Relationship between QRS duration and resynchronization window for CRT optimization: Implications for CRT in narrow QRS patients.

AIMS: Cardiac resynchronization therapy (CRT) response is proportional to QRS duration (QRSd). We hypothesize that this is, in part, due to slower conduction velocity and hence wider range of programmed device settings that produce adequate electrical wavefront fusion and resynchronization in wider QRSd patients. METHODS: CRT patients (n = 122) with left ventricular (LV) conduction delay, sinus rhythm and intact atrioventricular node conduction were studied. Patients were categorized by QRSd: narrow (<120 ms; n = 20); moderate (120-150 ms, n = 37); and prolonged (≥150 ms; n = 65). Electrocardiographic data was acquired during native rhythm and LV-only pacing at varying atrioventricular delays (AVDs). Electrical synchrony was quantified as cardiac resynchronization index (CRI) using multi­lead electrocardiographic systems and a proprietary algorithm that quantified wavefront fusion. A Gaussian distribution equation was fitted to CRI response. RESULTS: Peak CRI was high (87.6 ± 6.3%) and similar (p = 0.716) across QRSd groups. The standard deviation of the Gaussian distribution significantly correlated with QRSd (R = 0.614, p < 0.001), and progressively and significantly (p < 0.001) increased as QRSd increased from narrow (34.8 ± 10.0 ms), to moderate (50.6 ± 8.4 ms), to prolonged (67.6 ± 18.3 ms). At AVDs 20 and 40 ms from optimal, CRI differed significantly (p < 0.001) between groups, with progressively higher CRI values as native QRSd increased. CONCLUSION: Electrical resynchronization with optimally programmed LV-only pacing was similar between patients with varying QRSd, including patients with narrow QRSd. The resynchronization window that corresponded with optimal electrical resynchronization decreased as native QRSd decreased. This finding provides one potential explanation for the lack of significant benefit of CRT in narrow QRSd patients in previous studies.

Electrical dyssynchrony mapping and cardiac resynchronization therapy.

PURPOSE: There is no clinical methodology for quantification or display of electrical dyssynchrony over a wide range of atrial-ventricular delays (AVD) and ventricular-ventricular delays (VVD) in patients with cardiac resynchronization therapy (CRT). This study aimed to develop a new methodology, based on wavefront fusion, for mapping electrical synchrony. METHODS: A cardiac resynchronization index (CRI) was measured at multiple device settings in 90 patients. Electrical dyssynchrony maps (EDM) were constructed for each patient to display CRI at any combination of AVD and VVD. An optimal synchrony line (OSL) depicted the AVD/VVD combinations producing the highest CRIs. Fusion of right ventricular paced (RVp), left ventricular paced (LVp), and native wavefront offsets were calculated. RESULTS: CRI significantly increased (p < 0.0001) from 58.0 ± 28.1% at baseline to 98.3 ± 1.7% at optimized settings. EDMs in patients with high-grade heart block (n = 20) had an OSL parallel to the simultaneous biventricular pacing (BiVPVV-SIM) line with leftward shift across all AVDs (RVp-LVpOFFSET = 50.5 ± 29.8 ms). EDMs in patients with intact AV node conduction (n = 64) had an OSL parallel to the BiVPVV-SIM line with leftward shift at short AVDs (RVp-LVpOFFSET = 33.4 ± 23.3 ms), curvilinear at intermediate AVDs (triple fusion), and vertical at long AVDs (native-LVpOFFSET = 85.2 ± 22.8 ms) in all patients except those with poor LV lead position (n = 6). CONCLUSION: A new methodology is described for quantifying and graphing electrical dyssynchrony over a physiologic range of AVDs/VVDs. This methodology offers a noninvasive, practical, clinical approach for measuring electrical synchrony that could be applied to optimization of CRT devices.

Relation of secondhand smoke exposure to vascular phenotypes in children and adolescents.

BACKGROUND: Subclinical cardiovascular risks of secondhand smoke (SHS) exposure among children and adolescents remains insufficiently described. METHODS: This was a cross-sectional study of 298 children and adolescents (48.0% male, body mass index: 27.0 ± 8.9 kg/m2), including 49 self-reported cases with SHS. Arterial elasticity and stiffness (distensibility, compliance, incremental elastic modulus [IEM]) were obtained via ultrasound imaging in the abdominal aorta, brachial, and carotid arteries. A one-way analysis of variance compared differences between groups, and multiple linear regression adjusted for covariates. RESULTS: SHS was associated with lower abdominal aorta diameter distensibility (aDD) (13.4 ± 3.6% vs. 16.0 ± 5.2%, p = 0.009) and abdominal aorta cross-sectional distensibility (aCSD) (28.8 ± 8.3% vs. 35.1 ± 12.2%, p = 0.009), as well as higher abdominal aorta IEM (aIEM) (1241 ± 794 vs. 935 ± 388 mmHg, p = 0.001). After adjustment for covariates, aDD (p = 0.047), aCSD (p = 0.040), and aIEM (p = 0.017) remained significant; this significance persisted with the additional adjustment of percent body fat. Measures of brachial and carotid compliance and distensibility were not associated with SHS. CONCLUSIONS: SHS was associated with abdominal aorta stiffness; the majority of vascular measures within the brachial and carotid artery remained unaffected following adjustment for covariates, including hypertension and adiposity. SHS may predispose individuals to increased abdominal aorta stiffness, an artery previously reported to exhibit increased susceptibility to atherosclerosis.

Early Life Adversity with Height Stunting Is Associated with Cardiometabolic Risk in Adolescents Independent of Body Mass Index.

OBJECTIVE: To evaluate cardiovascular and metabolic function in youths adopted internationally from orphanages/institutions (postinstitutionalized) who were height-stunted at adoption. STUDY DESIGN: A total of 30 postinstitutionalized youths (age, 9-18 years; body mass index [BMI] percentile, 7.2-90.4) who were height-stunted at adoption were compared with age- and BMI percentile-matched youths (n = 90). Measurements included total body fat and visceral adipose tissue (dual radiograph absorptiometry), arterial stiffness (augmentation index and pulse wave velocity), cardiac autonomic function (heart rate variability), blood pressure, and fasting lipid, glucose, and insulin levels. Linear regression analyses were computed controlling for parent education, age, trunk tissue fat, height-for-age, sex, and race. RESULTS: Compared with controls of the same age, sex, and BMI, the postinstitutionalized children had higher systolic blood pressure (P = .018), augmentation index (P= .033), total cholesterol (P= .047), low-density lipoprotein cholesterol (P= .03), triglycerides (P= .048), insulin (P= .005), and HOMA-IR (P= .01) values. The postinstitutionalized children had a lower low-frequency to high-frequency ratio (P = .008), indicating lower sympathetic tone, as well as a lower total lean mass (P = .016), a lower gynoid lean mass (P = .039), and a higher proportion of trunk tissue fat (P = .017). The postinstitutionalized and control children did not differ in any other body composition measures. CONCLUSIONS: Early life stress, as represented by height-stunted growth in institutional care, may be associated with early pathways to cardiovascular and metabolic risk in youths even after moving into well-resourced homes early in life and in the absence of increased adiposity. These findings suggest that postinstitutionalized youths with a history of height stunting may need to be closely monitored for emergent cardiometabolic risk factors.

Effects of Atrioventricular Optimization on Left Ventricular Reverse Remodeling With Cardiac Resynchronization Therapy: Results of the SMART-CRT Trial.

BACKGROUND: The role of atrioventricular optimization (AVO) to improve cardiac resynchronization therapy outcomes remains controversial. Previous post hoc analyses of a multicenter trial showed that measures of electrical dyssynchrony (right ventricular-left ventricular [LV] or LV electrical delay durations) are associated with patients who benefit from AVO. METHODS: This was a global, multicenter, prospective, randomized trial of de novo cardiac resynchronization therapy implant patients with an right ventricular-LV duration ≥70 ms to determine whether AVO results in greater reverse remodeling. Patients were randomized 1:1 for either an AVO algorithm (SmartDelay) that determines atrioventricular delay and pacing chamber, biventricular or LV only, or a fixed atrioventricular delay of 120 ms with biventricular pacing. Paired echocardiograms performed at baseline and 6 months were evaluated. The primary end point was echocardiographic cardiac resynchronization therapy response, defined dichotomously as a >15% reduction in LV end-systolic volume. RESULTS: A total of 310 patients (n=120 women) were randomized and had completed 6 months of follow-up. The echocardiographic cardiac resynchronization therapy response rate did not statistically differ between the groups (SmartDelay, 74.8%; fixed, 67.7%; P=0.17). Analyses of prespecified secondary end points demonstrated significant improvements in the absolute (median: SmartDelay, -41.0 mL; fixed, -33.0 mL; P=0.01) and relative change in LV end-systolic volume (SmartDelay, -38.3%; fixed, -27.8%; P=0.03) for patients with SmartDelay optimization. Similar results were observed for the relative improvement in LV ejection fraction (SmartDelay, 46.7%; fixed, 32.1%; P=0.050); absolute improvement in LV ejection fraction trended to be higher with SmartDelay (P=0.06). CONCLUSIONS: Analysis of reverse remodeling parameters demonstrated that AVO via SmartDelay, relative to the nonoptimized fixed atrioventricular delay comparator group, improved absolute and relative changes in LV function in patients with longer right ventricular-LV duration. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03089281.

Cardiac resynchronization therapy optimization in nonresponders and incomplete responders using electrical dyssynchrony mapping.

BACKGROUND: Nonresponse to cardiac resynchronization therapy (CRT) occurs in ∼30%-50% of patients. There are no well-accepted clinical approaches for optimizing CRT in nonresponders. OBJECTIVE: The purpose of this study was to demonstrate the effect of CRT optimization using electrical dyssynchrony mapping on left ventricular (LV) function, size, and dyssynchrony in selected patients with nonresponse/incomplete response to CRT. METHODS: We studied 39 patients with underlying left bundle branch block or interventricular conduction delay who had an LV ejection fraction of ≤40% after receiving CRT and had significant electrical dyssynchrony. Electrical dyssynchrony was measured at multiple atrioventricular delays and interventricular delays. The QRS area between combinations of 9 anterior and 9 posterior electrograms (QRS area under the curve) was calculated, and cardiac resynchronization index (CRI) was defined as the percent change in QRS area under the curve compared to native conduction. Electrical dyssynchrony maps depicted CRI over the wide range of settings tested. Patients were programmed to an optimal device setting, and echocardiograms were recorded 5.9 ± 3.7 months postoptimization. RESULTS: CRI increased from 49.4% ± 24.0% to 90.8% ± 10.5%. CRT optimization significantly improved LV ejection fraction from 31.8% ± 4.7% to 36.3% ± 5.9% (P < .001) and LV end-systolic volume from 108.5 ± 37.6 to 98.0 ± 37.5 mL (P = .009). Speckle-tracking measures of LV strain significantly improved by 2.4% ± 4.5% (transverse; P = .002) and 1.0% ± 2.6% (longitudinal; P = .017). Aortic to pulmonic valve opening time, a measure of interventricular dyssynchrony, significantly (P = .040) decreased by 14.9 ± 39.4 ms. CONCLUSION: CRT optimization of electrical dyssynchrony using a novel electrical dyssynchrony mapping technology significantly improves LV systolic function, LV end-systolic volume, and mechanical dyssynchrony. This methodology offers a noninvasive, practical clinical approach to treating nonresponders and incomplete responders to CRT.

May-Thurner syndrome: History of understanding and need for defining population prevalence.

Patients with May-Thurner syndrome (MTS) are at elevated risk of developing an extensive left iliofemoral deep vein thrombosis (DVT; localized blood clot) due to an anatomical variant where the right common iliac artery compresses the left common iliac vein against the lumbar spine. While MTS was initially presumed to be rare when it was first anatomically defined in 1957, case reports of this syndrome have recently become more frequent, perhaps due to improved imaging techniques allowing for enhanced visualization of the iliac veins. Still, the population burden of this condition is unknown, and there is speculation it may be higher than generally perceived. In the present review, we (a) review history of how MTS became recognized, (b) describe practical challenges of studying MTS in population-based settings due to the specialized imaging required for diagnosis, (c) discuss why the contribution of MTS to DVT may be underestimated, (d) describe uncertainty regarding the degree of venous compression which leads to DVT, and (e) outline future research needs. Our goal is to raise awareness of MTS and spark additional research into the epidemiology of this condition, which may be an underappreciated causative venous thromboembolism risk factor.

Validation of a three-dimensional body scanner for body composition measures.

The accuracy of an infrared three-dimensional (3D) body scanner in determining body composition was compared against hydrostatic weighing (HW), bioelectrical impedance analysis (BIA), and anthropometry. A total of 265 adults (119 males; age = 22.1 ± 2.5 years; body mass index = 24.5 ± 3.9 kg/m2) had their body fat percent (BF%) estimated from 3D scanning, HW, BIA, skinfolds, and girths. A repeated measures analysis of variance (ANOVA) indicated significant differences among methods (p < 0.001). Multivariate ANOVA indicated a significant main effect of sex and method (p < 0.001), with a non-significant interaction (p = 0.101). Bonferroni post-hoc comparisons identified that BF% from 3D scanning (18.1 ± 7.8%) was significantly less than HW (22.8 ± 8.5%, p < 0.001), BIA (20.1 ± 9.1%, p < 0.001), skinfolds (19.7 ± 9.7%, p < 0.001), and girths (21.2 ± 10.4%, p < 0.001). The 3D scanner decreased in precision with increasing adiposity, potentially resulting from inconsistences in the 3D scanner's analysis algorithm. A correction factor within the algorithm is required before infrared 3D scanning can be considered valid in measuring BF%.

Intra- and inter-day reproducibility of low-flow mediated constriction response in young adults.

PURPOSE: When assessing brachial endothelial function by reactive hyperaemia, stopping blood flow creates a period of low-flow-mediated constriction (L-FMC). As little is known about how this parameter influences flow-mediated vasodilation (FMD), the purpose of this study was to better understand this relationship and to determine the intra- and interday reproducibility of brachial L-FMC. METHODS: Brachial L-FMC and FMD were measured on 26 healthy, young adults (13 males, 13 females; 24·6 ± 2·7 years). Each participant had two assessments conducted on two separate visits, separated by a minimum of seven days. Brachial artery baseline diameter was imaged during rest. Continuous imaging of the artery was performed during the last 20 s of cuff-occlusion to 180 s postcuff release. An L-FMC was considered present if the relative change from pre-occlusion baseline to L-FMC artery diameter was less than -0·1%. RESULTS: Overall, there was a strong, positive correlation between increased brachial L-FMC and blunted FMD (visit 1 test 1: r = 0·758, P<0·001; visit 1 test 2: r = 0·706, P<0·001; visit 2 test 1: r = 0·836, P<0·001; visit 2 test 2: r = 0·857, P<0·001). The reproducibility of intra- and interday L-FMC diameter was intraclass correlation coefficients (ICC) = 0·627, coefficient of variation (CV) = 54·4% and ICC = 0·734, CV = 43·5%, respectively. CONCLUSION: Vasoconstriction to low-flow conditions influences the subsequent maximal dilation during reactive hyperaemia. However, L-FMC is variable as evidenced by the weak intra- and interday reproducibility of the measure. Further research should study brachial L-FMC reproducibility among varying populations and the implications L-FMC has on the interpretation of FMD results.

Associations of sex, age and adiposity in endothelium-independent dilation in children.

OBJECTIVE: To examine the association of age, sex, and obesity status on endothelial-independent dilation (EID) among children and adolescents. STUDY DESIGN: This study examined 264 children (143 males) between 8 to 18 years old (mean ± SD: age = 14.3 ± 2.7 years). Endothelial-independent dilation was assessed via ultrasound imaging of the brachial artery following administration of 0.3 milligrams of sublingual nitroglycerin. A one-way analysis of variance with Bonferroni post hoc comparisons assessed sex-differences in percent peak EID dilation (EID%-peak) and EID area under the curve (EID%-AUC), while analysis of covariance (ANCOVA) adjusted for race, age, body mass index percentile (BMI-percentile), and brachial artery diameter. Multiple linear regression evaluated the association of sex, age, BMI-percentile, percent body fat (%BF), and brachial artery diameter on EID. RESULTS: Prior to adjustment, EID%-peak was significantly higher among females than males (mean ± SE: 26.9 ± 0.5% versus 22.9 ± 0.6%, p < 0.001, respectively); similar findings for EID%-AUC (4214% ± 105%·s versus 3398% ± 97%·s, p < 0.001) were observed. After adjusting for covariates, EID%-AUC remained consistent (p = 0.03) while EID%-peak was not significantly different between sexes (p = 0.21). EID%-peak was significantly higher among normal weight compared to obese participants (p = 0.04), while no differences were observed between obesity status after adjustment for brachial artery diameter (p = 0.64). Both unadjusted (p = 0.16) and adjusted EID%-AUC (p = 0.24) was not significantly different between obesity status. BMI-percentile was not associated with EID%-peak (p = 0.76) or EID%-AUC (p = 0.30). Additionally, %BF was not associated with EID%-peak (p = 0.56) or EID%-AUC (p = 0.15). After adjusting for brachial artery diameter, BMI-percentile, and age, males had lower EID%-AUC (p = 0.03) and lower but not significant EID%-peak (p = 0.21). SIGNIFICANCE: Vascular smooth muscle function was significantly lower among male children and adolescents, which is suggestive that impaired EID and increased cardiovascular disease risk among males may begin in childhood. Interestingly, obesity status and BMI-percentile was not associated with EID in children and adolescents after adjusting for brachial artery diameter.

Measurement of Central Aortic Blood Pressure in Youth: Role of Obesity and Sex.

BACKGROUND: The relationship between pediatric severe obesity (SO) and central aortic blood pressure (BP) has yet to be established. METHODS: We conducted a cross-sectional study of 348 youth (48.5% male, age 12.7 ± 0.1 years) with a wide range of body mass index (BMI) values: normal weight (NW; ≥5th and <85th BMI percentiles), overweight/obesity (OW/OB; 85th to <120% of the 95th BMI percentile), and SO (≥120% of the 95th BMI percentile). Measures of central aortic BP were obtained via applanation tonometry with SphygmoCor MM3 software. RESULTS: After adjustment for covariates, no significant sex differences were observed for radial-aortic systolic blood pressure (SBP) (P = 0.39), carotid-aortic SBP (P = 0.99), radial-aortic diastolic blood pressure (DBP) (P = 0.44), and carotid-aortic DBP (P = 0.53). Compared to youth with NW, youth with SO exhibited higher radial-aortic SBP (SO vs. NW: 102 ± 1 mm Hg vs. 90 ± 1 mm Hg, P<0.001), carotid-aortic SBP (SO vs. NW: 121 ± 1 mm Hg vs. 109 ± 1 mm Hg, P<0.001), and carotid-aortic DBP (SO vs. NW: 60 ± 1 mm Hg vs. 56 ± 1 mm Hg, P = 0.04). Compared to youth with OW/OB, youth with SO had higher radial-aortic SBP (OW/OB: 97 ± 1 mm Hg, P = 0.002) and carotid-aortic SBP (OW/OB: 114 ± 1 mm Hg, P = 0.007). After adjusting for either total-body percent fat mass or visceral adipose tissue, BMI was still a significant predictor of both radial-aortic and carotid-aortic SBP and DBP (P<0.001, all). CONCLUSIONS: In a cohort of youth with a wide range of adiposity levels, central aortic BP was elevated among individuals with SO and associated with BMI but not body fatness.