Preclinical Left Ventricular Diastolic Dysfunction Research Articles

The role of polycystic ovary syndrome in preclinical left ventricular diastolic dysfunction: an echocardiographic approach: a systematic review and meta-analysis.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting women of childbearing age, causing hormonal imbalances, reproductive issues, and metabolic disturbances. Women with PCOS have an increased risk of cardiovascular disease due to insulin resistance, obesity, and hyperandrogenism. Detecting impaired left ventricular (LV) function is important in managing this condition. Echocardiography, a non-invasive imaging technique, can effectively detect LV dysfunction. The goal of this systematic review was to assess whether there are any variations in echocardiographic measures between women with PCOS and those without the condition in order to determine the potential impact of PCOS on LV function. This review followed the PRISMA reporting guidelines. A thorough search of databases including PubMed, Scopus, Web of Science, and Cochrane was conducted. The quality of the selected studies was assessed using the Joanna Briggs Institute appraisal instruments. After applying strict eligibility criteria, data were extracted and organized in Microsoft Excel sheets. Review Manager (RevMan) software was used for the analysis. Analysis of 29 studies revealed significant differences in echocardiographic measures related to diastolic function between women with PCOS and healthy controls. However, there were no significant differences in measures of systolic function. These findings indicate that PCOS may be linked to impaired LV function, thereby increasing the risk of cardiovascular disease. Further research is necessary to better understand this association and its clinical implications. Early detection and management of PCOS could potentially help prevent cardiovascular complications in affected women.

Relationships between kidney dysfunction and left ventricular diastolic dysfunction: a hospital-based retrospective study.

Preclinical left ventricular diastolic dysfunction (LVDD) is a high-risk state for heart failure. Kidney dysfunction is a known risk factor for heart failure, but its association with asymptomatic LVDD is not well-known. A hospital-based retrospective cohort study was conducted on patients who underwent echocardiogram between 2006 and 2016 to assess the association between baseline kidney function and LVDD on echocardiogram. E/e' ratio was defined as the ratio of peak velocity of early diastolic left ventricular inflow (E) to mitral annular velocity (e'). The primary outcome was time to development of LVDD, which was defined as E/e' ratio > 14. The changes in the E/e' ratio and other echocardiographic parameters were assessed using a mixed effects model. Among 1167 patients, the mean age was 61 years, and the mean baseline E/e' ratio and ejection fraction were 9.6 and 69%, respectively. During a median follow-up of 3.2 years, 231 (19.8%) people developed LVDD. According to eGFR (mL/min/1.73m2), the risk for LVDD based on hazard ratio [95% confidence interval (95% CI)] was 1.20 (0.82, 1.75) for 60 to < 90, 1.42 (0.87, 2.31) for 45 to < 60, and 2.57 (1.61, 4.09) for < 45 (P trend < 0.001). The adjusted risks (95% CI) for annual change in E/e' ratio was 0.09 (0.03, 0.14) overall and 0.28 (0.11, 0.45) in the lowest eGFR group; the trend in changes in annual E/e' ratio by baseline eGFR was significant (P trend = 0.01). Relatively low kidney function was related with the risks for LVDD. Long-term cohort studies are warranted to confirm the association between LVDD and symptomatic heart failure in patients with kidney dysfunction.

Cell‐based hormone therapy prevents diastolic dysfunction after estrogen loss in the Spontaneously Hypertensive Rat (SHR)

Introduction. Preclinical left ventricular diastolic dysfunction (LVDD) is a forerunner to heart failure with preserved ejection fraction, which is seen more often in older women than men of the same age. While hormone therapy plays an important role in the management of vasomotor and genitourinary symptoms experienced by many women during the menopausal transition, its efficacy with regard to maintenance of cardiac structure and function and prevention of LVDD disease progression with aging has not been tested due to the concern for off‐target health risks (e.g., cancer, blood clots). We developed a cell‐based hormone therapy (cHT) approach that recapitulates native cell–cell interactions between ovarian granulosa and theca cells in a 3D bioengineered construct to mimic the dynamic release of sex hormones into the circulation. Our first report in ovariectomized rats shows that ovarian constructs are able to ameliorate various somatic adverse effects of hormone deficiency (e.g. bone loss). To extend these findings to cardiac health, we sought to determine the efficacy of cHT in preserving cardiac diastolic function after estrogen loss using a hypertensive rodent model.Methods14 SHR females underwent bilateral ovariectomy (OVX) while 5 SHRs received sham surgery at 12 weeks of age; 8 weeks post‐surgery, OVX rats were randomized (n=4–5/group) to vehicle, cHT, or pharmacologic hormone therapy (pHT: E2 (10mg/kg/day) and P4 (2mg/kg/day) subcutaneous pellets) and compared to gonad‐intact rats treated with vehicle (VEH). Body weights and tail cuff systolic blood pressure (SBP) were measured biweekly. Following 10 weeks of treatment, rats were lightly anesthetized (isoflurane) for Doppler measures of diastolic function. Data were analyzed by one‐way ANOVA. P&lt;0.05 was significant.ResultsOVX rats, irrespective of treatment, had higher body weights when compared to sham (P&lt;0.001). Uterine atrophy by OVX was minimized by pHT and cHT, reflecting modest E2‐related effects (Figure A). SBP increased progressively over time (P&lt;0.01), without overt differences across treatment groups. Even so, both cHT and pHT prevented adverse OVX‐related effects on myocardial relaxation (e') and Doppler‐derived filling pressures (E/e') when compared to vehicle (Figures B, C).ConclusionThese data show that novel cell‐based hormone therapy is effective in preventing diastolic dysfunction from surgically‐induced menopause in the SHR. Additional studies are underway to determine cHT’s long‐term (6 months) treatment efficacy in middle‐to‐advanced aged OVX rats.Support or Funding InformationNIH AG061588Figure 1

Comparison of Predictors of Heart Failure With Preserved Versus Reduced Ejection Fraction in a Multiracial Cohort of Preclinical Left Ventricular Diastolic Dysfunction

Preclinical diastolic dysfunction (PDD) is a well-known but poorly understood risk factor for heart failure. We aimed to investigate risk factors contributing to progression of PDD to heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). Patients with echocardiogram from 2003 to 2008 with left ventricular ejection fraction ≥50%, grade I diastolic dysfunction, and free of clinical heart failure were included. The end point was incident HFpEF or HFrEF. Cumulative probabilities were estimated and multivariable adjusted Cox proportional hazards regressions were performed to examine predictors of incident HFpEF and HFrEF. In total, 7,878 patients with PDD (79.2% nonwhite) were included. At the end of follow-up (median 5.9years), 146 patients developed HFrEF, and 635 patients developed HFpEF. The 10-year cumulative probabilities of HFrEF and HFpEF were 3.1% and 12.6%, respectively. Incidence of HFrEF was significantly lower in non-Hispanic blacks (2.2%) compared with non-Hispanic whites (4.5%). Age, diabetes, myocardial infarction, and renal disease were independent predictors of both HFrEF and HFpEF. Male gender, cerebrovascular accident, and low baseline left ventricular ejection fraction were associated with HFrEF only; whereas pulmonary disease, blood urea nitrogen, and anemia were predictors of HFpEF only. In conclusion, our results revealed a distinct set of predictors of HFrEF and HFpEF in patients with PDD and underscored a differential approach of risk stratification, prevention, and early treatment based on heart failure subtypes.

1 Peripheral blood natriuretic peptide is associated with myocardial fibrosis and cardiac tissue expression of natriuretic peptide and fibro-inflammatory genes in patients with normal ejection fraction

Introduction The St Vincent’s Screening TO Prevent Heart Failure (STOP-HF) study showed that preclinical left ventricular diastolic dysfunction (PCDD) is more prevalent than left ventricular systolic function, that peripheral blood natriuretic peptide (NP) can be used to identify asymptomatic myocardial disease and that NP correlates with disease severity. Methods We investigated peripheral blood biomarkers associated with PCDD and corresponding myocardial gene expression of the biomarkers in 35 consecutive, consenting stable patients with normal ejection fraction (EF > 45%) undergoing elective CABG surgery. Atrial tissue was obtained adjacent to the venous cannulation site and was stained for collagen using picosirus red and macrophage markers. Patients were categorised as PCDD or controls based on Doppler Echocardiography. Biomarkers and genes of interest included fibro-inflammatory genes, NP and its main transmembrane receptor Natriuretic Peptide Receptor A (NPRA). Results Patients were aged 67.4 ± 9.8 years, 25 (69%) were male, 18 (53%) had hypertension and 5 (14%) had diabetes. Preclinical LVDD patients (n = 10) had greater tissue collagen volume fraction, E/Eprime (12.5 ± 2.6 vs. 8.4 ± 2.0), LAVI (30.6 ± 4.2 vs. 27.8 ± 3.4) and atrial fibrillation (70% vs 8%) than controls (all p Conclusion PCDD is associated with elevated peripheral blood NP, myocardial fibrosis and altered expression of fibro-inflammatory genes in the myocardium. Unlike other markers of fibro-inflammation, peripheral blood NP was correlated with myocardial tissue expression of its corresponding gene and these data underline the value of peripheral blood NP in risk stratification in PCDD.

Echocardiographic assessment of maximum and minimum left atrial volumes: a population-based study of middle-aged and older subjects without apparent cardiovascular disease.

The aim of the present study was to obtain reference values of maximum and minimum left atrial volumes (maxLAV and minLAV, respectively) in a population-based subset without apparent cardiovascular disease or other factors potentially associated with left atrial enlargement. Because left ventricular diastolic dysfunction is commonly found in elderly subjects, we also tried to identify the presence of possible preclinical diastolic dysfunction in the study population. A population-based sample of 168 subjects (127 men and 41 women) underwent two-dimensional echocardiography using the single-plane disc method to determine maxLAV and minLAV. maxLAV and minLAV were indexed to body surface area (maxLAVi and minLAVi, respectively). maxLAVi was independent of age and sex, and produced reference limits (mean ± 1.96 SD) of 15–37 mL/m2. minLAVi was correlated with age, and produced estimated reference limits of 3–15 and 7–23 mL/m2 in 40- and 80-year-old subjects, respectively. Based on the age-dependent reference values from the European Association of Cardiovascular Imaging, <5 % of the study population had possible preclinical left ventricular diastolic dysfunction. The present study established normal ranges for maxLAVi and minLAVi in a well-characterized population-based subset without apparent cardiovascular disease or other factors potentially associated with left atrial volume enlargement.

Albuminuria and left ventricular mass index are associated with left ventricular diastolic dysfunction in type 2 diabetes mellitus patients

Background Diabetes mellitus (DM) is associated with a substantially increased risk of developing heart failure. To verify the risk factors of preclinical left ventricular diastolic dysfunction (LVDD) in type 2 diabetic patients, we assessed the LVDD by tissue Doppler echocardiography and its relationship with various parameters in asymptomatic patients with type 2 DM.

ASYMPTOMATIC LEFT VENTRICULAR DIASTOLIC DYSFUNCTION AND RISK OF DEATH IN THE COMMUNITY

LV to untwist in diastole is dependent on systolic twist. We hypothesise that patients with heart failure and normal ejection fraction (HFNEF) have reduced LV untwist to facilitate rapid early diastolic filling particularly during exercise thus symptoms of exertional dyspnoea. Methods: 34 clinically diagnosed HFNEF patients with proven cardiac limitation (72± 7 years, 23 females, LVEF 60± 7%, VO2max 17.9± 3.0ml/(min kg)) and 23 agematched healthy controls (70± 8 years, 15 females, LVEF 63± 8%, VO2max 30.9± 4.6ml/(min kg)) were recruited. Rest and submaximal supine exercise echocardiography were performed to comparable heart rate and blood pressure. Apical rotation and untwist were studied by speckle tracking. The mitral flow propagation velocity (Vp) was derived from colour M-mode Doppler. Results: LV apical systolic rotation and early diastolic untwist are significantly less at rest and on exercise in patients. Vp at rest is comparable between the two groups. However, the increase in Vp on exercise is significantly less in patients hence Vp is significantly lower than controls. LV early untwist correlates significantly with the increase in Vp (r= 0.43, p= 0.005) and VO2max (r= 0.526, p= 0.007). Exercise Vp also correlates with VO2max (r= 0.347, p= 0.03). Patients Controls p-Value Rotation rest (◦) 10.7 ± 4.1 13.9 ± 3.2 0.002 Rotation exercise (◦) 13.5 ± 4.8 17.6 ± 4.0 0.006 Untwist rest (◦) 24.3 ± 9.4 30.9 ± 9.7 0.013 Untwist exercise (◦) 22.1 ± 8.9 29.5 ± 7.8 0.008 Vp rest (m/s) 40.2 ± 10.8 39.8 ± 7.3 0.875 Vp exercise (m/s) 52.6 ± 12.0 62.4 ± 13.8 0.012 Conclusion: LV rotation and untwist mechanics are impaired in HFNEF. This is associated with reduced LV suction in early diastole and reduced exercise tolerance. The efficiency of LV rotation and untwist is crucial to aid rapid early diastolic filling particularly on exercise when heart rate is increased and diastole shortens. doi:10.1016/j.hlc.2009.03.042 Tuesday Young Investigators ASYMPTOMATIC LEFT VENTRICULAR DIASTOLIC DYSFUNCTION AND RISK OF DEATH IN THE COMMUNITY Walter Abhayaratna, Katrina Hayes, Christine O’Reilly, Satoru Sakuragi, Niels Becker Australian National University, Canberra, ACT, Australia Background: There is limited information regarding the risk of death in asymptomatic individuals with left ventricular (LV) diastolic dysfunction (LVDD) and ejection fraction (EF) >50%. In this population-based study, we assessed mortality rates of subjects with LVDD without a history or clinical evidence of congestive heart failure. Methods and results:Weassessed diastolic function using comprehensive Doppler echocardiography in 1275 Canberra Heart Study participants (mean age 69 years; 50% men). Diastolic dysfunction was classified as mild or advanced (with elevated LV filling pressure). Prevalence rates of mild and advanced preclinical LVDD were 26% and 7.5% in women, respectively; and 24% and 6.9% in men, respectively. During a mean follow-up of 4.8 years, there were 61 deaths in preclinical subjects with EF> 50%. Death rates among individuals with normal LV diastolic function and mild LVDD were similar (0.8 vs. 1.1 per 100 person-years, respectively; p= 0.24). However, the rate of death among those with advanced LVDD (3.0 per 100 person-years)was higherwhen compared to subjectswith normal diastolic function and mild LVDD (p< 0.01 for both). After adjustment for age, sex, EF and cardiovascular risk factors, preclinical advanced LVDDwas associated with an increased mortality risk (adjusted Hazards Ratio 2.2, CI 1.1–4.2). Conclusion: Community-based adults with preclinical LVDD are at increased risk of death only when the condition is advanced and is associatedwith increased LVfilling pressures. doi:10.1016/j.hlc.2009.03.043 LEFT VENTRICULAR DYSSYNCHRONY EARLY AFTER NON-ST ELEVATION MYOCARDIAL INFARCTION INDEPENDENTLY PREDICTED LONG-TERM LEFT VENTRICULAR REMODELLING A. Ng, J. Vidiac, D.Y. Leung Liverpool Hospital, Sydney, NSW, Australia We evaluated the prognostic significance of LV dyssynchrony early after non-ST elevation myocardial infarction (NSTEMI). Methods: LV dyssynchrony was measured as standard deviation of times to 12 regional peak Smvelocities (SDTs) in 100 NSTEMI patients (age 60.0± 11.8 years, 71 men) prior to angiography, at 6 and 12 months. Significant dyssynchrony was defined as SDTs≥ 32.6ms. Results: LV end-diastolic volume (EDV) index decreased with time (47.1± 14.2mL/m2 vs. 46.4± 13.6mL/m2 vs. 43.1± 12.8mL/m2, p< 0.001) and was independently predicted by lower number of diseased vessels (p= 0.001) and revascularization (p= 0.041). LV end-systolic volume (ESV)

Aortic stiffness for the detection of preclinical left ventricular diastolic dysfunction: pulse wave velocity versus pulse pressure

An age-dependent relationship between aortic and left ventricular (LV) stiffening has been observed in community-based adults. Our aim was to compare the performances of wave reflection-dependent (pulse pressure) and independent [carotid-femoral pulse wave velocity (PWV)] indexes of aortic stiffness to detect preclinical LV diastolic dysfunction. In this case-control study, a stratified subsample of participants of a population-based echocardiographic survey with LV ejection fraction higher than 45% and without overt heart failure was randomly selected to undergo assessment of brachial blood pressure, LV diastolic function by Doppler echocardiography, and estimation of central aortic pressures and PWV by applanation tonometry. Of the 233 subjects (mean age 73 +/- 6 years, 54% men), 84 had normal diastolic function, 99 had mild diastolic dysfunction, and 50 had moderate or severe diastolic dysfunction. Brachial pulse pressure, central pulse pressure, and PWV progressively increased according to the severity of diastolic dysfunction, independent of age and sex. The overall performance of PWV was superior to brachial pulse pressure [area under receiver operating characteristic curve (AUC): 0.70 versus 0.59, respectively; P = 0.005] and central pulse pressure (AUC: 0.70 versus 0.56, respectively; P = 0.001) for the detection of any diastolic dysfunction. PWV appeared to be superior to central and brachial pulse pressure for the detection of diastolic dysfunction in older adults with 'preserved' LV ejection fraction.

New Molecular Mechanism in Diastolic Heart Failure

In contrast to systolic heart failure (SHF), for which knowledge of pathophysiology and therapy has advanced rapidly over the past decade, little is known about diastolic heart failure (DHF). The article by van Heerebeek et al1 in this issue of Circulation that describes an abnormal distribution of titin isoforms in DHF may herald a new approach to understanding the pathophysiology of this syndrome. Article p 1966 Recognition of 2 forms of heart failure is not new; almost 70 years ago, Fishberg2 described “those forms of cardiac insufficiency which are due to inadequate diastolic filling of the heart (hypodiastolic failure) [and] the far more common ones in which the heart fills adequately but does not empty to the normal extent (hyposystolic failure)” (p 23). This distinction has stood the test of time, because there is a growing consensus that these 2 clinical syndromes differ in epidemiology, demographics, and origin. Because DHF and SHF represent subgroups of patients with heart failure, they share many clinical features, notably the hemodynamic findings, but it is now clear that they are caused by different pathophysiological mechanisms. Hearts in SHF are characterized by eccentric hypertrophy, progressive left ventricular (LV) dilation, and abnormal LV systolic properties, whereas in DHF, the hearts generally exhibit concentric hypertrophy, normal or reduced LV volume, concentric remodeling, and abnormal diastolic function.3,4 In addition, cardiomyocyte size, shape, and molecular composition differ in these 2 syndromes. Diastolic dysfunction refers to mechanical and functional abnormalities present during relaxation and filling, whereas DHF refers to clinical syndromes in which patients with heart failure have little or no ventricular dilatation and significant, often dominant diastolic dysfunction. Diastolic dysfunction can be quantified with indices of LV pressure decline and filling. Abnormal pressure decline is characterized by decreased peak −dP/dt, prolonged isovolumic time constant (τ), and …