Nishimura, Rick

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.

Objective A subset of patients at the time of transcatheter mitral valve repair (TMVR) will have normal left atrial pressure (LAP) (<13 mm Hg) despite having severe mitral regurgitation (MR). The goal of this study was to determine clinical characteristics and outcomes in patients with normal LAP undergoing TMVR. Methods A single-centre retrospective cohort of consecutive patients who underwent transcatheter edge-to-edge mitral valve clip and continuous LAP monitoring between 5/1/2014 and 5/1/2018 was analysed. One-year mortality was compared by Kaplan–Meier survival curves. Multivariable analysis was performed to identify predictors of normal LAP and 1 year mortality. Results Of the 204 patients undergoing TMVR, 65% were men and the mean age was 81. Of these patients, 31 (15%) had normal LAP (mean LAP 10.5 mm Hg, mean V wave 16.5 mm Hg) and 173 had elevated LAP (mean LAP 19 mm Hg, mean V wave 32.5 mm Hg). The prevalence of severe MR was not different between groups, although the normal LAP group had significantly lower effective regurgitant orifice area and regurgitant volume. Other notable baseline characteristics including prior cardiac surgery, atrial fibrillation, hypertension, diabetes, congestive heart failure, body mass index, mechanism of MR and ejection fraction were similar between groups. However, there was an increased prevalence of chronic lung disease (CLD) (45.2% vs 17.3%, p<0.001) in the normal LAP group. On multivariate analysis, the only significant predictor of normal LAP was the presence of CLD (OR 4.79 (1.83–12.36), p=0.001) and 1-year mortality was significantly higher in the normal LAP group (32.3% vs 12.7%, p=0.006). After adjustment for comorbidities, normal LAP was no longer a predictor of 1-year mortality (RR 1.62 (0.64–4.06), p=0.32); however, CLD (RR 3.44 (1.37–8.67), p=0.01) remained a statistically significant predictor. Conclusion Normal LAP at the time of TMVR is associated with a higher incidence of CLD which independently predicts increased 1-year mortality. In patients with CLD and apparently severe MR, measurement of LAP may help identify those with lower likelihood of benefit from TMVR.

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.

Abstract Background Coronary microvascular inflammation is hypothesized to play a fundamental role in the pathophysiology of heart failure with preserved ejection fraction (HFpEF). No study has directly evaluated both endothelium-dependent and independent coronary microvascular function in HFpEF. Methods and results Consecutive patients with HFpEF undergoing invasive coronary physiologic testing and echocardiography were examined. Endothelial function was quantified by the increase in coronary blood flow in response to intracoronary infusion of acetylcholine (10−6–10−4 mol/L) using a Doppler flow wire with quantitative angiography. Endothelium-independent coronary microvascular function was assessed by the hyperaemic increase in coronary flow reserve in response to adenosine infusion. Among 162 HFpEF patients (67% women), coronary microvascular function was abnormal in 117 (72%). Isolated endothelium-dependent microvascular dysfunction was present in 47 patients (29%), isolated endothelium-independent microvascular dysfunction in 53 patients (33%), and combined microvascular dysfunction in 17 patients (10%). The presence of coronary microvascular dysfunction was not identifiable from medical co-morbidities or other clinical characteristics. As compared to patients with normal endothelium-independent function, HFpEF patients with endothelium-independent coronary microvascular dysfunction displayed lower diastolic relaxation velocities (7.0 ± 1.8 vs. 8.4 ± 2.9 cm/s, P = 0.002) and higher estimated filling pressures (E/e’ 13.1 ± 4.1 vs. 9.6 ± 3.4, P &lt; 0.001). There were no relationships between left ventricular structure, function, or haemodynamics and endothelium-dependent coronary vasodilatation. Endothelium-independent microvascular dysfunction was associated with increased mortality. Conclusions Coronary microvascular dysfunction is common in patients with HFpEF and is caused equally by endothelium-dependent and independent mechanisms, but the presence of microvascular dysfunction cannot be identified from clinical markers and co-morbidities alone. Patients with HFpEF and endothelium-independent microvascular dysfunction display worse diastolic dysfunction and outcomes.

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.

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.