Associations Between Coronary Artery Calcification and Left Ventricular Global Longitudinal Strain and Diastolic Parameters: the ELSA-Brasil Study.

Atherosclerosis burden can be evaluated in asymptomatic patients by measuring coronary artery calcification (CAC), whereas the global longitudinal strain (GLS) and diastolic function parameters (mitral E/e' ratio, septal e', and lateral e') are used to evaluate subclinical left ventricular (LV) dysfunction. We investigated whether subjects with CAC (CAC >0 Agatston units) would present with an impairment in LV functional parameters. Among the participants of the ELSA-Brasil cohort free of clinically prevalent cardiovascular disease who performed cardiac computed tomography and echocardiography within the study protocol, we tested whether those with CAC >0 presented with worse GLS and diastolic function parameters. CAC >0 was present in 203 of the 612 included participants (33.17%; age 51.4 ± 8.6 years, 52.1% women). Absolute CAC values did not correlate with GLS (ro = 0.07, p = 0.105) but did so with E/e' (ro = 0.19, p <0.001), septal e' (ro = 0.28, p <0.001), and lateral e' (ro = 0.30, p <0.001), with stronger correlations in men. Those with CAC >0 had worse mitral E/e' ratios (7.75 ± 0.13 vs 7.01 ± 0.09; p ≤0.001), septal e' (8.25 ± 0.15 vs 9.59 ± 0.11 cm/s; p <0.001), and lateral e' (10.13 ± 0.20 vs 11.99 ± 0.14 cm/s; p ≤0.001), respectively. However, these associations were not independent of diabetes, obesity, hypertension, smoking, and low-density lipoprotein cholesterol, persisting only as significant associations of CAC >0 with mitral E/e' ratio and septal e' in men. There is an association between subclinical coronary atherosclerosis and impaired LV functional parameters. These associations are more likely attributed to the presence of common cardiovascular risk factors in the general population. However, in men, it seems to exist as an independent association.

Reproducibility of right ventricular function by longitudinal strain and other echocardiographic parameters in the ELSA-Brasil study.

Right ventricular (RV) free wall longitudinal strain (RVFWLS), and four-chamber longitudinal strain (RV4CLS) using speckle tracking echocardiography have demonstrated increased accuracy and discrimination to measure right ventricular function in different clinical conditions. Reproducibility data of these measures are scarce and mainly tested in small or reference populations. The main objective of this study was to investigate their reproducibility, and of other traditional RV parameters, from unselected participants of a large cohort study. RV strain reproducibility was analyzed using echocardiographic images of 50 participants from a randomly selected sample from The ELSA-Brasil Cohort. Images were acquired and analyzed following the study protocols. The mean RVFWLS was - 26.9 ± 2.6% and the mean RV4CLS was - 24.4 ± 1.9%. The intra-observer reproducibility parameters of RVFWLS demonstrated a coefficient of variation (CV) of 5.1% and an intraclass correlation coefficient (ICC [95%CI] 0.78[0.67-0.89]), and for RV4CLS were CV = 5.1% and ICC = 0.78[0.67-0.89]. Reproducibility for RV fractional area change was CV = 12.1%; ICC = 0.66 [0.50-0.81] and for RV basal diameter was CV = 6.3%; ICC = 0.82 [0.73-0.91]. The inter-observer reproducibility for RVFWLS was CV = 8.3%; ICC 0.54[0.34-0.74] and for RV4CLS, CV = 6.3%; ICC = 0.53[0.34-0.73], following the same pattern among conventional RV parameters. We found adequate reproducibility of RV longitudinal strain parameters. This information is relevant for the long-term follow-up of cohort participants and reinforces the utility of RV longitudinal strain as a tool to monitor subclinical changes in RV systolic function.

Effects of Antihypertensive Treatment on Left and Right Ventricular Global Longitudinal Strain and Diastolic Parameters in Patients with Hypertension and Obstructive Sleep Apnea: Randomized Clinical Trial of Chlorthalidone plus Amiloride vs. Amlodipine.

Hypertension is highly prevalent in patients with obstructive sleep apnea (OSA), and fluid retention with its nighttime rostral distribution is one potential mechanism. We tested whether or not diuretics differ from amlodipine in their impact on echocardiographic parameters. Patients with moderate OSA and hypertension were randomized to receive diuretics (chlorthalidone plus amiloride) or amlodipine daily for 8 weeks. We compared their effects on left and right ventricular global longitudinal strain (LV-GLS and RV-GLS, respectively), on LV diastolic parameters, and on LV remodeling. In the 55 participants who had echocardiographic images feasible for strain analysis, all echocardiographic parameters were within normal ranges. After 8 weeks, the 24 h blood pressure (BP) reduction values were similar, while most echocardiographic metrics were kept unchanged, except for LV-GLS and LV mass. In conclusion, the use of diuretics or amlodipine had small and similar effects on echocardiographic parameters in patients with moderate OSA and hypertension, suggesting that they do not have important effects on mediating the interaction between OSA and hypertension.

Regional contributions to impaired myocardial mechanical function in heart failure with preserved ejection fraction.

AIMS: Hypertensive heart disease (HHD) is recognized as a key clinical precursor to heart failure with preserved ejection fraction (HFPEF). However, pathophysiological transition from HHD to HFPEF is not well understood. We sought determine whether regional differences in impaired myocardial function may underlie the greater mechanical dysfunction seen in HFPEF compared to HHD. METHODS AND RESULTS: We used standardized echocardiography to assess regional myocardial deformation in a cohort of n = 327 adults with preserved left ventricular (LV) ejection fraction (≥45%), including: n = 129 with HFPEF, n = 158 with HHD and no heart failure, and n = 40 normotensive controls. From detailed measurements of LV systolic strain performed in multiple views, we derived and then compared regional measures of basal, mid-ventricular, and apical longitudinal strains. In models adjusting for clinical covariates, basal and mid-ventricular LV myocardial deformation was more impaired in HHD than in controls (P ≤ 0.003), whereas apical deformation was more impaired in HFPEF than in HHD (P = 0.005). In multivariable-adjusted analyses, only apical strain remained independently associated with HFPEF vs. HHD status [odds ratio 1.18 (1.02-1.37), P = 0.030 per 1% decrease in apical strain]. Compared to other regional strains, apical longitudinal strain optimally differentiated HFPEF from HHD (area under the receiver operating curve: apical longitudinal strain = 0.67; mid-ventricular longitudinal strain = 0.59; basal longitudinal strain = 0.60). CONCLUSION: We found that while apical mechanical function is preserved in HHD, it was impaired in HFPEF and may contribute to the transition from an asymptomatic heart disease to a symptomatic heart disease.

Rapid prognostic stratification using Point of Care ultrasound in critically ill COVID patients: The role of epicardial fat thickness, myocardial injury and age.

PURPOSE: The burden of critical COVID-19 patients in intensive care units (ICU) demands new tools to stratify patient risk. We aimed to investigate the role of cardiac and lung ultrasound, together with clinical variables, to propose a simple score to help predict short-term mortality in these patients. MATERIAL AND METHODS: We collected clinical and laboratorial data, and a point-of-care cardiac and lung ultrasound was performed in the first 36 h of admission in the ICU. RESULTS: Out of 78 patients (61 ± 12y-o, 55% male), 33 (42%) died during the hospitalization. Deceased patients were generally older, had worse values for SOFA score, baseline troponin levels, left ventricular ejection fraction (LVEF), LV diastolic function, and increased epicardial fat thickness (EFT), despite a similar prevalence of severe lung ultrasound scores. Based on the multivariable model, we created the POCOVID score, including age (>60 years), myocardial injury (LVEF<50% and/or usTnI>99til), and increased EFT (>0.8 cm). The presence of two out of these three criteria identified patients with almost twice the risk of death. CONCLUSIONS: A higher POCOVID score at ICU admission can be helpful to stratify critical COVID-19 patients with increased in-hospital mortality and to optimize medical resources allocation in more strict-resource settings.

Prognostic Value of Minimal Left Atrial Volume in Heart Failure With Preserved Ejection Fraction.

Background Maximal left atrial (LA) volume is reported by most echocardiography laboratories and is associated with clinical outcomes in patients with heart failure (HF). Recent studies suggest that minimal LA volume may better reflect left ventricular filling pressure and may be more prognostic than maximal LA volume. This study assessed the prognostic value of indexed minimal LA volume (LAVImin) in patients with HF with preserved ejection fraction. Methods and Results We assessed the relationship of LAVImin with a primary composite end point of cardiovascular death, aborted cardiac death, or HF hospitalization in 347 patients with HF with preserved ejection fraction enrolled from the Americas region in TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial). We compared LAVImin with indexed maximal LA volume with respect to their prognostic values. In addition, we assessed if LA functional parameters provide additional prognostic information over LAVImin. During a median follow-up of 2.5 years, 107 patients (31%) experienced a primary composite end point. LAVImin was associated with increased risk of a primary composite outcome (hazard ratio [HR], 1.35; 95% CI, 1.12-1.61) and HF hospitalization alone (HR, 1.42; 95% CI, 1.17-1.71) after adjusting for clinical confounders and ejection fraction. In contrast, indexed maximal LA volume was not related to the primary composite outcome, but related to HF alone (HR, 1.25; 95% CI, 1.02-1.54). In comparison with indexed maximal LA volume, LAVImin was significantly more prognostic for primary composite outcome (P for comparison=0.032). Both LA emptying fraction and LA strain were prognostic of primary outcome independent of LAVImin (all P<0.05). Conclusions In patients with HF with preserved ejection fraction, LAVImin was more predictive of cardiovascular outcome than indexed maximal LA volume, suggesting this measure may be more physiologically relevant and might better identify patients at high risk for cardiovascular events. LA functional parameters provide prognostic information independent of LAVImin. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00094302.

Donor-recipient predicted heart mass ratio and right ventricular-pulmonary arterial coupling in heart transplant.

OBJECTIVES: Right ventricular-pulmonary arterial (RV-PA) coupling interactions are largely unexplored in heart transplant patients. The outcome of this study was RV-PA coupling at 7 and 30 days after heart transplant and its association with donor-recipient size matching. METHODS: Clinical, echocardiographic and haemodynamic data from a retrospective cohort of heart transplant recipients and respective donors were reviewed. Coupling between RV-PA was examined by assessing the RV fractional area change and pulmonary artery systolic pressure ratio. Donor-recipient size matching was assessed by the predicted heart mass (PHM) ratio, and groups with a PHM ratio <1 and ≥1 were compared. RESULTS: Forty-four heart transplant recipients were included in this study (50 years, 57% male sex). Postoperative RV-PA coupling improved from 7 to 30 days (RV fractional area change/pulmonary artery systolic pressure 0.9 ± 0.3 vs 1.2 ± 0.3; P < 0.001). A positive association was found between an adequate PHM ratio and improvement of RV fractional area change/pulmonary artery systolic pressure at 30 days, independent of graft ischaemic time and pre-existent pulmonary hypertension (B coefficient 0.54; 95% confidence interval 0.11-0.97; P = 0.016; adjusted R2 = 0.24). CONCLUSIONS: These findings highlight the role of PHM as a metric to help donor selection and suggest its impact in RV-PA coupling interactions post-heart transplant.

Stage I hypertension is associated with impaired systolic function by strain imaging compared with prehypertension: A report from the prever study.

High blood pressure (BP) is associated with higher rates of cardiovascular events, even in stage I hypertension (HTN) and prehypertension (preHTN). Lower left ventricular (LV) systolic function, assessed by global longitudinal strain (GLS), has been demonstrated in individuals with HTN compared to individuals with normal BP, but a comparison of individuals with preHTN and stage I HTN was not described to date. The PREVER study includes two randomized double-blind controlled trials, performed in volunteers with preHTN (PREVER-prevention trial) or stage I HTN (PREVER-treatment trial), aged 30-70 years. A subsample of patients of both trials had GLS measured from 2D echocardiograms performed at baseline and after 18 months of follow-up. We compared baseline data from both studies and, among stage I HTN patients, clinical and echocardiographic correlates of GLS were determined. Participants with preHTN (n = 91;53% female; 55 ± 9 yo) and stage I HTN (n = 105; 44% female; 55 ± 8 yo) had similar clinical parameters beyond the expected differences in BP levels. Participants with stage I HTN had lower GLS (-17.5 ± 2.5% vs -18.2 ± 2.4%, P = .03) compared with those with preHTN. In stage I HTN, lower GLS was associated with lower e' and lower LV ejection fraction. In conclusion, patients in Stage I HTN may already express changes in GLS compared with individuals with preHTN, suggesting that even mildly difference in BP can be impact in subclinical systolic function.

Central Obesity is the Key Component in the Association of Metabolic Syndrome With Left Ventricular Global Longitudinal Strain Impairment.

INTRODUCTION AND OBJECTIVES: Subclinical systolic dysfunction is one of the proposed mechanisms for increased cardiovascular risk associated with metabolic syndrome (MS). This study investigated the association between MS and impaired left ventricular global longitudinal strain (GLS) and the role of each MS criteria in this association. METHODS: We analyzed a random sample of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) after excluding participants with prevalent heart disease. RESULTS: Among the 1055 participants fulfilling the inclusion criteria (53% women; 52±9 years), 444 (42%) had MS. Those with MS had worse GLS (-18.0%±2.5%) than those without (-19.0%±2.4%; P<.0001). In multiple linear regression models, MS was associated with worse GLS after adjustment for various risk factors (GLS difference=0.86%; P <.0001), even after inclusion of body mass index. Adjusted PR for impaired GLS as assessed by 3 cutoffs (1, 1.5, and 2 standard deviations) were higher among participants with than without MS: GLS -16.1% (PR, 1.76; 95%CI, 1.30-2.39); GLS -14.8% (PR, 2.35; 95%CI, 1.45-3.81); and GLS -13.5% (PR, 2.07; 95%CI, 0.97-4.41). After inclusion of body mass index in the models, these associations were attenuated, suggesting that they may, at least in part, be mediated by obesity. In quantile regression analyses, elevated waist circumference was the only MS component found to be independently associated with GLS across the whole range of values. CONCLUSIONS: Metabolic syndrome is independently associated with impaired GLS. Among the MS criteria, central obesity best depicted the link between metabolic derangement and cardiac function.

Reproducibilidad del strain longitudinal global del ventrículo izquierdo por ecocardiografía bidimensional speckle tracking: Estudio Longitudinal de Salud del Adulto (ELSA-Brasil) / Reproducibility of left ventricular global longitudinal strain using two-dimensional ultrasound speckle tracking: Longitudinal Study of Adult Health (ELSA-Brasil)

Resumen Introducción: Se han propuesto técnicas ecocardiográficas avanzadas como el strain longitudinal global por ecocardiografía bidimensional speckle tracking para la detección de alteraciones precoces de la función sistólica del ventrículo izquierdo. La evaluación de la reproducibilidad del strain longitudinal global es fundamental para su aplicación clínica en diferentes escenarios. Objetivo: Estimar la reproducibilidad del strain longitudinal global del ventrículo izquierdo en individuos de un estudio de cohorte del Brasil. Métodos: La reproducibilidad del strain longitudinal global del ventrículo izquierdo fue evaluada mediante lectura y análisis de imágenes de ecocardiografía de una muestra aleatoria de 50 participantes de la línea de base del Estudio Longitudinal de Salud del Adulto (ELSA-Brasil). Resultados: Los participantes tenían una edad promedio de 49,7 ± 7,3 años, 54% eran mujeres y la media del strain longitudinal global fue -19,5% ± 1,9%. La reproducibilidad interobservador de la medida del strain longitudinal global mostró un coeficiente de variación de 7,4% y un coeficiente de correlación intraclase de 0,76 (IC 95%: 0,61, 0,86). El análisis del acuerdo interobservador de las medidas del strain longitudinal global mediante el método de Bland & Altman evidenció un promedio de diferencias de 0,1% ± 1,4% y unos límites de acuerdo superior de 2,9 e inferior de -2,7. Conclusiones: Hubo una reproducibilidad adecuada de las medidas del strain longitudinal global del ventrículo izquierdo en participantes del ELSA-Brasil y los valores fueron similares a los reportados en otros estudios epidemiológicos longitudinales. Los hallazgos refuerzan la utilidad del strain longitudinal global como un índice clínico de deformación miocárdica, capaz de detectar alteraciones subclínicas de la contractilidad miocárdica.

Abstract Introduction: Advanced echocardiography techniques, such as the global longitudinal strain using two-dimensional ultrasound speckle tracking, have been proposed for the detection of early changes in the left ventricular systolic function. The evaluation of the reproducibility of left ventricular global longitudinal strain is essential for its clinical application in different scenarios. Objective: To determine the reproducibility of left ventricular global longitudinal strain in individuals from a Brazil cohort study. Methods: The reproducibility of left ventricular global longitudinal strain was evaluated by the reading and analysis of echocardiograph images of a random sample of 50 participants of the baseline Longitudinal Study of Adult Health (ELSA-Brasil). Results: The mean age of the participants was 49.7 ± 7.3 years, of whom 54% were women, and the mean global longitudinal strain was -19.5% ± 1.9%. The inter-observer reproducibility of the mean global longitudinal strain, had a coefficient of variation of 7.4%, and an intra-class correlation of 0.76 (95% CI: 0.61 - 0.86). The analysis of the inter-observer agreement of the global longitudinal strain measurements using the Bland and Altman method showed a mean differences of 0.1% ± 1.4%, and upper and lower limits of agreement of 2.9 and -2.7, respectively. Conclusions: There was adequate reproducibility of the left ventricular global longitudinal strain measurements in participants of the ELSA-Brasil study, and the values were similar to those reported in other longitudinal epidemiological studies. The findings reinforce the use of the global longitudinal strain as a clinical marker of myocardial deformation, capable of detecting subclinical changes in myocardial contractility.

Association of Weight and Body Composition on Cardiac Structure and Function in the ARIC Study (Atherosclerosis Risk in Communities).

BACKGROUND: Obesity increases cardiovascular risk. However, the extent to which various measures of body composition are associated with abnormalities in cardiac structure and function, independent of comorbidities commonly affecting obese individuals, is not clear. This study sought to examine the relationship between body mass index, waist circumference, and percent body fat with conventional and advanced measures of cardiac structure and function. METHODS AND RESULTS: We studied 4343 participants of the ARIC study (Atherosclerosis Risk in Communities) who were aged 69 to 82 years, free of coronary heart disease and heart failure, and underwent comprehensive echocardiography. Increasing body mass index, waist circumference, and body fat were associated with greater left ventricular (LV) mass and left atrial volume indexed to height(2.7) in both men and women (P<0.001). In women, all 3 measures were associated with abnormal LV geometry, and increasing waist circumference and body fat were associated with worse global longitudinal strain, a measure of LV systolic function. In both sexes, increasing body mass index was associated with greater right ventricular end-diastolic area and worse right ventricular fractional area change (P≤0.001). We observed similar associations for both waist circumference and percent body fat. CONCLUSIONS: In a large, biracial cohort of older adults free of clinically overt coronary heart disease or heart failure, obesity was associated with subclinical abnormalities in cardiac structure in both men and women and with adverse LV remodeling and impaired LV systolic function in women. These data highlight the association of obesity and subclinical abnormalities of cardiac structure and function, particularly in women.

Prognostic Relevance of Left Atrial Dysfunction in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Left atrial (LA) size is an established marker of risk for adverse outcomes in heart failure with preserved ejection fraction (HFpEF). However, the independent prognostic importance of LA function in HFpEF is not known. METHODS AND RESULTS: We assessed LA function measured by speckle-tracking echocardiography in 357 patients with HFpEF enrolled in the Treatment Of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trial who were in sinus rhythm at the time of echocardiography. Lower peak LA strain, indicating LA dysfunction, was associated with older age, higher prevalence of atrial fibrillation and left ventricular (LV) hypertrophy, worse LV and right ventricular systolic function, and worse LV diastolic function. At a mean follow-up of 31 months (interquartile range, 18-43months), 91 patients (25.5%) experienced the primary composite end point of cardiovascular death, HF hospitalization, and aborted sudden death. Lower peak LA strain was associated with a higher risk of the composite end point (hazard ratio, 0.96 per unit of reduction in strain; 95% confidence interval, 0.94-0.99; P=0.009) and of HF hospitalization alone (hazard ratio, 0.95 per unit of reduction in strain; 95% confidence interval, 0.92-0.98; P=0.003). The association of LA strain with incident HF hospitalization remained significant after adjustment for clinical confounders, but not after further adjustment for LV global longitudinal strain and the E/E' ratio, parameters of LV systolic and diastolic function, respectively. CONCLUSIONS: LA dysfunction in HFpEF is associated with a higher risk of HF hospitalization independent of potential clinical confounders, but not independent of LV strain and filling pressure. Impairment in LV systolic and diastolic function largely explains the association between impaired LA function and higher risk of HF hospitalization in HFpEF. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00094302.

Prehypertension is Associated With Abnormalities of Cardiac Structure and Function in the Atherosclerosis Risk in Communities Study.

BACKGROUND: Prehypertension (blood pressure (BP) of 120-139 mm Hg systolic and/or 80-89 mm Hg diastolic) is highly prevalent and is associated with increased cardiovascular risk. Our goal was to investigate the extent to which prehypertension is associated with end-organ alterations in cardiac structure and function in a large biracial cohort of older men and women. METHODS: We studied 4,871 participants of the Atherosclerosis Risk in Communities (ARIC) study who attended visit 5 (2011-2013) and underwent two-dimensional echocardiography while free of prevalent coronary heart disease or heart failure. We categorized participants into 3 groups: optimal BP (BP <120 mm Hg and <80 mm Hg) (n = 402), prehypertension (n = 537), and hypertension (n = 3,932). RESULTS: Individuals with prehypertension (75±5 years) had higher left ventricular (LV) mass index and wall thickness, and higher prevalence of abnormal LV geometry than those with optimal BP (74±5 years), but lower than those with frank hypertension (76±5 years). In addition, participants with prehypertension had impairment of diastolic parameters (E/A, E' and E/E'), and had higher prevalence of mild and moderate-severe diastolic dysfunction compared to those with optimal BP, but no differences in systolic parameters. These differences in cardiac structure and function remained significant after adjusting for important clinical covariates. CONCLUSION: In the ARIC cohort at visit 5, prehypertension was associated with increased LV remodeling and impaired diastolic function, but not systolic function, suggesting that even mildly elevated BP within the normal range is associated with cardiac end-organ damage.

Impaired left atrial function in heart failure with preserved ejection fraction.

AIMS: Left atrial (LA) enlargement is present in the majority of heart failure with preserved ejection fraction (HFpEF) patients and is a marker of risk. However, the importance of LA function in HFpEF is less well understood. METHODS AND RESULTS: The PARAMOUNT trial enrolled HFpEF patients (LVEF ≥45%, NT-proBNP >400 pg/mL). We assessed LA reservoir, conduit, and pump function using two-dimensional volume indices and speckle tracking echocardiography in 135 HFpEF patients in sinus rhythm at the time of echocardiography and 40 healthy controls of similar age and gender. Systolic LA strain was related to clinical characteristics and measures of cardiac structure and function. Compared with controls, HFpEF patients had worse LA reservoir, conduit, and pump function. The differences in systolic LA strain (controls 39.2 ± 6.6% vs. HFpEF 24.6 ± 7.3%) between groups remained significant after adjustments and even in the subsets of HFpEF patients with normal LA size or without a history of AF. Among HFpEF patients, lower systolic LA strain was associated with higher prevalence of prior HF hospitalization and history of AF, as well as worse LV systolic function, and higher LV mass and LA volume. However, NT-proBNP and E/E' were similar across the quartiles of LA function. CONCLUSIONS: In this HFpEF cohort, we observed impairment in all phases of LA function, and systolic LA strain was decreased independent of LA size or history of AF. LA dysfunction may be a marker of severity and play a pathophysiological role in HFpEF. TRIAL REGISTRATION: NCT00887588.

Association between renal function and cardiovascular structure and function in heart failure with preserved ejection fraction.

AIM: Renal dysfunction is a common comorbidity in patients with heart failure and preserved ejection fraction (HFpEF). We sought to determine whether renal dysfunction was associated with measures of cardiovascular structure/function in patients with HFpEF. METHODS: We studied 217 participants from the PARAMOUNT study with HFpEF who had echocardiography and measures of kidney function. We evaluated the relationships between renal dysfunction [estimated glomerular filtration rate (eGFR) >30 and <60 mL/min/1.73 m(2) and/or albuminuria] and cardiovascular structure/function. RESULTS: The mean age of the study population was 71 years, 55% were women, 94% hypertensive, and 40% diabetic. Impairment of at least one parameter of kidney function was present in 62% of patients (16% only albuminuria, 23% only low eGFR, 23% both). Renal dysfunction was associated with abnormal LV geometry (defined as concentric hypertrophy, or eccentric hypertrophy, or concentric remodelling) (adjusted P = 0.048), lower midwall fractional shortening (MWFS) (P = 0.009), and higher NT-proBNP (P = 0.006). Compared with patients without renal dysfunction, those with low eGFR and no albuminuria had a higher prevalence of abnormal LV geometry (P = 0.032) and lower MWFS (P < 0.01), as opposed to those with only albuminuria. Conversely, albuminuria alone was associated with greater LV dimensions (P < 0.05). Patients with combined renal impairment had mixed abnormalities (higher LV wall thicknesses, NT-proBNP; lower MWFS). CONCLUSION: Renal dysfunction, as determined by both eGFR and albuminuria, is highly prevalent in HFpEF, and associated with cardiac remodelling and subtle systolic dysfunction. The observed differences in cardiac structure/function between each type of renal damage suggest that both parameters of kidney function might play a distinct role in HFpEF.

Sex-specific cardiovascular structure and function in heart failure with preserved ejection fraction.

AIMS: Women are more likely to develop heart failure with preserved ejection fraction (HFpEF) than men. We studied the relationship between sex and cardiovascular structure and function in patients with HFpEF. METHODS AND RESULTS: The study included 279 participants from the PARAMOUNT study (57% women) with analysable baseline echocardiograms (mean age 71 years, 94% hypertensive, 38% diabetic). We assessed sex-based differences in baseline clinical characteristics and measures of cardiovascular structure/function. Coronary artery disease was less common in women than in men. Women were more obese and symptomatic, and less likely to have albuminuria. Women had higher indexed left ventricular (LV) wall thicknesses, worse diastolic function (lower E', P = 0.002; higher E/E', P < 0.001), while LV mass and LV volumes indexed for height(2.7) were similar. Nonetheless, female sex was associated with a trend towards higher prevalence of abnormal LV geometry (defined as concentric hypertrophy, or eccentric hypertrophy, or concentric remodelling) at baseline (unadjusted P = 0.028, adjusted P = 0.056) and 12 weeks' follow up (unadjusted P = 0.001, adjusted P = 0.006), but not at 36 weeks' follow up (unadjusted P = 0.81, adjusted P = 0.99). Despite higher LV ejection fraction in women, global LV strain was similar between the sexes, while Tissue Doppler Imaging S' mitral velocity was lower in women. Both LV diastolic and systolic stiffness were higher in women than men (P < 0.001), even adjusting for LV concentricity and clinical covariates. We observed no sex differences in systolic arterial-LV coupling, as women also had higher absolute arterial elastance compared with men, although this difference was not significant after adjusting for height(2.7) . CONCLUSION: More pronounced diastolic dysfunction may contribute to the greater predisposition for HFpEF in women compared with men.

Left ventricular dyssynchrony in patients with heart failure and preserved ejection fraction.

AIMS: Mechanical dyssynchrony has been postulated to play a pathophysiologic role in heart failure with preserved ejection fraction (HFpEF). METHODS AND RESULTS: We quantified left ventricular (LV) systolic dyssynchrony in 130 HFpEF patients with NYHA class II-IV symptoms, ejection fraction (EF) ≥45%, and NT-proBNP levels >400 pg/mL enrolled in the PARAMOUNT trial, and compared them to 40 healthy controls of similar age and gender. Dyssynchrony was assessed by 2D speckle tracking as standard deviation (SD) of time to peak longitudinal systolic strain in 12 ventricular segments and related to measures of systolic and diastolic function. Heart failure with preserved ejection fraction patients (62% women, mean age of 71 ± 9 years, body mass index of 30.2 ± 5.9 kg/m(2), systolic blood pressure 139 ± 15 mmHg) demonstrated significantly greater dyssynchrony than controls (SD of time to peak longitudinal strain; 90.6 ± 50.9 vs. 56.4 ± 33.5 ms, P < 0.001), even in the subset of patients (n = 63) with LVEF ≥55% and narrow QRS (≤100 ms). Among HFpEF patients, dyssynchrony was related to wider QRS interval, higher LV mass, and lower early diastolic tissue Doppler myocardial velocity (E'). Greater dyssynchrony remained significantly associated with worse diastolic function even after restricting the analysis to patients with EF≥55% and adjusting for age, gender, systolic blood pressure, LV mass index, and LVEF. CONCLUSION: Heart failure with preserved EF is associated with greater mechanical dyssynchrony compared with healthy controls of similar age and gender. Within an HFpEF population, the severity of dyssynchrony is related to the width of QRS complex, LV hypertrophy, and diastolic dysfunction.

Alteração precoce da matriz extracelular e parâmetros diastólicos na síndrome metabólica / Early change of extracellular matrix and diastolic parameters in metabolic syndrome

FUNDAMENTOS: Síndrome Metabólica (SM) está associada com maior risco cardiovascular, porém não está claro se as alterações miocárdicas presentes nessa condição, como a disfunção diastólica, são consequência de mecanismos sistêmicos ou de efeitos diretos no miocárdio. OBJETIVOS: Comparar função diastólica, biomarcadores de atividade da Matriz Extracelular (MEC), inflamação e estresse hemodinâmico, em pacientes com SM e controles saudáveis. MÉTODOS: Pacientes com SM (n = 76) e controles saudáveis (n = 30) foram avaliados clinicamente e submetidos a exame ecocardiográfico e mensuração dos níveis plasmáticos de metaloproteinase-9 (MMP9), inibidor tecidual da metaloproteinase-1 (TIMP1), proteína C reativa ultrassensível (PCR-us), resistência insulínica (HOMA-RI) e NT-proBNP. RESULTADOS: O grupo SM apresentou menor onda E' (10,1 ± 3,0 cm/s vs. 11,9 ± 2,6 cm/s, p = 0,005), maiores valores para onda A (63,4 ± 14,1 vs. 53,1 ± 8,9 cm/s, p < 0,001), razão E/E'(8,0 ± 2,2 vs. 6,3 ± 1,2; p < 0,001), MMP9 (502,9 ± 237,1 vs. 330,4 ± 162,7 ng/mL, p < 0,001), PCR-us (p = 0,001) e HOMA-RI (p < 0,001), sem diferença nos níveis de TIMP1 e NT-proBNP. Na análise multivariada, apenas MMP9 foi independentemente associada a SM. CONCLUSÃO: Pacientes com SM apresentaram diferenças em medidas ecocardiográficas de função diastólica, na atividade da MEC, PCR-us e HOMA-RI em relação aos controles. Porém, somente MMP9 foi independentemente associada com SM. Esses achados sugerem que os efeitos precoces da SM sobre a atividade da MEC podem não ser detectados nas medidas ecocardiográficas de função diastólica usuais.

BACKGROUND: Metabolic syndrome (MS) is associated with increased cardiovascular risk. It is not clear whether myocardial changes showed in this syndrome, such as diastolic dysfunction, are due to the systemic effects of the syndrome, or to specific myocardial effects. OBJECTIVES: Compare diastolic function, biomarkers representing extracellular matrix activity (ECM), inflammation and cardiac hemodynamic stress in patients with the MS and healthy controls. METHODS: MS patients (n=76) and healthy controls (n=30) were submitted to a clinical assessment, echocardiographic study, and measurement of plasma levels of metalloproteinase-9 (MMP9), tissue inhibitor of metalloproteinase-1 (TIMP1), ultrasensitive-reactive-C-Protein (us-CRP), insulin resistance (HOMA-IR) and natriuretic peptide (NT-proBNP). RESULTS: MS group showed lower E' wave (10.1 ± 3.0 cm/s vs 11.9 ± 2.6 cm/s, p = 0.005), increased A wave (63.4 ± 14.1 cm/s vs. 53.1 ± 8.9 cm/s; p < 0.001), E/E' ratio (8.0 ± 2.2 vs. 6.3 ± 1.2; p < 0.001), MMP9 (502.9 ± 237.1 ng/mL vs. 330.4±162.7 ng/mL; p < 0.001), us-CRP (p = 0.001) and HOMA-IR (p < 0.001), but no difference for TIMP1 or NT-proBNP levels. In a multivariable analysis, only MMP9 was independently associated with MS. CONCLUSION: MS patients showed differences for echocardiographic measures of diastolic function, ECM activity, us-CRP and HOMA-IR when compared to controls. However, only MMP9 was independently associated with the MS. These findings suggest that there are early effects on ECM activity, which cannot be tracked by routine echocardiographic measures of diastolic function.

Early change of extracellular matrix and diastolic parameters in metabolic syndrome.

BACKGROUND: Metabolic syndrome (MS) is associated with increased cardiovascular risk. It is not clear whether myocardial changes showed in this syndrome, such as diastolic dysfunction, are due to the systemic effects of the syndrome, or to specific myocardial effects. OBJECTIVES: Compare diastolic function, biomarkers representing extracellular matrix activity (ECM), inflammation and cardiac hemodynamic stress in patients with the MS and healthy controls. METHODS: MS patients (n = 76) and healthy controls (n=30) were submitted to a clinical assessment, echocardiographic study, and measurement of plasma levels of metalloproteinase-9 (MMP9), tissue inhibitor of metalloproteinase-1 (TIMP1), ultrasensitive-reactive-C-Protein (us-CRP), insulin resistance (HOMA-IR) and natriuretic peptide (NT-proBNP). RESULTS: MS group showed lower E' wave (10.1 ± 3.0 cm/s vs 11.9 ± 2.6 cm/s, p = 0.005), increased A wave (63.4 ± 14.1 cm/s vs. 53.1 ± 8.9 cm/s; p < 0.001), E/E' ratio (8.0 ± 2.2 vs. 6.3 ± 1.2; p < 0.001), MMP9 (502.9 ± 237.1 ng/mL vs. 330.4 ± 162.7 ng/mL; p < 0.001), us-CRP (p = 0.001) and HOMA-IR (p < 0.001), but no difference for TIMP1 or NT-proBNP levels. In a multivariable analysis, only MMP9 was independently associated with MS. CONCLUSION: MS patients showed differences for echocardiographic measures of diastolic function, ECM activity, us-CRP and HOMA-IR when compared to controls. However, only MMP9 was independently associated with the MS. These findings suggest that there are early effects on ECM activity, which cannot be tracked by routine echocardiographic measures of diastolic function.