High-throughput digitization of analog human echocardiography data.

Echocardiographic imaging has been acquired in historical longitudinal cohorts of cardiovascular disease. Many cohorts were established prior to digital recording of echocardiography, and thus have preserved their archival imaging on Video Home System (VHS) tapes. These tapes require large physical storage space, are affected by physical degradation, and cannot be analyzed using modern digital techniques. We have designed and implemented a standardized methodology for digitizing analog data in historical longitudinal cohorts. The methodology creates a pipeline through critical steps of initial review, digitization, anonymization, quality control, and storage. The methodology has been implemented in the Framingham Offspring Study, a community-based epidemiological cohort study with echocardiography performed during serial examinations between 1987 and 1998. We present this method as an accessible pipeline for preserving and repurposing historical imaging data acquired from large cohort studies. The described technique:•Outlines a generalizable pipeline for digitization of analog recordings of echocardiography stored on VHS tapes•Addresses research concerns including quality control, anonymization, and storage•Expresses the authors' individual experience regarding observed image quality, training needs, and potential limitations to help readers understand the costs and benefits of this method.

Heritability of Mitral Regurgitation: Observations From the Framingham Heart Study and Swedish Population.

BACKGROUND: Familial aggregation has been described for primary mitral regurgitation (MR) caused by mitral valve prolapse. We hypothesized that heritability of MR exists across different MR subtypes including nonprimary MR. METHODS AND RESULTS: Study participants were FHS (Framingham Heart Study) Generation 3 (Gen 3) and Gen 2 cohort participants and all adult Swedish siblings born after 1932 identified in 1997 and followed through 2010. MR was defined as ≥ mild regurgitation on color Doppler in FHS and from International Classification of Diseases codes in Sweden. We estimated the association of sibling MR with MR in Gen 2/Gen 3/Swedish siblings. We also estimated heritability of MR in 539 FHS pedigrees (7580 individuals). Among 5132 FHS Gen 2/Gen 3 participants with sibling information, 1062 had MR. Of siblings with sibling MR, 28% (500/1797) had MR compared with 17% (562/3335) without sibling MR (multivariable-adjusted odds ratio, 1.20; 95% confidence interval [CI], 1.01-1.43; P=0.04). When we combined parental and sibling data in FHS pedigrees, heritability of MR was estimated at 0.15 (95% CI, 0.07-0.23), 0.12 (95% CI, 0.04-0.20) excluding mitral valve prolapse, and 0.44 (95% CI, 0.15-0.73) for ≥ moderate MR only (all P<0.05). In Sweden, sibling MR was associated with a hazard ratio of 3.57 (95% CI, 2.21-5.76; P<0.001) for development of MR. CONCLUSIONS: Familial clustering of MR exists in the community, supporting a genetic susceptibility common to primary and nonprimary MR. Further studies are needed to elucidate the common regulatory pathways that may lead to MR irrespective of its cause.

Relations Between Aortic Stiffness and Left Ventricular Mechanical Function in the Community.

BACKGROUND: Aortic stiffness impairs optimal ventricular-vascular coupling and left ventricular systolic function, particularly in the long axis. Left ventricular global longitudinal strain (GLS) has recently emerged as a sensitive measure of early cardiac dysfunction. In this study, we investigated the relation between aortic stiffness and GLS in a large community-based sample. METHODS AND RESULTS: In 2495 participants (age 39-90 years, 57% women) of the Framingham Offspring and Omni cohorts, free of cardiovascular disease, we performed tonometry to measure arterial hemodynamics and echocardiography to assess cardiac function. Aortic stiffness was evaluated as carotid-femoral pulse wave velocity and as characteristic impedance, and GLS was calculated using speckle tracking-based measurements. In multivariable analyses adjusting for age, sex, height, systolic blood pressure, augmentation index, left ventricular structure, and additional cardiovascular risk factors, increased carotid-femoral pulse wave velocity (B±SE: 0.122±0.030% strain per SD, P<0.0001) and characteristic impedance (0.090±0.029, P=0.002) were both associated with worse GLS. We observed effect modification by sex on the relation between characteristic impedance and GLS (P=0.004); in sex-stratified multivariable analyses, the relation between greater characteristic impedance and worse GLS persisted in women (0.145±0.039, P=0.0003) but not in men (P=0.73). CONCLUSIONS: Multiple measures of increased aortic stiffness were cross-sectionally associated with worse GLS after adjusting for hemodynamic variables. Parallel reductions in left ventricular long axis shortening and proximal aortic longitudinal strain in individuals with a stiffened proximal aorta, from direct mechanical ventricular-vascular coupling, offers an alternative explanation for the observed relations.

Distinct Aspects of Left Ventricular Mechanical Function Are Differentially Associated With Cardiovascular Outcomes and All-Cause Mortality in the Community.

BACKGROUND: There are few data relating novel measures of left ventricular (LV) mechanical function to cardiovascular disease (CVD) outcomes in the community. Whether distinct components of LV mechanical function provide information regarding risk for different CVD outcomes is unclear. METHODS AND RESULTS: We used speckle tracking echocardiography to quantify distinct components of LV mechanical function (measured as LV strain in multiple planes) in 2831 Framingham Offspring Study participants (mean age, 66 years; 57% women, 97% with LV fractional shortening >0.29). Participants were followed for 6.0±1.2 years for onset of 69 coronary heart disease (CHD), 71 heart failure (HF), and 199 mortality events. Adjusting for CVD risk factors, longitudinal LV strain appeared associated with incident CHD (hazards ratio [HR] per SD increment, 1.29; 95% confidence interval [CI], 1.00-1.67; P=0.05), whereas circumferential and radial strain were not (P>0.37 for both); however, the association of longitudinal strain with CHD was nonsignificant after Bonferroni correction. By contrast, circumferential strain was a significant predictor of incident HF (HR per SD increment, 1.79; 95% CI, 1.35-2.37; P<0.0001). Decrements in circumferential, radial, and longitudinal strain measures were related to all-cause mortality (P<0.008 for all). Results remained similar in multivariable models adjusting additionally for the conventional echocardiographic measures of LV mass and fractional shortening. CONCLUSIONS: In our large, community-based sample, distinct components of LV mechanical function were associated with specific CVD outcomes. Additional studies are needed to replicate these findings and investigate the prognostic and therapeutic utility of these novel measures of LV mechanical function.

Left ventricular mechanical function: clinical correlates, heritability, and association with parental heart failure.

AIMS: Non-invasive measures of cardiac mechanical function may have the potential to serve as markers of risk for heart failure; however, limited data exist regarding clinical correlates and heritability of these measures in the community. METHODS AND RESULTS: We used speckle-tracking echocardiography to assess LV strain and synchrony in the Framingham Offspring Study (n = 2816; mean age 67 years, 54% women). In multivariable regression analyses, male gender (vs. female, P < 0.001), higher heart rate (P < 0.0001), and presence of cardiovascular disease (P < 0.001) were associated with worse global peak strains across all planes analysed (longitudinal, transverse, circumferential, and radial). Higher diastolic blood pressure and diabetes were associated with worse longitudinal strain (P < 0.01), and greater body mass index was associated with worse radial strain (P = 0.0004). Overall, however, clinical correlates accounted for only 4-19% of the variation in measures of LV mechanical function. Select measures of LV strain were heritable: longitudinal strain (h(2) = 16%, P = 0.002), transverse strain (h(2) = 15%, P = 0.006), and circumferential strain (h(2) = 30%, P < 0.0001). Furthermore, in a subset of 1437 participants with parental data available, parental heart failure was associated with worse circumferential strain in the offspring free of heart failure (P = 0.01). CONCLUSIONS: Our investigation in a large community-based sample identified heritablity and clinical correlates of LV mechanical function, and highlighted an association of parental heart failure with worse global circumferential strain in offspring.

Age- and sex-based reference limits and clinical correlates of myocardial strain and synchrony: the Framingham Heart Study.

BACKGROUND: There is rapidly growing interest in applying measures of myocardial strain and synchrony in clinical investigations and in practice; data are limited regarding their reference ranges in healthy individuals. METHODS AND RESULTS: We performed speckle-tracking-based echocardiographic measures of left ventricular myocardial strain and synchrony in healthy adults (n=739, mean age 63 years, 64% women) without cardiovascular disease. Reference values were estimated using quantile regression. Age- and sex-based upper (97.5th quantile) limits were: -14.4% to -17.1% (women) and -14.4 to -15.2% (men) for longitudinal strain; -22.3% to -24.7% (women) and -17.9% to -23.7% (men) for circumferential strain; 121 to 165 ms (women) and 143 to 230 ms (men) for longitudinal segmental synchrony (SD of regional time-to-peak strains); and 200 to 222 ms (women) and 216 to 303 ms (men) for transverse segmental synchrony. In multivariable analyses, women had ≈1.7% greater longitudinal strain, ≈2.2% greater transverse strain, and ≈3.2% greater circumferential strain (P<0.0001 for all) compared with men. Older age and higher diastolic blood pressure, even within the normal range, were associated with worse transverse segmental synchrony (P<0.001). Overall, covariates contributed to ≤12% of the variation in myocardial strain or synchrony in this healthy sample. CONCLUSIONS: We estimated age- and sex-specific reference limits for measures of left ventricular strain and synchrony in a healthy community-based sample, wherein clinical covariates contributed to only a modest proportion of the variation. These data may facilitate the interpretation of left ventricular strain-based measures obtained in future clinical research and practice.

Reproducibility of speckle-tracking-based strain measures of left ventricular function in a community-based study.

BACKGROUND: The reproducibility of echocardiographic measurements of myocardial strain, performed in a community-based setting, has not been reported previously. METHODS: The reproducibility of left ventricular strain measurements was examined in two samples of 20 participants each from the Offspring Cohort of the Framingham Heart Study (mean age, 63 ± 9 years; 59% women). Two-dimensional speckle-tracking-based measurements of global peak left ventricular strain in systole were performed in the apical four-chamber, apical two-chamber, and midventricular parasternal short-axis views. RESULTS: Interobserver intraclass correlation coefficients were ≥0.84 for all global strain measurements, with average coefficients of variation of ≤4% for global longitudinal and circumferential strain and <8% for global transverse and radial strain. For left ventricular strain measurements performed in each of the three views, intraobserver intraclass correlation coefficients were ≥0.91 among time points spanning a total 8-month period. The average coefficients of variation were <6% for global longitudinal and circumferential strain and <9% for global transverse and radial strain. Interobserver and intraobserver reproducibility findings were similar in analyses adjusting for frame rate. CONCLUSIONS: Excellent reproducibility of global longitudinal and circumferential strain measurements and very good reproducibility of global transverse and radial strain measurements were observed. Taken together, these findings demonstrate the reproducibility of performing echocardiographic strain measurements in a large, epidemiologic community-based setting.

Relation of brachial and digital measures of vascular function in the community: the Framingham heart study.

Impaired vascular function contributes to the development of clinical cardiovascular disease. The relation between vasodilator function assessed noninvasively in the brachial and digital arteries remains incompletely defined. In the Framingham Offspring, Third Generation and Omni Cohorts, we measured flow-mediated dilation (FMD; n = 7031; age 48 ± 13 years; age range, 19 to 88 years; 54% women) and peripheral arterial tonometry (PAT) ratio (n = 4352; 55 ± 16 years; age range, 19 to 90 years; 51% women). Abnormal vascular function for each measure was defined by the sex-specific fifth percentile in a reference group free of conventional cardiovascular risk factors. The prevalence of abnormal FMD but not abnormal PAT ratio was higher with advancing age. In multivariable models, higher body mass index was associated with a higher prevalence of both abnormal FMD and PAT ratio. Additional correlates of abnormal FMD included increasing age and higher systolic blood pressure. In contrast, correlates of abnormal PAT ratio included lower systolic blood pressure, increasing total/high-density lipoprotein cholesterol ratio, diabetes, smoking, and lipid-lowering medication. Whereas women had higher FMD and PAT ratios compared with men, using sex-specific reference values, women had a higher prevalence of abnormal brachial and digital vascular function. In participants who had concurrent testing (n = 1843), PAT ratio was not significantly associated with FMD in multivariable models. In this large, community-based cohort, brachial and digital measures of vascular function had differing relations with cardiovascular risk factors and were nearly uncorrelated with each other. These results suggest that FMD and PAT provide distinct information regarding vascular function in conduit versus smaller digital vessels.

Brachial artery vasodilator function and systemic inflammation in the Framingham Offspring Study.

BACKGROUND: In experimental studies, traditional risk factors and proinflammatory processes alter the regulatory functions of the vascular endothelium to promote atherosclerosis. These alterations include expression of leukocyte adhesion molecules and decreased bioavailability of endothelium-derived nitric oxide, an important regulator of vascular homeostasis and tone. The precise relations among risk factors, inflammation, and nitric oxide bioavailability remain uncertain. METHODS AND RESULTS: To test the hypothesis that inflammation impairs endothelial function in humans, we measured brachial artery flow-mediated dilation, reactive hyperemia, and serum concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), soluble intracellular adhesion molecule-1 (sICAM-1), and monocyte chemotactic protein-1 (MCP-1) in 2701 participants from the Framingham Study (mean age 61 years, 53% women). There were modest unadjusted inverse correlations between flow-mediated dilation and CRP, IL-6, and sICAM-1 (P<0.001 for all) that were rendered nonsignificant after accounting for traditional coronary risk factors. For reactive hyperemia, we observed inverse correlations with markers of inflammation in unadjusted models that were attenuated 57% to 74% after accounting for risk factors. However, partial correlations of CRP, IL-6, and sICAM-1 with reactive hyperemia remained significant. CONCLUSIONS: Our observations are consistent with the hypothesis that risk factors induce a state of inflammation that impairs vascular function. For flow-mediated dilation, we found no evidence that inflammation has additional effects beyond those attributable to traditional risk factors. The incremental contribution of CRP, IL-6, and sICAM-1 to reactive hyperemia above and beyond known risk factors suggests that systemic inflammation may contribute to impaired vasomotor function in forearm microvessels.

Clinical correlates and heritability of flow-mediated dilation in the community: the Framingham Heart Study.

BACKGROUND: Studies in selected samples have linked impaired endothelial function with cardiovascular disease and its risk factors. The clinical correlates and heritability of endothelial function in the community have not been described. METHODS AND RESULTS: We examined a measure of endothelial function, brachial artery flow-mediated dilation (FMD), expressed as both percent (FMD%) and actual dilation by ultrasound with the occlusion cuff below the elbow in 2883 Framingham Study participants (52.9% women; mean age, 61 years). A subset of 1096 participants performed a 6-minute walk test before FMD determination. Mean FMD% was 3.3+/-3.0% in women and 2.4+/-2.4% in men. In stepwise multivariable linear regression models, FMD% was inversely related to age, systolic blood pressure, body mass index (BMI), lipid-lowering medication, and smoking, whereas it was positively related to female gender, heart rate, and prior walk test. The estimated heritability of FMD% was 0.14. FMD actual dilation findings were similar, except that female sex and BMI were not significantly associated. CONCLUSIONS: Increasing age, systolic blood pressure, BMI, and smoking were associated with lower FMD% in our community-based sample, whereas prior exercise and increasing heart rate were associated with higher FMD%. The estimated heritability of FMD was modest. Future research will permit more complete characterization of the genetic and environmental determinants of endothelial function and its prognostic value in the community.