Objectives This study sought to examine the relationship between left ventricular mass (LVM) regression and clinical outcomes after transcatheter aortic valve replacement (TAVR). Background LVM ...regression after valve replacement for aortic stenosis is assumed to be a favorable effect of LV unloading, but its relationship to improved clinical outcomes is unclear. Methods Of 2,115 patients with symptomatic aortic stenosis at high surgical risk receiving TAVR in the PARTNER (Placement of Aortic Transcatheter Valves) randomized trial or continued access registry, 690 had both severe LV hypertrophy (left ventricular mass index LVMi ≥149 g/m2 men, ≥122 g/m2 women) at baseline and an LVMi measurement at 30-day post-TAVR follow-up. Clinical outcomes were compared for patients with greater than versus lesser than median percentage change in LVMi between baseline and 30 days using Cox proportional hazard models to evaluate event rates from 30 to 365 days. Results Compared with patients with lesser regression, patients with greater LVMi regression had a similar rate of all-cause mortality (14.1% vs. 14.3%, p = 0.99), but a lower rate of rehospitalization (9.5% vs. 18.5%, hazard ratio HR: 0.50, 95% confidence interval CI: 0.32 to 0.78; p = 0.002) and a lower rate of rehospitalization specifically for heart failure (7.3% vs. 13.6%, p = 0.01). The association with a lower rate of rehospitalization was consistent across subgroups and remained significant after multivariable adjustment (HR: 0.53, 95% CI: 0.34 to 0.84; p = 0.007). Patients with greater LVMi regression had lower B-type natriuretic peptide (p = 0.002) and a trend toward better quality of life (p = 0.06) at 1-year follow-up than did those with lesser regression. Conclusions In high-risk patients with severe aortic stenosis and severe LV hypertrophy undergoing TAVR, those with greater early LVM regression had one-half the rate of rehospitalization over the subsequent year compared to those with lesser regression.
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 R2 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.
Nomograms to predict normal aortic root diameter for body surface area (BSA) in broad ranges of age have been widely used but are limited by lack of consideration of gender effects, jumps in upper ...limits of aortic diameter among age strata, and data from older teenagers. Sinus of Valsalva diameter was measured by American Society of Echocardiography convention in normal-weight, nonhypertensive, nondiabetic subjects ≥15 years old without aortic valve disease from clinical or population-based samples. Analyses of covariance and linear regression with assessment of residuals identified determinants and developed predictive models for normal aortic root diameter. In 1,207 apparently normal subjects ≥15 years old (54% women), aortic root diameter was 2.1 to 4.3 cm. Aortic root diameter was strongly related to BSA and height (r = 0.48 for the 2 comparisons), age (r = 0.36), and male gender (+2.7 mm adjusted for BSA and age, p <0.001 for all comparisons). Multivariable equations using age, gender, and BSA or height predicted aortic diameter strongly (R = 0.674 for the 2 comparisons, p <0.001) with minimal relation of residuals to age or body size: for BSA 2.423 + (age years × 0.009) + (BSA square meters × 0.461) − (gender 1 = man, 2 = woman × 0.267), SEE 0.261 cm; for height 1.519 + (age years × 0.010) + (height centimeters × 0.010) − (gender 1 = man, 2 = woman × 0.247), SEE 0.215 cm. In conclusion, aortic root diameter is larger in men and increases with body size and age. Regression models incorporating body size, age, and gender are applicable to adolescents and adults without limitations of previous nomograms.
Prognostic Value of Multidetector Coronary Computed Tomographic Angiography for Prediction of All-Cause Mortality James K. Min, Leslee J. Shaw, Richard B. Devereux, Peter M. Okin, Jonathan W. ...Weinsaft, Donald J. Russo, Nicholas J. Lippolis, Daniel S. Berman, Tracy Q. Callister This study examined the prediction of death from all-causes by the results of coronary computed tomographic angiography (CCTA). The CCTA measurements predictive of death included severity of stenosis in the proximal left anterior descending artery (p = 0.001) and the extent of coronary artery disease (CAD) by the number of vessels with ≥50% stenosis (p < 0.0001) and ≥70% stenosis (p < 0.0001). A modified Duke prognostic CAD index, a previously validated angiographic score integrating proximal disease, disease extent, and left main disease, improved stratification of death (p < 0.0001). In patients presenting with chest pain, CCTA identifies individuals at increased risk for all-cause death. Importantly, a negative CCTA portends an extremely low risk for death.
Hypertension and coronary heart disease are common in aortic stenosis (AS) and may impair prognosis for similar AS severity. Different changes in the electrocardiogram may be reflective of the ...separate impacts of AS, hypertension, and coronary heart disease, which could lead to enhanced risk stratification in AS. The aim of this study was therefore to examine if combining prognostically relevant electrocardiographic (ECG) findings improves prediction of cardiovascular mortality in asymptomatic AS. All patients with baseline electrocardiograms in the SEAS study were included. The primary end point was cardiovascular death. Backward elimination (p >0.01) identified heart rate, Q waves, and Cornell voltage-duration product as independently associated with cardiovascular death. Multivariate logistic and Cox regression models were used to evaluate if these 3 ECG variables improved prediction of cardiovascular death. In 1,473 patients followed for a mean of 4.3 years (6,362 patient-years of follow-up), 70 cardiovascular deaths (5%) occurred. In multivariate analysis, heart rate (hazard ratio HR 1.5 per 11.2 minute−1 1 SD, 95% confidence interval CI 1.2 to 1.8), sum of Q-wave amplitude (HR 1.3 per 2.0 mm 1 SD, 95% CI 1.1 to 1.6), and Cornell voltage-duration product (HR 1.4 per 763 mm × ms 1 SD, 95% CI 1.2 to 1.7) remained independently associated with cardiovascular death. Combining the prognostic information contained in each of the 3 ECG variables improved integrated discrimination for prediction of cardiovascular death by 2.5%, net reclassification by 14.3%, and area under the curve by 0.06 (all p ≤0.04) beyond other important risk factors. ECG findings add incremental predictive information for cardiovascular mortality in asymptomatic patients with AS.
Objectives The aim of this study was to determine which combination therapy in patients with hypertension and diabetes most effectively decreases cardiovascular events. Background The ACCOMPLISH ...(Avoiding Cardiovascular Events Through COMbination Therapy in Patients Living With Systolic Hypertension) trial compared the outcomes effects of a renin-angiotensin system blocker, benazepril, combined with amlodipine (B+A) or hydrochlorothiazide (B+H). A separate analysis in diabetic patients was pre-specified. Methods A total of 6,946 patients with diabetes were randomized to treatment with B+A or B+H. A subgroup of 2,842 diabetic patients at very high risk (previous cardiovascular or stroke events) was also analyzed, as were 4,559 patients without diabetes. The primary end point was a composite of cardiovascular death, myocardial infarction, stroke, hospitalization for angina, resuscitated arrest, and coronary revascularization. Results In the full diabetes group, the mean achieved blood pressures in the B+A and B+H groups were 131.5/72.6 and 132.7/73.7 mm Hg; during 30 months, there were 307 (8.8%) and 383 (11.0%) primary events (hazard ratio HR: 0.79, 95% confidence interval CI: 0.68 to 0.92, p = 0.003). For the diabetic patients at very high risk, there were 195 (13.6%) and 244 (17.3%) primary events (HR: 0.77, 95% CI: 0.64 to 0.93, p = 0.007). In the nondiabetic patients, there were 245 (10.8%) and 296 (12.9%) primary events (HR: 0.82, 95% CI: 0.69 to 0.97, p = 0.020). In the diabetic patients, there were clear coronary benefits with B+A, including both acute clinical events (p = 0.013) and revascularizations (p = 0.024). There were no unexpected adverse events. Conclusions In patients with diabetes and hypertension, combining a renin-angiotensin system blocker with amlodipine, compared with hydrochlorothiazide, was superior in reducing cardiovascular events and could influence future management of hypertension in patients with diabetes. (Avoiding Cardiovascular Events Through COMbination Therapy in Patients Living With Systolic Hypertension ACCOMPLISH; NCT00170950 )
At a given level of left ventricular (LV) systolic function, LV pump performance (assessed by stroke index SVi) may differ, depending on LV size. We evaluated whether low SVi may be considered a ...marker of risk for incident congestive heart failure (HF), independent of LV geometry and systolic function, assessed by ejection fraction (EF) or midwall fractional shortening (MFS), in a large population-based sample with normal EF. Clinical and echocardiographic data from the second Strong Heart Study (SHS) examination, including 2,885 American Indians (59 ± 8 years; 63% women) with normal EF (EF ≥51% in men and EF ≥55% in women) and without prevalent HF or significant valve disease, were analyzed. Low SVi was defined as SVi ≤22 ml/m2.04 . Low SVi was more common among men and associated with lower body mass index, systolic blood pressure, LV mass index, left atrial dimension, EF, and MFS and with higher relative wall thickness. During a mean 12-year follow-up, 209 participants developed HF and 246 had acute myocardial infarction. In Cox regression analysis, low SVi was associated with higher risk of incident HF (hazard ratio 1.38; 95% confidence interval 1.06 to 1.80), independently of age, gender, body mass index, heart rate, hypertension, prevalent cardiovascular disease, left atrial dimension index, LV mass index, LV concentric geometry, EF or MFS, and abnormal wall motion, also accounting for myocardial infarction as a competing risk event. In conclusion, in the SHS, low SVi was associated with higher incident rate of HF, independently of LV geometry and systolic function and other major confounders.
Objectives This study sought to compare contrast-enhanced anatomic imaging and contrast-enhanced tissue characterization (delayed-enhancement cardiac magnetic resonance DE-CMR) for left ventricular ...(LV) thrombus detection. Background Contrast echocardiography (echo) detects LV thrombus based on anatomic appearance, whereas DE-CMR imaging detects thrombus based on tissue characteristics. Although DE-CMR has been validated as an accurate technique for thrombus, its utility compared with contrast echo is unknown. Methods Multimodality imaging was performed in 121 patients at high risk for thrombus due to myocardial infarction or heart failure. Imaging included 3 anatomic imaging techniques for thrombus detection (contrast echo, noncontrast echo, cine-CMR) and a reference of DE-CMR tissue characterization. LV structural parameters were quantified to identify markers for thrombus and predictors of additive utility of contrast-enhanced thrombus imaging. Results Twenty-four patients had thrombus by DE-CMR. Patients with thrombus had larger infarcts (by DE-CMR), more aneurysms, and lower LV ejection fraction (by CMR and echo) than those without thrombus. Contrast echo nearly doubled sensitivity (61% vs. 33%, p < 0.05) and yielded improved accuracy (92% vs. 82%, p < 0.01) versus noncontrast echo. Patients who derived incremental diagnostic utility from DE-CMR had lower LV ejection fraction versus those in whom noncontrast echo alone accurately assessed thrombus (35 ± 9% vs. 42 ± 14%, p < 0.01), with a similar trend for patients who derived incremental benefit from contrast echo (p = 0.08). Contrast echo and cine-CMR closely agreed on the diagnosis of thrombus (κ = 0.79, p < 0.001). Thrombus prevalence was lower by contrast echo than DE-CMR (p < 0.05). Thrombus detected by DE-CMR but not by contrast echo was more likely to be mural in shape or, when apical, small in volume (p < 0.05). Conclusions Echo contrast in high-risk patients markedly improves detection of LV thrombus, but does not detect a substantial number of thrombi identified by DE-CMR tissue characterization. Thrombi detected by DE-CMR but not by contrast echo are typically mural in shape or small in volume.
Central But Not Brachial Blood Pressure Predicts Cardiovascular Events in an Unselected Geriatric Population: The ICARe Dicomano Study Riccardo Pini, M. Chiara Cavallini, Vittorio Palmieri, Niccolò ...Marchionni, Mauro Di Bari, Richard B. Devereux, Giulio Masotti, Mary J. Roman We investigated whether central blood pressure (BP) predicts cardiovascular (CV) events better than brachial BP in normotensive and untreated hypertensive elderly individuals. During 8 years of follow-up, 122 (31%) CV events were recorded. Both central and brachial systolic blood pressure (SBP) and pulse pressure (PP) predicted CV events (p < 0.0001); however, in multivariate analyses, adjusting for age and gender, higher carotid SBP and PP (hazard ratios 1.19/10 and 1.23/10 mm Hg, respectively, both p < 0.0001) but neither brachial SBP nor PP independently predicted CV events.Our prospective study in a community-dwelling geriatric population demonstrates the superior prognostic utility of central compared with brachial BP.
Rationale A number of randomized trials are underway, which will address the effects of angiotensin receptor blockers (ARBs) on aortic root enlargement and a range of other end points in patients ...with Marfan syndrome. If individual participant data from these trials were to be combined, a meta-analysis of the resulting data, totaling approximately 2,300 patients, would allow estimation across a number of trials of the treatment effects both of ARB therapy and of β-blockade. Such an analysis would also allow estimation of treatment effects in particular subgroups of patients on a range of end points of interest and would allow a more powerful estimate of the effects of these treatments on a composite end point of several clinical outcomes than would be available from any individual trial. Design A prospective, collaborative meta-analysis based on individual patient data from all randomized trials in Marfan syndrome of (i) ARBs versus placebo (or open-label control) and (ii) ARBs versus β-blockers will be performed. A prospective study design, in which the principal hypotheses, trial eligibility criteria, analyses, and methods are specified in advance of the unblinding of the component trials, will help to limit bias owing to data-dependent emphasis on the results of particular trials. The use of individual patient data will allow for analysis of the effects of ARBs in particular patient subgroups and for time-to-event analysis for clinical outcomes. The meta-analysis protocol summarized in this report was written on behalf of the Marfan Treatment Trialists' Collaboration and finalized in late 2012, without foreknowledge of the results of any component trial, and will be made available online ( http://www.ctsu.ox.ac.uk/research/meta-trials ).
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