Gender Differences in Cardiac Organ Damage in Arterial Hypertension: Assessing the Role of Drug Nonadherence.

INTRODUCTION: Cardiac organ damage like left ventricular (LV) hypertrophy and left atrial (LA) enlargement is more prevalent in women than men with hypertension, but the mechanisms underlying this gender difference remain unclear. METHODS: We tested the association of drug nonadherence with the presence of LV hypertrophy and LA enlargement by echocardiography in 186 women and 337 men with uncontrolled hypertension defined as daytime systolic blood pressure (BP) ≥ 135mmHg despite the prescription of at least two antihypertensive drugs. Drug adherence was assessed by measurements of serum drug concentrations interpreted by an experienced pharmacologist. Aldosterone-renin-ratio (ARR) was measured on actual medication. RESULTS: Women had a higher prevalence of LV hypertrophy (46% vs. 33%) and LA enlargement (79% vs 65%, both p < 0.05) than men, while drug nonadherence (8% vs. 9%, p > 0.514) did not differ. Women were older and had lower serum renin concentration and higher ARR than men, while 24-h systolic BP (141 ± 9 mmHg vs. 142 ± 9 mmHg), and the prevalences of obesity (43% vs. 50%) did not differ (all p > 0.10). In multivariable analyses, female gender was independently associated with a two-fold increased risk of LV hypertrophy (OR 2.01[95% CI 1.30-3.10], p = 0.002) and LA enlargement (OR 1.90 [95% CI 1.17-3.10], p = 0.010), while no association with drug nonadherence was found. Higher ARR was independently associated with LV hypertrophy in men only (OR 2.12 [95% CI 1.12-4.00] p = 0.02). CONCLUSIONS: Among patients with uncontrolled hypertension, the higher prevalence of LV hypertrophy and LA enlargement in women was not explained by differences in drug nonadherence. REGISTRATION: URL:  https://www. CLINICALTRIALS: gov ; Unique identifier: NCT03209154.

Possible beneficial effect of olmesartan medoxomil on left atrial function in patients with hypertension : noninvasive assessment by acoustic quantification.

BACKGROUND AND OBJECTIVE: Hypertension alters the diastolic properties of the left ventricle and results in deterioration in the structure and function of the left atrium. We aimed to evaluate whether olmesartan medoxomil has an effect on left atrial function in hypertensive patients. METHODS: Fifty hypertensive patients and 20 controls were included in the study. Hypertensive patients were treated with olmesartan medoxomil for 8 weeks. Before and after treatment, study participants were examined by acoustic quantification and tissue Doppler imaging. Left atrial reservoir function was assessed by end-diastolic volume (EDV), end-systolic volume (ESV), reservoir volume (RV) and peak filling rate (PFR). Left atrial booster pump function was assessed by atrial emptying volume (AEV), atrial emptying fraction (AEF) and peak atrial emptying rate (PAER). Left atrial conduit function was assessed by rapid emptying volume (REV), rapid emptying fraction (REF), REV/AEV ratio, and the ratio of peak rapid emptying rate and PAER (PRER/PAER). RESULTS: Atrial RV and PFR were significantly increased in hypertensive subjects (48.30 +/- 19.28 mL vs 34.35 +/- 14.26 mL, p < 0.001; 267.26 +/- 126.52 mL/s vs 206.81 +/- 107.17 mL/s, p < 0.05) compared with controls, while the REV/AEV ratio was decreased in hypertensive patients compared with controls (2.86 +/- 0.85 vs 3.69 +/- 2.13, p < 0.001). After therapy with olmesartan medoxomil, atrial RV (48.30 +/- 19.28 mL vs 40.50 +/- 17.59 mL) and PFR decreased (267.26 +/- 126.52 mL/s vs 220.40 +/- 108.56 mL/s, p < 0.05) and the REV/AEV ratio increased (2.86 +/- 0.85 vs 3.14 +/- 0.43, p < 0.05) in hypertensive patients. CONCLUSION: Our novel findings indicate that left atrial function is impaired in hypertensive patients, and that olmesartan medoxomil can improve left atrial function in this context. Our study also showed that acoustic quantification is useful for non-invasive evaluation of the benefits of treatment on left atrial function.

Noninvasive assessment of left atrial function by strain rate imaging in patients with hypertension: a possible beneficial effect of renin-angiotensin system inhibition on left atrial function.

Renin-angiotensin system (RAS) inhibitors are likely to reduce the development of atrial fibrillation by preventing atrial fibrosis. Strain rate (SR) imaging is a novel echocardiographic technique to quantify left atrial (LA) function. However, it has not been determined whether SR imaging is applicable for detection of LA dysfunction in hypertensive (HT) patients. We used SR imaging to assess alteration in LA function in HT patients and its modification by RAS inhibitors. SR imaging was performed in 80 HT patients and 50 age-matched normotensive (NT) subjects. HT patients were divided into two groups according to left ventricular hypertrophy (LVH) and LA dilatation. Peak SR was measured at each LA segment (septal, lateral, posterior, anterior, and inferior) and mean peak systolic SR (SR-LAs) was calculated by averaging data in each segment. Mean SR-LAs levels in the dilated LA group (1.97+/-0.45 s(-1), n=25) and non-dilated LA group (2.15+/-0.57 s(-1), n=55) were significantly (p<0.05) lower than that in NT subjects (2.53+/-0.71 s(-1)). Irrespective of the presence or absence of LVH, mean SR-LAs in HT patients was lower than that in NT subjects. When RAS inhibitors were used, the mean SR-LAs level in the non-dilated LA group was equivalent to that in NT subjects. In HT patients, mean SR-LAs, an index of LA reservoir function, decreases before development of LA enlargement and LVH. Treatment with RAS inhibitors appears to preserve LA reservoir function in HT patients without dilated LA. SR imaging can detect LA dysfunction in HT patients and is useful for evaluation of the therapeutic benefit on LA reservoir function.

Assessment of left atrial pressure-area relation in humans by means of retrograde left atrial catheterization and echocardiographic automatic boundary detection: effects of dobutamine.

OBJECTIVES: This study sought to validate and apply a new method for obtaining the left atrial (LA) pressure-area relation. BACKGROUND: In physiologic investigations, the pressure-area relation is the most accurate and representative index of LA hemodynamic status. METHODS: We applied real-time two-dimensional echocardiographic imaging with automatic boundary detection to estimate LA area changes. To obtain LA pressure, a catheter-tipped micromanometer was introduced retrogradely into the left atrium using a steerable cardiac catheter developed at our institution. Twenty-five patients (11 normal subjects, 7 patients with an enlarged left atrium due to heart failure, 7 patients with atrial fibrillation) were studied before and after dobutamine administration. From the LA pressure-area relation, the area of the A loop (the first counterclockwise loop) and the V loop (the second clockwise loop), the pressure-minimal area relation and the LA passive elastic chamber stiffness constant were measured. RESULTS: Normalized pressure-minimal area relation was highly linear and sensitive to changes in inotropic state (normal subjects: from 0.96 to 1.27 mm Hg/cm2, p < 0.01; patients with heart failure: from 0.59 to 0.68 mm Hg/cm2, p = NS; patients with atrial fibrillation: from 0.80 to 1.06 mm Hg/cm2, p < 0.05). The LA stroke work index was accurately calculated, and a very good correlation was found with LA preload. LA stroke work index was lower in patients with heart failure (3.9 +/- 0.8 cm2 x mm Hg, p < 0.001), whereas the LA stiffness constant was increased in patients with heart failure (0.801 +/- 0.097 cm(-2), p < 0.01) and atrial fibrillation (0.796 +/- 0.091 cm(-2), p < 0.01) compared with normal subjects (stroke work index 7.3 +/- 1.9 cm2 x mm Hg, stiffness constant 0.623 +/- 0.107 cm(-2), respectively). In addition, increased inotropic state after dobutamine administration resulted in improved LA pump function (stroke work index) in normal subjects (from 10.2 +/- 0.9 to 13.8 +/- 1.9 cm2 x mm Hg, p < 0.001) and patients with heart failure (from 4.3 +/- 0.4 to 7.6 +/- 0.4 cm2 x mm Hg, p < 0.001), as well as in decreased stiffness constant in all groups of patients (normal subjects: from 0.712 +/- 0.141 to 0.473 +/- 0.089 cm(-2); patients with heart failure: from 0.896 +/- 0.181 to 0.494 +/- 0.093 cm(-2); patients with atrial fibrillation: from 0.779 +/- 0.145 to 0.467 +/- 0.086 cm(-2), p < 0.001). CONCLUSIONS: The method described here is both safe and reproducible for obtaining the LA pressure-area relation. LA function is impaired in patients with heart failure and in those with atrial fibrillation and may be acutely improved with inotropic agents in both normal and diseased atria.

In vivo assessment of left atrial contractile performance in normal and pathological conditions using a time-varying elastance model.

BACKGROUND: Contractile function of the ex vivo, isolated left atrium (LA) has been described by a time-varying elastance, but this atrial chamber property has not been shown in vivo. METHODS AND RESULTS: Instantaneous LA pressure-volume (P-V) relations were studied in 12 anesthetized, autonomically blocked, atrially paced dogs. LA volume was calculated from orthogonal sonomicrometer pairs using a cast-validated formula. Data were collected during increases in LA pressure produced by a phenylephrine bolus (200 to 400 micrograms IV). Isochronal P-V points from 5 beats, representing a wide range of atrial pressures, were fitted by linear regression analysis (range of R2, .92 to .99). There were significant time-dependent increases in the slopes [E(t)] and small but statistically insignificant decreases in the volume axis intercepts [VO(t)] of the instantaneous LA P-V relations during atrial contraction; maximal elastance (Emax) occurred 29 +/- 16 milliseconds before atrial end systole (minimal LA volume). Emax was not significantly different than the slopes of either the nonisochronal end-systolic P-V relation (Ees) or the nonisochronal maximal P-to-V relation (EmaxPV): 5.5 +/- 2.8, 4.3 +/- 1.5, and 5.4 +/- 4.2 mm Hg/mL, respectively. In 7 dogs, data were collected both before and after a rapid infusion of calcium gluconate (1 to 2 g IV). Emax increased significantly with a calcium-induced increase in inotropic state (4.5 +/- 1.6 to 5.7 +/- 1.8 mm Hg/mL, P < .01), but the volume axis intercept was unchanged (3.6 +/- 0.7 versus 3.4 +/- 1.9, P = NS). In 4 additional dogs with heart failure (mean LA pressure, 26 +/- 6 mm Hg) produced by 3 weeks of rapid right ventricular pacing, LA stroke volume was significantly greater than and elastance determinations were similar to those of normal dogs. However, the effects of calcium infusion on LA function were attenuated in these animals. CONCLUSIONS: We conclude that (1) in the intact heart, LA contraction may be approximated by time-varying elastance with time-dependent changes in E(t) and that (2) LA systolic P-V relations using either the nonisochronal maximum P-to-V ratio or end systole may be useful as an estimate of Emax, are highly linear and sensitive to calcium-induced changes in inotropic state, and may be useful in identifying LA chamber adaptation to chronic hemodynamic loads.