Left ventricular geometry predicts optimal response to percutaneous mitral repair via MitraClip: Integrated assessment by two- and three-dimensional echocardiography.

OBJECTIVES: To assess impact of left ventricular (LV) chamber remodeling on MitraClip (MClp) response. BACKGROUND: MitraClip is the sole percutaneous therapy approved for mitral regurgitation (MR) but response varies. LV dilation affects mitral coaptation; determinants of MClp response are uncertain. METHODS: LV and mitral geometry were quantified on pre- and post-procedure two-dimensional (2D) transthoracic echocardiography (TTE) and intra-procedural three-dimensional (3D) transesophageal echocardiography (TEE). Optimal MClp response was defined as ≤mild MR at early (1-6 month) follow-up. RESULTS: Sixty-seven degenerative MR patients underwent MClp: Whereas MR decreased ≥1 grade in 94%, 39% of patients had optimal response (≤mild MR). Responders had smaller pre-procedural LV end-diastolic volume (94 ± 24 vs. 109 ± 25 mL/m2 , p = 0.02), paralleling smaller annular diameter (3.1 ± 0.4 vs. 3.5 ± 0.5 cm, p = 0.002), and inter-papillary distance (2.2 ± 0.7 vs. 2.5 ± 0.6 cm, p = 0.04). 3D TEE-derived annular area correlated with 2D TTE (r = 0.59, p < 0.001) and was smaller among optimal responders (12.8 ± 2.1 cm2 vs. 16.8 ± 4.4 cm2 , p = 0.001). Both 2D and 3D mitral annular size yielded good diagnostic performance for optimal MClp response (AUC 0.73-0.84, p < 0.01). In multivariate analysis, sub-optimal MClp response was associated with LV end-diastolic diameter (OR 3.10 per-cm [1.26-7.62], p = 0.01) independent of LA size (1.10 per-cm2 [1.02-1.19], p = 0.01); substitution of mitral annular diameter for LV size yielded an independent association with MClp response (4.06 per-cm2 [1.03-15.96], p = 0.045). CONCLUSIONS: Among degenerative MR patients undergoing MClp, LV and mitral annular dilation augment risk for residual or recurrent MR, supporting the concept that MClp therapeutic response is linked to sub-valvular remodeling.

Impact of Mitral Regurgitation Severity and Cause on Effort Tolerance-Integrated Stress Myocardial Perfusion Imaging and Echocardiographic Assessment of Patients With Known or Suspected Coronary Artery Disease Undergoing Exercise Treadmill Testing.

Background Mitral regurgitation ( MR ) has the potential to impede exercise capacity; it is uncertain whether this is because of regurgitation itself or the underlying cause of valvular insufficiency. Methods and Results The population comprised 3267 patients who underwent exercise treadmill myocardial perfusion imaging and transthoracic echocardiography within 6±8 days. MR was present in 28%, including 176 patients (5%) with moderate or greater MR . Left ventricular systolic function significantly decreased and chamber size increased in relation to MR , paralleling increments in stress and rest myocardial perfusion deficits (all P<0.001). Exercise tolerance (metabolic equivalents of task) decreased stepwise in relation to graded MR severity ( P<0.05). Workload was significantly lower with mild versus no MR (mean±SD, 9.8±3.0 versus 10.1±3.0; P=0.02); magnitude of workload reduction significantly increased among patients with advanced versus those with mild MR (mean±SD, 8.6±3.0 versus 9.8±3.0; P<0.001). MR -associated exercise impairment was accompanied by lower heart rate and blood pressure augmentation and greater dyspnea (all P<0.05). Both functional and nonfunctional MR subgroups demonstrated significantly decreased effort tolerance in relation to MR severity ( P≤0.01); impairment was greater with functional MR ( P=0.04) corresponding to more advanced left ventricular dysfunction and dilation (both P<0.001). Functional MR predicted reduced metabolic equivalent of task-based effort (B=-0.39 [95% CI, -0.62 to -0.17]; P=0.001) independent of MR severity. Among the overall cohort, advanced (moderate or greater) MR was associated with reduced effort tolerance (B=-1.36 [95% CI, -1.80 to -0.93]; P<0.001) and remained significant ( P=0.01) after controlling for age, clinical indexes, stress perfusion defects, and left ventricular dysfunction. Conclusions MR impairs exercise tolerance independent of left ventricular ischemia, dysfunction, and clinical indexes. Magnitude of exercise impairment parallels severity of MR .

Multiplanar strain quantification for assessment of right ventricular dysfunction and non-ischemic fibrosis among patients with ischemic mitral regurgitation.

BACKGROUND: Ischemic mitral regurgitation (iMR) predisposes to right ventricular (RV) pressure and volume overload, providing a nidus for RV dysfunction (RVDYS) and non-ischemic fibrosis (NIF). Echocardiography (echo) is widely used to assess iMR, but performance of different indices as markers of RVDYS and NIF is unknown. METHODS: iMR patients prospectively underwent echo and cardiac magnetic resonance (CMR) within 72 hours. Echo quantified iMR, assessed conventional RV indices (TAPSE, RV-S', fractional area change [FAC]), and strain via speckle tracking in apical 4-chamber (global longitudinal strain [RV-GLS]) and parasternal long axis orientation (transverse strain). CMR volumetrically quantified RVEF, and assessed ischemic pattern myocardial infarction (MI) and septal NIF. RESULTS: 73 iMR patients were studied; 36% had RVDYS (EF<50%) on CMR among whom LVEF was lower, PA systolic pressure higher, and MI size larger (all p<0.05). CMR RVEF was paralleled by echo results; correlations were highest for RV-GLS (r = 0.73) and lowest for RV-S' (r = 0.43; all p<0.001). RVDYS patients more often had CMR-evidenced NIF (54% vs. 7%; p<0.001). Whereas all RV indices were lower among NIF-affected patients (all p≤0.006), percent change was largest for transverse strain (48.3%). CMR RVEF was independently associated with RV-GLS (partial r = 0.57, p<0.001) and transverse strain (r = 0.38, p = 0.002) (R = 0.78, p<0.001). Overall diagnostic performance of RV-GLS and transverse strain were similar (AUC = 0.93[0.87-0.99]|0.91[0.84-0.99], both p<0.001), and yielded near equivalent sensitivity and specificity (85%|83% and 80%|79% respectively). CONCLUSION: Compared to conventional echo indices, RV strain parameters yield stronger correlation with CMR-defined RVEF and potentially constitute better markers of CMR-evidenced NIF in iMR.

Echocardiographic Linear Dimensions for Assessment of Right Ventricular Chamber Volume as Demonstrated by Cardiac Magnetic Resonance.

BACKGROUND: Echocardiography-derived linear dimensions offer straightforward indices of right ventricular (RV) structure but have not been systematically compared with RV volumes on cardiac magnetic resonance (CMR). METHODS: Echocardiography and CMR were interpreted among patients with coronary artery disease imaged via prospective (90%) and retrospective (10%) registries. For echocardiography, American Society of Echocardiography-recommended RV dimensions were measured in apical four-chamber (basal RV width, mid RV width, and RV length), parasternal long-axis (proximal RV outflow tract [RVOT]), and short-axis (distal RVOT) views. For CMR, RV end-diastolic volume and RV end-systolic volume were quantified using border planimetry. RESULTS: Two hundred seventy-two patients underwent echocardiography and CMR within a narrow interval (0.4 ± 1.0 days); complete acquisition of all American Society of Echocardiography-recommended dimensions was feasible in 98%. All echocardiographic dimensions differed between patients with and those without RV dilation on CMR (P < .05). Basal RV width (r = 0.70), proximal RVOT width (r = 0.68), and RV length (r = 0.61) yielded the highest correlations with RV end-diastolic volume on CMR; end-systolic dimensions yielded similar correlations (r = 0.68, r = 0.66, and r = 0.65, respectively). In multivariate regression, basal RV width (regression coefficient = 1.96 per mm; 95% CI, 1.22-2.70; P < .001), RV length (regression coefficient = 0.97; 95% CI, 0.56-1.37; P < .001), and proximal RVOT width (regression coefficient = 2.62; 95% CI, 1.79-3.44; P < .001) were independently associated with CMR RV end-diastolic volume (r = 0.80). RV end-systolic volume was similarly associated with echocardiographic dimensions (basal RV width: 1.59 per mm [95% CI, 1.06-2.13], P < .001; RV length: 1.00 [95% CI, 0.66-1.34], P < .001; proximal RVOT width: 1.80 [95% CI, 1.22-2.39], P < .001) (r = 0.79). CONCLUSIONS: RV linear dimensions provide readily obtainable markers of RV chamber size. Proximal RVOT and basal width are independently associated with CMR volumes, supporting the use of multiple linear dimensions when assessing RV size on echocardiography.

Costs and in-hospital outcomes of transcatheter aortic valve implantation versus surgical aortic valve replacement in commercial cases using a propensity score matched model.

The aim of this study was to compare in-hospital cost and outcomes between transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR). TAVI is an effective treatment option in patients with symptomatic aortic stenosis who are at high risk for traditional SAVR. Several studies using trial data or outside United States registry data have addressed TAVI cost issues, although there is a paucity of cost data involving commercial cases in the United States. Using Agency for Healthcare Research and Quality Healthcare Cost and Utilization Project Nationwide Inpatient Sample files, a propensity score-matched analysis of all commercial TAVI and SAVR cases performed in 2011 was conducted. Overall hospital cost and length of stay, as well as procedural complications, were compared between the 2 matched cohorts: 595 TAVI patients were matched to 1,785 SAVR patients in a 1:3 ratio. There was no difference in mean ($181,912 vs $196,298) or median ($152,993 vs $155,974) hospital cost between TAVI and SAVR (p = 0.60). The TAVI group had significantly shorter lengths of hospital stay than the SAVR group (mean 9.76 vs 12.01 days, p <0.001). There was no difference in postprocedural in-hospital death or stroke, but TAVI patients were more likely to have bleeding complications, to have vascular complications, and to require pacemakers. In conclusion, when analyzing in-hospital cost of commercial TAVI and SAVR cases using the Nationwide Inpatient Sample data set, TAVI is an economically satisfactory alternative to SAVR and results in an approximately 2-day shorter length of stay during the index hospitalization.

Reference values for echocardiographic assessment of the diameter of the aortic root and ascending aorta spanning all age categories.

Thoracic aortic dilatation requires accurate and timely detection to prevent progression to thoracic aortic aneurysm and aortic dissection. The detection of thoracic aortic dilatation necessitates the availability of cut-off values for normal aortic diameters. Tools to evaluate aortic dimension above the root are scarce and inconsistent regarding age groups. The aim of this study was to provide reference values for aortic root and ascending aortic diameters on the basis of transthoracic echocardiographic measurements in a large cohort of children and adults. Diameters at the level of the sinuses of Valsalva (SoV) and ascending aorta (AA) were assessed with transthoracic echocardiography in 849 subjects (453 females, age range 1 to 85 years, mean 40.1 ± 21.3 years) and measured according to published guidelines. Linear regression analysis was applied to create nomograms, as well as equations for upper limits of normal and z-scores. SoV and AA diameters were strongly correlated with age, body surface area (BSA), and weight (r = 0.67 to 0.79, p <0.001 for all). Male subjects had significantly larger aortic dimensions at all levels in adulthood, even after BSA correction (p ≤0.004 for all age intervals). Gender-, age-, and BSA-specific upper limits of normal and z-score equations were developed from a multivariate regression model, which strongly predicts SoV and AA diameters (adjusted R(2) for SoV = 0.84 and 0.67 and for AA = 0.82 and 0.74, for male and female subjects, respectively). In conclusion, this study provides widely applicable reference values for thoracic aortic dilatation screening purposes. Age, BSA, and gender must be taken into account when assessing an individual patient.

P wave area for quantitative electrocardiographic assessment of left atrial remodeling.

BACKGROUND: Left atrial (LA) dilation provides a substrate for mitral regurgitation (MR) and atrial arrhythmias. ECG can screen for LA dilation but standard approaches do not assess LA geometry as a continuum, as does non-invasive imaging. This study tested ECG-quantified P wave area as an index of LA geometry. METHODS AND RESULTS: 342 patients with CAD underwent ECG and CMR within 7 (0.1±1.4) days. LA area on CMR correlated best with P wave area in ECG lead V1 (r = 0.42, p<0.001), with lesser correlations for P wave amplitude and duration. P wave area increased stepwise in relation to CMR-evidenced MR severity (p<0.001), with similar results for MR on echocardiography (performed in 86% of patients). Pulmonary arterial (PA) pressure on echo was increased by 50% among patients in the highest (45±14 mmHg) vs. the lowest (31±9 mmHg) P wave area quartile of the population. In multivariate regression, CMR and echo-specific models demonstrated P wave area to be independently associated with LA size after controlling for MR, as well as echo-evidenced PA pressure. Clinical follow-up (mean 2.4±1.9 years) demonstrated ECG and CMR to yield similar results for stratification of arrhythmic risk, with a 2.6-fold increase in risk for atrial fibrillation/flutter among patients in the top P wave area quartile of the population (CI 1.1-5.9, p = 0.02), and a 3.2-fold increase among patients in the top LA area quartile (CI 1.4-7.0, p = 0.005). CONCLUSIONS: ECG-quantified P wave area provides an index of LA remodeling that parallels CMR-evidenced LA chamber geometry, and provides similar predictive value for stratification of atrial arrhythmic risk.

Socioeconomic and ethnic disparities in the use of biventricular pacemakers in heart failure patients with left ventricular systolic dysfunction.

OBJECTIVES: Biventricular pacing (BiV) is an important therapy for symptomatic heart failure (HF) patients with reduced left ventricular (LV) ejection fraction (EF). The aim of our study was to determine if ethnic disparities in use of BiV in HF patients with LV systolic dysfunction are independent of socioeconomic status. DESIGN, SETTING, PARTICIPANTS: Data collected on 32,911 hospitalized HF patients with EF < or = 35% from Pennsylvania hospitals that implanted BiVs in 2004 and 2005 were submitted to the Pennsylvania Health Care Cost Containment Council. Multivariate analysis used patient clinical, insurance and hospital characteristics to identify independent predictors of BiV in symptomatic HF patitents with EF < or = 35%. MAIN OUTCOME MEASURES: Use of BiV in symptomatic HF patients with LV systolic dysfunction. RESULTS: BiV was implanted in 2,065/ 15,861 (13%) Whites, 182/3107 (5.9%) African Americans and 175/1301 (13.5%) others. Older age, male sex, intraventricular conduction delay and prior myocardial infarction or bypass surgery (all P < .001) were positively associated with BiV while diabetes (P < .01), higher EF or higher Mediqual Atlas severity score (both P < .0001) were negatively associated with BiV. Adjusting for these variables, African American ethnicity (odds ratio [OR] .56, 95% CI,.46-68, P < .0001) and poverty, comparing the poorest quintile to other quintiles (OR .86, 95% CI, .76-98, P < .02), were associated with less BiV, independent of fixed effects of hospitals (P < .0001) and a positive association of BiV with Medicare vs Medicaid (P < .01). CONCLUSIONS: In a large statewide sample, BiV was implanted less frequently in African Americans and in lower-income patients, independent of clinical, hospital and insurance characteristics, identifying persisting disparities in use of advanced cardiac technology.

Mitral apparatus assessment by delayed enhancement CMR: relative impact of infarct distribution on mitral regurgitation.

OBJECTIVES: This study sought to assess patterns and functional consequences of mitral apparatus infarction after acute myocardial infarction (AMI). BACKGROUND: The mitral apparatus contains 2 myocardial components: papillary muscles and the adjacent left ventricular (LV) wall. Delayed-enhancement cardiac magnetic resonance (DE-CMR) enables in vivo study of inter-relationships and potential contributions of LV wall and papillary muscle infarction (PMI) to mitral regurgitation (MR). METHODS: Multimodality imaging was performed: CMR was used to assess mitral geometry and infarct pattern, including 3D DE-CMR for PMI. Echocardiography was used to measure MR. Imaging occurred 27 ± 8 days after AMI (CMR, echocardiography within 1 day). RESULTS: A total of 153 patients with first AMI were studied; PMI was present in 30% (n = 46 [72% posteromedial, 39% anterolateral]). When stratified by angiographic culprit vessel, PMI occurred in 65% of patients with left circumflex, 48% with right coronary, and only 14% of patients with left anterior descending infarctions (p <0.001). Patients with PMI had more advanced remodeling as measured by LV size and mitral annular diameter (p <0.05). Increased extent of PMI was accompanied by a stepwise increase in mean infarct transmurality within regional LV segments underlying each papillary muscle (p <0.001). Prevalence of lateral wall infarction was 3-fold higher among patients with PMI compared to patients without PMI (65% vs. 22%, p <0.001). Infarct distribution also impacted MR, with greater MR among patients with lateral wall infarction (p = 0.002). Conversely, MR severity did not differ on the basis of presence (p = 0.19) or extent (p = 0.12) of PMI, or by angiographic culprit vessel. In multivariable analysis, lateral wall infarct size (odds ratio 1.20/% LV myocardium [95% confidence interval: 1.05 to 1.39], p = 0.01) was independently associated with substantial (moderate or greater) MR even after controlling for mitral annular (odds ratio 1.22/mm [1.04 to 1.43], p = 0.01), and LV end-diastolic diameter (odds ratio 1.11/mm [0.99 to 1.23], p = 0.056). CONCLUSIONS: Papillary muscle infarction is common after AMI, affecting nearly one-third of patients. Extent of PMI parallels adjacent LV wall injury, with lateral infarction-rather than PMI-associated with increased severity of post-AMI MR.

Serial assessment of the electrocardiographic strain pattern for prediction of new-onset heart failure during antihypertensive treatment: the LIFE study.

AIMS: Although the presence of the electrocardiographic (ECG) strain pattern has been associated with an increased risk of developing heart failure (HF), the relationship of regression vs. persistence vs. development of new ECG strain to subsequent HF is unclear. METHODS AND RESULTS: Electrocardiographic strain was evaluated at baseline and at year-1 in 7265 hypertensive patients without HF treated with atenolol- or losartan-based regimens. During 3.9 ± 0.7 years of follow-up after the year-1 ECG, 154 patients (2.1%) were hospitalized for HF. Five-year HF incidence was lowest in patients with no ECG strain (1.6%), intermediate in patients with regression of strain (5.4%), and highest in patients with persistent (7.1%) or new strain (7.0%; P< 0.0001 across groups). In the Cox multivariable analyses adjusting for the known predictive value of in-treatment ECG left ventricular hypertrophy by the Cornell product and Sokolow-Lyon voltage, in-treatment QRS duration, systolic and diastolic pressure, incident myocardial infarction and atrial fibrillation, randomized treatment and other risk factors for HF, regression of strain [hazards ratio (HR) 2.4, 95% confidence interval (CI) 1.2-5.0], persistence of strain (HR 1.9, 95% CI 1.2-3.2), and development of new ECG strain (HR 2.3, 95% CI 1.2-4.4) were all independently associated with an increased risk of new HF compared with the absence of ECG strain on both baseline and year-1 ECGs. CONCLUSION: The development of new ECG strain or persistence of ECG strain between baseline and year-1 is associated with an increased risk of HF. The regression of ECG strain between baseline and year-1 does not convey a decreased risk of HF. CLINICAL TRIALS REGISTRATION: http://clinicaltrials.gov/ct/show/NCT00338260.

Impact of diastolic dysfunction severity on global left ventricular volumetric filling - assessment by automated segmentation of routine cine cardiovascular magnetic resonance.

OBJECTIVES: To examine relationships between severity of echocardiography (echo) -evidenced diastolic dysfunction (DD) and volumetric filling by automated processing of routine cine cardiovascular magnetic resonance (CMR). BACKGROUND: Cine-CMR provides high-resolution assessment of left ventricular (LV) chamber volumes. Automated segmentation (LV-METRIC) yields LV filling curves by segmenting all short-axis images across all temporal phases. This study used cine-CMR to assess filling changes that occur with progressive DD. METHODS: 115 post-MI patients underwent CMR and echo within 1 day. LV-METRIC yielded multiple diastolic indices - E:A ratio, peak filling rate (PFR), time to peak filling rate (TPFR), and diastolic volume recovery (DVR80 - proportion of diastole required to recover 80% stroke volume). Echo was the reference for DD. RESULTS: LV-METRIC successfully generated LV filling curves in all patients. CMR indices were reproducible (< or = 1% inter-reader differences) and required minimal processing time (175 +/- 34 images/exam, 2:09 +/- 0:51 minutes). CMR E:A ratio decreased with grade 1 and increased with grades 2-3 DD. Diastolic filling intervals, measured by DVR80 or TPFR, prolonged with grade 1 and shortened with grade 3 DD, paralleling echo deceleration time (p < 0.001). PFR by CMR increased with DD grade, similar to E/e' (p < 0.001). Prolonged DVR80 identified 71% of patients with echo-evidenced grade 1 but no patients with grade 3 DD, and stroke-volume adjusted PFR identified 67% with grade 3 but none with grade 1 DD (matched specificity = 83%). The combination of DVR80 and PFR identified 53% of patients with grade 2 DD. Prolonged DVR80 was associated with grade 1 (OR 2.79, CI 1.65-4.05, p = 0.001) with a similar trend for grade 2 (OR 1.35, CI 0.98-1.74, p = 0.06), whereas high PFR was associated with grade 3 (OR 1.14, CI 1.02-1.25, p = 0.02) DD. CONCLUSIONS: Automated cine-CMR segmentation can discern LV filling changes that occur with increasing severity of echo-evidenced DD. Impaired relaxation is associated with prolonged filling intervals whereas restrictive filling is characterized by increased filling rates.

Automated segmentation of routine clinical cardiac magnetic resonance imaging for assessment of left ventricular diastolic dysfunction.

BACKGROUND: Cardiac magnetic resonance (CMR) is established for assessment of left ventricular (LV) systolic function but has not been widely used to assess diastolic function. This study tested performance of a novel CMR segmentation algorithm (LV-METRIC) for automated assessment of diastolic function. METHODS AND RESULTS: A total of 101 patients with normal LV systolic function underwent CMR and echocardiography (echo) within 7 days. LV-METRIC generated LV filling profiles via automated segmentation of contiguous short-axis images (204+/-39 images, 2:04+/-0:53 minutes). Diastolic function by CMR was assessed via early:atrial filling ratios, peak diastolic filling rate, time to peak filling rate, and a novel index-diastolic volume recovery (DVR), calculated as percent diastole required for recovery of 80% stroke volume. Using an echo standard, patients with versus without diastolic dysfunction had lower early:atrial filling ratios, longer time to peak filling rate, lower stroke volume-adjusted peak diastolic filling rate, and greater DVR (all P<0.05). Prevalence of abnormal CMR filling indices increased in relation to clinical symptoms classified by New York Heart Association functional class (P=0.04) or dyspnea (P=0.006). Among all parameters tested, DVR yielded optimal performance versus echo (area under the curve: 0.87+/-0.04, P<0.001). Using a 90% specificity cutoff, DVR yielded 74% sensitivity for diastolic dysfunction. In multivariate analysis, DVR (odds ratio, 1.82; 95% CI, 1.13 to 2.57; P=0.02) was independently associated with echo-evidenced diastolic dysfunction after controlling for age, hypertension, and LV mass (chi(2)=73.4, P<0.001). CONCLUSIONS: Automated CMR segmentation can provide LV filling profiles that may offer insight into diastolic dysfunction. Patients with diastolic dysfunction have prolonged diastolic filling intervals, which are associated with echo-evidenced diastolic dysfunction independent of clinical and imaging variables.

Prognostic value of changes in the electrocardiographic strain pattern during antihypertensive treatment: the Losartan Intervention for End-Point Reduction in Hypertension Study (LIFE).

BACKGROUND: The presence of the ECG strain pattern of lateral ST depression and T-wave inversion at baseline has been associated with an increased risk of cardiovascular morbidity and mortality; however, the independent predictive value for cardiovascular outcomes of regression versus persistence versus development of new ECG strain during antihypertensive therapy is unclear. METHODS AND RESULTS: ECG strain was evaluated at baseline and after 1 year of therapy in 7409 hypertensive patients in the LIFE study (Losartan Intervention For End-point reduction in hypertension) treated in a blinded manner with atenolol- or losartan-based regimens. During 3.8+/-0.8 years of follow-up after the year 1 ECG, cardiovascular death occurred in 236 patients (3.2%), myocardial infarction in 198 (2.7%), stroke in 313 (4.2%), the LIFE composite end point of these 3 events in 600 (8.1%), sudden death in 92 (1.2%), and death due to any cause in 486 (6.6%). Strain was absent on both baseline and year 1 ECGs in 6323 patients (85.3%), regressed from baseline to year 1 in 245 (3.3%), persisted on both ECGs in 549 (7.4%), and was absent at baseline but developed by year 1 in 292 patients (3.9%). Compared with absence of strain on both ECGs, development of new ECG strain was associated with 2.8- to 4.7-fold higher event rates; patients with regression or persistence of strain had intermediate event rates. In Cox multivariable analyses with adjustment for the known predictive value of in-treatment ECG left ventricular hypertrophy by Cornell product and Sokolow-Lyon voltage, in-treatment systolic and diastolic pressure, randomized treatment, and standard cardiovascular risk factors, development of new ECG strain was independently associated with increased risks of cardiovascular death (hazard ratio [HR] 2.42, 95% confidence interval [CI] 1.56 to 3.76), myocardial infarction (HR 1.95, 95% CI 1.11 to 3.44), stroke (HR 1.98, 95% CI 1.30 to 3.01), the LIFE composite end point (HR 2.05, 95% CI 1.51 to 2.78), sudden cardiac death (HR 2.19, 95% CI 1.06 to 4.53), and all-cause mortality (HR 1.92, 95% CI 1.37 to 2.69), whereas the risk associated with regression or persistence of strain was attenuated. CONCLUSIONS: Development of new ECG strain is associated with an increased risk of cardiovascular morbidity and mortality and of all-cause mortality in the setting of antihypertensive therapy and regression of ECG left ventricular hypertrophy.

Assessment of the thoracic aorta by multidetector computed tomography: age- and sex-specific reference values in adults without evident cardiovascular disease.

BACKGROUND: Dilatation of the aortic root and other segments of the thoracic aorta is important in the pathogenesis of aortic regurgitation and of aortic dissection. Although echocardiographic criteria exist to detect aortic root dilation, comparably standardized methods have not been developed to detect enlargement of the remainder of the thoracic aorta. Nongated axial chest computed tomography (CT), traditionally used to evaluate aortic size, does not account for the obliquity, systolic expansion, and nonaxial motion of the aorta during the cardiac cycle. Reference values for aortic diameters in anatomically correct double-oblique short axis images have not been established with the use of electrocardiogram (ECG)-gated 64-detector row multidetector CT (MDCT). OBJECTIVES: To establish reference values for thoracic aortic diameters MDCT in healthy normotensive nonobese adults without evident cardiovascular disease. METHODS: A total of 103 (43% women, age 51 +/- 14 years) consecutive normotensive, nonobese adults free of cardiac or aortic structural disease or arrhythmia underwent MDCT examination to determine aortic dimensions. RESULTS: End-diastolic diameter 95% confidence intervals were 2.5-3.7 cm for the aortic root, 2.1-3.5 cm for the ascending aorta, and 1.7-2.6 cm for the descending thoracic aorta. Aortic diameters were significantly greater at end systole than end diastole (mean difference 1.9 +/- 1.2 mm for ascending and 1.3 +/- 1.8 for descending thoracic aorta, P < 0.001). Aortic root and ascending aortic diameter increased significantly with age and body surface area. CONCLUSIONS: This study establishes age- and sex-specific ECG-gated MDCT reference values for thoracic aortic diameters in healthy, normotensive, nonobese adults to identify aortic pathology by MDCT. MDCT measurements of the thoracic aorta should use ECG-gated double-oblique short-axis images for accurate quantification.

Costs and clinical outcomes after coronary multidetector CT angiography in patients without known coronary artery disease: comparison to myocardial perfusion SPECT.

PURPOSE: To assess costs and clinical outcomes in individuals without known coronary artery disease (CAD) who underwent multidetector computed tomographic (CT) angiography compared with those in matched patients who underwent myocardial perfusion single photon emission computed tomography (SPECT). MATERIALS AND METHODS: Data were captured from a deidentified, HIPAA-compliant data warehouse. We examined 1-year CAD costs (additional diagnostic coronary testing, CAD hospitalization, and coronary procedural and revascularization costs) and clinical outcomes in individuals without known CAD who underwent multidetector CT (n = 1647) compared with those in a matched cohort of patients who underwent myocardial perfusion SPECT (n = 6588). Cox proportional hazards models were employed for clinical outcome measures, including CAD hospitalization, myocardial infarction, and angina. RESULTS: Adjusted CAD costs in the multidetector CT group were 25.9% lower than in the myocardial perfusion SPECT group, by an average of $1075 (95% confidence interval [CI]: $243, $2570) per patient. Those in the multidetector CT group were more likely to undergo downstream testing with myocardial perfusion SPECT (odds ratio, 6.65; 95% CI: 5.05, 8.75; P < .001), while those in the myocardial perfusion SPECT group were more likely to undergo downstream testing with invasive angiography (odds ratio, 6.25; 95% CI: 4.35, 9.09; P < .001). The multidetector CT group was less likely to undergo coronary revascularization (hazard ratio, 0.76; 95% CI: 0.75, 0.77; P < .001) than the myocardial perfusion SPECT group. There was no significant difference between multidetector CT and myocardial perfusion SPECT groups for rates of myocardial infarction (0.4% for both) or CAD hospitalization (0.7% vs 1.1%, respectively), while rates of angina were significantly lower in the multidetector CT group (4.3% vs 6.4%, P < .001). CONCLUSION: Individuals without known CAD who underwent multidetector CT as an initial diagnostic test, compared with those who underwent myocardial perfusion SPECT, incurred lower health care costs with similar rates of myocardial infarction and CAD-related hospitalization.

Prognostic implications of relations of left ventricular systolic dysfunction with body composition and myocardial energy expenditure: the Strong Heart Study.

OBJECTIVE: We sought to investigate prognostic implications of the relationships of estimated left ventricular (LV) myocardial energy expenditure (MEE) with LV systolic dysfunction, body composition, and inflammation in a population-based sample of adults without overt congestive heart failure. METHODS: Echocardiography was used to assess LV ejection fraction (EF) and MEE. Body composition was evaluated by bioelectric impedance. Dietary recall was used to assess 24-hour calorie intake. Participants in the Strong Heart Study without prior congestive heart failure and with all needed data available (n = 3087) were divided based on LV EF (>55%, 54%-45%, or <45%). RESULTS: Participants with EF less than 45% were older and they had lower body mass index, adipose mass, fat-free mass, and 24-hour calorie intake than participants with normal EF (>/=55%), and had greatest reductions of body mass index and physical activity in a time interval of 3.5 years, on average, elapsed between an initial clinical assessment and the evaluation at the time of the echocardiographic examination (P < .01). Lower EF was associated with male sex, hypertension, diabetes, coronary heart disease, and higher fibrinogen, C-reactive protein, and plasma creatinine levels (all P < .01). MEE was higher with lower EF (all P < .001). In Cox regression models, during approximately 8 years of observation, MEE comprised between 97 and 123 cal/min and MEE greater than 123 cal/min were associated with 2.5-fold and additional 3.3-fold higher rates of cardiac death, respectively, compared with MEE less than 97 cal/min, independently of EF, body composition, and other covariates. However, lower adipose mass predicted increased risk of cardiac death independent of MEE and EF. CONCLUSION: In a population-based sample of adults including ambulatory individuals with depressed LV systolic function but without overt congestive heart failure, depressed EF was associated independently with higher MEE, lower adipose mass, and higher fibrinogen. However, increased MEE and lower adipose mass predicted cardiac death independently of EF and other covariates.

Prognostic value of multidetector coronary computed tomographic angiography for prediction of all-cause mortality.

OBJECTIVES: The purpose of this study was to examine the association of all-cause death with the coronary computed tomographic angiography (CCTA)-defined extent and severity of coronary artery disease (CAD). BACKGROUND: The prognostic value of identifying CAD by CCTA remains undefined. METHODS: We examined a single-center consecutive cohort of 1,127 patients > or =45 years old with chest symptoms. Stenosis by CCTA was scored as minimal (<30%), mild (30% to 49%), moderate (50% to 69%), or severe (> or =70%) for each coronary artery. Plaque was assessed in 3 ways: 1) moderate or obstructive plaque; 2) CCTA score modified from Duke coronary artery score; and 3) simple clinical scores grading plaque extent and distribution. A 15.3 +/- 3.9-month follow-up of all-cause death was assessed using Cox proportional hazards models adjusted for pretest CAD likelihood and risk factors. Deaths were verified by the Social Security Death Index. RESULTS: The CCTA predictors of death included proximal left anterior descending artery stenosis and number of vessels with > or =50% and > or =70% stenosis (all p < 0.0001). A modified Duke CAD index, an angiographic score integrating proximal CAD, plaque extent, and left main (LM) disease, improved risk stratification (p < 0.0001). Patients with <50% stenosis had the highest survival at 99.7%. Survival worsened with higher-risk Duke scores, ranging from 96% survival for 1 stenosis > or =70% or 2 stenoses > or =50% (p = 0.013) to 85% survival for > or =50% LM artery stenosis (p < 0.0001). Clinical scores measuring plaque burden and distribution predicted 5% to 6% higher absolute death rate (6.6% vs. 1.6% and 8.4% vs. 2.5%; p = 0.05 for both). CONCLUSIONS: In patients with chest pain, CCTA identifies increased risk for all-cause death. Importantly, a negative CCTA portends an extremely low risk for death.

Assessment of the interaction of heritability of volume load and left ventricular mass: the HyperGEN offspring study.

BACKGROUND: Left ventricular mass (LVM) is more closely associated with volume load than pressure load. We assessed whether part of the genetic heritability of LVM can be explained by stroke volume (SV) inheritance. METHODS: Echocardiographic LVM, SV and peripheral resistance were measured in 527 families with at least two relatives from the HyperGEN study (51% African-American, 43% men, 44% obese, 53% hypertensive). Included were 1792 subjects without prevalent cardiovascular disease, diabetes and renal failure. Ethnic-specific genetic correlations were estimated using a variance components procedure (SOLAR). RESULTS: Significant genetic correlations existed between LVM and SV after adjusting for age, sex, race, field center, systolic blood pressure, number of antihypertensive medications, and body mass index (rhog = 0.93 in African-Americans and 0.70 in Caucasians; both P < 0.0001). Urinary Na excretion or serum creatinine did not influence these correlations. After adjusting for covariates, heritability of LVM was greater (h = 0.46 in African-Americans and 0.47 in Caucasians; both P < 0.0001) than that for SV (h = 0.18 in African-Americans and 0.29 in Caucasians; both P < 0.02). Heritability of LVM slightly decreased in African-Americans (h = 0.34), but not in Caucasians (h = 0.45; both P < 0.0001) when SV was added to covariates. Heritability of SV almost disappeared by addition of LVM into the model in African-Americans (h = 0.04, P = not significant), whereas it was slightly reduced in Caucasians (h = 0.20, P < 0.005). CONCLUSION: LVM and SV share a common genetic profile, but with only a modest reciprocal influence. Variability of LVM has some effect on calculated heritability of SV, especially in African-Americans, whereas the role of heritable volume load in determining the variability of LVM was modest only in African-Americans.

Usefulness of quantitative assessment of electrocardiographic ST depression for predicting new-onset heart failure in American Indians (from the Strong Heart Study).

The qualitative electrocardiographic strain pattern of ST depression (STD) and T-wave inversion is strongly associated with coronary heart disease and left ventricular hypertrophy and is an independent predictor of new-onset heart failure in hypertensive participants. However, whether quantitative measures of STD in the lateral precordial leads predict new heart failure is unclear. Digital electrocardiograms were examined in 2,059 American-Indian participants in the second Strong Heart Study examination with no history of heart failure. The absolute magnitude of ST segment deviation was measured using computer to the nearest 5 microV in leads V(5) and V(6). During 5.7 +/-1.4 years of follow-up, heart failure developed in 77 participants (3.7%). Participants who developed heart failure had greater STD in leads V(5) or V(6) (-11 +/- 35 vs 12 +/- 27 microV; p <0.001) than those who did not. In univariate Cox analyses, STD was a significant predictor of new heart failure, with each 10-microV greater STD associated with a 31% greater risk of heart failure (hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.24 to 1.39). Increasing STD grouped according to quartiles was strongly associated with the development of heart failure, with stepwise increasing risk of heart failure compared with the lowest quartile of STD for the second (HR 2.39, 95% CI 0.77 to 7.40), third (HR 3.01, 95% CI 1.00 to 9.08), and fourth quartiles of STD (HR 9.06, 95% CI 3.26 to 25.16). In Cox multivariate analyses controlling for age, gender, diabetes, coronary heart disease, albuminuria, and other baseline risk factors, STD remained a significant predictor of incident heart failure (HR 1.22, 95% CI 1.13 to 1.32 per 10-muV increment in STD; p <0.001). In conclusion, increasing STD in lateral precordial leads is strongly associated with increased risk of developing heart failure independent of other risk factors for new heart failure.