cohort, n=411), and then tested on the validation cohort (n=410). The goodness of fit and discrimination power was compared using C statistics and risk score. Results: The median follow-up in the derivation cohort was 8.2 (4.0–11.1) years, and 59 (14%) patients had cardiovascular events during this period. Right heart hemodynamic score was independently associated with cardiovascular events (hazard ratio, 1.64 [95% CI, 1.38–2.17]) for every unit increase in right heart hemodynamic score after adjustment for clinical and echocardiographic indices (C statistic, 0.718 [95% CI, 0.682–0.746]). The right heart hemodynamic score was also independently associated with cardiovascular events in the validation cohort (C statistic, 0.711 [95% CI, 0.679–0.741]). The C statistic difference (0.007 [95% CI, 0.014–0.022]) and risk score (0.86 [95% CI, 0.54–1.17]) suggest a good model fit. Conclusions: The current study underscores the prognostic importance of right heart dysfunction in patients with coarctation of aorta and suggests that right heart indices should be used for risks stratification in this population.

Background: We sought to investigate temporal trends in patient characteristics, waitlist, and posttransplant outcomes after heart transplantation in the United States. Methods: Using data from the United Network of Organ Sharing, we identified adults listed for heart transplantation between 1991 and 2019. Patients were divided into 4 eras based on the 3 time points in which changes were made to the patient selection/allocation policy (Era 1=January 1991–January 1999; Era 2=January 1999–July 2006; Era 3=July 2006–October 2018; and Era 4=October 2018–March 2020), and patient characteristics, waitlist, and posttransplant outcomes were evaluated for each era. Results: Between 1991 and 2019, 95 179 patients were added to the heart transplantation waitlist. Compared with Era 1, patients listed in Era 4 were older (mean age: 50 versus 52 years) and with higher risk comorbidities (eg, 10% versus 28.8% diabetes, 23.3% versus 35.6% obese). Over the study period, 22 738 patients died or were permanently delisted for deterioration on the waitlist while 61 687 were transplanted. Compared with the preceding era, there was significant decrease in death or deterioration in the last 2 eras (sub-hazard ratio, 0.67 [95% CI, 0.65–0.70] for Era 3 versus Era 2 and sub-hazard ratio, 0.65 [95% CI, 0.58–0.73] for Era 4 versus 3). Across the years, 27.1% to 40.5% of those on the waitlist were transplanted. Among those transplanted, there was increase in the rates of in-hospital stroke (2.8% in Era 1 to 3.7% in Era 4), renal failure requiring dialysis (7.2%–17.1%), and length-of-stay (14–17days), P <0.001. However, this did not negatively impact short-term survival when compared with the preceding era (1-year graft survival from Era 1 to Era 4=84.1%, 86.4%, 90.4%, and 89.7%, respectively). Conclusions: There have been significant changes in the characteristics of patients listed for heart transplantation. Although transplant volume has increased, the wide supply-demand gap persisted. The last two changes in the allocation policy achieved their primary objective of reducing waitlist mortality.

Abstract Background The relationship between office vs ambulatory blood pressure (BP) indices is well-studied in patients with idiopathic hypertension, and based on these data, it is known that average 24-hour ambulatory BP is typically lower than office BP. However, emerging data show that office systolic BP (SBP) underestimates arterial afterload in patients with coarctation of aorta (COA), and minimal increase in stroke volume during low intensity exercise results in exaggerated rise in SBP as compared to those with idiopathic hypertension. We hypothesized that COA patients will have higher ambulatory SBP and a higher prevalence of masked hypertension compared to patients with idiopathic hypertension. Methods Case-control study of 118 COA patients and 118 patients with idiopathic hypertension matched by age, sex, body mass index and office SBP. Results Although both groups had similar office SBP (132±17 mmHg) by design, the COA group had paradoxical increases in 24-hour ambulatory SBP (135±14 vs 126±13, p&lt;0.001) and daytime ambulatory SBP (142±16 vs 130±13, p&lt;0.001), and less nocturnal dipping (−3±5 vs −9±4, p&lt;0.001). The COA group also had a higher prevalence of masked hypertension (36 [31%] vs 14 [12%], p&lt;0.001), and worse arterial function indices. Conclusion These findings underscore the potential limitations of relying on office SBP for screening/monitoring of hypertension in COA and potential pitfalls in extrapolating idiopathic hypertension guidelines recommendations to the treatment of COA. It also provides rationale for further studies to determine if pharmacologic BP interventions guided by ambulatory BP data will improve clinical outcomes in the COA population. Funding Acknowledgement Type of funding sources: None.

Abstract Background Left atrial dysfunction (LAD) and left ventricular diastolic dysfunction (LVDD) has been described in patients with coarctation of aorta (COA). However, it is unknown whether LA function and LV diastolic function indices can be used for prognostication in this population. The purpose of this study was to determine whether LAD and LVDD were associated with mortality in adults with COA. We hypothesized that LA and LV diastolic function indices will predict transplant-free survival in COA patients. Methods Retrospective study of COA patients (age ≥18) at Mayo Clinic (2000–2018). LVDD was determined using the 2016 guidelines for LVDD assessment, and LAD was assessed using LA reservoir strain. Results Of 721 patients, LV diastolic function could be determined in 635 (88%), while 86 (12%) were classified as indeterminate diastolic function. Of 635 patients, 414 (65%) had no LVDD, while 146 (23%), 53 (8%), and 22 (4%) had grade I/II/III LVDD respectively. The mean LA reservoir strain was −39±11%, and patients were divided into quartiles: top quartile (reference group), mild LAD, moderate LAD, and severe LAD. Of 635 patients, 49 died and 4 underwent heart transplant. On multivariate analysis, Grade III diastolic dysfunction (but not Grade I and II) was associated with mortality as compared to normal diastolic function. On the other hand, there was an incremental risk of mortality across LA strain quartiles: mild LAD (HR 1.16, 1.04–2.06), moderate LAD (HR 1.75, 1.27–3.58), and severe LAD (HR 3.49, 1.88–7.16). Of the 86 patients with indeterminate diastolic function, LAD was associated with a lower 5-year transplant-free survival as compared to normal LA function (83% vs 91%, p=0.06). Conclusions LAD (but not LVDD) was associated with incremental risk of mortality, and thus can be used for prognostication in all patients including those with indeterminate diastolic function. Although the current study did not identify a consistent relationship between LVDD severity classifications and mortality among COA patients, it does not imply that LVDD is benign. Rather it suggests that the conventional criteria for LVDD severity classifications may not be generalizable to every disease subgroup Funding Acknowledgement Type of funding sources: None.