Antifungal activities of vineyard-habitat wild yeast for grape gray-mold disease and its effects on spontaneous winemaking.

Microorganisms, including native yeasts, are abundant in vineyard fields. Herein, we studied the possibility of using vineyard-derived wild yeast as a microbial pesticide against Botrytis cinerea, a pathogen that causes grape gray mold disease, to boost the initial alcohol production of spontaneously fermented wine. We identified the Saccharomyces cerevisiae strain KONDO170908, which showed the most effective antifungal activity in an ex vivo yeast dripping experiment on grape berries. This strain was utilized in an in vivo spray test on grape bunches in vineyard fields and was proven to significantly suppress gray mold disease on the grape berries in test plot #16 when the yeast was sprayed during both the flowering and ripening periods (morbidity 11.2% against 15.3% of the control plot, χ2 test, p < 0.0001). However, in test plot #17, spraying the yeast during only the ripening period had no effect (morbidity 16.3%). The grapes from each test plot were also submitted for spontaneous wine fermentation. Alcoholic fermentation of the grapes from test plot #16 provided the most active bubbling of CO2 gas and the highest ethanol production and colony counts over seven days of fermentation. Unique changes in the different strains of S. cerevisiae among the plots were observed throughout the early fermentation stage. Thus, yeast spraying during the flowering period might trigger modification of the entire microbiota and could ultimately contribute to promoting alcohol production in the spontaneously fermented wine, although it decreased the grape yield by 20%.

Diagnostic value of reduced left atrial compliance during ergometry exercise in heart failure with preserved ejection fraction.

AIMS: Diagnosis of heart failure with preserved ejection fraction (HFpEF) remains challenging in patients presenting with chronic dyspnoea. We sought to determine the diagnostic value of reduced left atrial (LA) compliance during exercise to diagnose HFpEF. METHODS AND RESULTS: Ergometry exercise stress echocardiography was performed in 225 patients with HFpEF and 262 non-heart failure controls (non-cardiac dyspnoea [NCD]) in Protocol 1, where the diagnosis of HFpEF was defined by the HFA-PEFF algorithm. In Protocol 2, the diagnosis of HFpEF was ascertained by exercise right heart catheterization in 67 participants (49 HFpEF and 18 NCD). Speckle-tracking echocardiography was performed at rest and during exercise to determine LA compliance (ratio of LA reservoir strain to E/e'). As compared with NCD, patients with HFpEF demonstrated decreased LA reservoir strain and compliance at rest, and these differences further increased during exercise in Protocol 1. Exercise LA compliance discriminated HFpEF from NCD (area under the curve 0.87, p < 0.0001), with a superior diagnostic ability to exercise E/e' ratio (DeLong p = 0.005). Exercise LA compliance demonstrated incremental diagnostic value over clinical factors (age, systemic hypertension, and atrial fibrillation) and resting LA compliance (χ2 212.4 vs. 166.2, p < 0.0001). These findings were confirmed in Protocol 2. CONCLUSION: Left atrial compliance during exercise demonstrated superior diagnostic ability to exercise E/e' ratio, with incremental diagnostic value over the resting LA compliance. Exercise LA compliance may enhance the diagnosis of HFpEF among patients with dyspnoea.

A Comparative Study on Fungal Diversity in Organic and Conventionally Cultivated Lemons During Accelerated Storage.

There has been a growing interest in organic farming as a countermeasure to the environmental burden caused by chemical pesticides. We analyzed and compared the fungal diversity of lemon fruits from organic and conventional cultivation by automated rRNA intergenic spacer analysis (ARISA), accompanied by isolation of cultured colonies and metagenomic analysis. Lemon peels were cut out and subjected to the analyses at purchase and after accelerated storage at 28 °C. The organic lemons did not decay even after 14 weeks, while most of the conventional lemons did decay. The fungal colony counts were not significantly different, although the number of fungal species together with the Shannon index, considering the abundance of each species, clearly showed more diversity in organic lemons than in conventional lemons (p = 0.011). Fusarium sp. (putative F. solani) accounted for as much as 90% of the relative abundance in the decayed conventional lemons. Metagenomic analysis also supported the lack of fungal diversity in conventional lemons. These results may suggest that organic cultivation maintains the diversity of native fungal flora in lemon fruit and could contribute to preventing decay during ambient storage.

Impaired Right Atrial Reserve Function in Heart Failure with Preserved Ejection Fraction.

BACKGROUND: Patients with heart failure with preserved ejection fraction (HFpEF) have multiple cardiac reserve limitations during exercise. However, no data are available regarding right atrial (RA) reserve capacity in HFpEF. The aim of this study was to determine the association of RA reserve impairments with right ventricular function and exercise capacity in HFpEF and to explore its diagnostic value. METHODS: Patients with HFpEF (n = 89) and control subjects without heart failure (n = 108) underwent bicycle exercise echocardiography. RA reservoir, conduit, and booster pump strain at rest and during exercise were measured using speckle-tracking echocardiography. In a subset, simultaneous expired gas analysis was performed to measure peak oxygen consumption. RESULTS: At rest, RA reservoir strain was lower in patients with HFpEF than control subjects (27.0 ± 17.1% vs 38.6 ± 17.1%, P < .0001), while RA conduit and booster pump strain were similar between groups. During peak exercise, patients with HFpEF displayed marked reserve limitations in RA reservoir and booster pump function compared with control subjects, and the differences remained significant even after adjusting for confounding factors. During peak exercise, RA reservoir and booster pump strain were correlated with right ventricular systolic function. Lower RA booster pump strain during exercise was also weakly associated with lower cardiac output (r = 0.34, P < .0001) and reduced peak oxygen consumption (r = 0.47, P < .0001). RA reservoir strain during exercise had incremental diagnostic value to differentiate patients with HFpEF from control subjects over the established HFpEF diagnostic algorithms and left-sided strain parameters. CONCLUSIONS: Limitations in RA reservoir and booster pump function during exercise are present in patients with HFpEF, and the severity is associated with right ventricular systolic reserve, poor cardiac output, and depressed exercise capacity. Exercise RA strain assessment may help in the diagnosis of HFpEF.

Cardiac Power Output Is Independently and Incrementally Associated With Adverse Outcomes in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Cardiac power output is a measure of cardiac performance, and its prognostic significance has been shown in heart failure (HF) with reduced ejection fraction. Patients with HF with preserved ejection fraction may have altered cardiac performance, but the prognostic relevance of cardiac power output is unknown. This study sought to determine the association between cardiac power output and clinical outcomes in HF with preserved ejection fraction and to compare its prognostic effect to other measures of cardiac performance including ventricular-arterial coupling and mechanical efficiency. METHODS: Cardiac power output normalized to left ventricular mass was assessed by echocardiography in 408 patients with HF with preserved ejection fraction. Load-independent contractility (end-systolic elastance), arterial elastance, its coupling (arterial elastance/end-systolic elastance), left ventricular global longitudinal strain, and mechanical efficiency (stroke work/pressure-volume area) were also estimated noninvasively. The primary end point was a composite of cardiovascular mortality or HF hospitalization. RESULTS: The primary composite outcome occurred in 84 patients during a median follow-up of 19.4 months. There was a dose-dependent association between cardiac power output and the composite outcomes, in which patients with the lowest tertile of cardiac power output had >3-fold risk than those with the highest tertile (hazard ratio, 3.04 [95% CI, 1.66-5.57]; P=0.0003). In a multivariable model, lower cardiac power output was independently associated with adverse outcomes (hazard ratio, 0.70 per 1 SD [95% CI, 0.49-0.97]; P=0.03). In contrast, left ventricular size, end-systolic elastance, arterial elastance, arterial elastance/end-systolic elastance ratio, and left ventricular mechanical efficiency were not associated with outcomes. Cardiac power output provided an incremental prognostic effect over the model based on clinical (age, gender, diastolic blood pressure, and atrial fibrillation) and echocardiographic markers (left atrial size, pulmonary pressures, global longitudinal strain, and the ratio of early diastolic mitral inflow velocity to early diastolic mitral annular tissue velocity; P=0.03). CONCLUSIONS: In patients with HF with preserved ejection fraction, cardiac power output was independently and incrementally associated with adverse outcomes whereas other markers of cardiac performance were not.

The H2FPEF and HFA-PEFF algorithms for predicting exercise intolerance and abnormal hemodynamics in heart failure with preserved ejection fraction.

Exercise intolerance is a primary manifestation in patients with heart failure with preserved ejection fraction (HFpEF) and is associated with abnormal hemodynamics and a poor quality of life. Two multiparametric scoring systems have been proposed to diagnose HFpEF. This study sought to determine the performance of the H2FPEF and HFA-PEFF scores for predicting exercise capacity and echocardiographic findings of intracardiac pressures during exercise in subjects with dyspnea on exertion referred for bicycle stress echocardiography. In a subset, simultaneous expired gas analysis was performed to measure the peak oxygen consumption (VO2). Patients with HFpEF (n = 83) and controls without HF (n = 104) were enrolled. The H2FPEF score was obtainable for all patients while the HFA-PEFF score could not be calculated for 23 patients (feasibility 88%). Both H2FPEF and HFA-PEFF scores correlated with a higher E/e' ratio (r = 0.49 and r = 0.46), lower systolic tricuspid annular velocity (r = - 0.44 and = - 0.24), and lower cardiac output (r = - 0.28 and r = - 0.24) during peak exercise. Peak VO2 and exercise duration decreased with an increase in H2FPEF scores (r = - 0.40 and r = - 0.32). The H2FPEF score predicted a reduced aerobic capacity (AUC 0.71, p = 0.0005), but the HFA-PEFF score did not (p = 0.07). These data provide insights into the role of the H2FPEF and HFA-PEFF scores for predicting exercise intolerance and abnormal hemodynamics in patients presenting with exertional dyspnea.

Functional Tricuspid Regurgitation and Right Atrial Remodeling in Heart Failure With Preserved Ejection Fraction.

Tricuspid regurgitation (TR) is common in patients with heart failure with preserved ejection fraction (HFpEF), but it has not been well characterized. We hypothesized that right atrial (RA) remodeling would be associated with TR in HFpEF, forming a type of atrial functional TR (AFTR). Echocardiography was performed in 328 patients with HFpEF. TR severity was defined using a guidelines-based approach. Ventricular functional TR was defined as the presence of right ventricular (RV) systolic pressure >50 mm Hg or RV dilation, and the remaining patients were classified as having AFTR if they had RA dilation or tricuspid annular enlargement. RA dilation was common (78%) in the significant TR group (more than mild), exceeding the prevalence of RV dilation (32%), and RA dilation was correlated with tricuspid annular diameter and TR vena contracta width (r = 0.67 and r = 0.70, both p <0.0001). Despite the absence of RV dilation and pulmonary hypertension, 38% of patients with significant TR had AFTR. Patients with AFTR and those with ventricular functional TR displayed higher heart failure hospitalization rates than those with nonsignificant TR (adjusted hazard ratios, 2.45 and 4.31; 95% confidence interval 1.12 to 5.35 and 2.44 to 7.62, p = 0.02 and p <0.0001, respectively). In conclusion, TR in HFpEF is related to RA remodeling, and the presence of AFTR was associated with poor clinical outcomes. The current data highlight the importance of RA remodeling in the pathophysiology of TR in HFpEF.

Pathophysiological and diagnostic importance of fatty acid-binding protein 1 in heart failure with preserved ejection fraction.

Elevated intracardiac pressure at rest and/or exercise is a fundamental abnormality in heart failure with preserved ejection fraction (HFpEF). Fatty acid-binding protein 1 (FABP1) is proposed to be a sensitive biomarker for liver injury. We sought to determine whether FABP1 at rest would be elevated in HFpEF and would correlate with echocardiographic markers of intracardiac pressures at rest and during exercise. In this prospective study, subjects with HFpEF (n = 22) and control subjects without HF (n = 23) underwent resting FABP1 measurements and supine bicycle exercise echocardiography. Although levels of conventional hepatic enzymes were similar between groups, FABP1 levels were elevated in HFpEF compared to controls (45 [25-68] vs. 18 [14-24] ng/mL, p = 0.0008). FABP1 levels were correlated with radiographic and blood-based markers of congestion, hemodynamic derangements during peak exercise (E/e', r = 0.50; right atrial pressure, r = 0.35; pulmonary artery systolic pressure, r = 0.46), reduced exercise cardiac output (r = - 0.49), and poor exercise workload achieved (r = - 0.40, all p < 0.05). FABP1 distinguished HFpEF from controls with an area under the curve of 0.79 (p = 0.003) and had an incremental diagnostic value over the H2FPEF score (p = 0.007). In conclusion, FABP1 could be a novel hepatic biomarker that associates with hemodynamic derangements, reduced cardiac output, and poor exercise capacity in HFpEF.

Association between lung ultrasound B-lines and exercise-induced pulmonary hypertension in patients with connective tissue disease.

BACKGROUND: Identification of elevation in pulmonary pressures during exercise may provide prognostic and therapeutic implications in patients with connective tissue disease (CTD). Interstitial lung disease (ILD) is common in CTD patients and subtle interstitial abnormalities detected by lung ultrasound could predict exercise-induced pulmonary hypertension (PH). METHODS AND RESULTS: Echocardiography and lung ultrasound were performed at rest and bicycle exercise in CTD patients (n = 41) and control subjects without CTD (n = 24). Ultrasound B-lines were quantified by scanning four intercostal spaces in the right hemithorax. We examined the association between total B-lines at rest and the development of exercise-induced PH during ergometry exercise. Compared to controls, the number of total B-lines at rest was higher in CTD patients (0 [0, 0] vs 2 [0, 9], P < .0001) and was correlated with radiological severity of ILD assessed by computed tomography (fibrosis score, r = .70, P < .0001). Pulmonary artery systolic pressure (PASP) was increased with ergometry exercise in CTD compared to controls (48 ± 14 vs 35 ± 13 mm Hg, P = .0006). The number of total B-lines at rest was highly correlated with higher PASP (r = .52, P < .0001) and poor right ventricular pulmonary artery coupling (tricuspid annular plane systolic excursion/PASP ratio, r = -.31, P = .01) during peak exercise. The number of resting B-lines predicted the development of exercise-induced PH with an area under the curve .79 (P = .0003). CONCLUSIONS: These data may suggest the value of a simple resting assessment of lung ultrasound as a potential tool for assessing the risk of exercise-induced PH in CTD patients.

Pulmonary Vascular Alterations on Computed Tomography Imaging and Outcomes in Heart Failure With Preserved Ejection Fraction: a Preliminary Data.

BACKGROUND: Pulmonary vascular disease may play an important role in the pathophysiology of heart failure (HF) with preserved ejection fraction (HFpEF). However, no study has demonstrated noninvasive quantification of pulmonary vascular alterations in HFpEF. This study sought to determine the association between pulmonary vascular alterations quantified by chest computed tomography scan and clinical outcomes in HFpEF. METHODS AND RESULTS: Pulmonary vascular alterations were quantified in 151 patients with HFpEF who underwent noncontrast chest computed tomography scan by measuring the percentage of total cross-sectional area (CSA) of pulmonary vessels less than 5 mm2 to the total lung area (%CSA<5). We divided the patients by the median value of %CSA<5 (=1.45%) and examined the association between %CSA<5 and a composite outcome of all-cause mortality or HF hospitalization. During a median follow-up of 17.3 months, there were 44 (29%) composite outcomes. Event rates were significantly higher in patients with higher %CSA<5 than those with lower %CSA<5 (log-rank P = .02). %CSA<5 was associated with an increased risk of the outcome (hazard ratio per 1.0% increment, 1.46; 95% confidence interval 1.06-1.98; P = .02) in an unadjusted Cox model, and was independently and incrementally associated with the outcome over age, the presence of atrial fibrillation, E/e' ratio, and estimated pulmonary artery systolic pressure (global χ2 17.3 vs 11.5, P = .02). CONCLUSIONS: A higher %CSA<5 was associated with an increased risk of all-cause mortality or HF hospitalization in patients with HFpEF, with an incremental prognostic value over age, atrial fibrillation, E/e' ratio, and pulmonary artery systolic pressure.

Prognostic impact of elevated fatty acid-binding protein 1 in patients with heart failure.

AIMS: Few biomarkers to evaluate pathophysiological changes in extra-cardiac tissues have been identified in patients with heart failure (HF). Fatty acid-binding protein 1 (FABP), also known as liver FABP, is predominantly expressed in the liver. Circulating FABP1 has been proposed to be a sensitive biomarker for liver injury. However, little is known about the potential role of FABP1 as a biomarker for HF. METHODS AND RESULTS: Measurements of serum FABP1 and echocardiography were performed in subjects with compensated HF (n = 162) and control subjects without HF (n = 20). Patients were prospectively followed-up for a composite outcome of all-cause mortality or HF hospitalization. Compared with control subjects, levels of FABP1 were elevated in HF patients [7.9 (6.4-11.7) vs. 17.6 (10.4-28.9) ng/mL, P < 0.0001]. There were significant correlations between FABP1 levels and estimated right ventricular systolic pressure and right atrial pressure. During a median follow-up of 12.0 months, there were 55 primary composite endpoints in the HF cohort. The highest FABP1 tertile was associated with a three-fold increased risk of the composite outcome compared with the lowest tertile [95% confidence interval (1.46-6.68), P = 0.003], but other conventional hepatobiliary markers did not predict the outcome. After adjusting for age, sex, atrial fibrillation, and N-terminal pro-B-type natriuretic peptide levels, serum FABP1 remained independently associated with the outcome. Adding FABP1 to the model based on clinical factors and N-terminal pro-B-type natriuretic peptide significantly improved the prognostic value (global χ2 20.8 vs. 15.5, P = 0.01). CONCLUSION: Serum FABP1 levels are elevated in compensated HF patients, and the magnitude of elevation is independently associated with pulmonary hypertension, right atrial hypertension, and worse clinical outcomes. FABP1 may serve as a new potential biomarker for the assessment of hitherto unrecognized derangement of cardio-hepatic interaction in HF.

Impact of Right Atrial Remodeling in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Few studies have investigated right atrial (RA) remodeling in heart failure (HF) with preserved ejection fraction (HFpEF). This study sought to characterize the RA remodeling in HFpEF and to determine its prognostic significance. METHODS AND RESULTS: Patients with HFpEF were classified based on the presence of RA enlargement (RA volume index >39 mL/m2 in men and >33 mL/m2 in women). Compared with patients with normal RA size (n = 234), patients with RA dilation (n = 67) showed a higher prevalence of atrial fibrillation (AF), worse right ventricular systolic function, more severe pulmonary hypertension, and a greater prevalence of mild tricuspid regurgitation, as well as impaired RA reservoir function, with increased hepatobiliary enzyme levels. AF was strongly associated with the presence of RA dilation (odds ratio [OR] 10.2, 95% confidence interval [CI] 4.00-26.1 in current AF vs no AF and odds ratio 3.38, 95% CI 1.26-9.07, earlier AF vs no AF). Patients with RA dilation had more than a two-fold increased risk of composite outcomes of all-cause mortality or HF hospitalization (adjusted hazard ratio 2.01, 95% CI 1.09-3.70, P = .02). The presence of RA dilation also displayed an additive prognostic value over left atrial dilation alone. CONCLUSIONS: These data demonstrate that HFpEF with RA remodeling is associated with distinct echocardiographic features characterizing advanced right heart dysfunction with an increased risk of adverse outcomes.

Independent and incremental prognostic value of semiquantitative measures of tricuspid regurgitation severity in heart failure with preserved ejection fraction.

AIMS: This study sought to determine the independent and incremental prognostic value of semiquantitative measures of tricuspid regurgitation (TR) severity over right heart remodelling and pulmonary hypertension (PH) in heart failure with preserved ejection fraction (HFpEF). METHODS AND RESULTS: Echocardiography was performed on 311 HFpEF patients. TR severity was defined by the semiquantitative measures [i.e. vena contracta width (VCW) and jet area] and by the guideline-based integrated qualitative approach (absent, mild, moderate, or severe). All-cause mortality or heart failure hospitalization occurred in 101 patients over a 2.1-year median follow-up. There was a continuous association between TR severity and the composite outcome with a hazard ratio (HR) of 1.17 per 1 mm increase of VCW [95% confidence interval (CI) 1.08-1.26, P < 0.0001]. Compared with patients with the lowest VCW category (≤1 mm), RV-adjusted HRs for the outcome were 1.99 (95% CI 1.05-3.77), 2.63 (95% CI 1.16-5.95), and 5.00 (95% CI 1.60-15.7) for 1-3, 3-7, and ≥7 mm VCW categories, respectively. TR severity as defined by the guideline-based approach showed a similarly graded association, but it was no longer significant in models including PH. In contrast, VCW remained independently and incrementally associated with the outcome after adjusting for established prognostic factors, as well as RV diameter and PH (fully adjusted HR 1.14 per 1 mm, 95% CI 1.02-1.27, P = 0.02; χ2 58.8 vs. 51.5, P = 0.03). CONCLUSION: The current data highlight the potential value of the semiquantitative measures of TR severity for the risk stratification in patients with HFpEF.

Pathophysiological role of fatty acid-binding protein 4 in Asian patients with heart failure and preserved ejection fraction.

AIMS: Systemic metabolic impairment is the key pathophysiology of heart failure (HF) with preserved ejection fraction (HFpEF). Fatty acid-binding protein 4 (FABP4) is highly expressed in adipocytes and secreted in response to lipolytic signals. We hypothesized that circulating FABP4 levels would be elevated in patients with HFpEF, would correlate with cardiac structural and functional abnormalities, and could predict clinical outcomes. METHODS AND RESULTS: Serum FABP4 measurements and echocardiography were performed in patients with HFpEF (n = 92) and those with coronary artery disease free of HF (n = 20). Patients were prospectively followed-up for a composite endpoint of all-cause mortality or HF hospitalization. Compared with patients with coronary artery disease, those with HFpEF had higher FABP4 levels [12.5 (9.1-21.0) vs. 43.5 (24.6-77.4) ng/mL, P < 0.0001]. FABP4 levels were associated with cardiac remodelling (left ventricular mass index: r = 0.29, P = 0.002; left atrial volume index: r = 0.40, P < 0.0001), left ventricular systolic and diastolic dysfunction (global longitudinal strain: r = -0.24, P = 0.01; E/e' ratio: r = 0.29, P = 0.002; and N-terminal pro-B-type natriuretic peptide: r = 0.62, P < 0.0001), and right ventricular dysfunction (tricuspid annular plane systolic excursion: r = -0.43, P < 0.0001). During a median follow-up of 9.1 months, there were 28 primary endpoints in the HFpEF cohort. Event-free survival was significantly decreased in patients with FABP4 levels ≥43.5 ng/mL than in those with FABP4 levels <43.5 ng/mL (P = 0.003). CONCLUSIONS: Serum FABP4 levels were increased in HFpEF and were associated with cardiac remodelling and dysfunction, and poor outcomes. Thus, FABP4 could be a potential biomarker in the complex pathophysiology of HFpEF.

Sex differences in left ventricular afterload and diastolic function are independent from the aortic size.

BACKGROUND: Women have a greater risk of heart failure with preserved ejection fraction (HFPEF) than men do, yet the basis for this disparity remains unclear. Greater arterial stiffness and afterload causes left ventricular (LV) diastolic dysfunction, a central mechanism of HFPEF. Because of smaller body habitus, previous reports have used body surface area as a surrogate of the size of the aorta. We performed a comprehensive hemodynamic evaluation of elderly patients with preserved EF and evaluated sex differences in the associations between LV function and afterload, before and after adjusting for the aortic sizes. METHODS AND RESULTS: Four hundred and forty-three patients (mean age: 73 years, 169 women) who underwent clinically indicated echocardiography and computed tomography (CT) were identified. Linear regression analyses were performed to assess the independent contributions of sex to and its interaction with LV function before and after adjusting for CT-derived aortic length and volume. Although blood pressures were similar between the sexes, women had greater arterial elastance, lower arterial compliance, and greater LV ejection fraction (all p<0.001). Sex differences were detected in the associations between LV afterload and relaxation (mitral e') as well as in the left atrial (LA) emptying fraction, but not in LA size. These differences remained significant after adjusting for the aortic length and volume. Sensitivity analyses in an age-matched subgroup (n = 324; 162 of each sex) confirmed the robustness of these sex disparities in LV diastolic function and afterload. CONCLUSION: Women had worse LV relaxation than men did against the same degree of afterload, before and even after adjusting for the aortic sizes.

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.

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.