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Background: There is limited data regarding longitudinal changes of diastolic function in the very old, who are at the highest risk for heart failure (HF)., Objectives: This study aims to quantify intraindividual longitudinal changes of diastolic function over 6 years in late life., Methods: The authors studied 2,524 older adult participants in the prospective community-based ARIC (Atherosclerosis Risk In Communities) study who underwent protocol-based echocardiography at study visits 5 (2011-2013) and 7 (2018-2019). The primary diastolic measures were tissue Doppler e', E/e' ratio, and left atrial volume index (LAVI)., Results: Mean age was 74 ± 4 years at visit 5 and 80 ± 4 at visit 7, 59% were women, and 24% were Black. At visit 5, mean e' septal was 5.8 ± 1.4 cm/s, E/e' septal 11.7 ± 3.5, and LAVI 24.3 ± 6.7 mL/m 2 . Over a mean of 6.6 ± 0.8 years, e' septal decreased by 0.6 ± 1.4 cm/s, E/e' septal increased by 3.1 ± 4.4, and LAVI increased by 2.3 ± 6.4 mL/m 2 . The proportion with 2 or more abnormal diastolic measures increased from 17% to 42% (P < 0.001). Compared with participants free of cardiovascular (CV) risk factors or diseases at visit 5 (n = 234), those with prevalent CV risk factors or diseases but without prevalent or incident HF (n = 2,150) demonstrated greater increases in E/e' septal and LAVI. Increases of E/e' septal and LAVI were both associated with the development of dyspnea between visits in analyses adjusted for CV risk factors., Conclusions: Diastolic function generally deteriorates over 6.6 years in late life, particularly among persons with CV risk factors, and is associated with development of dyspnea. Further studies are necessary to determine if risk factor prevention or control will mitigate these changes., Competing Interests: Funding Support and Author Disclosures The ARIC study has been funded in whole or in part with federal funds from the National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), under contract numbers HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700005I, and HHSN268201700004I. Dr Shah was supported by NIH/NHLBI grants R01HL135008, R01HL143224, R01HL150342, R01HL148218, R01HL160025, and K24HL152008; and has received research support not related to the present work from Novartis and Philips Ultrasound; and consulting fees from Philips Ultrasound. Dr Claggett has received consulting fees from Myokardia, Gilead, AOBiome, Boehringer Ingelheim, Novartis, Amgen, and Corvia. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background Frailty and heart failure frequently coexist in late life. Limited data exist regarding the longitudinal associations of frailty and subclinical cardiac dysfunction. We aim to quantify the association of frailty with longitudinal changes in cardiac function and of cardiac function with progression in frailty status in older adults. Methods and Results Participants in the Atherosclerosis Risk in Communities cohort underwent frailty assessments at Visit 5 (V5; 2011-2013), V6 (2016-2017), and V7 (2018-2019), and echocardiographic assessments at V5 and V7. We assessed the association between frailty status at V5 and changes in frailty status from V5 to V7 and changes in cardiac function over 6 years. We then evaluated the association of cardiac function measured at Visit 5 with progression in frailty status over 4 years. Multivariable regression models adjusted for demographics and comorbidities. Among 2574 participants free of heart failure at V5 and V7 (age 74±4 years at V5 and 81±4 years at V7), 3% (n=83) were frail. Frailty at V5 was associated with greater left atrial volume index and E/e' ratio at V5 and 7. Participants who transitioned from robust at V5 to frail at V7 demonstrated greater increases in left ventricular mass index, left atrial volume index, and E/e' over the same period. Among 1648 robust participants at Visit 5, greater left ventricular mass index and mean wall thickness, lower tissue Doppler imaging e', and higher E/e' ratio at Visit 5 were associated with progression in frailty status. Conclusions Among robust, older adults free of heart failure, progression in frailty and subclinical left ventricular remodeling and diastolic dysfunction are interrelated.

Background: The associations of kidney dysfunction and damage with heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF), as well as adverse cardiac remodeling, in late-life remain incompletely understood., Objectives: The authors sought to define the associations between kidney dysfunction and damage and incident HFrEF and HFpEF and cardiac structure and function in late-life., Methods: This study included 5,170 adults initially free of a heart failure (HF) diagnosis who had estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) measured at visit 5 (2011-2013) of the ARIC (Atherosclerosis Risk In Communities) study. Multivariable Cox proportional hazards models were used to estimate the associations of eGFR and UACR with incident HF, HFrEF, and HFpEF through 2019. Multivariable linear regression models were used to investigate the associations of eGFR and UACR at visit 5 with changes in cardiac structure and function between visits 5 and 7 in 2,313 participants with available echocardiograms., Results: The mean age of participants was 76 ± 5 years, and 2,225 (43%) were men. The mean eGFR and median UACR were 66 ± 18 mL/min/1.73 m 2 and 11 mg/g (25th, 75th percentile: 6, 22 mg/g), respectively. In fully adjusted models, both lower eGFR and higher UACR were associated with greater risk of any HF, HFrEF, and HFpEF. Lower eGFR was associated with larger increases in left ventricular end-diastolic volume index and worsening of diastolic measures. UACR did not associate with changes in cardiac structure or function., Conclusions: Mild to moderate kidney dysfunction and damage associate with incident HF and adverse cardiac remodeling in late-life., Competing Interests: Funding Support and Author Disclosures The ARIC study was funded in whole or in part with federal funds from the National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Department of Health and Human Services, under contract nos. HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700004I, and HHSN268201700005I. Dr Buckley was supported by NIH/NHLBI grant K23HL150311. Dr Shah was supported by NIH/NHLBI grants R01HL135008, R01HL143224, R01HL150342, R01HL148218, and K24HL152008. Dr Shah has received research support not related to this study from Novartis and Philips Ultrasound, and consulting fees from Philips Ultrasound. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Importance: Limited data exist regarding the association of subtle subclinical systolic dysfunction and incident heart failure (HF) in late life., Objective: To assess the independent associations of subclinical impairments in systolic performance with incident HF in late life., Design, Setting, and Participants: This study was a time-to-event analysis of participants without heart failure in the Atherosclerosis Risk in Communities (ARIC) study, a prospective, community-based cohort study, who underwent protocol echocardiography at the fifth study visit (January 1, 2011, to December 31, 2013). Findings were validated independently in participants in the Copenhagen City Heart Study (CCHS). Data analysis was performed from June 1, 2018, to February 28, 2020., Exposures: Left ventricular ejection fraction (LVEF), longitudinal strain (LS), and circumferential strain (CS) measured by 2-dimensional and strain echocardiography., Main Outcomes and Measures: Main outcomes were incident adjudicated HF and HF with preserved and reduced LVEF at a median follow-up of 5.5 years (interquartile range, 5.0-5.8 years). Cox proportional hazards regression models adjusted for demographics, hypertension, diabetes, obesity, smoking, coronary disease, estimated glomerular filtration rate, LV mass index, e', E/e', and left atrial volume index. Lower 10th percentile limits were determined in 374 participants free of cardiovascular disease or risk factors., Results: Among 4960 ARIC participants (mean [SD] age, 75 [5] years; 2933 [59.0%] female; 965 [19%] Black), LVEF was less than 50% in only 76 (1.5%). In the 3552 participants with complete assessment of LVEF, LS, and CS, 983 (27.7%) had 1 or more of the following findings: LVEF less than 60%, LS less than 16.0%, or CS less than 23.7%. Modeled continuously or dichotomized, worse LVEF, LS, and CS were each independently associated with incident HF. The adjusted hazard ratio (HR) per SD decrease in LVEF was 1.41 (95% CI, 1.29-1.55); the HR for LVEF less than 60% was 2.59 (95% CI, 1.99-3.37). Similar findings were observed for continuous LS (HR, 1.37; 95% CI, 1.22-1.53) and dichotomized LS (HR, 1.93; 95% CI, 1.46-2.55) and for continuous CS (HR, 1.39; 95% CI, 1.22-1.57) and dichotomized CS (HR, 2.30; 95% CI, 1.64-3.22). Although the magnitude of risk for incident HF or death associated with impaired LVEF was greater using guideline (HR, 2.99; 95% CI, 2.19-4.09) compared with ARIC-based limits (HR, 1.88; 95% CI, 1.58-2.25), the number of participants classified as impaired was less (104 [2.1%] based on guideline thresholds compared with 692 [13.9%] based on LVEF <60%). The population-attributable risk associated with LVEF less than 60% was 11% compared with 5% using guideline-based limits, a finding replicated in 908 participants in the CCHS., Conclusions and Relevance: These findings suggest that relatively subtle impairments of systolic function (detected based on LVEF or strain) are independently associated with incident HF and HF with reduced LVEF in late life. Current recommended assessments of LV function may substantially underestimate the prevalence of prognostically important impairments in systolic function in this population.

Importance: Undifferentiated dyspnea is common in late life, but the relative contribution of subclinical cardiac dysfunction is unknown. Impairments in cardiac structure and function may be characteristics of undifferentiated dyspnea in elderly people, providing potential insights into occult heart failure (HF)., Objective: To quantify the association of undifferentiated dyspnea with cardiac dysfunction after accounting for other potential contributors., Design, Setting, and Participants: This cross-sectional study used data from Atherosclerosis Risk in Communities study participants 65 years and older who attended the fifth study visit (from 2011 to 2013) and had not been diagnosed with HF, chronic obstructive pulmonary disease, morbid obesity, or severe kidney disease. Analyses were conducted from October 2017 to June 2018., Exposures: Dyspnea measured using the modified Medical Research Council scale, with a score less than 2 classified as none to mild and a score of 2 or more classified as moderate to severe., Main Outcomes and Measures: Using multivariable logistic regression, the association of undifferentiated dyspnea was defined using cardiac structure, systolic and diastolic function, pulmonary pressure (echocardiography), pulmonary function (spirometry), glomerular filtration rate, hemoglobin, body mass index, depression, and physical performance. The population-attributable risk was calculated for each dysfunction metric., Results: Among 4342 participants (mean [SD] age, 75.9 [5.0] years; 2533 [58.3%] women), 1173 (27.0%) had undifferentiated dyspnea. Moderate to severe dyspnea was present in 574 participants (13.2%) and was associated with left ventricular (LV) hypertrophy (odds ratio [OR], 1.53; 95% CI, 1.25-1.87; P < .001) and LV diastolic (OR, 1.46; 95% CI, 1.20-1.78; P < .001) and systolic (OR, 1.28; 95% CI, 1.05-1.56; P = .02) dysfunction. Moderate to severe dyspnea was also associated with obstructive (OR, 1.59; 95% CI, 1.28-1.99; P < .001) and restrictive (OR, 2.56; 95% CI, 1.99-3.27; P < .001) findings on spirometry, renal impairment (OR, 1.32; 95% CI, 1.08-1.61; P = .01), anemia (OR, 1.72; 95% CI, 1.39-2.12; P < .001), lower (OR, 2.77; 95% CI, 2.18-3.51; P < .001) and upper (OR, 1.82; 95% CI, 1.49-2.23; P < .001) extremity weakness, depression (OR, 3.01; 95% CI, 2.24-4.25; P < .001), and obesity (OR, 2.35; 95% CI, 1.95-2.83; P < .001). After accounting for these, moderate to severe dyspnea was associated with LV hypertrophy (OR, 1.30; 95% CI, 1.01-1.67; P = .04) and was not associated with systolic or diastolic function. In contrast, in the fully adjusted model, other organ system measures were associated with dyspnea, except for glomerular filtration rate and grip strength. The population-attributable risk of dyspnea associated with obesity alone was 22.6% compared with 5.8% for LV hypertrophy., Conclusions and Relevance: Undifferentiated dyspnea is multifactorial in older adults, and this study showed an association with obesity. When accounting for other relevant organ systems, cardiovascular function poorly discriminated those with vs those without dyspnea. Therefore, dyspnea should not be assumed to represent occult HF in this population.

Background: Heart failure is one of the most important complications of chronic kidney disease (CKD). However, few studies comprehensively investigated left ventricular (LV) structure and function in relation to 2 key CKD measures, estimated glomerular filtration rate (eGFR) and urine albumin/creatinine ratio (ACR)., Methods and Results: Among 4175 ARIC (Atherosclerosis Risk in Communities) participants (aged 66-90 years during 2011-2013), we quantified the association of eGFR and ACR with echocardiogram parameters of LV mass, size, systolic function, and diastolic function. Adjusting for demographic variables, both CKD measures were significantly associated with most echocardiogram parameters. Additionally accounting for other potential confounders, we observed significantly higher LV mass index according to reduced eGFR (82.3 [95% confidence interval (CI), 77.6-87.0] g/m 2 for eGFR <30 mL/min per 1.73 m 2 , 80.9 [95% CI, 77.3-84.6] g/m 2 for eGFR 30-44 mL/min per 1.73 m 2 , and 80.1 [95% CI, 76.7-83.5] g/m 2 for eGFR 45-59 mL/min per 1.73 m 2 compared with 78.7 [95% CI, 75.3-82.1] g/m 2 for eGFR 75-89 mL/min per 1.73 m 2 ; trend P <0.001). Regarding LV size and function, significant differences were observed for some parameters, particularly at eGFR <30 mL/min per 1.73 m 2 . For ACR, the associations remained significant for most parameters (eg, LV mass index, 91.5 [95% CI, 86.6-96.5] g/m 2 for ACR ≥300 mg/g and 82.9 [95% CI, 79.4-86.3] g/m 2 for ACR 30-299 mg/g compared with 77.7 [95% CI, 74.4-81.1] g/m 2 for ACR <10 mg/g [trend P <0.001]; left arterial volume index, 24.9 [95% CI, 22.9-26.8] and 24.7 [95% CI, 23.4-26.1] mL/m 2 compared with 23.4 [95% CI, 22.1-24.7] mL/m 2 , respectively [trend P =0.010]). Dichotomizing echo parameters with clinical thresholds, the stronger relationships of ACR over eGFR were further evident., Conclusions: LV mass was related to both CKD measures, whereas LV size and function were robustly associated with albuminuria. These results have implications for pathophysiological processes behind cardiorenal syndrome and targeted cardiac assessment in patients with CKD., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Aims: Global measures of left ventricular (LV) function, in particular LV ejection fraction (LVEF) and global myocardial strain measures, are powerful predictors of outcomes in patients with LV dysfunction, heart failure, or both. However, less is known about the relationship between regional myocardial function, especially that assessed by strain echocardiography and clinical prognosis., Methods and Results: We studied 248 patients with LV dysfunction, heart failure, or both 5 days after first myocardial infarction (MI) from the VALIANT study. We assessed peak longitudinal strain (LS) via B-mode speckle tracking in 12 segments from the apical 4- and 2-chamber views and visually assessed LV wall motion score (WMS). We related these measures of regional myocardial function to each other and to clinical outcomes over 20-month follow-up. Normal reference values for segmental LS were derived from 50 healthy controls. Regional LS (-7.7%, Q1: -11.2%, Q3: -4.9%) was worse in segments with abnormal WMS, although was significantly impaired even in segments scored as normokinetic compared with normal controls (-10.4 ± 5.2% vs. -20.0 ± 7.6%, P < 0.001). In multivariable Cox proportional hazards models, each additional abnormal LS segment was associated with an increased risk of all-cause mortality (hazard ratio: 1.42, 95% confidence interval: 1.06-1.90, P = 0.02) even after adjustment for clinical covariates, including LVEF, LV end-systolic volume, and number of abnormal segments by WMS., Conclusion: In patients with LV dysfunction, heart failure, or both after MI, regional LS is significantly depressed even in segments with normal WMS, and this measure was related to adverse outcome., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Background: Individuals with diabetes mellitus and pre-diabetes mellitus are at particularly high risk of incident heart failure or death, even after accounting for known confounders. Nevertheless, the extent of impairments in cardiac structure and function in elderly individuals with diabetes mellitus and pre-diabetes mellitus is not well known. We aimed to assess the relationship between echocardiographic measures of cardiac structure and function and dysglycemia., Methods and Results: We assessed measures of cardiac structure and function in 4419 participants without prevalent coronary heart disease or heart failure who attended the Atherosclerosis Risk In the Community (ARIC) visit 5 examination (2011-2013) and underwent transthoracic echocardiography (age, 75±6 years; 61% women, 23% black). Subjects were grouped across the dysglycemia spectrum as normal (39%), pre-diabetes mellitus (31%), or diabetes mellitus (30%) based on medical history, antidiabetic medication use, and glycated hemoglobin levels. Glycemic status was related to measures of cardiac structure and function. Worsening dysglycemia was associated with increased left ventricular mass, worse diastolic function, and subtle reduction in left ventricular systolic function (P≤0.01 for all). For every 1% higher glycated hemoglobin, left ventricular mass was higher by 3.0 g (95% confidence interval, 1.5-4.6 g), E/E' by 0.5 (95% confidence interval, 0.4-0.7), and global longitudinal strain by 0.3% (95% confidence interval, 0.2-0.4) in multivariable analyses., Conclusions: In a large contemporary biracial cohort of elderly subjects without prevalent cardiovascular disease or heart failure, dysglycemia was associated with subtle and subclinical alterations of cardiac structure, and left ventricular systolic and diastolic function. It remains unclear whether these are sufficient to explain the heightened risk of heart failure in individuals with diabetes mellitus., (© 2015 American Heart Association, Inc.)

Aims: The mechanisms responsible for the increased risk of heart failure (HF) post-myocardial infarction (MI) may differ between patients with versus without diabetes. We hypothesized that after high-risk MI, patients with diabetes would demonstrate patterns of remodeling that are suggestive of reduced ventricular compliance and that are associated with an increased risk of death or HF., Methods and Results: We performed quantitative echocardiographic analysis in 153 patients with diabetes and 451 patients without diabetes enrolled in the VALIANT Echo study. Diabetes was associated with a higher risk of death or HF in age-adjusted models (hazard ratio 1.44, 95% CI 1.04-2.00, P = .028). Diabetic patients were similar to nondiabetic patients with respect to left ventricular (LV) volume and ejection fraction but had higher LV mass index (104.1 ± 27.5 vs 97.1 ± 28.6 g/m(2), P = .009), relative wall thickness (0.41 ± 0.08 vs 0.38 ± 0.07, P < .0001), and left atrial volume index (LAVi) (26.2 ± 8.1 vs 24.0 ± 8.2 mL/m(2), P = .008)-all parameters that were significantly related to the risk of death or HF hospitalization. Changes in LV volume and ejection fraction from baseline to 20 months were not different, although diabetic patients demonstrated greater increase in LAVi (4.4 ± 7.7 vs 2.2 ± 6.7 mL/m(2), P = .01)., Conclusions: After high-risk MI, diabetic patients were at higher risk of death or HF and demonstrated greater baseline LV mass index, relative wall thickness, and LAVi as well as greater left atrial enlargement at 20-month follow-up. These findings suggest greater baseline concentric remodeling and long-term elevation in LV diastolic pressure post-MI among diabetic patients, which may partially mediate this risk., (Copyright © 2011 Mosby, Inc. All rights reserved.)

The evaluation of left ventricular systolic function is one of the most common reasons for referral for a non-invasive cardiac imaging study. In addition to its diagnostic and prognostic value, an assessment of ejection fraction can also be used to guide medical and device therapy. Thus, obtaining an accurate and reproducible assessment of LVEF is essential for patient management. This review will focus on novel multi-modality techniques used for the quantification of left ventricular systolic function. Emerging echocardiography techniques such as three-dimensional echocardiography and strain imaging and their incremental role over traditional 2D imaging will be discussed. In addition, new developments expanding nuclear imaging techniques' evaluation of left ventricular systolic function will be reviewed. Finally, an overview of advances in imaging techniques such as cardiac magnetic resonance and cardiac computed tomography, which now allow for an accurate and highly reproducible assessment of LVEF, will be presented.

Aims: Direct renin inhibitors provide an alternative approach to inhibiting the renin-angiotensin-aldosterone system (RAAS) at the most proximal, specific, and rate-limiting step. We tested the hypothesis that direct renin inhibition would attenuate left ventricular remodelling in patients following acute myocardial infarction receiving stable, individually optimized therapy, including another inhibitor of the RAAS., Methods and Results: We randomly assigned 820 patients between ∼2 and 8 weeks following acute myocardial infarction, with the left ventricular ejection fraction (LVEF) ≤45%, and regional wall motion abnormalities (≥20% akinetic area), to receive aliskiren (n = 423), titrated to 300 mg, or matched placebo (n = 397), added to the standard therapy. All patients were required to be on a stable dose of an ACE-inhibitor or ARB, and beta-blocker unless contraindicated or not tolerated. Echocardiograms were obtained at baseline, and following 26-36 weeks of treatment. The primary endpoint was change in left ventricular end-systolic volume from baseline to 36 weeks, and was evaluable in 329 patients in the placebo group and 343 patients in the aliskiren group. We observed no difference in the primary endpoint of end-systolic volume change between patients randomized to aliskiren (-4.4 ± 16.8 mL) or placebo (-3.5 ± 16.3 mL), or in secondary measures of end-diastolic volume, or LVEF. We also observed no differences in a composite endpoint of cardiovascular death, hospitalization for heart failure, or reduction in LVEF >6 points. There were more investigator reported adverse events in the aliskiren group, including hypotension, increases in creatinine and hyperkalaemia., Conclusion: Adding the direct renin inhibitor aliskiren to the standard therapy, including an inhibitor of the RAAS, in high-risk post-MI patients did not result in further attenuation of left ventricular remodelling, and was associated with more adverse effects. These findings do not suggest that dual RAAS blockade with aliskiren would provide additional benefit in these high-risk post-MI patients.

Background: The frequency of sudden unexpected death is highest in the early post-myocardial infarction (MI) period; nevertheless, 2 recent trials showed no improvement in mortality with early placement of an implantable cardioverter-defibrillator after MI., Methods and Results: To better understand the pathophysiological events that lead to sudden death after MI, we assessed autopsy records in a series of cases classified as sudden death events in patients from the VALsartan In Acute myocardial infarctioN Trial (VALIANT). Autopsy records were available in 398 cases (14% of deaths). We determined that 105 patients had clinical circumstances consistent with sudden death. On the basis of the autopsy findings, we assessed the probable cause of sudden death and evaluated how these causes varied with time after MI. Of 105 deaths considered sudden on clinical grounds, autopsy suggested the following causes: 3 index MIs in the first 7 days (2.9%); 28 recurrent MIs (26.6%); 13 cardiac ruptures (12.4%); 4 pump failures (3.8%); 2 other cardiovascular causes (stroke or pulmonary embolism; 1.9%); and 1 noncardiovascular cause (1%). Fifty-four cases (51.4%) had no acute specific autopsy evidence other than the index MI and were thus presumed arrhythmic. The percentage of sudden death due to recurrent MI or rupture was highest in the first month after the index MI. By contrast, after 3 months, the percentage of presumed arrhythmic death was higher than recurrent MI or rupture (chi(2)=23.3, P<0.0001)., Conclusions: Recurrent MI or cardiac rupture accounts for a high proportion of sudden death in the early period after acute MI, whereas arrhythmic death may be more likely subsequently. These findings may help explain the lack of benefit of early implantable cardioverter-defibrillator therapy.

Aims: Mitral regurgitation (MR) confers independent risk in patients with acute myocardial infarction. We utilized data from the VALsartan In Acute myocardial iNfarcTion echo study to relate baseline MR to left ventricular (LV) size, shape, and function, and to assess the relationship between baseline MR and progression of MR and cardiovascular (CV) outcomes., Methods and Results: We studied 496 patients with heart failure (HF) and/or systolic dysfunction after MI who underwent echocardiography at a median of 5 days after MI. MR severity, quantified as the regurgitant jet area/left atrial area ratio, was assessed at baseline, one and 20 months post-MI and related to LV size, shape, function, and clinical outcomes. Increased MR at baseline was associated with larger LV end-diastolic and end-systolic volumes, increased sphericity index, and reduced ejection fraction (P trend < 0.001). Moderate-severe MR was an independent predictor of total mortality [adjusted hazard ratio (HR) 2.4 (1.1-5.3)], CV mortality [adjusted HR 2.7 (1.2-6.1)], hospitalization for HF [adjusted HR 2.5 (1.1-5.5)], or death or HF hospitalization [adjusted HR 2.5 (1.4-4.6)]. Patients with progression of MR during the first post-MI month were substantially more likely to die or develop HF (adjusted HR per increased MR grade 3.0, 95% CI 1.8-4.9). Progression of MR over 20 months in survivors was associated with increased hospitalizations for HF (P < 0.001)., Conclusion: Following high-risk myocardial infarction, baseline mitral regurgitant severity is associated with larger LV volumes and worse LV function. Both baseline MR severity and progression of MR are associated with an increased likelihood of adverse outcomes.

Background: Left ventricular (LV) ejection fraction (EF) and wall-motion index (WMI) have both been shown to be independent predictors of outcome after myocardial infarction (MI)., Objectives: We sought to determine whether these two measurements of LV systolic function provide similar or complementary information about prognosis after MI., Methods: Echocardiography was performed in 610 patients with LV dysfunction, heart failure, or both after MI enrolled in the Valsartan in Acute MI trial. LVEF was estimated by biplane Simpson's rule, and WMI was assessed using a 16-segment model in 502 patients with echocardiograms of sufficient quality for wall-motion assessment., Results: Both LVEF and WMI were independent predictors of adverse outcome after MI. LVEF conferred no additional prognostic information in multivariable analysis including WMI (P = .39) or number of affected segments (P = .53), whereas WMI (P = .02) and total number of affected segments (P = .006) remained significant even when adjusting for LVEF., Conclusions: Assessment of regional dysfunction by WMI or the number of affected segments has slightly more prognostic value than LVEF in patients with LV dysfunction, heart failure, or both after MI. Regional assessment might be a more sensitive predictor of outcome than global assessment in patients with acute MI.

Baseline renal function is a potent independent risk factor for adverse events after acute myocardial infarction (MI). Worsening renal function (WRF) has been shown to influence outcomes in the heart failure population, but its impact on cardiovascular risk in the post-MI period has not been well defined. For assessment of the prognostic importance of WRF, 2231 patients who had left ventricular dysfunction and were enrolled in the Survival and Ventricular Enlargement (SAVE) trial were studied. Patients were randomly assigned between 3 and 16 d (average 11 d) after acute MI to receive captopril or placebo; those with a serum creatinine of >2.5 mg/dl were excluded from SAVE. WRF was defined as an increase in creatinine of >0.3 mg/dl measured from baseline to 2 wk after randomization. The predictive value of WRF on cardiovascular morbidity and mortality was examined during 42 mo of follow-up. Paired serum creatinine measurements at baseline and 2 wk were available in 1854 patients. WRF occurred in 223 (12.0%) patients and was a stronger predictor of death (hazard ratio [HR] 1.46; 95% confidence interval [CI] 1.05 to 2.02) than baseline creatinine (HR 1.31; 95% CI 1.01 to 1.70). WRF also showed an increased risk for cardiovascular death (HR 1.62; 95% CI 1.14 to 2.30) and the composite end point (HR 1.32; 95% CI 1.03 to 1.70). When stratified by treatment, 104 (5.7%) and 116 (6.4%) patients with WRF in the placebo and captopril groups had no significant association between treatment group and WRF (P = 0.38). The risk for death associated with WRF was HR 1.63 (95% CI 1.05 to 2.52) in the placebo group compared with HR 1.33 (95% CI 0.81 to 2.21) in the captopril group (P = 0.49 for interaction). WRF as early as 2 wk after MI was not uncommon (12.0%) and was associated with increased mortality in patients without renal dysfunction at baseline. Patients who received captopril did not demonstrate more WRF than patients who received placebo. Monitoring serum creatinine in patients during the first few weeks after MI may help to identify those who are at highest risk and guide effective long-term therapeutic choices.

Background: Prolongation of the QRS duration has been shown to be associated with adverse outcomes among heart failure (HF) patients. The association of QRS duration with clinical outcomes in the post-myocardial infarction (MI) setting is less well defined., Objectives: To assess the prognostic significance of QRS duration prolongation on initial electrocardiogram after acute MI., Methods: QRS duration was measured in 403 patients with MI complicated by left ventricular dysfunction, signs or symptoms of HF, or both, who were enrolled in the Valsartan in Acute Myocardial Infarction (VALIANT) echo study. The cohort was divided into quartiles of QRS duration (<75 ms, 75-88 ms, 89-108 ms, >108 ms). The number of clinical events were determined and compared across the groups., Results: Increasing QRS duration is associated with a higher incidence of HF, sudden death (SD), and cardiovascular (CV) death (P-trend <0.05) but not with stroke or recurrent MI. The univariate relative risks for HF, SD, and CV death with increasing QRS duration quartiles were 1.31 (95% CI, 1.06-1.64), 1.57 (95% CI, 1.03-2.40), and 1.31 (95% CI, 1.03-1.66), respectively, but QRS duration did not remain independently predictive of adverse outcome after adjusting for the 10 most predictive baseline covariates. Baseline end-diastolic and end-systolic volumes were larger and ejection fraction was lower in the higher QRS quartile groups., Conclusions: Prolonged QRS duration, even within the normal range, is associated with larger ventricular volumes, reduced systolic function, and an increased risk for development of HF, SD, and CV death after MI but appears to be a marker, rather than an independent predictor, for increased risk.

Background: Myocardial performance index (MPI) is a noninvasive, quantitative Doppler measure of global cardiac function, integrating systolic and diastolic functions. The prognostic significance of MPI is less clear for cardiovascular (CV) events after myocardial infarction (MI) among individuals at high risk with depressed left ventricular (LV) systolic function., Methods: We analyzed echocardiograms from 512 patients with depressed LV function after MI enrolled in the Survival and Ventricular Enlargement (SAVE) echocardiographic substudy. Baseline MPI measures were obtainable in 226 patients. The cohort was separated by median MPI (0.50). MPI was related to baseline clinical and echocardiographic characteristics, ventricular remodeling, and subsequent CV events, including recurrent MI, heart failure, CV death, and a composite of all CV end points., Results: An MPI of 0.5 or more was associated with larger infarct size and reduced LV systolic function at baseline; other baseline characteristics between the groups were similar. A total of 64 (28.3%) patients experienced CV events. Baseline MPI did not influence ventricular remodeling and did not modify the relationship between ventricular dilatation and CV events. After covariate adjustment, an MPI of 0.50 or higher remained an independent predictor for adverse CV events (hazard ratio [HR], 2.00, 95% confidence interval 1.17-3.43)., Conclusions: An MPI of 0.50 or greater is an independent predictor for CV events after MI in patients with known LV dysfunction.

Background: Angiotensin-converting enzyme (ACE) inhibitors have been shown to attenuate left ventricular (LV) enlargement in association with reducing mortality after myocardial infarction (MI). Preclinical data suggest that angiotensin receptor blockers (ARBs) may have similar structural and functional effects after MI. The Valsartan in Acute Myocardial Infarction (VALIANT) Echo study was designed to test the hypothesis that the ARB valsartan, either alone or in combination with captopril, could attenuate progressive LV enlargement or improve LV ejection fraction to a greater extent than captopril alone., Methods and Results: Six hundred ten patients enrolled in the main VALIANT study who experienced MI and evidence of LV dysfunction, heart failure, or both were enrolled in the VALIANT Echo study. Patients were randomized to receive valsartan 160 mg PO BID, captopril 50 mg PO TID, or valsartan 80 mg PO BID plus captopril 50 mg PO TID between 1 and 10 days after MI. Six hundred three patients had echocardiograms of sufficient quality for quantitative analysis. Echocardiograms were digitized, and endocardial borders were traced manually from 2 short-axis and 2 apical views. Ventricular volumes, ejection fractions, combined areas, and infarct segment length were measured, and changes in echocardiographic measures from baseline to 20 months were compared between treatment groups. Baseline clinical and echocardiographic characteristics were similar in the 3 treatment arms. The changes from baseline to 20 months in all echocardiographic parameters were similar in all 3 treatment arms. Baseline echocardiographic measures of ejection fraction, end-diastolic volume, and infarct segment length were highly predictive of outcomes including total mortality, death or hospitalization for heart failure, or death or any cardiovascular event (heart failure, MI, stroke, resuscitated sudden death), even after adjustment for known covariates., Conclusions: Treatment with the ACE inhibitor captopril, valsartan, or the combination of captopril plus valsartan resulted in similar changes in cardiac volume, ejection fraction, and infarct segment length between baseline and 20 months after MI. Baseline echocardiographic measures were powerfully and independently predictive of all major outcomes.

Background: Diabetes is a major risk factor for developing coronary heart disease. In patients with diabetes who survived myocardial infarction (MI), less is known about subsequent morbidity and mortality. We evaluated the effects of diabetes in post-MI patients with left ventricular dysfunction on cardiovascular events and death., Methods: The Survival and Ventricular Enlargement, a randomized, double-blind, placebo-controlled multicenter trial, evaluated the efficacy of captopril vs placebo in 2231 patients following acute MI with left ventricular dysfunction defined as an ejection fraction less than or equal to 40%. Patients were randomly assigned to captopril or placebo 3 to 16 days following MI and were followed up for 2 to 5 years (mean, 3.5 years)., Results: Among the 2231, 496 (22.2%) were patients with a history of diabetes, of which 168 (33.9%) were treated with insulin. Patients with diabetes were significantly older; more likely to be women; have a history of prior MI or hypertension; be obese or manifest Killip class II or greater; and have higher systolic blood pressure, pulse pressure, and heart rate, as well as lower ejection fraction. During follow-up, 31.3% of patients with diabetes and 20.1% of nondiabetic patients died (P<.001). Furthermore, 50% of the patients with diabetes had at least 1 major cardiovascular event compared with 32.3% among the nondiabetic patients (P<.001). In multivariate analysis that adjusted for all significant differences in baseline characteristics, patients with diabetes had a 39% higher total mortality (P = .001) and 49% more cardiovascular events (P = .001). Among the patients with diabetes, baseline insulin treatment was associated with a greater risk of death (41.1% vs 26.2%; P = .001) and cardiovascular events (58.3% vs 45.7%; P = .008)., Conclusions: In patients who survived MI with left ventricular dysfunction, diabetes increased risk of death from all causes even after controlling for differences in other risk factors. Patients with diabetes treated with insulin have a particularly higher mortality risk. Patients with diabetes who survived MI with left ventricular dysfunction, in particular those receiving insulin, are at high risk of subsequent mortality and cardiovascular events and thus require intensive risk factor modification, as well as evaluation for novel therapies.

Objectives: We assessed the influence of alcohol intake on the development of symptomatic heart failure (HF) in patients with left ventricular (LV) dysfunction after a myocardial infarction (MI)., Background: In contrast to protection from coronary heart disease, alcohol consumption has been linked to cardiodepressant effects and has been considered contraindicated in patients with HF., Methods: The Survival And Ventricular Enlargement (SAVE) trial randomized 2231 patients with a LV ejection fraction (EF) <40% following MI to an angiotensin-converting enzyme inhibitor or placebo. Patients were classified as nondrinkers, light-to-moderate drinkers (1 to 10 drinks/week), or heavy drinkers (>10 drinks/week) based on alcohol consumption reported at baseline. The primary outcome was hospitalization for HF or need for an open-label angiotensin-converting enzyme inhibitor. Analyses were repeated using alcohol consumption reported three months after MI., Results: Nondrinkers were older and had more comorbidities than light-to-moderate and heavy drinkers. In univariate analyses, baseline light-to-moderate alcohol intake was associated with a lower incidence of HF compared with nondrinkers (hazard ratio [HR] 0.71; 95% confidence interval [CI] 0.57 to 0.87), whereas heavy drinking was not (HR 0.91; 95% CI 0.67 to 1.23). After adjustment for baseline differences, light-to-moderate baseline alcohol consumption no longer significantly influenced the development of HF (light-to-moderate drinkers HR 0.93; 95% CI 0.75 to 1.17; heavy drinkers HR 1.25; 95% CI 0.91 to 1.72). Alcohol consumption reported three months after the MI similarly did not modify the risk of adverse outcome., Conclusions: In patients with LV dysfunction after an MI, light-to-moderate alcohol intake either at baseline or following MI did not alter the risk for the development of HF requiring hospitalization or an open-label angiotensin-converting enzyme inhibitor.