Citations

Objectives Women with Turner syndrome (TS) are frequently counselled against pregnancy due to lack of data and unclear aortic dissection risk. However, with advances in fertility therapy, more women with TS are contemplating pregnancy. This study compared rates of adverse cardiovascular (CV) outcomes among: (1) pregnant and non-pregnant women with TS and (2) pregnant women with TS with/without structural heart disease. Methods Retrospective analysis of pregnant and age-matched non-pregnant controls with TS (2005–2017) across 10 CV centres was done. Data were collected at initial evaluation in pregnancy and outcomes were assessed to 6 months postpartum. Adverse CV events were defined as CV death, aortic dissection/rupture and/or aortic intervention. Non-pregnant age-matched controls were followed over the same time period. Results Sixty-eight pregnancies were included (60 women, mean age 33 years, 48% primigravid, 49% fertility therapy, 80% structurally normal heart, 25% XO karyotype). Based on American Society of Reproductive Medicine criteria, 10 pregnancies occurred in women stratified to high-risk category. There were no CV events in the pregnant women or in the non-pregnant women with TS. Obstetric events complicated 12 (18%) pregnancies with 9 (13%) attributed to hypertensive disorder of pregnancy. Fetal events included small for gestational age neonates (18%), preterm delivery (15%) and fetal death (3%). Conclusions This study helps to refine the approach to pregnancy in women with TS. Among women with TS without structural heart disease, pregnancy does not impose an increased risk of CV outcomes. Among women with TS with structural heart disease, the risk of pregnancy is not as prohibitive as previously described but does require ongoing evaluation.

Abstract Aims Right atrial pressure (RAP) provides a composite measure of right ventricular diastolic dysfunction, right atrial compliance, and volume status, and these three variables are typically abnormal in adults with repaired tetralogy of Fallot (TOF). RAP is a well-established prognostic metric in patients with pulmonary hypertension, and recent data suggest that RAP is associated with clinical outcomes in TOF. The purpose of this study was to determine the role of inferior vena cava (IVC) haemodynamics (size and collapsibility) for the assessment of RAP and its potential application for risk stratification and prognostication in the TOF population. Methods and results Adult TOF patients with echocardiographic assessment of IVC haemodynamics were divided into patients with (derivation cohort, n = 256) and without (validation cohort, n = 492) cardiac catheterization data. We assessed the correlation between IVC haemodynamics, RAP, and disease severity indices [arrhythmias, peak oxygen consumption (VO2), and heart failure hospitalization] in derivation cohort and compared it with the correlations in the validation cohort. IVC haemodynamics correlated with RAP (r = 0.52, P < 0.001), with disease severity indices {atrial arrhythmias [area under the curve (AUC) 0.81], ventricular arrhythmias [AUC 0.67], heart failure hospitalizations [AUC 0.78], and peak VO2 [r = 0.53]}, and with transplant-free survival in the derivation cohort. Similar correlations between IVC haemodynamics, disease severity indices, and transplant-free survival were also observed in the validation cohort. Conclusions These findings suggest that IVC haemodynamics can potentially be used for risk stratification and prognostication in TOF patients and can complement the current risk models that are based predominately on right ventricular volumes and systolic function.

Background: Coarctation of aorta (COA) results in chronic left ventricular (LV) pressure overload and subsequently leads to LV diastolic dysfunction and heart failure over time. The goal of COA intervention is to prevent these complications. The timing of COA interventions is based on the presence of these COA severity indices: doppler mean COA gradient, systolic blood pressure, upper-to-lower-extremity SBP gradient, aortic isthmus ratio, presence of collaterals, and exercise-induced hypertension. Although these indices are physiologically intuitive, the relationship between these indices and LV diastolic dysfunction and exertional symptoms has not been studied. The purpose of this study was to evaluate the association between the indices of COA severity and LV diastolic function and symptoms. Methods: In this cross-sectional study, multivariate linear and logistic regression analyses were used to assess the correlation between indices of COA severity, LV diastolic function (average e’ and E/e’), and exertional symptoms (NYHA II–IV and peak oxygen consumption). Results: Of all the COA indices analyzed in 546 adult COA patients, aortic isthmus ratio had the strongest correlation with e’ (β [95% CI]: 3.11 [2.02–4.31]; P =0.014) per 1 cm/second; E/e’ (−13.4 [−22.3 to −4.81]; P =0.009) per 1 unit; peak oxygen consumption (4.05 [1.97–6.59] per 1% change, P =0.019), and NYHA II to IV symptoms (odds ratio, 2.16 [1.65–3.18]; P =0.006). Conclusions: Of all the COA severity indices stipulated in the guidelines, aortic isthmus ratio had the strongest correlation with LV diastolic function and exertional symptoms. As LV diastolic dysfunction typically precede heart failure symptoms, we anticipate that the results of this study will improve and simplify patient selection for COA intervention and potentially improve long-term outcomes.

Background: Patients with vascular stiffening may display increased arterial afterload that is out of proportion to systolic blood pressure (SBP). Since vascular and endothelial dysfunction develop in patients with coarctation of aorta (COA), we hypothesized that for any SBP, patients with mild COA (COA peak velocity <2 m/s) will have a higher arterial afterload and increased left ventricular mass index (LVMI) compared with controls, and that Doppler-derived arterial load indices would be a better predictor of LVMI compared with SBP alone. Methods: We studied 204 COA patients (age 35±12 y) and 204 matched controls. Doppler-derived arterial afterload was assessed using effective arterial elastance index and total arterial compliance index. Results: Despite similar SBP, the mild COA group displayed higher arterial afterload as evidenced by a higher elastance index (3.3±0.9 versus 2.9±0.7 mm Hg/mL·m 2 ; P <0.001) and lower total arterial compliance index (0.8±0.3 versus 1.2±0.5 mL/mm Hg·m 2 ; P <0.001). This was associated with higher LVMI in COA (109±35 versus 93±32, g/m 2 ; P <0.001). Compared with SBP (β=0.24 [95% CI, 0.02–0.45]), elastance index (β=20.2 [95% CI, 15.8–44.1]) and total arterial compliance index (β=−32.5 [95% CI, −43.8 to −123.6]) were better predictors of LVMI. Elastance index (but not SBP) was predictive of longitudinal increases in LVMI ( r =0.43, P <0.001). Conclusions: COA patients had higher arterial afterload compared with controls with similar SBP. In comparison to SBP, Doppler-derived arterial load indices correlate more strongly with LV hypertrophy. These data suggest that SBP may underestimate LV afterload in this population. This has important clinical implications since titration of antihypertensive therapy is currently based on SBP.

ABSTRACT Aims Mild to moderate functional mitral regurgitation (MR) is common in patients with heart failure and preserved ejection fraction (HFpEF) where it is usually considered as an innocent bystander. We hypothesized that MR in HFpEF reflects greater left atrial (LA) myopathy, leading to more adverse haemodynamics and poorer exercise reserve. Methods and results Patients with HFpEF (n = 280) with and without MR underwent echocardiography, invasive haemodynamic exercise testing, and expired gas analysis. As compared to non-MR-HFpEF (n = 163), patients with MR-HFpEF (n = 117; 78 mild and 39 moderate, central jet in 90%) were older, more likely female, with lower body mass and higher prevalence of atrial fibrillation (AF). HFpEF patients with MR displayed greater LA volume, reduced LA strain and compliance, and greater mitral annular dilatation, which was strongly correlated with LA dilatation (r = 0.63, P &lt; 0.0001) but was only weakly related to left ventricular remodelling (r = 0.37). Patients with MR-HFpEF displayed worse biventricular function, more adverse pulmonary haemodynamics, impaired pulmonary vasodilatation, blunted right ventricular reserve, and reduced cardiac output with exercise as compared to non-MR-HFpEF. Importantly, these findings were maintained after excluding patients with HFpEF and AF, suggesting a role for LA myopathy in contributing to MR in HFpEF, independent of rhythm. Conclusions Functional MR in patients with HFpEF reflects LA myopathy, even in the absence of AF, and is associated with greater haemodynamic severity of disease and poorer functional capacity. Further study is required to better define causal mechanisms and potential treatments for MR and LA dysfunction in patients with HFpEF.

Background Right atrial pressure ( RAP ), a composite metric of right ventricular diastolic function, volume status, and right heart compliance, is a predictor of mortality in patients with heart failure due to acquired heart disease. Because patients with tetralogy of Fallot ( TOF ) might have abnormal right atrial and ventricular mechanics caused by myocardial injury and remodeling, we hypothesized that RAP would be associated with disease severity and cardiovascular adverse events in this population. Methods and Results We performed a cohort study of adults with TOF who underwent right heart catheterization at the Mayo Clinic Rochester between 1990 and 2017. The objective was to determine the association between RAP and multiple domains of disease severity in TOF (percentage of predicted peak oxygen consumption, atrial or ventricular arrhythmia, and heart failure hospitalization), as well as cardiovascular adverse events, defined as sustained ventricular tachycardia, resuscitated or aborted sudden death, heart transplantation, or death. Among 225 patients (113 male; mean age: 39±14 years), mean RAP was 10.7±5.2 mm Hg and median was 10 mm Hg (interquartile range: 7–13 mm Hg). Increasing RAP was associated with atrial or ventricular arrhythmias (odds ratio: 5.01; 95% CI, 1.22–23.49; P <0.001), heart failure hospitalization (odds ratio: 1.47; 95% CI, 1.10–2.39; P =0.033) per 5 mm Hg, and worsening exercise capacity (peak oxygen consumption; R 2 =0.74, r =−0.86, P <0.001). RAP was a predictor of cardiovascular adverse events (hazard ratio: 1.28; 95% CI, 1.10–1.47; P =0.028) per 5 mm Hg. Conclusions In symptomatic patients with TOF , increasing RAP correlates with multiple domains of disease severity (risk stratification) and predicts future cardiovascular events (prognostication). These data have potential clinical implications in the target population of symptomatic TOF patients.

Exercise-induced hypertension is a predictor of cardiovascular events in patients with coarctation of aorta (COA). However, it is unclear whether mild COA diagnosis is an independent risk factor of exercise-induced hypertension. We hypothesized that for every unit increase in exercise, patients with COA (without hemodynamically significant coarctation) will have a higher rise in systolic blood pressure (SBP) compared with matched controls. One hundred forty-nine patients with COA (aortic coarctation peak velocity <2 m/s) who underwent exercise testing were matched 1:1 to controls using propensity score method based on age, sex, body mass index, hypertension diagnosis, and SBP at rest. We compared exercise-induced change in SBP between patients with COA and controls and also assessed the correlation between Doppler-derived aortic vascular function indices (effective arterial elastance index and total arterial compliance index) and exercise-induced changes in SBP. Compared with controls, patients with COA had a greater change in SBP per unit metabolic equivalent (β=2.86; 95% CI, 1.96–4.77 versus 1.07, 95% CI, −0.15 to 1.75; P =0.018) and per unit oxygen pulse (β=4.57; 95% CI, 2.97–7.12 versus 1.45, 95% CI, −0.79 to 2.09, P <0.001). There was a correlation between SBP peak −SBP rest and elastance index ( r =0.38, P =0.032) and between SBP peak −SBP rest and total arterial compliance index ( r =−0.51, P =0.001), suggesting an association between vascular dysfunction and exercise-induced BP changes. Patients with COA, without significant obstruction, had higher exercise-induced changes in SBP after adjustment for other risk factors for hypertension. Considering the already known prognostic importance of exercise-induced hypertension, the current study highlights the potential role of exercise testing for risk stratification of patients with mild COA.

Abstract Background Mild to moderate mitral regurgitation (MR) is a common finding in heart failure with preserved ejection fraction (HFpEF). MR is often considered to be an innocent bystander, yet little data is available regarding its implications. Aim Determine the pathophysiologic correlates of MR in HFpEF Methods We retrospectively studied 280 patients with invasively proven HFpEF. MR was absent (None or trivial) in 163 subjects (Non-MR-HFpEF), and present in 117 (MR-HFpEF; 78 mild and 39 moderate MR). 247 subjects also underwent invasive cardiopulmonary exercise testing. Results At rest, MR-HFpEF subjects displayed higher pulmonary artery pressures (PAP), PCWP, and pulmonary vascular resistance (PVR; Table). During exercise, PAP and PCWP were not significantly different among groups, but MR-HFpEF displayed reduced ability to enhance cardiac output (CO) in response to heightened metabolic demand (oxygen consumption, VO2; Figure). Baseline characteristics and haemodynamic characterization at baseline and peak exercise Baseline characteristics Non-MR-HFpEF (N=163) MR-HFpEF (N=117) p value Age 66±11 71±10 0.0002 Female (%) 56 69 0.02 AFib (%) 13 38 <0.0001 Nt proBNP 192 [66, 557] 870 [401, 2135] <0.0001 E/E' 12.3±5.5 15.6±7.2 0.0006 LVEF (%) 64±6 62±6 0.0001 RV fractional area change (%) 51±9 47±10 0.0001 Mean PA (mmHg) 25±7 28±9 0.001 Mean PCWP (mmHg) 15±5 17±6 0.0002 PVR (Woods) 2.0±1.1 2.5±1.4 0.015 CO (L/min) 5.5±1.6 4.8±1.3 0.12 Peak exercise hemodynamics Non-MR-HFpEF (N=152) MR-HFpEF (N=95) p value Mean PA (mmHg 45±10 46.5±10 0.07 Mean PCWP (mmHg) 32±6 31±6 0.6 PVR (Woods) 1.8±1.6 2.7±2.4 0.002 CO (L/min) 9.1±3 7.2±3 0.01 P value adjusted for age, gender and BMI. CO change in response to VO2 increase Conclusion The presence of even mild MR in HFpEF is associated with more adverse hemodynamics, greater pulmonary vascular dysfunction and impaired CO reserve with exercise. Further study is required to better understand the natural history and treatment for MR in HFpEF. Acknowledgement/Funding None

Abstract Aims Increases in extravascular lung water (EVLW) during exercise contribute to symptoms, morbidity, and mortality in patients with heart failure and preserved ejection fraction (HFpEF), but the mechanisms leading to pulmonary congestion during exercise are not well-understood. Methods and results Compensated, ambulatory patients with HFpEF (n = 61) underwent invasive haemodynamic exercise testing using high-fidelity micromanometers with simultaneous lung ultrasound, echocardiography, and expired gas analysis at rest and during submaximal exercise. The presence or absence of EVLW was determined by lung ultrasound to evaluate for sonographic B-line artefacts. An increase in EVLW during exercise was observed in 33 patients (HFpEFLW+, 54%), while 28 (46%) did not develop EVLW (HFpEFLW−). Resting left ventricular function was similar in the groups, but right ventricular (RV) dysfunction was two-fold more common in HFpEFLW+ (64 vs. 31%), with lower RV systolic velocity and RV fractional area change. As compared to HFpEFLW−, the HFpEFLW+ group displayed higher pulmonary capillary wedge pressure (PCWP), higher pulmonary artery (PA) pressures, worse RV-PA coupling, and higher right atrial (RA) pressures during exercise, with increased haemoconcentration indicating greater loss of water from the vascular space. The development of lung congestion during exercise was significantly associated with elevations in PCWP and RA pressure as well as impairments in RV-PA coupling (area under the curve values 0.76–0.84). Conclusion Over half of stable outpatients with HFpEF develop increases in interstitial lung water, even during submaximal exercise. The acute development of lung congestion is correlated with increases in pulmonary capillary hydrostatic pressure that favours fluid filtration, and systemic venous hypertension due to altered RV-PA coupling, which may interfere with fluid clearance. Clinical trial registration NCT02885636.