Association of Female Menopause With Atrioventricular Mechanics and Outcomes

BACKGROUND: Despite known sex differences in cardiac structure and function, little is known about how menopause and estrogen associate with atrioventricular mechanics and outcomes. OBJECTIVE: To study how, sex differences, loss of estrogen in menopause and duration of menopause, relate to atrioventricular mechanics and outcomes. METHODS: Among 4051 asymptomatic adults (49.8 ± 10.8 years, 35%women), left ventricular (LV) and left atrial (LA) mechanics were assessed using speckle-tracking. RESULTS: Post-menopausal (vs. pre-menopausal) women had similar LV ejection fraction but reduced GLS, reduced PALS, increased LA stiffness, higher LV sphericity and LV torsion (all p < 0.001). Multivariable analysis showed menopause to be associated with greater LV sphericity (0.02, 95%CI 0.01, 0.03), higher indexed LV mass (LVMi), lower mitral e’, lower LV GLS (0.37, 95%CI 0.04–0.70), higher LV torsion, larger LA volume, worse PALS (∼2.4-fold) and greater LA stiffness (0.028, 95%CI 0.01–0.05). Increasing years of menopause was associated with further reduction in GLS, markedly worse LA mechanics despite greater LV sphericity and higher torsion. Lower estradiol levels correlated with more impaired LV diastolic function, impaired LV GLS, greater LA stiffness, and increased LV sphericity and LV torsion (all p < 0.05). Approximately 5.5% (37/669) of post-menopausal women incident HF over 2.9 years of follow-up. Greater LV sphericity [adjusted hazard ratio (aHR) 1.04, 95%CI 1.00–1.07], impaired GLS (aHR 0.87, 95%CI 0.78–0.97), reduced peak left atrial longitudinal strain (PALS, aHR 0.94, 95%CI 0.90–0.99) and higher LA stiffness (aHR 10.5, 95%CI 1.69–64.6) were independently associated with the primary outcome of HF hospitalizations in post-menopause. Both PALS < 23% (aHR:1.32, 95%CI 1.01–3.49) and GLS < 16% (aHR:5.80, 95%CI 1.79–18.8) remained prognostic for the incidence of HF in post-menopausal women in dichotomous analyses, even after adjusting for confounders. Results were consistent with composite outcomes of HF hospitalizations and 1-year all-cause mortality as well. CONCLUSION: Menopause was associated with greater LV/LA remodeling and reduced LV longitudinal and LA function in women. The cardiac functional deficit with menopause and lower estradiol levels, along with their independent prognostic value post-menopause, may elucidate sex differences in heart failure further

The associations among co-morbidity, cardiac geometries and mechanics in hospitalized heart failure with or without preserved ejection fraction

Background: The associations among chronic health conditions, ventricular geometric alterations or cardiac contractile mechanics in different phenotypes heart failure (HF) remain largely unexplored. Methods: We studied 438 consecutive hospitalized patients (mean age: 64.9 ± 16.6 years, 52.5% female) with or without clinical evidence of HF. We examined the associations among clinical co-morbidities, LV geometries and systolic mechanics in terms of global myocardial strains. Results: Increasing clinical co-morbidities was associated with greater LV mass, worse longitudinal deformations and higher proportion of admission with HF diagnosis, which was more pronounced in HFpEF (from 6.4% to 40.7%, X2 < 0.001). The independent association between co-morbidity burden and longitudinal functional decay remained unchanged after adjusting for age and sex for all admissions and in HFpEF (Coef: 0.82 & 0.71, SE: 0.13 & 0.21, both p≤0.001). By using co-morbidity scores, the area under receiver operating characteristic curves (AUROC) in identifying HFpEF was 0.71 (95% CI: 0.65 to 0.77), 0.64 (95% CI: 0.58 to 0.71) for HFrEF and 0.72 for both (95% CI: 0.67 to 0.77). Co-morbidity burden superimposed on LV mass index and LV filling pressure (E/E’) further expanded the AUROC significantly in diagnosing both types HF (c-statistics from 0.73 to 0.81, p for ΔAUROC: 0.0012). Conclusion: Chronic health conditions in the admission population were associated with unfavorable cardiac remodeling, impair cardiac contractile mechanics and further added significantly incremental value in HF diagnosis. Our data suggested the potentiality for better cardiac function by controlling baseline co-morbidities in hospitalized HF patients, especially HFpEF. Abbreviations: CAD: coronary artery disease; CKD: chronic kidney disease; DT: deceleration time; eGFR: Estimated glomerular filtration rate; HF: heart failure; IVRT: iso-volumic relaxation time; LV: left ventricular; LVEF: left ventricular ejection fraction; RWT: relative wall thickness; TDI: Tissue Doppler imagin

Myths and Facts About Heart Failure with Preserved Ejection Fraction: Risk Factors, Longevity, Potential Pharmacological and Exercise Interventions

Significant progress in our understanding of risk factors and interventions in heart failure, a leading cause of death and disability, has occurred in recent years. Several advances in therapy for heart failure with reduced left ventricular systolic function (i.e., systolic heart failure) have led to significantly improved outcomes. Treatment options for diastolic heart failure, also known as heart failure with preserved ejection fraction (HFpEF), by contrast, remain comparatively limited. In part, this is due to gaps in our understanding of the underlying pathophysiology and the lack of standardized criteria for its diagnosis and classification. Aging and hypertension remain the leading causes of HFpEF; increased ventricular and vascular stiffness is a feature of both. Comorbidities such as diabetes, renal insufficiency, and metabolic abnormalities further aggravate disease process, and data regarding effective treatment are lacking. This article discusses the risks, mechanisms, and outcomes of HFpEF from previous studies, and summarizes potential interventions that may provide new insights into our understanding of the disease and its treatment

Cardiac Mechanics and Ventricular Twist by Three-Dimensional Strain Analysis in Relation to B-Type Natriuretic Peptide as a Clinical Prognosticator for Heart Failure Patients

<div><p>Background</p><p>Three dimensional (3D) echocardiography-derived measurements of myocardial deformation and twist have recently advanced as novel clinical tools. However, with the exception of left ventricular ejection fraction and mass quantifications in hypertension and heart failure populations, the prognostic value of such imaging techniques remains largely unexplored.</p><p>Methods</p><p>We studied 200 subjects (mean age: 60.2±16 years, 54% female, female n = 107) with known hypertension (n = 51), diastolic heart failure (n = 61), or systolic heart failure (n = 30), recruited from heart failure outpatient clinics. Fifty-eight healthy volunteers were used as a control group. All participants underwent 3D-based myocardial deformation and twist analysis (Artida, Toshiba Medical Systems, Tokyo, Japan). We further investigated associations between these measures and brain natriuretic peptide levels and clinical outcomes.</p><p>Results</p><p>The global 3D strain measurements of the healthy, hypertension, diastolic heart failure, and systolic heart failure groups were 28.03%, 24.43%, 19.70%, and 11.95%, respectively (all <i>p</i><0.001). Global twist measurements were estimated to be 9.49°, 9.77°, 8.32°, and 4.56°, respectively. We observed significant differences regarding 3D-derived longitudinal, radial, and global 3D strains between the different disease categories (<i>p</i><0.05), even when age, gender, BMI and heart rate were matched. In addition, 3D-derived longitudinal, circumferential, and 3D strains were all highly correlated with brain natriuretic peptide levels (<i>p</i><0.001). At a mean 567.7 days follow-up (25^th–75^th IQR: 197–909 days), poorer 3D-derived longitudinal, radial, and global 3D strain measurements remained independently associated with a higher risk of cardiovascular related death or hospitalization due to heart failure, after adjusting for age, gender, and left ventricular ejection fraction (all <i>p</i><0.05).</p><p>Conclusions</p><p>3D-based strain analysis may be a feasible and useful diagnostic tool for discriminating the extent of myocardial dysfunction. Furthermore, it is able to provide a prognostic value beyond traditional echocardiographic parameters in terms of ejection fraction.</p></div

The cut-off values of each strain parameter or twist for clinical outcome prediction.

<p>Abbreviations: 3D: 3-dimensional, S: strain.</p><p>The cut-off values of each strain parameter or twist for clinical outcome prediction.</p

Gender-differences in the associations between circulating creatine kinase, blood pressure, body mass and non-alcoholic fatty liver disease in asymptomatic asians

<div><p>Background</p><p>Creatine kinase (CK) is a pivotal regulatory enzyme in energy metabolism linked to both blood pressure and cardio-metabolic components. However, data is lacking in a large population of asymptomatic Asians.</p><p>Methods and results</p><p>Cardio-metabolic assessment including anthropometric measures and non-alcoholic fatty liver disease (NAFLD) were evaluated by abdominal echo in 4,562 consecutive subjects who underwent an annual health survey. Serum CK levels were related to blood pressure components [systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP)], anthropometric measures, and excessive adiposity in liver as indicated by NAFLD. Circulating CK levels ranged from 4 to 1842 IU/L (mean [SE]: 108.7 [1.1] IU/L) in the study population which consisted of 2522 males (mean age: 48.7 ± 11.2) and 2040 females (mean age: 49.4±11.5). In general, male subjects presented with higher circulating CK levels than females (mean ± SE: 127.3 ± 1.5 vs. 85.5 ± 1.3 IU/L, respectively, p < .001). Gender-differences in circulating CK levels were also observed with increasing age, which showed a more pronounced positive relationship with age in female subjects (gender interaction: p < .05). Furthermore, an elevated circulating CK level was independently associated with higher blood pressure, waist circumference and fat mass (FM), greater body mass index (BMI), increased lower estimated glomerular filtration rate (eGFR) and presence of NAFLD in multivariate analysis (all p < .05), with CK elevation more pronounced with greater BMI and FM in males compared with females (sex interaction: p < .05).</p><p>Conclusion</p><p>In a large asymptomatic Asian population, circulating CK levels were increased with more advanced age, higher blood pressure, and greater body mass with gender differences. Our findings may be useful in interpreting elevated CK from subjects free of ongoing myocardial damage.</p></div

Baseline echocardiography parameters or diastolic indices.

<p>*<i>p</i><0.05 vs. control group;</p>†<p><i>p</i><0.05 vs. HTN group;</p>‡<p><i>p</i><0.05 vs. DHF group; and ^§<i>p</i><0.05 vs. SHF group.</p><p>Abbreviations: LA: left atrium, 2D: 2-dimensional, IVS: inter-ventricular septum, RWT: relative wall thickness, LVEDV: left ventricular end diastolic volume, 3D: 3-dimensional, LVESV: left ventricular end systolic volume, LVEF: left ventricular ejection fraction, LV: left ventricular, IVRT: isovolumic relaxation time, DT: deceleration time, PWCP: pulmonary capillary wedge pressure.</p><p>Baseline echocardiography parameters or diastolic indices.</p

The associations between all 3D strain, cardiac twist, and baseline echocardiography parameters or diastolic indices.

§<p>M-mode method.</p><p>Data are expressed as coefficient (<i>p</i> value).</p><p>Abbreviations as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0115260#pone-0115260-t002" target="_blank">Table 2</a>.</p><p>The strain parameters were expressed and calculated as the “absolute values” in 3D longitudinal strain and 3D circumferential strain.</p><p>The associations between all 3D strain, cardiac twist, and baseline echocardiography parameters or diastolic indices.</p

The corresponding AUROC generated in predicting clinical outcomes when superimposed on 3D LVEF by 3D-based LS, RS, CS, 3D strain, and twist, respectively.

<p>3D LS, 3D RS, and 3D strain yielded significant incremental values in the clinical outcome prediction model beyond 3D LVEF (all <i>p</i> for delta AUROC: <0.05).</p