Regional myocardial functional patterns: Quantitative tagged magnetic resonance imaging in an adult population free of cardiovascular risk factors: The multi-ethnic study of atherosclerosis (MESA).

PURPOSE: To characterize the left ventricular (LV) regional deformation patterns and identify normal values of left ventricular strains from tagged magnetic resonance imaging (MRI) in a population with low-risk-factor (LRF) exposure. MATERIALS AND METHODS: Tagged CMR on three LV short axis slices was performed in participants of the MESA study who were free of cardiovascular disease at baseline. Images were analyzed by the harmonic phase imaging method to obtain: peak torsion, circumferential (Ecc) and radial (Err) strains, and systolic (SRs) and early-diastolic (SRe) strain rates. An LRF group was created from the overall population based on strict exclusion criteria (n = 129) based on risk factors and events observed over a 10-year follow-up. RESULTS: The normative prediction intervals for the averaged peak Ecc (%) and torsion (deg/cm) measures were: in 45-59-year-old women: (-20.8, -13.2) and (2.1, 6.3); 60-84-year-old women: (-20.6, -12.8) and (2.2, 6.9); 45-59-year-old men: (-21.3, -13.5) and (1.9, 5.7); 60-84-year-old men: (-20.5, -12.5) and (1.5, 5.2). In general, African-Americans (Ecc = -15.9, torsion = 3.3) had lower strains as compared to Chinese (Ecc = -17.1, torsion = 3.9), while Caucasians and Hispanics were intermediate and not significantly different. Circumferential shortening increased spatially from the epicardium to the endocardium (-16.9 to -18.2 at the mid-ventricle) and from the base to the apex (-15.1 to -17.5 at the midwall). CONCLUSION: The present study provides reference ranges and deformation patterns of deformation values from a large healthy population free of cardiovascular disease at baseline.

Multi-ethnic study of atherosclerosis: association between left atrial function using tissue tracking from cine MR imaging and myocardial fibrosis.

PURPOSE: To investigate the association between left atrial ( LA left atrium ) function and left ventricular myocardial fibrosis using cardiac magnetic resonance (MR) imaging in a multi-ethnic population. MATERIALS AND METHODS: For this HIPAA-compliant study, the institutional review board at each participating center approved the study protocol, and all participants provided informed consent. Of 2839 participants who had undergone cardiac MR in 2010-2012, 143 participants with myocardial scar determined with late gadolinium enhancement and 286 age-, sex-, and ethnicity-matched control participants were identified. LA left atrium volume, strain, and strain rate were analyzed by using multimodality tissue tracking from cine MR imaging. T1 mapping was applied to assess diffuse myocardial fibrosis. The association between LA left atrium parameters and myocardial fibrosis was evaluated with the Student t test and multivariable regression analysis. RESULTS: The scar group had significantly higher minimum LA left atrium volume than the control group (mean, 22.0 ± 10.5 [standard deviation] vs 19.0 ± 7.8, P = .002) and lower LA left atrium ejection fraction (45.9 ± 10.7 vs 51.3 ± 8.7, P < .001), maximal LA left atrium strain ( Smax maximum LA strain ) (25.4 ± 10.7 vs 30.6 ± 10.6, P < .001) and maximum LA left atrium strain rate ( SRmax maximum LA strain rate ) (1.08 ± 0.45 vs 1.29 ± 0.51, P < .001), and lower absolute LA left atrium strain rate at early diastolic peak ( SRE LA strain rate at early diastolic peak ) (-0.77 ± 0.42 vs -1.01 ± 0.48, P < .001) and LA left atrium strain rate at atrial contraction peak ( SRA LA strain rate at atrial contraction peak ) (-1.50 ± 0.62 vs -1.78 ± 0.69, P < .001) than the control group. T1 time 12 minutes after contrast material injection was significantly associated with Smax maximum LA strain (ß coefficient = 0.043, P = .013), SRmax maximum LA strain rate (ß coefficient = 0.0025, P = .001), SRE LA strain rate at early diastolic peak (ß coefficient = -0.0016, P = .027), and SRA LA strain rate at atrial contraction peak LA strain rate at atrial contraction peak (ß coefficient -0.0028, P = .01) in the regression model. T1 time 25 minutes after contrast material injection was significantly associated with SRmax maximum LA strain rate (ß coefficient = 0.0019, P = .016) and SRA LA strain rate at atrial contraction peak (ß coefficient = -0.0022, P = .034). CONCLUSION: Reduced LA left atrium regional and global function are related to both replacement and diffuse myocardial fibrosis processes. Clinical trial registration no.: NCT00005487

Prognostic value of myocardial circumferential strain for incident heart failure and cardiovascular events in asymptomatic individuals: the Multi-Ethnic Study of Atherosclerosis.

AIMS: Left ventricular (LV) circumferential strain (Ecc) is a sensitive index of regional myocardial function. Currently, no studies have assessed its prognostic value in general population. We sought to investigate whether Ecc has a prognostic value for predicting incident heart failure (HF) and other major cardiovascular events in asymptomatic individuals without a history of previous cardiovascular diseases. METHODS AND RESULTS: We, prospectively, assessed incident HF and atherosclerotic events during a 5.5 ± 1.3-year period in 1768 asymptomatic individuals aged 45-84 (mean age 65 years; 47% female) who underwent tagged magnetic resonance imaging for strain determination. During the follow-up period, 39 (2.2%) participants experienced incident HF and 108 (6.1%) participants had atherosclerotic cardiovascular events. Average of peak Ecc of 12-LV segments (Ecc-global) and mid-slice (Ecc-mid) was -17.0 ± 2.4 and -17.5 ± 2.7%, respectively. Participants with average absolute Ecc-mid lower than -16.9% had a higher cumulative hazard of incident HF (log-rank test, P = 0.001). In cox regression analysis, Ecc-mid predicted incident HF independent of age, diabetes status, hypertension, interim myocardial infarction, LV mass index, and LV ejection fraction (hazard ratio 1.15 per 1%, 95% CI: 1.01-1.31, P = 0.03). This relationship remained significant after adjustment for LV-end-systolic wall stress into covariates. In addition, by adding Ecc-mid to risk factors, LV ejection fraction, and the LV mass index, both the global χ(2) value (76.6 vs. 82.4, P = 0.04) and category-less net-reclassification index (P = 0.01, SE = 0.18, z = 2.53) were augmented for predicting HF. Circumferential strain was also significantly related to the composite atherosclerotic cardiovascular events, but its relationship was attenuated after introducing the LV mass index. CONCLUSION: Circumferential shortening provides robust, independent, and incremental predictive value for incident HF in asymptomatic subjects without any history of previous clinical cardiovascular disease. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT00005487.

Inter-study reproducibility of cardiovascular magnetic resonance tagging.

BACKGROUND: The aim of this study is to determine the test-retest reliability of the measurement of regional myocardial function by cardiovascular magnetic resonance (CMR) tagging using spatial modulation of magnetization. METHODS: Twenty-five participants underwent CMR tagging twice over 12 ± 7 days. To assess the role of slice orientation on strain measurement, two healthy volunteers had a first exam, followed by image acquisition repeated with slices rotated ±15 degrees out of true short axis, followed by a second exam in the true short axis plane. To assess the role of slice location, two healthy volunteers had whole heart tagging. The harmonic phase (HARP) method was used to analyze the tagged images. Peak midwall circumferential strain (Ecc), radial strain (Err), Lambda 1, Lambda 2, and Angle α were determined in basal, mid and apical slices. LV torsion, systolic and early diastolic circumferential strain and torsion rates were also determined. RESULTS: LV Ecc and torsion had excellent intra-, interobserver, and inter-study intra-class correlation coefficients (ICC range, 0.7 to 0.9). Err, Lambda 1, Lambda 2 and angle had excellent intra- and interobserver ICC than inter-study ICC. Angle had least inter-study reproducibility. Torsion rates had superior intra-, interobserver, and inter-study reproducibility to strain rates. The measurements of LV Ecc were comparable in all three slices with different short axis orientations (standard deviation of mean Ecc was 0.09, 0.18 and 0.16 at basal, mid and apical slices, respectively). The mean difference in LV Ecc between slices was more pronounced in most of the basal slices compared to the rest of the heart. CONCLUSIONS: Intraobserver and interobserver reproducibility of all strain and torsion parameters was excellent. Inter-study reproducibility of CMR tagging by SPAMM varied between different parameters as described in the results above and was superior for Ecc and LV torsion. The variation in LV Ecc measurement due to altered slice orientation is negligible compared to the variation due to slice location. TRIAL REGISTRATION: This trial is registered as NCT00005487 at National Heart, Lung and Blood institute.

Cardiovascular Interactions of Renin-Angiotensin-Aldosterone System Assessed by Cardiac Magnetic Resonance: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: The effects of the renin-angiotensin-aldosterone system in cardiovascular system have been described based on small studies. The aim of this study was to evaluate the relationship between aldosterone and plasma renin activity (PRA) and cardiovascular structure and function. METHODS: We studied a random sample of Multi-Ethnic Study of Atherosclerosis participants who had aldosterone and PRA blood assays at 2003-2005 and underwent cardiac magnetic resonance at 2010. Participants taking angiotensin-converting enzyme inhibitors or angiotensin receptor blockers were excluded. RESULTS: The aldosterone group was composed by 615 participants, mean age 61.6 ± 8.9 years, while the renin group was 580 participants, mean age 61.5 ± 8.8 years and both groups had roughly 50% females. In multivariable analysis, 1 SD increment of log-transformed aldosterone level was associated with 0.07 g/m2 higher left ventricle (LV) mass index (P = 0.04) and 0.11 ml/m2 higher left atrium (LA) minimal volume index (P < 0.01). Additionally, higher log-transformed aldosterone was associated with lower LA maximum strain and LA emptying fraction (P < 0.01). Aldosterone levels were not significantly associated with aortic measures. Log-transformed PRA was associated with lower LV end diastolic volume index (ß standardized = 0.08, P = 0.05). PRA levels were not significantly associated with LA and aortic structural or functional differences. CONCLUSIONS: Higher levels of aldosterone and PRA are associated with concentric LV remodeling changes. Moreover, aldosterone was related to deleterious LA remodeling changes.

Spontaneous pneumomediastinum and subcutaneous emphysema in a child with unknown aetiology.

Spontaneous subcutaneous emphysema and pneumomediastinum in children without any predisposing factors is a rare entity. We present a case of an adolescent boy with spontaneous pneumomediastinum. He is a 14-year-old boy brought to the hospital with an odd feeling in the neck and chest. Initial chest X-ray revealed subcutaneous emphysema and pneumomediastinum. He was further evaluated with CT thorax and abdomen with contrast which revealed extensive pneumomediastinum with associated surgical emphysema in the chest wall and neck. Expert opinions from the cardiothoracic and respiratory teams were obtained. The child was discharged with safety netting and description of red flag signs. Repeat chest X-ray in 2 weeks showed complete resolution of the pneumomediastinum and subcutaneous emphysema. We will briefly discuss about the diagnosis and treatment of spontaneous pneumomediastinum and subcutaneous emphysema.

Association of myocardial fibrosis and cardiovascular events: the multi-ethnic study of atherosclerosis.

Aims: We used contrast-enhanced cardiac magnetic resonance (CMR) to evaluate differences in myocardial fibrosis measured at the year-10 examination between participants with and without cardiovascular (CV) events accrued in a large population based study over the preceding 10-year follow-up period in this retrospective study. Methods and results: The MESA study enrolled 6814 participants free of CV disease at baseline (2000-2002). We included MESA participants who underwent contrast-enhanced CMR at the MESA year-10 exam (N = 1840). We defined a composite CV endpoint of coronary heart disease, heart failure, atrial fibrillation, stroke, and peripheral artery disease. Using CMR, we characterized myocardial fibrosis with late-gadolinium enhancement for scar and T1 mapping indices of diffuse fibrosis. Demographic and CV-risk adjusted logistic (presence of scar) and linear regression (pre-contrast T1, T1 at 12 and 25 min post-contrast, and extracellular volume fraction or ECV) models were used to assess the relationship between fibrosis and events. The mean values of T1 indices were-pre-contrast T1: 977 ± 45 ms; T1 at 12': 456 ± 40 ms; T1 at 25': 519 ± 41 ms; ECV: 27.1 ± 3.2%. One-hundred and forty-six (7.9%) participants had myocardial scar. The presence of scar was strongly associated with prior CV events (adjusted coeff: 1.36, P < 0.001). Lower post-contrast T1 times and higher ECV, indicative of greater diffuse fibrosis were strongly associated with CV events (T1 at 12': coeff = -10.0 ms, P = 0.004; T1 at 25': coeff =-9.2 ms, P = 0.008; ECV: coeff = 1.31%, P < 0.001). Conclusion: Individuals who suffered prior CV events have greater likelihood of diffuse myocardial fibrosis when compared with event-free individuals living in the same community.

Association of Cardiovascular Risk Factors and Myocardial Fibrosis With Early Cardiac Dysfunction in Type 1 Diabetes: The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study.

OBJECTIVE: We investigated the association of cardiovascular risk factors and myocardial fibrosis with early cardiac dysfunction in type 1 diabetes. RESEARCH DESIGN AND METHODS: Participants with type 1 diabetes aged 13-39 years without a known history of cardiovascular disease (CVD) (n = 1,441) were recruited into the Diabetes Control and Complications Trial (1983-1993) and subsequently followed in the Epidemiology of Diabetes Interventions and Complications study (1994 to present). Seven hundred fourteen participants underwent cardiac magnetic resonance (CMR) imaging (2007-2009) with late gadolinium enhancement sequences to assess ischemic and nonischemic scars and tagging sequences to evaluate circumferential strain. CMR-derived T1 mapping also was used to assess interstitial fibrosis. The influence of cardiovascular risk factors and myocardial scar on circumferential strain was assessed using linear regression. RESULTS: Circumferential dysfunction was consistently associated with older age, male sex, smoking history, obesity, higher blood pressure, lower HDL cholesterol, and higher mean HbA1c. Participants with nonischemic scars (n = 16) had the worst circumferential function compared with those without scars (ß ± SE 1.32 ± 0.60; P = 0.03). In sex-adjusted models, the correlation between T1 times and circumferential strain was not significant. In the fully adjusted models, a trend toward circumferential dysfunction in participants with nonischemic scars was found. Left ventricular ejection fraction was not associated with risk factors but was significantly lower if a myocardial scar was present. CONCLUSIONS: Traditional CVD risk factors and elevated HbA1c levels are major factors related to early cardiac dysfunction in type 1 diabetes. Nonischemic myocardial scar, possibly as a marker of chronic exposure to known risk factors, may predict early cardiac dysfunction mediated by diffuse myocardial fibrosis as seen in diabetic cardiomyopathy.

Comparison of effectiveness and safety of drug-eluting stents versus vascular brachytherapy for saphenous vein graft in-stent restenosis.

We investigated the safety and efficacy of drug-eluting stents (DESs) for the treatment of patients who presented with in-stent restenosis (ISR) of saphenous vein grafts (SVGs) and compared the in-hospital and 6-month clinical outcomes of DESs with those of intravascular brachytherapy and balloon angioplasty alone. Records of 187 patients who presented with ISR of SVGs were analyzed. Of these, 34 consecutive patients were treated with DES implantation, 93 were treated with intravascular brachytherapy (n = 60 with gamma-radiation, n = 33 with beta-radiation), and 60 patients underwent conventional treatment with balloon angioplasty alone. Clinical and angiographic characteristics at baseline were comparable between groups. The DES group had less non-Q-wave myocardial infarction than did the intravascular brachytherapy and balloon angioplasty groups (0%, 20%, and 26%, p = 0.003 and <0.001, respectively). At 6 months, death occurred in 0% of the DES group, 2% of the intravascular brachytherapy group, and 5% of the balloon angioplasty group (p = 0.36 and <0.18, respectively). Target lesion revascularization/major adverse cardiac events were similar in the intravascular brachytherapy and DES groups (12% and 3%, p = 0.13) and significantly decreased compared with patients who were treated with balloon angioplasty alone (55%, p <0.001 for the 2 comparisons). The results of this retrospective analysis suggest that DES implantation is at least as effective and safe as intravascular brachytherapy for the treatment of SVG ISR and that these treatment modalities are superior to balloon angioplasty alone.

Natural History of Myocardial Function in an Adult Human Population: Serial Longitudinal Observations From MESA.

OBJECTIVES: The aim of this longitudinal study was to define the determinants of aging-related left ventricular (LV) remodeling and function in a large multiethnic population. BACKGROUND: The influence of risk factor exposure on myocardial remodeling and function in humans across adult life remains incompletely understood. MESA (Multi-Ethnic Study of Atherosclerosis) is a longitudinal population-based cohort of asymptomatic adults at baseline. METHODS: We examined 757 participants who were free of clinical cardiovascular disease and underwent tagged cardiac magnetic resonance both at baseline and at the 10-year follow-up as part of the MESA study. LV remodeling, circumferential shortening (CS), and torsion were assessed by tagged cardiac magnetic resonance. Multivariable linear regression was used to determine the association of changes in risk factors with changes in cardiac geometry and function. RESULTS: The mean age of participants was 63 ± 9 years at baseline; 50% were women. Overall, the LV mass-to-volume ratio increased by 10% over 10 years (p < 0.01). CS was unchanged (17.8% to 17.9%, p = 0.246), whereas torsion increased by 13% (3.8°/cm to 4.3°/cm, p < 0.001). Increased systolic blood pressure was associated with reduced CS (-0.02%/mm Hg, p < 0.01). Participants who remained on antihypertensive therapy during the whole study had a greater decrease in LV mass-to-volume ratio (-0.045 vs. no medication, p < 0.05) with a greater increase in CS (0.78% vs. no medication, p < 0.01). Moreover, greater LV mass at baseline was significantly associated with reduced CS (-0.02%/g, p < 0.01) and torsion (-0.02°/cm/g, p < 0.01) independently of risk factors. CONCLUSIONS: Longitudinal observation demonstrates that LV mass and worsening risk factors are fundamental determinants of reduced regional myocardial shortening over 10 years. Increased torsion of the myocardial wall is seen with progressive concentric remodeling and may explain why systolic function is maintained with aging.

Association of Aortic Stiffness With Left Ventricular Remodeling and Reduced Left Ventricular Function Measured by Magnetic Resonance Imaging: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: This study sought to assess cross-sectional associations of aortic stiffness assessed by magnetic resonance imaging with left ventricular (LV) remodeling and myocardial deformation in the Multi-Ethnic Study of Atherosclerosis (MESA). METHODS AND RESULTS: Aortic arch pulse wave velocity (PWV) was measured with phase contrast cine magnetic resonance imaging. LV circumferential strain (Ecc), torsion, and early diastolic strain rate were determined by tagged magnetic resonance imaging. Multivariable linear regression models were used to adjust for demographics and cardiovascular risk factors. Of 2093 participants, multivariable linear regression models demonstrated that higher arch PWV was associated with higher LV mass index (B=0.53 per 1 SD increase for log-transformed PWV, P<0.05) and LV mass to volume ratio (B=0.015, P<0.01), impaired LV ejection fraction (LVEF; B=-0.84; P<0.001), Ecc (B=0.55; P<0.001), torsion (B=-0.11; P<0.001), and early diastolic strain rate (B=-0.003; P<0.05). In sex stratified analysis, higher arch PWV was associated with higher MVR (B=0.02; P<0.05), impaired Ecc (B=0.60; P<0.001), and LVEF (B=-0.45; P<0.05), but with maintained torsion in women. Higher PWV was associated with impaired Ecc (B=0.49; P<0.001) and LVEF (B=-1.21; P<0.001), with lower torsion (B=-0.17; P<0.001) in men. CONCLUSIONS: Higher arch PWV is associated with LV remodeling, and reduced LV systolic and diastolic function in a large multiethnic population. Greater aortic arch stiffness is associated with concentric LV remodeling and relatively preserved LVEF with maintained torsion in women, whereas greater aortic arch stiffness is associated with greater LV dysfunction demonstrated as impaired Ecc, torsion, and LVEF, with less concentric LV remodeling in men.

Association of subclinical atherosclerosis using carotid intima-media thickness, carotid plaque, and coronary calcium score with left ventricular dyssynchrony: the multi-ethnic Study of Atherosclerosis.

BACKGROUND: The role of atherosclerosis in the progression of global left ventricular dysfunction and cardiovascular events has been well recognized. Left ventricular (LV) dyssynchrony is a measure of regional myocardial dysfunction. Our objective was to investigate the relationship of subclinical atherosclerosis with mechanical LV dyssynchrony in a population-based asymptomatic multi-ethnic cohort. METHODS AND RESULTS: Participants of the Multi-Ethnic Study of Atherosclerosis (MESA) at exam 5 were evaluated using 1.5T cardiac magnetic resonance (CMR) imaging, carotid ultrasound (n = 2062) for common carotid artery (CCA) and internal carotid artery (ICA) intima-media thickness (IMT), and cardiac computed tomography (n = 2039) for coronary artery calcium (CAC) assessment (Agatston method). Dyssynchrony indices were defined as the standard deviation of time to peak systolic circumferential strain (SD-TPS) and the difference between maximum and minimum (max-min) time to peak strain using harmonic phase imaging in 12 segments (3-slices × 4 segments). Multivariable regression analyses were performed to assess associations after adjusting for participant demographics, cardiovascular risk factors, LV mass, and ejection fraction. In multivariable analyses, SD-TPS was significantly related to measures of atherosclerosis, including CCA-IMT (8.7 ms/mm change in IMT, p = 0.020), ICA-IMT (19.2 ms/mm change in IMT, p < 0.001), carotid plaque score (1.2 ms/unit change in score, p < 0.001), and log transformed CAC+1 (0.66 ms/unit log-CAC+1, p = 0.018). These findings were consistent with other parameter of LV dyssynchrony i.e. max-min. CONCLUSION: In the MESA cohort, measures of atherosclerosis are associated with parameters of subclinical LV dyssynchrony in the absence of clinical coronary event and left-bundle-branch block.

Interstitial fibrosis, left ventricular remodeling, and myocardial mechanical behavior in a population-based multiethnic cohort: the Multi-Ethnic Study of Atherosclerosis (MESA) study.

BACKGROUND: Tagged cardiac magnetic resonance provides detailed information on regional myocardial function and mechanical behavior. T1 mapping by cardiac magnetic resonance allows noninvasive quantification of myocardial extracellular expansion (ECE), which has been related to interstitial fibrosis in previous clinical and subclinical studies. We assessed sex-associated differences in the relation of ECE to left ventricular (LV) remodeling and myocardial systolic and diastolic deformation in a large community-based multiethnic population. METHODS AND RESULTS: Midventricular midwall peak circumferential shortening and early diastolic strain rate and LV torsion and torsional recoil rate were determined using cardiac magnetic resonance tagging. Midventricular short-axis T1 maps were acquired in the same examination pre- and postcontrast injection using Modified Look-Locker Inversion-Recovery sequence. Multivariable linear regression (estimated regression coefficient, B) was used to adjust for risk factors and subclinical disease measures. Of 1230 participants, 114 had a visible myocardial scar by late gadolinium enhancement. Participants without a visible myocardial scar (n=1116) had no history of previous clinical events. In the latter group, multivariable linear regression demonstrated that lower postcontrast T1 times, reflecting greater ECE, were associated with lower circumferential shortening (B=-0.1; P=0.0001), lower LV end-diastolic volume index (B=0.6; P=0.0001), and lower LV end-diastolic mass index (B=0.4; P=0.0001). In addition, lower postcontrast T1 times were associated with lower early diastolic strain rate (B=0.01; P=0.03) in women only and lower LV torsion (B=0.005; P=0.03) and lower LV ejection fraction (B=0.2, P=0.01) in men only. CONCLUSIONS: Greater ECE is associated with reduced LV end-diastolic volume index and LV end-diastolic mass index in a large multiethnic population without history of previous cardiovascular events. In addition, greater ECE is associated with reduced circumferential shortening, lower early diastolic strain rate, and a preserved ejection fraction in women, whereas in men, greater ECE is associated with greater LV dysfunction manifested as reduced circumferential shortening, reduced LV torsion, and reduced ejection fraction.

Diastolic function assessed from tagged MRI predicts heart failure and atrial fibrillation over an 8-year follow-up period: the multi-ethnic study of atherosclerosis.

OBJECTIVES: The strain relaxation index (SRI), a novel diastolic functional parameter derived from tagged magnetic resonance imaging (MRI), is used to assess myocardial deformation during left ventricular relaxation. We investigated whether diastolic function indexed by SRI predicts heart failure (HF) and atrial fibrillation (AF) over an 8-year follow-up. METHODS: As a part of the multi-ethnic study of atherosclerosis, 1544 participants free of known cardiovascular disease (CVD) underwent tagged MRI in 2000-02. Harmonic phase analysis was used to compute circumferential strain. Standard parameters, early diastolic strain rate (EDSR) and the peak torsion recoil rate were calculated. An SRI was calculated as difference between post-systolic and systolic times of the strain peaks, divided by the EDSR peak. It was normalized by the total interval of relaxation. Over an 8-year follow-up period, we defined AF (n = 57) or HF (n = 36) as combined (n = 80) end-points. Cox regression assessed the ability of SRI to predict events adjusted for risk factors and markers of subclinical disease. Integrated discrimination index (IDI) and net reclassification index (NRI) of SRI, compared with conventional indices, were also assessed. RESULTS: The hazard ratio for SRI remained significant for the combined HF and AF end-points as well as for HF alone after adjustment. For the combined end-point, IDI was 1.5% (P < 0.05) and NRI was 11.4% (P < 0.05) for SRI. Finally, SRI was more robust than all other existing cardiovascular magnetic resonance diastolic functional parameters. CONCLUSION: SRI predicts HF and AF over an 8-year follow-up period in a large population free of known CVD, independent of established risk factors and markers of subclinical CVD.

Association of longitudinal changes in left ventricular structure and function with myocardial fibrosis: the Multi-Ethnic Study of Atherosclerosis study.

The association of longitudinal changes in left ventricular (LV) structure and function with myocardial fibrosis is unclear. We relate temporal changes in body size-indexed LV mass (LVMi) and end-diastolic volume indexed to body surface area, LV mass-to-volume ratio, and LV ejection fraction (LVEF) from cine cardiac magnetic resonance for 10 years, with replacement scar assessed from late gadolinium enhancement, and lower postcontrast T1 times reflecting greater diffuse myocardial fibrosis measured at the end of the follow-up period. All participants (n=1813) who underwent cardiac magnetic resonance twice as part of the Multi-Ethnic Study of Atherosclerosis 10 years apart were included. Multivariable logistic and linear regression models adjusted for cardiovascular risk factors measured the association of 10-year changes in LV structure and function, with fibrosis measured at follow-up. The presence of LV scar at year 10 was cross-sectionally associated with higher LVMi (≈10 g/m(2)), higher mass-to-volume ratio (0.1-0.2 g/mL), but lower LVEF (≈4%) and longitudinally with 3% decrease in LVEF and 0.7% greater end-diastolic volume indexed to body surface area in men for 10 years. Lower postcontrast T1 times at year 10 were associated cross-sectionally with lower LVMi (r=0.33), end-diastolic volume indexed to body surface area (r=0.25), and LVEF (in men only: r=0.14) and longitudinally with a decrease in LVMi (r=0.20) and reduction in LVEF (in men only: r=0.15). Sustained hypertension for 10 years was associated with increased LVMi and higher diffuse and replacement fibrosis at follow-up. During a 10-year period, increased concentric hypertrophy in women and LV dilatation in men were associated with replacement fibrosis, whereas decreasing LVMi was associated with diffuse fibrosis. Hypertension-induced remodeling was related to enhanced replacement and diffuse fibrosis, as well as hypertrophy.

Prognostic implications of left ventricular dyssynchrony for major adverse cardiovascular events in asymptomatic women and men: the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Left ventricular (LV) dyssynchrony is related to adverse outcomes in systolic heart failure, but its prognostic importance in asymptomatic population is not known. Our objective was to assess the prognostic implications of LV mechanical dyssynchrony in a large multiethnic population before the occurrence of global LV dysfunction. METHODS AND RESULTS: A total of 1392 participants in the Multi-Ethnic Study of Atherosclerosis (MESA; mean age: 64.7 years; 46% were women) with cardiac magnetic resonance imaging at baseline were followed for a median duration of 8.3 years. Harmonic phase imaging analysis was used to derive systolic circumferential strain. Greater standard deviation of time to peak systolic strain (SD-TPS) indicates greater dyssynchrony. With SD-TPS as a continuous variable, Cox proportional hazards analysis was used to assess hazards ratio after adjusting for demographics, cardiovascular risk factors, LV mass-to-volume ratio, and ejection fraction. Using the 75th percentile of SD-TPS as a cutoff, Kaplan-Meier analysis was performed between 2 categorical groups for each gender. Higher values of dyssynchrony in women predicted major adverse cardiovascular events, defined as myocardial infarction, heart failure, stroke, and death (hazard ratio: 1.01 per 1-ms increment in SD-TPS, P=0.015), hard coronary events (hazard ratio: 1.05 per 1-ms increment in SD-TPS, P=0.026), and cerebrovascular events (hazard ratio: 1.03 per 1-ms increment in SD-TPS, P=0.013). In contrast, dyssynchrony in men was not predictive of events. Kaplan-Meier analyses in women revealed increased event occurrence in the higher dyssynchrony group, but this was not the case in men. CONCLUSIONS: In an asymptomatic cohort, greater LV dyssynchrony determined by cardiac magnetic resonance imaging predicts adverse cardiovascular outcome in women but not in men. CLINICAL TRIAL REGISTRATION URL: http://clinicaltrials.gov. Unique identifier: NCT00005487.

Effectiveness of the novel anti-diabetes medication exenatide in everyday practice: Comparison with clinical trials.

We evaluated effectiveness of exenatide in 81 unselected patients and compared the results with clinical trials. Patients achieved a similar reduction in A1C and lost more weight than patients in the clinical trials. Thirty-seven (46%) were treated off-label. Exenatide was effective on and off-label in this unselected patient group.