Preclinical Systolic Dysfunction Research Articles

Preclinical systolic dysfunction relating to ankle-brachial index among high-risk PAD population with preserved left ventricular ejection fraction

Peripheral artery disease (PAD) shares common clinical risk factors, for example, endothelial dysfunction, with preserved ejection fraction (LVEF) heart failure (HFpEF). Whether PAD is associated with preclinical systolic dysfunction and higher HF risk among individuals presenting preserved LVEF remains uncertain. We retrospectively included outpatients with at least one known or established cardiovascular (CV) risk factor with LVEF ≥ 50%. Patients were categorized into high risk and low risk of developing PAD (PAD vs Non-PAD) by ankle-brachial index (ABI) (≤ 0.90 or > 1.4) and further stratified based on their history of HFpEF (HFpEF vs. Non-HFpEF), resulting in the formation of four distinct strata. Preclinical systolic dysfunction was defined using dedicated speckle-tracking algorithm. A total of 2130 consecutive patients were enrolled in the study, with a median follow-up of 4.4 years. The analysis revealed a higher prevalence of high risk of developing PAD in patients with HFpEF compared to those without HFpEF (25.1% vs. 9.4%). Both high risk of developing PAD and HFpEF were independently associated with preclinical systolic dysfunction (global longitudinal strain, GLS ≥ − 18%) (odds ratio, OR: 1.38; 95% confidence interval, CI: 1.03–1.86). In comparison to patients at low risk of developing PAD without HFpEF (Non-PAD/Non-HFpEF group), those categorized as having a high risk of developing PAD with HFpEF (PAD/HFpEF group) exhibited the most impaired GLS and a heightened susceptibility to heart failure hospitalization (hazard ratio, HR: 6.51; 95% CI: 4.43–9.55), a twofold increased risk of all-cause mortality (HR: 2.01; 95% CI: 1.17–3.38), cardiovascular mortality (HR: 2.44; 95% CI: 1.08–5.51), and non-cardiovascular mortality (HR: 1.78; 95% CI: 0.82–3.84). A high risk of developing PAD was strongly linked to impaired preclinical systolic function and an increased likelihood for subsequent hospitalization for HF, all-cause mortality, CV mortality and non-CV mortality. There is a clear need for preventive strategies aimed at reducing hospitalizations for HF and mortality in this high-risk population.

Preventing broken hearts in women with breast cancer: a concise review on chemotherapy-mediated cardiotoxicity.

Cancer and cardiovascular disease are the leading causes of death for Canadian women. One in eight Canadian women will receive the life-changing diagnosis of breast cancer (BC) in their lifetime, with 1 in 34 dying from the disease. Although doxorubicin (DOX) and trastuzumab (TRZ) have significantly improved survival in women diagnosed with human epidermal growth factor receptor 2 (HER2)-positive BC, approximately one in four women who receive this treatment are at risk of developing chemotherapy-induced cardiotoxicity. Cardiotoxicity is defined as a decline in left ventricular ejection fraction (LVEF) of>10% to an absolute value of<53%. Current guidelines recommend the serial monitoring of LVEF in this patient population using non-invasive cardiac imaging modalities including transthoracic echocardiography or multi-gated acquisition scan; however, this will only allow for the detection of established cardiotoxicity. Recent studies have demonstrated that a reduction in global longitudinal strain by speckle tracking echocardiography can identify pre-clinical systolic dysfunction prior to a decline in overall LVEF. Implementation of early detection techniques would allow for the prompt initiation of cardioprotective strategies. In addition to the early detection of chemotherapy-mediated cardiotoxicity, the prophylactic use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, statins, exercise, and nutraceutical therapies have been studied in the setting of cardio-oncology.

Risk factors for the development of heart failure with a preserved left ventricular ejection fraction in workers of the main professions of the coal industry

Introduction. In the coal industry, 78.7% of employees work in places with harmful working conditions, which play a leading role in the development of not only professional, but also industrial diseases, the leading of which are diseases of the cardiovascular system. The identification of preclinical systolic dysfunction of the left ventricle and the assessment of the role of traditional and professionally determined risk factors for the development of systolic dysfunction of the left ventricle in workers of the main professions of the coal industry is of scientific interest.&#x0D; The study aims to assess the risk factors for the development of heart failure with a preserved left ventricular ejection fraction in workers of the main professions of the coal industry.&#x0D; Materials and methods. The study included 101 employees of the main professions of the coal industry and 80 employees of the paramilitary mine rescue unit. The subjects had no somatic pathology, which could lead to structural and functional changes of the heart. The scientists performed echocardiographic and ultrasound examinations of the main arteries according to standard methods and assessed the generally accepted risk factors for the development of cardiovascular pathology (smoking, abdominal obesity, body mass index, total cholesterol, triglycerides, high and low density lipoprotein cholesterol, glycated hemoglobin).&#x0D; Results. The researchers revealed systolic dysfunction of the left ventricle significantly in miners more often in the form of a decrease in longitudinal deformation (27.7% of miners versus 7.6% of paramilitary rescuers, p=0.0005), while its average value is also significantly lower in miners and has a value below the established norm (–17.2±0.044 and –19.3±0.03, p=0.0005). The authors found no significant differences in the frequency of commonly accepted risk factors: abdominal obesity, smoking, atherosclerosis of the main arteries, dyslipidemia and the level of glycated hemoglobin in miners and workers of the mine rescue unit, as well as in miners, depending on the index of longitudinal deformation of the left ventricle.&#x0D; Conclusion. The obtained results indicate the need for a prenosological diagnosis of systolic dysfunction of the left ventricle, studying it in dynamics and simultaneously expanding the search for risk factors, which will allow early prevention of this complication in workers in harmful working conditions.&#x0D; Ethics. The study was conducted in compliance with the standards of the Bioethical Committee of the Research Institute of Complex Problems of Hygiene and Occupational Diseases, established in accordance with the Helsinki Declaration of the World Association "Ethical Principles of Scientific Medical Research with Human Participation" as amended in 2013 and the "Rules of Good Clinical Practice" approved by Order of the Ministry of Health of the Russian Federation dated 01.04.2016 No. 200n. The subjects signed an informed consent to participate in the study.

Global Longitudinal Strain Predicts Survival and Left Ventricular Function After Mitral Valve Surgery: A Meta-analysis

The timing for surgical treatment in patients with primary organic severe mitral valve regurgitation and preserved left ventricular ejection fraction (LVEF) systolic is a challenge since it depends upon LV end systolic dimension and LVEF which may be late markers of LV dysfunction. Echocardiography is the most important tool in the diagnosis of mechanisms, etiology, severity, and hemodynamic consequences of mitral regurgitation. The global longitudinal strain (GLS), a new and sensitive method for the detection of LV dysfunction, might be a useful method for the evaluation of preclinical systolic dysfunction. Nevertheless, its role for predicting postoperative outcomes is not well established. A meta-analysis was performed to address the role of GLS in patients with severe mitral regurgitation and preserved LVEF who underwent mitral surgery. We included studies that compared outcomes according to preoperative GLS in regard to survival and postoperative LV function. We included 2358 patients enrolled in 8 studies. Patients with reduced GLS% had worse long term survival after mitral valve surgery (hazard ratio = 1.13, 95% confidence interval [CI]: 1.02-1.26). Patients with preoperatively reduced GLS% had lower LVEF after surgery (mean difference [MD] = -5.06%, 95% CI: -8.97-1.16%) and additionally, patients who presented postoperative LVEF dysfunction had worse preoperative GLS (MD = 4.33, 95% CI: 3.89-4.76). In patients with primary mitral regurgitation, preoperative GLS is a predictor for long term survival and postoperative LVEF. It is a useful parameter to be included when considering early surgery in patients with severe mitral regurgitation and normal LVEF.

Cardiac Versus Renal Response to Volume Expansion in Preclinical Systolic Dysfunction With PDEV Inhibition and BNP

Impaired cardiorenal response to acute saline volume expansion in preclinical systolic dysfunction (PSD) may lead to symptomatic heart failure. The objective was to determine if combination phosphodiesterase-V inhibition and exogenous B-type natriuretic peptide (BNP) administration may enhance cardiorenal response. A randomized double-blinded, placebo-controlled study was conducted in 21 subjects with PSD and renal dysfunction. Pre-treatment with tadalafil and subcutaneous BNP resulted in improved cardiac function, as evidenced by improvement in ejection fraction, left atrial volume index, and left ventricular end-diastolic volume. However, there was reduced renal response with reduction in renal plasma flow, glomerular filtration rate, and urine flow. (Tadalafil and Nesiritide as Therapy in Pre-clinical HeartFailure; NCT01544998).

Diffuse myocardial fibrosis and early strain abnormalities in asymptomatic type 2 diabetics without overt cardiovascular disease

Background Type 2 diabetes has been associated with a higher prevalence of diastolic dysfunction and congestive heart failure. A hypothesized contributor is the accelerated accumulation of diffuse myocardial fibrosis. In a cohort of type 2 diabetic patients without overt cardiovascular disease, we sought to explore the capacity of quantitative T1 mapping and feature-tracking based strain analysis. These protocols were utilized to identify the presence of diffuse myocardial fibrosis and related pre-clinical systolic dysfunction. Quantitative analyses were compared to healthy age-matched controls.

Abstract 12358: Abnormal Left Ventricular Midwall Fractional Shortening and Elevated Circulating Biomarkers Predict High Mortality in Elderly Individuals in the General Population

Background: Individuals in the general population with a minimal elevation of cardiac biomarkers and left ventricular hypertrophy are at high cardiovascular risk and may be candidate for early strategies of prevention and treatment. We investigated the combination of several circulating biomarkers with abnormal midwall fractional shortening (MFS), an early echocardiographic indicator of preclinical systolic dysfunction, with adverse outcomes. Methods: Circulating levels of N-terminal probrain natriuretic peptide (NT-proBNP), high sensitivity cardiac troponin T (hs-cTnT), and intercellular adhesion molecule-1 (ICAM-1) were measured in 550 elderly community-dwelling individuals (65-84 years) from the PREDICTOR study. Participants were referred to cardiology centers for clinical examination and Doppler echocardiography with centrally-measured MFS. Causes of death or hospitalization were available after a median follow-up of 46 [39-54] months from record-linkage of administrative data. Results: Individuals with LV midwall dysfunction (MFS&lt;15%, n= 204 (38%)) had higher levels of NT-proBNP (148 [57-311] ng/L), hs-cTnT (7.3 [3.9-11.6] ng/L)and ICAM-1 (211 [177-261] ng/mL) than those with normal function (82 [42-171] and 5.0 [3.0-8.3] ng/L, 193 [165-230], respectively, p&lt;0.001). The cumulative incidence of total mortality (n=36) among individuals with abnormal MFS and elevated NT-proBNP (&gt;75th age- and sex-specific percentile) was 14% vs. 2% (abnormal MFS, low NT-proBNP), 6% (normal MFS, high NT-proBNP) and 1% (normal MFS, low NT-proBNP). Corresponding values for hs-cTnT (&gt; 3ng/L) were 14, 0, 5 and 3% (p&lt;0.0001) and 15, 5, 7 and 2% for ICAM-1 above median concentration (all p&lt;0.0001). After adjustment for sex, age, eGFR and hypertension, subjects with abnormal MFS and an elevated biomarker had a higher risk of total mortality compared to those with normal MFS and low biomarker: HR = 11.4 [1.5-87.7] (p=0.02) for NT-proBNP and 7.4 [2.1-25.6] (p=0.002) for ICAM-1, but not for hs-cTnT. Similar trends were seen for GDF-15. Conclusions: Elevation of circulating biomarkers combined with early alterations in LV systolic function with MFS identifies a subgroup of individuals in the general population aged 65 or more at higher risk for mortality.

Differential Cardiac versus Renal Response to Acute Volume Overload in Human Preclinical Systolic Dysfunction and Renal Dysfunction with the Combination of PDEV Inhibition and BNP Administration

Preclinical systolic dysfunction (PSD) is defined by LVEF < 45% without symptoms of heart failure (HF) (Stage B HF). We have previously demonstrated that an impaired cardiorenal response to acute volume loading (AVL) exists in PSD. Type V phosphodiesterase (PDEV) metabolizes cGMP, second messenger of the B-type natriuretic peptide (BNP). Preclinical studies have demonstrated that PDEV inhibition (PVEVI) enhances the cardiorenal actions of BNP. The objective of the current study is to determine if the combination of PDEVI and BNP will result in a greater enhancement of the cardiorenal response to AVL as compared to PDEVI alone in PSD.

Chronic Subcutaneous BNP Administration in Human Preclinical Systolic Dysfunction (Stage B Heart Failure) Results in Sustained Renal Responsiveness to Acute Volume Overload

Preclinical systolic dysfunction (PSD) is defined by left ventricle ejection fraction (LVEF) < 45% without symptoms of heart failure (HF) (Stage B HF). We have previously demonstrated that an impaired cardiorenal endocrine response to acute volume loading (AVL) exists in PSD and that is corrected by acute administration of subcutaneous (SQ) B-type natriuretic peptide (BNP). We hypothesized that 12 weeks of SQ BNP administration twice daily would result in a sustained enhancement of the cardiorenal response to AVL. We performed a randomized placebo-controlled double blinded proof of concept clinical trial comparing 12 weeks of SQ BNP, 10 μg/Kg bid (n=22) with Placebo (n=12), in patients with EF<45% and NYHA Class I. Each subject had 2 study visits, one at baseline and the other after 12 weeks. At each visit, echocardiogram, neurohumoral assessment and renal clearance studies with iothalmate and PAH to measure glomerular filtration rate (GFR) and renal plasma flow (RPF) were done before and after AVL (0.25 ml/kg/min of normal saline for 60 minutes).(ClinicalTrials.gov Identifier: NCT00405639) 12 weeks of SQ BNP resulted in a strong trend for a greater decrease of LV mass index from baseline as compared to placebo (-5.8±15.7 vs 2.0±5.4 g/m2 p=0.07) with a significant decrease in LV end-systolic diameter (48.1±6.7 to 46.1±7.9 mm, p< 0.05) and significant increase in LV EF (38.9±8.9 to 41.4±9.2 %, p< 0.05) only in the BNP group. In response to AVL, SQ BNP resulted in a greater increase in GFR (4.4±15 vs -9.3±15.2 ml/min/1.73m2, p< 0.05) and urinary sodium excretion (184.9±301.4 vs -18.7±95.3 mEq/min, p< 0.05) as compared to placebo. Echocardiography revealed a greater increase in LVEF (4±5 vs -0.4±3.1%, p< 0.05), with smaller end-systolic diameter (-3.2±3.7 vs -0.4±1.3 mm, p< 0.05) and E/e’ ratio (12.1±6 vs 14.8±3.4, p< 0.05) and a trend for lower RV pressure (0.1±3.1 vs 3.6±3.8 mmHg, p= 0.06) in the SQ BNP group in response to AVL with normal saline as compared to the placebo group. In PSD, 12 weeks of SQ BNP administered twice a day resulted in improved and sustained ability of the kidney to respond to intravascular volume overload with an increase in GFR and sodium excretion compared to standard of care. This enhanced renal response was associated with enhanced myocardial structure and function with no evidence of pharmacological tolerance. Further studies are warranted to determine if these physiologic observations can be translated into a delay in the progression to symptomatic HF.

Chronic natriuretic peptide protein therapeutics

The natriuretic peptides (NP) consist of a group of genetically distinct peptides with a 17 amino acid disulfide ring structure that exert important paracrine and endocrine actions in cardiorenal homeostasis. ANP and BNP bind to the natriuretic peptide-A receptor (NPR-A), which via 3',5'-cyclic guanosine monophosphate (cGMP) mediates natriuresis, vasodilatation, renin-aldosterone inhibition, anti-mitogenesis, and positive lusitropism. CNP lacks natriuretic actions, but possesses vasodilating and important growth- and fibrotic-inhibiting actions via the guanylyl cyclase-linked natriuretic peptide-B receptor (NPR-B). CD-NP now represents the first designer NP which, unlike ANP, BNP or CNP, co-activates both NPR-A and NPR-B. In both experimental and human heart failure (HF), investigations have supported the hypothesis that the capacity of the cardiomyocytes to produce and/or release the NP may be overwhelmed in HF due to the increased demands of the system, thus leading to a state of relative deficiency of biologically active endogenous NP. Hence, giving the favorable cardiorenal and humoral proprieties of the NP, their chronic exogenous delivery is now viewed as favorable therapeutic opportunity for the treatment of cardiovascular diseases. We have previously reported that subcutaneous (SQ) administration of BNP in experimental HF resulted in improved cardiac output with reduced systemic vascular resistance and cardiac filling pressures. Importantly, we translated these studies to humans and completed a pilot study to establish safety and efficacy of 8 weeks of chronic SQ BNP administration in human symptomatic systolic HF. More importantly, we have recently completed 2 proof of concept studies to assess the biological effects of 12 weeks of SQ BNP administration in patients with preclinical systolic dysfunction and patients with preclinical diastolic dysfunction (Stage B HF). These studies demonstrated that chronic SQ BNP induced a sustained generation of cGMP, which, importantly, was associated with persistent enhanced renal natriuretic response to volume overload. Going beyond BNP, CD-NP (Cenderitide) is in clinical development as an outpatient therapy during the post-acute HF period, to be administered continuously for up to 90 days after hospital discharge via subcutaneous pump with the goals of reducing rehospitalization. Recently, a phase 1 study in HF patients was completed which demonstrated that SQ CD-NP infusion achieved desirable pharmacokinetic levels and was well tolerated. Pre-clinically, we have recently designed an in situ polymer precipitation delivery system suitable for the chronic and sustained release of CD-NP. With the appropriate polymer-gel formulation, CD-NP release could be sustained over 3 weeks, thus inducing prolonged cGMP activation and favourable biological actions. Preclinical and early phase clinical studies have demonstrated the potential beneficial actions of chronic NP therapeutics. Further studies are warranted to determine if these functional responses can be translated into improved clinical outcomes and contribute to delaying the progression of HF.

Mitral annular systolic velocity as a marker of preclinical systolic dysfunction among patients with arterial hypertension

BackgroundThe aim of this study was to investigate early changes in left ventricular longitudinal systolic function in patients with hypertension (HTN) with and without concomitant diastolic dysfunction (DD) and the clinical implications of these findings.MethodWe enrolled 299 patients with HTN and 297 age-matched patients with HTN and DD and compared both groups with an age-matched control group consisting of 100 healthy subjects. The long axis systolic function was investigated by determining the average peak systolic velocity of the septal and lateral mitral sites (Smavg) using spectral pulsed wave tissue Doppler imaging (TDI).ResultsWe found a strong negative trend toward the reduction of velocity, which is dependent on the grade of HTN, on the magnitude of DD, and also on the gender and age of the subjects (r=−0.891/-0.580; p<0.0001). The data showed that the beginning and evolution of HTN are related to a slight but significant reduction in the long axis systolic function (10.2-10.0 cm/s; p<0.0001), and DD worsens this initial finding (9.8-8.8 cm/s; p<0.0001).ConclusionThe strength of the study is the analysis of incremental changes in longitudinal contraction in patients with different stage of HTN but not so many the classification of the degree of systolic dysfunction. The importance of our results lies in the fact that these initial changes in systolic contraction could be used as an early sign that should prompt optimization of the treatment of HTN.

Impaired Natriuretic and Renal Endocrine Response to Acute Volume Expansion in Pre-Clinical Systolic and Diastolic Dysfunction

We hypothesized an impaired renal endocrine and natriuretic response to volume expansion (VE) in humans with pre-clinical systolic dysfunction (PSD) and pre-clinical diastolic dysfunction (PDD). We further hypothesized that exogenous B-type natriuretic peptide (BNP) could rescue an impaired natriuretic response in PSD and PDD. Recent reports suggest that in early systolic heart failure (HF), there is an impaired natriuretic response to acute VE. PSD was defined as left ventricular ejection fraction <40% without HF symptoms. PDD was defined as ejection fraction >50%, moderate to severe diastolic dysfunction by Doppler criteria, and no HF symptoms. A double-blinded, placebo-controlled, crossover study was employed to determine the renal response to VE (0.25 ml/kg/min of normal saline for 60 min) in the presence and absence of exogenous BNP. Twenty healthy control subjects, 20 PSD subjects, and 18 PDD subjects participated. In healthy control subjects, urinary cyclic guanosine monophosphate (cGMP) and natriuresis increased after VE. In contrast, among PSD and PDD subjects, there was a paradoxical decrease in urinary cGMP and attenuated natriuresis. Pre-treatment with subcutaneous BNP resulted in similar increases in both urinary cGMP and natriuresis among healthy normal, PSD, and PDD subjects. In PSD and PDD, there is impaired renal cGMP activation, which contributes to impaired natriuresis in response to VE. Impaired activation of urinary cGMP and reduced natriuresis may contribute to volume overload and the progression of HF among PSD and PDD subjects. Importantly, the impaired renal excretory response to VE is rescued by exogenous BNP in PSD and PDD.

Preclinical Systolic Dysfunction in Patients with Stage 3 Chronic Kidney Disease

Introduction: Chronic kidney disease (CKD) is associated with increased cardiovascular risk and mortality. We evaluated whether stage 3 (s3)-CKD is associated with abnormalities of the cardiovascular system. Methods: Thirty-nine asymptomatic s3-CKD patients, free of prevalent cardiovascular disease, were compared with 44 control subjects with comparable prevalence of hypertension (66% vs 69% in s3-CKD). In addition to standard echocardiographic parameters, we computed non-invasive effective arterial elastance (EAE, in mmHg/mL/beat), systolic left ventricular elastance (LVe, in mmHg/mL) and myocardial mechanic efficiency (MME, in mL/sec), using previously reported formulas. Results: s3-CKD and controls were comparable for age, sex, lipid profile and prevalence of diabetes mellitus and smoking habit. Left ventricular (LV) mass, geometry and stroke work were similar in the two groups, with both ejection fraction and midwall shortening (mS) significantly reduced in the CKD group (both p < 0.001). Within the s3-CKD group, 36% had clear-cut depressed mS. EAE and peripheral resistance were higher in s3-CKD than in controls (both p < 0.005), and MME was reduced in CKD (p < 0.005), an impairment even clearer after controlling for LV mass, and increasing with increasing values of LV mass (p < 0.001). In addition, at a given level of peripheral resistance, LV geometry was less concentric in s3-CKD than in controls (p < 0.05). Conclusions: s3-CKD asymptomatic patients show a peculiar cardiovascular phenotype, characterized by impaired mechano-energetic efficiency and reduced midwall mechanics, in the presence of inadequately compensating LV concentric remodelling. Whether these characteristics might result in higher cardiovascular risk in s3-CKD should be investigated.

Plasma Brain Natriuretic Peptide for the Detection of Pre-Clinical Systolic Dysfunction in the General Population

Plasma Brain Natriuretic Peptide for the Detection of Pre-Clinical Systolic Dysfunction in the General Population

Burden of systolic and diastolic ventricular dysfunction in the community appreciating the scope of the heart failure epidemic

Context Approximately half of patients with overt congestive heart failure (CHF) have diastolic dysfunction without reduced ejection fraction (EF). Yet, the prevalence of diastolic dysfunction and its relation to systolic dysfunction and CHF in the community remain undefined. Objectives To determine the prevalence of CHF and preclinical diastolic dysfunction and systolic dysfunction in the community and determine if diastolic dysfunction is predictive of all-cause mortality. Design, Setting, Participants Cross-sectional survey of 2042 randomly selected residents of Olmsted County, Minnesota, aged 45 years or older from June 1997 through September 2000. Main Outcome Measures Doppler echocardiographic assessment of systolic and diastolic function. Presence of CHF diagnosis by review of medical records with designation as validated CHF if Framingham criteria are satisfied. Subjects without a CHF diagnosis but with diastolic or systolic dysfunction were considered as having either preclinical diastolic or preclinical systolic dysfunction. Results The prevalence of validated CHF was 2.2% (95% confidence interval [CI], 1.6%-2.8%) with 44% having an EF higher than 50%. Overall, 20.8% (95% CI, 19.0%-22.7%) of the population had mild diastolic dysfunction, 6.6% (95% CI, 5.5%-7.8%) had moderate diastolic dysfunction, and 0.7% (95% CI, 0.3%-1.1%) had severe diastolic dysfunction with 5.6% (95% CI, 4.5%-6.7%) of the population having moderate or severe diastolic dysfunction with normal EF. The prevalence of any systolic dysfunction (EF ≤50%) was 6.0% (95% CI, 5.0%-7.1%) with moderate or severe systolic dysfunction (EF ≤40%) being present in 2.0% (95% CI, 1.4%-2.5%). CHF was much more common among those with systolic or diastolic dysfunction than in those with normal ventricular function. However, even among those with moderate or severe diastolic or systolic dysfunction, less than half had recognized CHF. In multivariate analysis, controlling for age, sex, and EF, mild diastolic dysfunction (hazard ratio, 8.31 [95% CI, 3.00-23.1],P Conclusions In the community, systolic dysfunction is frequently present in individuals without recognized CHF. Furthermore, diastolic dysfunction as rigorously defined by comprehensive Doppler techniques is common, often not accompanied by recognized CHF, and associated with marked increases in all-cause mortality.