Echocardiography-based pressure-volume loop assessment in the evaluation for the effects of indoxyl sulfate on cardiovascular function.

BACKGROUND: Indoxyl sulfate (IS), a uremic toxin, has been reported to have hypertrophic effects on the heart. Previous studies, however, have shown no association between elevated IS levels and cardiovascular outcomes in hemodialysis patients. We hypothesized that, despite left ventricular (LV) hypertrophy, myocardial contractility and ventricular-arterial coupling would remain preserved, and that this would explain the reason for the absence of prognostic impact of IS. METHODS: We evaluated the association of IS with LV structure, contractility, vascular function, and mechanical efficiency (ventricular-arterial coupling and stroke work/pressure volume area) in 154 patients on hemodialysis, using echocardiography-based pressure-volume loop assessment. RESULTS: As expected, subjects in the high IS group (IS ≥ 33.8 µg/mL) had greater LV mass index and end-diastolic volume index compared to subjects in the low IS group (IS < 33.8 µg/mL). These differences remained significant after adjusting for age, sex, body mass index, diabetic nephropathy, duration of hemodialysis, and NT-proBNP levels, suggesting a potential role of elevated IS levels in LV remodeling. However, no differences in LV contractility (preload recruitable stroke work, peak power index, and systolic mitral annular velocity) and mechanical efficiency (ventricular-arterial coupling and stroke work/pressure volume area) were observed between the groups. CONCLUSIONS: Deleterious effects of IS on LV remodeling are not accompanied by impaired LV contractility or mechanical efficiency, which could contribute to the absence of cardiovascular prognostic impact observed in previous studies performed on hemodialysis patients.

Relationships of high cardiac output with ventricular morphology, myocardial energetics, and energy costs in hemodialysis patients with preserved ejection fraction.

Hemodialysis patients have conditions that increase cardiac output (CO), including arteriovenous fistula, fluid retention, vasodilator use, and anemia. We sought to determine the relationships between these factors and CO and to evaluate the effects of the high-output states on ventricular morphology, function, and myocardial energetics in hemodialysis patients, using noninvasive load-insensitive indices. Cardiovascular function was assessed in hemodialysis patients with high output [ejection fraction ≥ 50%, cardiac index (CI) > 3.5 L/min/m2, n = 30], those with normal output (CI < 3.0 L/min/m2, n = 161), and control subjects without hemodialysis (n = 155). As compared to control subjects and hemodialysis patients with normal CI, patients with elevated CI were anemic and displayed decreased systemic vascular resistance index (SVRI), excessive left ventricular (LV) contractility, larger LV volume, and tachycardia. Lower hemoglobin levels were correlated with decreased SVRI, excessive LV contractility, and higher heart rate, while estimated plasma volume and interdialytic weight gain were associated with larger LV volume, thus increasing CO. High output patients displayed markedly increased pressure-volume area (PVA) and PVA/stroke volume ratio, which were correlated directly with CO. The use of combination vasodilator therapy (angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker and calcium channel blocker) was not associated with high-output states. In conclusion, anemia and fluid retention are correlated with increased CO in hemodialysis patients. The high-output state is also associated with excessive myocardial work and energy cost.

Reduced variability of visual left ventricular ejection fraction assessment with reference images: The Japanese Association of Young Echocardiography Fellows multicenter study.

BACKGROUND: Visual estimation of left ventricular ejection fraction (LVEF) is widely applied to confirm quantitative EF. However, visual assessment is subjective, and variability may be influenced by observer experience. We hypothesized that a learning session might reduce the misclassification rate. METHODS: Protocol 1: Visual LVEFs for 30 cases were measured by 79 readers from 13 cardiovascular tertiary care centers. Readers were divided into 3 groups by their experience: limited (1-5 years, n=28), intermediate (6-11 years, n=26), and highly experienced (12-years, n=25). Protocol 2: All readers were randomized to assess the effect of a learning session with reference images only or feedback plus reference images. After the session, 20 new cases were shown to all readers following the same methodology. To assess the concordance and accuracy pre- and post-intervention, each visual LVEF measurement was compared to overall average values as a reference. RESULTS: Experience affected the concordance in visual EF values among the readers. Groups with intermediate and high experience showed significantly better mean difference (MD), standard deviation (SD), and coefficient of variation (CV) than those with limited experience at baseline. The learning session with reference image reduced the MD, SD, and CV in readers with limited experience. The learning session with reference images plus feedback also reduced proportional bias. Importantly, the misclassification rate for mid-range EF cases was reduced regardless of experience. CONCLUSION: This large multicenter study suggested that a simple learning session with reference images can successfully reduce the misclassification rate for LVEF assessment.

Effect of Sex Differences on the Association Between Stroke Risk and Left Atrial Anatomy or Mechanics in Patients With Atrial Fibrillation.

BACKGROUND: Embolic stroke in atrial fibrillation is more prevalent in women than in men, yet the basis for this difference remains unclear. This study seeks to elucidate whether there are any sex differences in the relationships between stroke risk (CHADS2 score, CHA2DS2-VASc score without a sex category, and estimated stroke rate) and left atrial (LA) anatomy or mechanics in patients with atrial fibrillation. METHODS AND RESULTS: LA emptying fraction and global peak atrial longitudinal strain were assessed in 414 subjects with paroxysmal or persistent atrial fibrillation (156 women and 258 men). Linear regression models with an interaction term were performed to test the effect of sex difference on associations between the embolic risk and LA function or anatomy. Sensitivity analyses were performed in 228 age, heart rate, and rhythm-matched subjects (114 women and men). Women were older and had larger LA volumes and lower LA mechanics than men. Significant negative association between the CHADS2 score and LA emptying fraction was only demonstrated in women with a significant interaction between sexes. Similar significant interactions were found in global peak atrial longitudinal strain but not in LA volume. These findings were corroborated in the comparisons against CHA2DS2-VASc score without a sex category and the estimated stroke rate. Sensitivity analyses in the matched subgroup also confirmed the robustness of these sex differences in LA emptying fraction, but less so in global peak atrial longitudinal strain. CONCLUSIONS: Significant sex interactions on the association between global LA function and risk stratification schemes exist, which may be a reason for the higher prevalence of embolic stroke in women.