American Journal of Cardiology - Articles in Press

Cardiac Biomarkers, Mortality, and Post-Traumatic Stress Disorder in Military Veterans - Corrected Proof

2012-02-06

Post-traumatic stress disorder (PTSD) is gaining increasing recognition as a risk factor for morbidity and mortality. The aim of this study was to examine the impact of PTSD and abnormal cardiovascular biomarkers on mortality in military veterans. Eight hundred ninety-one patients presenting for routine echocardiography were enrolled. Baseline clinical data and serum samples for biomarker measurement were obtained and echocardiography was performed at the time of enrollment. Patients were followed for up to 7.5 years for the end point of all-cause mortality. Ninety-one patients had PTSD at the time of enrollment. There were 33 deaths in patients with PTSD and 221 deaths in those without PTSD. Patients with PTSD had a trend toward worse survival on Kaplan-Meier analysis (p = 0.057). Among patients with elevated B-type natriuretic peptide (>60 pg/ml), those with PTSD had significantly increased mortality (p = 0.024). Among patients with PTSD, midregional proadrenomedullin (MR-proADM), creatinine, and C-terminal proendothelin-1 were significant univariate predictors of mortality (p = 0.006, p = 0.024, and p = 0.003, respectively). In a multivariate model, PTSD, B-type natriuretic peptide, and MR-proADM were independent predictors of mortality. In patients with PTSD, MR-proADM was a significant independent predictor of mortality after adjusting for B-type natriuretic peptide, cardiovascular risk factors, cancer, and sleep apnea. Adding MR-proADM to clinical predictors of mortality increased the C-statistic from 0.572 to 0.697 (p = 0.007). In conclusion, this study demonstrates an association among PTSD, abnormal cardiac biomarker levels, and increased mortality.

Long-Term Outcomes With Use of Intravascular Ultrasound for the Treatment of Coronary Bifurcation Lesions - Corrected Proof

2012-02-02

Percutaneous coronary intervention (PCI) of bifurcation lesions remains challenging with a higher risk of adverse outcomes. Whether adjunctive intravascular ultrasound (IVUS) imaging improves outcomes of PCI of bifurcation lesions remains unclear. This study sought to determine the long-term clinical outcomes associated with using IVUS for percutaneous treatment of coronary bifurcation lesions. From April 2003 through August 2010, 449 patients with 471 bifurcation lesions underwent PCI with (n = 247) and without (n = 202) the use of IVUS. Clinical outcomes (death, myocardial infarction [MI], periprocedural MI, stent thrombosis, target vessel revascularization [TVR], and target lesion revascularization [TLR]) were compared between patients undergoing PCI with and without IVUS using univariate and propensity score-adjusted analyses. Most patients (61%) presented with acute coronary syndrome and 89% of bifurcations lesions were Medina class 1,1,1. After propensity score adjustment, use of IVUS was associated with significantly lower rates of death or MI (odds ratio 0.38, 95% confidence interval 0.20 to 0.74, p = 0.005), death (odds ratio 0.40, 95% confidence interval 0.18 to 0.88, p = 0.02), MI (odds ratio 0.37, 95% confidence interval 0.14 to 0.98, p = 0.04), periprocedural MI (odds ratio 0.45, 95% confidence interval 0.20 to 0.97, p = 0.04), TVR (odds ratio 0.28, 95% confidence interval 0.14 to 0.53, p <0.0001), and TLR (odds ratio 0.27, 95% confidence interval 0.14 to 0.53, p = 0.0003) compared to no IVUS. In conclusion, IVUS-guided treatment of complex bifurcation lesions was associated with significantly lower rates of adverse cardiac events at late follow-up. Further study is warranted to evaluate the role of IVUS guidance in improving long-term outcomes after PCI of bifurcation lesions.

Left Ventricular Dyssynchrony Using Three-Dimensional Speckle-Tracking Imaging as a Determinant of Torsional Mechanics in Patients With Idiopathic Dilated Cardiomyopathy - Corrected Proof

2012-01-30

The aim of this study was to use 3-dimensional (3D) speckle-tracking echocardiography to test the hypothesis that left ventricular (LV) dyssynchrony may negatively affect LV torsional mechanics in patients with idiopathic dilated cardiomyopathy (IDC) and that LV torsion may improve after cardiac resynchronization therapy. This study included 65 subjects; 20 with IDC with ejection fractions ≤35% and wide QRS complexes (≥120 ms), 20 with IDC with ejection fractions ≤35% and narrow QRS complexes (<120 ms), and 25 controls. LV dyssynchrony index was determined as the SD of time to peak 3D speckle-tracking radial strain and regional heterogeneity of LV rotation (rotational dispersion index) as the SD of 3D speckle-tracking time to peak rotation. All rotational indexes were significantly impaired in patients with IDC, while LV torsion in patients with IDC with wide QRS complexes was significantly smaller than that in patients with IDC with narrow QRS complexes and controls. Conversely, LV dyssynchrony index (127.3 ± 24.0 ms [p <0.01 vs controls and vs patients with narrow QRS complexes] vs 88.8 ± 22.5 ms [p <0.01 versus controls] vs 30.9 ± 10.0 ms) and rotational dispersion index (115.1 ± 27.5 ms [p <0.01 vs controls and vs patients with narrow QRS complexes] vs 96.0 ± 23.4 ms [p <0.01 versus controls] vs 45.0 ± 13.7 ms) were significantly higher in patients with IDC with wide QRS complexes. Multivariate analysis showed that the LV ejection fraction (β = 0.688, p <0.001) and rotational dispersion index (β = −0.249, p <0.01) were independent determinants of LV torsion. Moreover, LV torsion in patients with IDC with wide QRS complexes improved after cardiac resynchronization therapy (p <0.05), along with reductions in LV dyssynchrony and rotational dispersion indexes. In conclusion, these findings obtained with a novel 3D speckle-tracking system feature a novel aspect of LV torsional mechanics and demonstrate its association with LV dyssynchrony.

Body Mass Index, Playing Position, Race, and the Cardiovascular Mortality of Retired Professional Football Players - Corrected Proof

Sherry L. Baron, Misty J. Hein, Everett Lehman, Christine M. Gersic — 2012-01-27

Concern exists about cardiovascular disease (CVD) in professional football players. We examined whether playing position and size influence CVD mortality in 3,439 National Football League players with ≥5 pension-credited playing seasons from 1959 to 1988. Standardized mortality ratios (SMRs) compared player mortality through 2007 to the United States population of men stratified by age, race, and calendar year. Cox proportional hazards models evaluated associations of playing-time body mass index (BMI), race, and position with CVD mortality. Overall player mortality was significantly decreased (SMR 0.53, 95% confidence interval [CI] 0.48 to 0.59) as was mortality from cancer (SMR 0.58, 95% CI 0.46 to 0.72), and CVD (SMR 0.68, 95% CI 0.56 to 0.81). CVD mortality was increased for defensive linemen (SMR 1.42, 95% CI 1.02 to 1.92) but not for offensive linemen (SMR 0.70, 95% CI 0.45 to 1.05). Defensive linemen's cardiomyopathy mortality was also increased (SMR 5.34, 95% CI 2.30 to 10.5). Internal analyses found that CVD mortality was increased for players of nonwhite race (hazard ratio 1.69, 95% CI 1.13 to 2.51). After adjusting for age, race, and calendar year, CVD mortality was increased for those with a playing-time BMI ≥30 kg/m2 (hazard ratio 2.02, 95% CI 1.06 to 3.85) and for defensive linemen compared to offensive linemen (hazard ratio 2.07, 95% CI 1.24 to 3.46). In conclusion, National Football League players from the 1959 through 1988 seasons had decreased overall mortality but those with a playing-time BMI ≥30 kg/m2 had 2 times the risk of CVD mortality compared to other players and African-American players and defensive linemen had higher CVD mortality compared to other players even after adjusting for playing-time BMI.

Impact of Anemia on Platelet Response to Clopidogrel in Patients Undergoing Percutaneous Coronary Stenting - Corrected Proof

2012-01-27

High residual platelet reactivity (HRPR) on clopidogrel is a predictor of recurrent ischemic events in patients undergoing percutaneous coronary interventions (PCI). Significant intraindividual variability in platelet aggregation on repeat testing has been reported. To understand factors contributing to the variability in platelet aggregation testing, we examined clinical and laboratory elements linked to HRPR in 255 consecutive patients tested ≥12 hours after PCI using light transmission aggregometry (LTA) in response to adenosine diphosphate 5 μmol/L and VerifyNow P2Y12 assay (VNP2Y12; Accumetrics). HRPR was defined as >46% residual aggregation for LTA and >236 P2Y12 response units (PRUs) for VNP2Y12. On multivariate analysis the only variable independently associated with HRPR with both LTA and VNP2Y12 was laboratory-defined anemia. Prevalences of HRPR by LTA were 34.3% in anemic patients, 15.6% in patients with normal hemoglobin levels, and 59.8% versus 25.9% by VNP2Y12 (p <0.005 for the 2 comparisons). In a subgroup of 50 patients, testing was done before and after the clopidogrel loading dose. At baseline there were no differences in platelet aggregation with either assay; however, absolute decrease in reactivity after the clopidogrel load was significantly less in anemic patients compared to patients with normal hemoglobin (change in residual aggregation by LTA 15.8 ± 5.8% vs 28.8 ± 3.2%, p <0.05; change in PRU by VNP2Y12 56.5 ± 35.5 vs 145.0 ± 14.2 PRUs, p <0.05, respectively). In conclusion, anemia is an important contributor to apparent HRPR on clopidogrel and may explain some of the intraindividual variability of platelet aggregation testing.

Usefulness of Pet Ownership as a Modulator of Cardiac Autonomic Imbalance in Patients With Diabetes Mellitus, Hypertension, and/or Hyperlipidemia - Corrected Proof

2012-01-27

Among patients with coronary artery disease, pet owners exhibit a greater 1-year survival rate than nonowners. Lifestyle-related diseases are well-known risk factors for coronary artery disease and induce imbalances in autonomic nervous activity. The purpose of the present study was to determine whether pet ownership modulates cardiac autonomic nervous activity imbalance in patients with lifestyle-related diseases such as diabetes mellitus, hypertension, and hyperlipidemia. A total of 191 patients (mean age 69 ± 8 years) were interviewed about their pet ownership status and were classified into pet owner and nonowner groups. After recording a 24-hour Holter electrocardiogram for heart rate variability analysis, frequency-domain and nonlinear-domain analyses were performed to determine the high-frequency (HF) and low-frequency (LF) components, LF/HF ratio, and entropy. The heart rate variability parameters were assessed for 24 hours, during the day (8.00 a.m. to 5.00 p.m.), and during the night (0:00 a.m. to 6.00 a.m.), and compared between the 2 groups. To evaluate the potential predictive factors for cardiac autonomic imbalance, univariate and multivariate analyses of HF and LF/HF were conducted for potential confounding variables. The pet owner group exhibited significantly greater HF24h, HFday, HFnight, entropy24h, entropyday, and entropynight and significantly lower LF/HF24h and LF/HFnight compared to the nonowner group. On multivariate analysis, pet ownership was independently and positively associated with HF24h, HFday, and HFnight and inversely associated with LF/HF24h and LF/HFnight. In conclusion, these results suggest that pet ownership is an independent modulator of cardiac autonomic imbalance in patients with lifestyle-related diseases.

Right Ventricular Function in Patients With Eisenmenger Syndrome - Corrected Proof

2012-01-27

To evaluate (1) whether right ventricular (RV) dysfunction, evaluated using tricuspid annular plane systolic excursion (TAPSE) is associated with a worse outcome in patients with the Eisenmenger syndrome, (2) which variables are related to RV dysfunction, and (3) whether differences exist among simple pretricuspid, simple post-tricuspid, and combined shunt lesions. Patients with Eisenmenger syndrome, aged >18 years, who underwent echocardiography, were selected from the Belgian Eisenmenger registry and prospectively followed up using a Web-based registry. Cox regression analysis was performed to evaluate the relation to outcomes, defined as all-cause mortality, transplantation, and hospitalization for cardiopulmonary causes. Comparative and bivariate analysis was performed, where applicable. A total of 58 patients (mean age 35.1 ± 13.2 years, 32.8% men) were included. During a mean follow-up of 3.2 years, 22 patients (37.9%) reached the predefined end point. Only TAPSE (hazard ratio 0.820, 95% confidence interval 0.708 to 0.950; p = 0.008) was related to the adverse outcomes on multivariate analysis. Patients with pretricuspid shunt lesions were older (p <0.0001) had greater left (p <0.0001) and right atrial (p <0.0001) dimensions, greater RV dimensions (p = 0.002), and more tricuspid regurgitation (p = 0.012) compared to patients with post-tricuspid lesions. Lower TAPSE was related to the presence of pulmonary artery thrombosis (R = −0.378; p = 0.006). In conclusion, in patients with Eisenmenger syndrome, RV dysfunction, evaluated using TAPSE, is related to worse outcomes. Patients with Eisenmenger syndrome with pretricuspid shunt lesions were older and had greater left atrial, right atrial, and RV dimensions compared to patients with post-tricuspid lesions, indicating a difference in the RV response. Lower TAPSE was associated with the presence of pulmonary artery thrombosis.

Effect of Obstructive Sleep Apnea on Mitral Valve Tenting - Corrected Proof

2012-01-24

Obstructive apneas produce high negative intrathoracic pressure that imposes an afterload burden on the left ventricle. Such episodes might produce structural changes in the left ventricle over time. Doppler echocardiograms were obtained within 2 months of attended polysomnography. Patients were grouped according to apnea–hypopnea index (AHI): mild/no obstructive sleep apnea (OSA; AHI <15) and moderate/severe OSA (AHI ≥15). Mitral valve tenting height and area, left ventricular (LV) long and short axes, and LV end-diastolic volume were measured in addition to tissue Doppler parameters. Comparisons of measurements at baseline and follow-up between and within groups were obtained; correlations between absolute changes (Δ) in echocardiographic parameters were also performed. After a mean follow-up of 240 days mitral valve tenting height increased significantly (1.17 ± 0.12 to 1.28 ± 0.17 cm, p = 0.001) in moderate/severe OSA as did tenting area (2.30 ± 0.41 to 2.66 ± 0.60 cm2, p = 0.0002); Δtenting height correlated with ΔLV end-diastolic volume (rho 0.43, p = 0.01) and Δtenting area (rho 0.35, p = 0.04). In patients with mild/no OSA there was no significant change in tenting height; there was a borderline significant increase in tenting area (2.20 ± 0.44 to 2.31 ± 0.43 cm2, p = 0.05). Septal tissue Doppler early diastolic wave decreased (8.04 ± 2.49 to 7.10 ± 1.83 cm/s, p = 0.005) in subjects with moderate/severe OSA but not in in those with mild/no OSA. In conclusion, in patients with moderate/severe OSA, mitral valve tenting height and tenting area increase significantly over time. This appears to be related, at least in part, to changes in LV geometry.

Red Blood Cell Indices and Development of Hospital-Acquired Anemia During Acute Myocardial Infarction - Corrected Proof

2012-01-24

Hospital-acquired anemia (HAA) is common, often develops in the absence of bleeding, and is associated with poor outcomes in patients with acute myocardial infarction (AMI). It is unknown whether red cell distribution width (RDW) and mean corpuscular volume (MCV), which are routinely available markers of iron deficiency, are associated with development of HAA during AMI. We studied 15,133 patients with AMI without anemia at admission. HAA was defined by nadir hemoglobin levels below age-, gender-, and race-specific thresholds and moderate–severe HAA was defined as nadir hemoglobin ≤11 g/dl. We examined the association between low MCV (<80 fL) and/or increased RDW (>15%) on patients' initial complete blood cell count and moderate–severe HAA using multivariable modified Poisson regression. Moderate–severe HAA was more common in patients with high RDW and low MCV (45.5%), high RDW and MCV ≥80 fL (33.0%), and normal RDW and low MCV (28.0%) than in those with normal RDW and MCV (18.3%, p <0.001). Compared to patients with normal RDW and MCV, those with increased RDW and low MCV (relative risk 1.72, 95% confidence interval 1.57 to 1.87), increased RDW and MCV ≥80 fL (relative risk 1.28, 95% confidence interval 1.16 to 1.42), or normal RDW and low MCV (relative risk 1.34, 95% confidence interval 1.08 to 1.65) were independently more likely to develop moderate–severe HAA. In conclusion, increased RDW and low MCV were independent predictors of moderate–severe HAA.

Myocardial Perfusion Magnetic Resonance Imaging Using Sliding-Window Conjugate-Gradient Highly Constrained Back-Projection Reconstruction for Detection of Coronary Artery Disease - Corrected Proof

2012-01-24

Myocardial perfusion magnetic resonance imaging (MRI) with sliding-window conjugate-gradient highly constrained back-projection reconstruction (SW-CG-HYPR) allows whole left ventricular coverage, improved temporal and spatial resolution and signal/noise ratio, and reduced cardiac motion-related image artifacts. The accuracy of this technique for detecting coronary artery disease (CAD) has not been determined in a large number of patients. We prospectively evaluated the diagnostic performance of myocardial perfusion MRI with SW-CG-HYPR in patients with suspected CAD. A total of 50 consecutive patients who were scheduled for coronary angiography with suspected CAD underwent myocardial perfusion MRI with SW-CG-HYPR at 3.0 T. The perfusion defects were interpreted qualitatively by 2 blinded observers and were correlated with x-ray angiographic stenoses ≥50%. The prevalence of CAD was 56%. In the per-patient analysis, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of SW-CG-HYPR was 96% (95% confidence interval 82% to 100%), 82% (95% confidence interval 60% to 95%), 87% (95% confidence interval 70% to 96%), 95% (95% confidence interval 74% to100%), and 90% (95% confidence interval 82% to 98%), respectively. In the per-vessel analysis, the corresponding values were 98% (95% confidence interval 91% to 100%), 89% (95% confidence interval 80% to 94%), 86% (95% confidence interval 76% to 93%), 99% (95% confidence interval 93% to 100%), and 93% (95% confidence interval 89% to 97%), respectively. In conclusion, myocardial perfusion MRI using SW-CG-HYPR allows whole left ventricular coverage and high resolution and has high diagnostic accuracy in patients with suspected CAD.

Outcomes of Nonstenting Percutaneous Coronary Intervention in Patients With Rheumatoid Arthritis - Corrected Proof

Jiunn-Horng Kang, Joseph J. Keller, Herng-Ching Lin — 2012-01-24

The aim of the present study was to explore the outcomes of percutaneous coronary intervention (PCI) in patients with rheumatoid arthritis (RA) and coronary heart disease. We identified 25,367 patients from the National Health Insurance Research Database who underwent nonstenting PCI in Taiwan in 2007. Of these patients, 240 had been diagnosed with RA. As a comparison group, we selected 1,200 patients who were matched with the study group by gender and age. We performed conditional logistic regression analysis to compare the outcomes of PCI between the 2 groups. We found no significant differences in the rates of in-hospital mortality (2.5% vs 3.1%, p = 0.628), 90-day readmission for PCI (8.3% vs 7.2%, p = 0.559), or 365-day readmission for PCI (22.5% vs 19.2%, p = 0.236) between the patients with and without RA. Similarly, the conditional logistic regression analyses revealed that patients with RA had no greater adjusted odds of in-hospital mortality (odds ratio 0.94, 95% confidence interval 0.37 to 2.36), 90-day readmission for PCI (odds ratio 1.20, 95% confidence interval 0.37 to 2.36), and 365-day readmission for PCI (odds ratio 1.30, 95% confidence interval 0.92 to 1.83) than the comparison group. In conclusion, our study did not find an increased risk of adverse outcomes among patients with RA after PCI.

Relation Between Strain Dyssynchrony Index Determined by Comprehensive Assessment Using Speckle-Tracking Imaging and Long-Term Outcome After Cardiac Resynchronization Therapy for Patients With Heart Failure - Corrected Proof

2012-01-24

Strain dyssynchrony index (SDI), which was a marker of dyssynchrony and residual myocardial contractility, can predict left ventricular reverse remodeling short-term after cardiac resynchronization therapy (CRT). We investigated SDI-predicted long-term outcome after CRT in patients with heart failure (HF). We studied 74 patients with HF who underwent CRT. SDI was calculated as the average difference between peak and end-systolic strain from 6 segments for radial and circumferential SDIs and 18 segments for longitudinal SDI using 2-dimensional speckle-tracking strain. Based on our previous findings, the predefined cutoff for significant dyssynchrony and residual myocardial contractility was a radial SDI ≥6.5%, a circumferential SDI ≥3.2%, and a longitudinal SDI ≥3.6%. The predefined principal outcome variable was the combined end point of death or hospitalization owing to deteriorating HF. Long-term follow-up after CRT was tracked over 4 years. The primary end point of prespecified events occurred in 14 patients (19%). An association with a favorable long-term outcome after CRT was observed in patients with significant radial, circumferential, and longitudinal SDIs (p <0.001, <0.005, and 0.010 vs patients without significant SDIs, respectively). Furthermore, cardiovascular event-free rate after CRT in patients with positivity of 3 for the 3 SDIs was 100% better than that in patients with positivity of 1 (52%, p <0.005) or 0 (31%, p <0.001) for the 3 SDIs. In conclusion, SDIs can successfully predict long-term outcome after CRT in patients with HF. Moreover, the approach combining the 3 types of SDI leads to a more accurate prediction than the use of individual parameters. These findings may have clinical implications in patients with CRT.

Detection of 18Fluoride Sodium Accumulation by Positron Emission Tomography in Calcified Stenotic Aortic Valves - Corrected Proof

2012-01-24

Aortic valve stenosis progression rate is highly variable among patients and to date remains unpredictable. Evaluation of osteoblastic activity inside aortic valves may help identify patients with fast aortic stenosis progression rates and worse prognoses. Fluoride-18 sodium (FNa) is a clinically approved positron emission tomographic (PET) radiotracer with high and rapid bone uptake. The aim of this study was to test whether FNa accumulates in degenerative aortic valves and can be detected with PET imaging. Five patients with severe aortic stenosis and 10 patients free of aortic valvular calcium on computed tomography underwent PET imaging 40 minutes after the injection of 4 MBq/kg of FNa for oncologic or rheumatologic purposes. Maximal standard uptake values (SUVs) were measured retrospectively in aortic valves using PET imaging. Tissue-to-background ratios were calculated for each patient by dividing the maximal SUV measured in aortic valves by the mean SUV of blood. In patients with severe aortic stenosis, an intense accumulation of FNa was detected in aortic valve region on PET imaging, whereas only low activity was found in patients free of valvular calcification (median maximal SUV 2.6 g/ml/kg [interquartile range (IQR) 2.3 to 3.6] vs 2.0 g/ml/kg [IQR 1.7 to 2.2] and median tissue-to-background ratio 2.2 [IQR 2.0 to 2.7] vs 1.5 [IQR 1.5 to 1.7], respectively, p = 0.008 for both). Intraobserver variability for maximal SUV and tissue-to-background ratio in aortic valves was measured at 0.99 and interobserver variability at 0.98 and 0.97, respectively. In conclusion, in this pilot study, FNa accumulated in patients with severe aortic stenosis and could be quantified on PET imaging with good reproducibility. FNa PET imaging represents a promising imaging modality to evaluate osteoblastic activity inside calcified aortic valves.

Findings in the Pulmonary Vascular Bed in the Remote Phase After Kawasaki Disease - Corrected Proof

2012-01-24

Kawasaki disease (KD) is a form of systemic vasculitis that causes chronic changes in arterial walls, including pulmonary arteries. The aim of this study was to test the hypothesis that pulmonary arterial wall properties and hemodynamics are abnormal after the resolution of KD. Pulmonary arterial input impedance was measured during cardiac catheterization (4.8 ± 4.5 years after disease onset) in 47 consecutive patients (mean age 7.8 ± 5.7 years) with KD and coronary artery lesions (CALs) in the acute phase and 42 control patients (mean age 6.7 ± 4.6 years). Patients with KD were subdivided into 2 groups: 28 with persistent CALs and 19 with regressed CALs. There were no significant differences in characteristic impedance and peripheral vascular resistance between patients with KD and controls. Compared with controls, patients with persistent CALs had significantly lower pulmonary arterial compliance, suggesting increased wall stiffness of the peripheral pulmonary vascular bed (p <0.05, analysis of variance). Patients with persistent CALs also exhibited increased wave reflection compared with other groups (p <0.05, analysis of variance). In conclusion, unlike patients with regressed CALs, patients with persistent CALs have abnormal mechanical properties and hemodynamics of the pulmonary artery after KD. Together with previous reports of abnormal properties of coronary and systemic arteries, these data suggest that KD vasculitis causes chronic changes in arterial wall properties in the entire arterial system to varying degrees and extent. The fate of these abnormalities in the pulmonary bed and other arterial systems and their potential adverse effects must be monitored in long-term follow-up.

Cardiac Transplantation in Adults With Aortic Valve Disease With Focus on the Bicuspid Aortic Valve - Corrected Proof

2012-01-20

The frequency of congenitally bicuspid aortic valves in patients having cardiac transplantation (CT) is unknown. We reviewed 243 explanted hearts in patients having CT at Baylor University Medical Center, Dallas from June 1997 through November 2011 to determine the frequency of a bicuspid aortic valve in this population. Of the 243 explanted hearts, 7 (2.9%) were found to have a congenitally bicuspid aortic valve: 3 had severe aortic valve stenosis and before CT had had the aortic valve replaced; the other 4 had normally functioning bicuspid valves and underwent CT for cardiomyopathy (ischemic in 1, idiopathic in 2, and hypertrophic in 1). Review of previously published reports of CT and aortic valve disease disclosed that 4 patients had had aortic valve replacement (AVR) from 2 to 8 years before CT, 3 had AVR or aortic valve repair of the donor heart at the time of CT, and 4 had AVR or transcatheter aortic valve implantation from 1 to 14 years after CT. Some of these aortic valve replacements, before, at the time of, or after CT were in patients with congenitally bicuspid aortic valves. In conclusion, congenitally bicuspid aortic valves were found in 7 of 243 explanted hearts in patients having CT at a single medical center in a 14-year period: 4 had functioned normally and 3 were severely stenotic. Previous reports of patients having AVR or repair before, during, and after CT were reviewed.

Comparison of Outcome of Higher Versus Lower Transvalvular Gradients in Patients With Severe Aortic Stenosis and Low (<40%) Left Ventricular Ejection Fraction - Corrected Proof

2012-01-19

Left ventricular systolic dysfunction in patients with severe aortic stenosis (AS) is associated with poor outcome. This analysis was designed primarily to describe the clinical course of a large series of consecutive patients with severe AS and low ejection fraction (EF) (<40%) who, because of high surgical risk, were referred for transcatheter aortic valve implantation consideration. A cohort of 270 patients with severe AS and low EF (<40%) who were referred to participate in a clinical trial of transcatheter aortic valve implantation was studied. Clinical, hemodynamic, and periprocedural complications and follow-up mortality data were collected and compared between patients with low mean transvalvular gradients (≤40 mm Hg, n = 170 [63%]) and high transvalvular gradients (>40 mm Hg, n = 100 [37%]). Patients with low gradients were younger (mean age 79.8 ± 9.1 vs 83.8 ± 7.7 years, p <0.001) and had higher incidences of coronary artery disease and renal failure. Mean aortic valve area was larger (0.73 ± 0.23 vs 0.53 ± 0.18 cm2, p <0.001), while mean EF (26.4 ± 6.9% vs 30.5% ± 6.6%, p <0.001), cardiac output (3.7 ± 1.1 vs 4.1 ± 1.3 L/min, p = 0.04), and cardiac index (1.9 ± 0.5 vs 2.1 ± 0.6 L/min/m2, p = 0.04) were lower in patients with lower gradients compared to those with higher gradients, respectively. Mortality was higher in patients with low gradients (53.8%) at a mean follow-up of 151 days compared to those with high gradients (41%) at a mean follow-up of 256 days (p = 0.01). In conclusion, patients with severe AS and low EF with low transvalvular gradients are at higher risk for worse outcomes compared to patients with high transvalvular gradients. Surgery or transcatheter aortic valve implantation treatment and high baseline transvalvular gradient are associated with EF improvement.

Midregional Pro–A-Type Natriuretic Peptide for Diagnosis and Prognosis in Patients With Suspected Acute Myocardial Infarction - Corrected Proof

2012-01-19

We hypothesized that midregional pro–A-type natriuretic peptide (MR-proANP), the stable midregional epitope of proANP, might be useful in the early diagnosis and risk stratification of patients with suspected acute myocardial infarction (AMI). In this multicenter study we measured MR-proANP, cardiac troponin T (cTnT), and high-sensitive cTnT (hs-cTnT) at presentation in 675 consecutive patients presenting to the emergency department with suspected AMI. The final diagnosis was adjudicated by 2 independent cardiologists. Patients were followed 360 days for mortality and AMI. AMI was the final diagnosis in 119 patients (18%). Median MR-proANP levels at presentation were significantly higher in patients with AMI (189 pmol/L, interquartile range 97 to 341) versus patients with another final diagnosis (83 pmol/L, 49 to 144, p <0.001). However, neither the combination of MR-proANP with cTnT nor its combination with hs-cTnT significantly improved diagnostic accuracy as quantified by area under the receiver operating characteristic curve (0.91 vs 0.89 for cTnT alone, p = 0.086; 0.95 vs 0.96 for hs-cTnT, respectively, p = 0.02). Cumulative 360-day mortality/AMI rates were 2.4% in the first, 3.6% in the second, 9.5% in the third, and 18.8% in the fourth quartiles of MR-proANP (p <0.001). MR-proANP (area under the curve 0.76) predicted mortality/AMI independently of and more accurately than cTnT (area under the curve 0.62), hs-cTnT (area under the curve 0.71), and Thrombolysis In Myocardial Infarction risk score (area under the curve 0.72). Net reclassification improvements offered by the additional use of MR-proANP were 0.388 (p <0.001), 0.425 (p <0.001), and 0.217 (p = 0.007), respectively. In conclusion, MR-proANP improves risk prediction for 360-day mortality/AMI but does not seem to help in the early diagnosis of AMI.

Contribution of Central Adiposity to Left Ventricular Diastolic Function (from the Baltimore Longitudinal Study of Aging) - Corrected Proof

2012-01-19

We examined the relations of central adiposity with left ventricular (LV) diastolic dysfunction in men and women who participated in the Baltimore Longitudinal Study of Aging, a prospective community-based study of older persons. The sample for this cross-sectional analysis included 399 women and 370 men. Central adiposity was estimated using the waist circumference (WC) and global adiposity using the body mass index (BMI). Using data from a comprehensive echocardiographic study that included tissue Doppler imaging, diastolic function was graded according to 3 parameters (E/A ratio, E/Em ratio, and left atrial volume index). In the logistic regression models adjusted for age, gender, cardiovascular risk factors, and hemodynamic parameters, WC and BMI were both independently associated with LV diastolic dysfunction. However, when both WC and BMI were in the same model, only WC remained significantly associated with LV diastolic dysfunction (odds ratio 1.04, 95% confidence interval 1.01 to 1.08, p = 0.02). In the gender-stratified analyses, WC was significantly associated with LV diastolic dysfunction—independently of BMI—in women (odds ratio 1.08, 95% confidence interval 1.04 to 1.14, p <0.001) but not in men (odds ratio 1.00, 95% confidence interval 0.95 to 1.05, p = 0.91). Additional adjustment for LV mass index failed to modify these relations. In conclusion, the adverse effect of central adiposity on LV diastolic function was independent of general adiposity and more pronounced among women. The effect of visceral adiposity on LV diastolic dysfunction would benefit from confirmation in longitudinal studies.

Functional Health Status in Adult Survivors of Operative Repair of Tetralogy of Fallot - Corrected Proof

2012-01-16

We aimed to determine late functional health status of the growing adult population with repaired tetralogy of Fallot (TOF). We studied all 840 patients with TOF born from 1927 through 1984 who survived to adulthood (>18 years of age). Clinical follow-up was by chart review, telephone interview (n = 706), and echocardiographic reports (n = 339). Functional health status was assessed using Short Form-36 (SF-36) surveys (n = 396) indexed to normative data. Risk of reoperation was low (≈1%/year) but increased beyond age 40 years. At latest follow-up moderate or severe pulmonary regurgitation was common (54%) and right ventricular outflow tract stenosis presented in 1/3. Consequently, evidence of right ventricular dilatation and dysfunction and tricuspid regurgitation was typical. Left-sided abnormalities were also common: hypertrophy (p <0.0001) and outflow tract dilation (p <0.0001) with at least mild aortic regurgitation in >50%. Cardiorespiratory symptoms were reported in 45% (palpitations 27%, dyspnea 21%, chest pain 17%). SF-36 scores were significantly below normal for 4 physical domains (p <0.001). Decrements in physical functioning were associated particularly with older age at follow-up (p <0.0001), associated syndromes/lesions, reoperations, ventricular dysfunction, tricuspid regurgitation, residual septal defects, and cardiorespiratory symptomatology. Echocardiographic abnormalities were more common in older patients (p <0.0001). All 3 SF-36 domains specific to psychosocial well-being were normal. In conclusion, despite excellent survival prospects, physical compromise is common in adults with repaired TOF. Greater decrements in older patients may reflect late deterioration with advancing age or cohort effects related to historical management. Efforts to limit ventricular and outflow tract dysfunction may translate into improved late functional status.

Usefulness of Minimal Luminal Coronary Area Determined by Intravascular Ultrasound to Predict Functional Significance in Stable and Unstable Angina Pectoris - Corrected Proof

2012-01-16

Little is known about the intravascular ultrasound (IVUS) minimal lumen area (MLA) criteria and their accuracy in lesion subsets assorted according to vessel type, lesion location, vessel size, and clinical settings. We therefore assessed the accuracy of subgroup-specific cut-off values in predicting fractional flow reserve (FFR) <0.80. In total 692 consecutive patients with 784 coronary lesions were assessed by IVUS and FFR before intervention. All patients had ≥1 target vessel with a de novo lesion (30% to 90% diameter stenosis). For prediction of FFR <0.80 in the group overall, the best cut-off value of MLA was 2.4 mm2 (sensitivity 84% and specificity 63%). Overall diagnostic accuracy was only 69%. In the subgroup analysis, the MLA cutoff was 2.4 mm2 for the left anterior descending coronary artery, 1.6 mm2 for the left circumflex coronary artery, and 2.4 mm2 for the right coronary artery. By lesion location, the optimal cutoff was 2.6 mm2 for proximal, 2.3 mm2 for mid, and 1.9 mm2 for distal segments. Furthermore, the cutoffs were 3.2 mm2 in lesions with a larger RLD >3.5 mm and 1.9 mm2 in lesions with a smaller RLD <2.75 mm. Nevertheless, diagnostic accuracies of all subgroup-specific criteria were <80%. In conclusion, because IVUS-measured MLA is only 1 of many factors affecting coronary flow hemodynamics, even subgroup-specific criteria were inaccurate in identifying ischemia-inducible stenosis. In conclusion, direct functional assessment is therefore essential in guiding treatment strategies for coronary lesions.

Effects of Swimming Training on Blood Pressure and Vascular Function in Adults >50 Years of Age - Corrected Proof

2012-01-16

Swimming is ideal for older adults because it includes minimum weight-bearing stress and decreased heat load. However, there is very little information available concerning the effects of regular swimming exercise on vascular risks. We determined if regular swimming exercise would decrease arterial blood pressure (BP) and improve vascular function. Forty-three otherwise healthy adults >50 years old (60 ± 2) with prehypertension or stage 1 hypertension and not on any medication were randomly assigned to 12 weeks of swimming exercise or attention time controls. Before the intervention period there were no significant differences in any of the variables between groups. Body mass, adiposity, and plasma concentrations of glucose and cholesterol did not change in either group throughout the intervention period. Casual systolic BP decreased significantly from 131 ± 3 to 122 ± 4 mm Hg in the swimming training group. Significant decreases in systolic BP were also observed in ambulatory (daytime) and central (carotid) BP measurements. Swimming exercise produced a 21% increase in carotid artery compliance (p <0.05). Flow-mediated dilation and cardiovagal baroreflex sensitivity improved after the swim training program (p <0.05). There were no significant changes in any measurements in the control group that performed gentle relaxation exercises. In conclusion, swimming exercise elicits hypotensive effects and improvements in vascular function in previously sedentary older adults.

A Pulmonary Hypertension Gas Exchange Severity (PH-GXS) Score to Assist With the Assessment and Monitoring of Pulmonary Arterial Hypertension - Corrected Proof

Paul R. Woods, Bryan J. Taylor, Robert P. Frantz, Bruce D. Johnson — 2012-01-16

Submaximal exercise gas analysis may be a useful method to assess and track pulmonary arterial hypertension (PAH) severity. The aim of the present study was to develop an algorithm, using exercise gas exchange data, to assess and monitor PAH severity. Forty patients with PAH participated in the study, completing a range of clinical tests and a novel submaximal exercise step test, which lasted 6 minutes and incorporated rest (2 minutes), exercise (3 minutes), and recovery (1 minute) ventilatory gas analysis. Using gas exchange data, including breathing efficiency, end-tidal carbon dioxide, oxygen saturation, and oxygen pulse, a pulmonary hypertension gas exchange severity (PH-GXS) score was developed. Patients were retested after about 6 months. There was significant separation between healthy controls and patients with moderate PAH (World Health Organization [WHO] class I/II) and those with more severe PAH (WHO class III/IV) for breathing efficiency, end-tidal carbon dioxide, oxygen saturation, and oxygen pulse. The PH-GXS score was significantly correlated with WHO class (r = 0.51), 6-minute walking distance (r = −0.59), right ventricular systolic pressure (r = 0.49), log N-terminal pro–B-type natriuretic peptide (r = 0.54), and pulmonary vascular resistance (r = 0.71). The PH-GXS score remained unchanged in 22 patients retested (1.50 ± 0.92 vs 1.48 ± 0.94), as did WHO class (2.3 ± 0.8 vs 2.3 ± 0.8) and 6-minute walking distance (455 ± 120 vs 456 ± 103 m). Small individual changes were observed in the PH-GXS score, with 8 patients improving and 8 deteriorating. In conclusion, the PH-GXS score differentiated between patients with PAH and was correlated with traditional clinical measures. The PH-GXS score was unchanged in our cohort after 6 months, consistent with traditional clinical metrics, but individual differences were evident. A PH-GXS score may be a useful way to track patient responses to therapy.

Age-Specific Gender Differences in In-Hospital Mortality by Type of Acute Myocardial Infarction - Corrected Proof

2012-01-16

Younger women hospitalized with an acute myocardial infarction (MI) have a poorer prognosis than men. Whether this is true for patients with acute ST-segment elevation MI (STEMI) and non-STEMI (NSTEMI) is not extensively studied. Using the MarketScan 2004 to 2007 Commercial and Medicare supplemental admission databases, we assessed gender differences in in-hospital mortality according to age in 91,088 patients (35,899 with STEMI, 55,189 with NSTEMI) who were 18 to 89 years old and had acute MI as their primary diagnosis. Patients with STEMI had significantly higher in-hospital mortality than those with NSTEMI (4.35% vs 3.53%, p <0.0001). Compared to men women were older, had higher co-morbidity scores, and were less likely to undergo revascularization during hospitalization in the STEMI and NSTEMI populations. In patients with STEMI the unadjusted women-to-men odds ratio for in-hospital mortality was 2.29 (95% confidence interval 1.48 to 3.55) for the 18- to 49-year age group, 1.68 (1.28 to 2.21) for 50 to 59, 1.48 (1.17 to 1.88) for 60 to 69, 1.28 (1.06 to 1.57) for 70 to 79, and 1.01 (0.83 to 1.23) for 80 to 89. Corresponding unadjusted odds ratios were 1.51 (0.87 to 2.61), 1.46 (1.11 to 1.92), 1.29 (1.04 to 1.61), 0.83 (0.70 to 0.99) and 0.82 (0.70 to 0.94) for patients with NSTEMI. After adjustment for potential confounding factors, excess risk for in-hospital mortality in younger women versus their men counterparts (<60 years old) persisted in STEMI. In patients with NSTEMI the difference between younger women and younger men was not statistically significant; however, older women (≥70 years old) had better survival than men. In conclusion, higher risk of in-hospital mortality in younger women compared to younger men is more evident in patients with STEMI.

Mitral Annular Calcium, Inducible Myocardial Ischemia, and Cardiovascular Events in Outpatients With Coronary Heart Disease (from the Heart and Soul Study) - Corrected Proof

2012-01-16

We sought to determine whether mitral annular calcium (MAC) is associated with inducible myocardial ischemia and adverse cardiovascular outcomes in ambulatory patients with coronary artery disease (CAD). MAC is associated with cardiovascular disease (CVD) in the general population, but its association with CVD outcomes in patients with CAD has not been evaluated. We examined the association of MAC with inducible ischemia and subsequent cardiovascular events in 1,020 ambulatory patients with CAD who were enrolled in the Heart and Soul Study. We used logistic regression to determine the association of MAC with inducible ischemia and Cox proportional hazards models to determine the association with CVD events (myocardial infarction, heart failure, stroke, transient ischemic attack or death). Models were adjusted for age, gender, race, smoking, history of heart failure, blood pressure, high-density lipoprotein, and estimated glomerular filtration rate. Of the 1,020 participants 192 (19%) had MAC. Participants with MAC were more likely than those without MAC to have inducible ischemia (adjusted odds ratio 2.06, 95% confidence interval 1.41 to 3.01, p = 0.0002). During an average of 6.26 ± 2.11 years of follow-up, there were 310 deaths, 161 hospitalizations for heart failure, 118 myocardial infarctions, and 55 cerebrovascular events. MAC was associated with an increased rate of cardiovascular events (adjusted hazard ratio 1.39, 95% confidence interval 1.08 to 1.79, p = 0.01). In conclusion, we found that MAC was associated with inducible ischemia and subsequent CVD events in ambulatory patients with CAD. MAC may indicate a high atherosclerotic burden and identify patients at increased risk for adverse cardiovascular outcomes.

Influence of Gender on Long-Term Mortality in Patients Presenting With Non–ST-Elevation Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention - Corrected Proof

2012-01-16

Although an invasive strategy has predominately been studied in men with non–ST-segment elevation acute coronary syndromes (NSTE-ACSs), its role in low-risk women is unclear. We sought to examine gender differences in a real-world registry of patients with NSTE-ACS who underwent percutaneous coronary intervention (PCI). Patients with NSTE-ACS undergoing PCI at the Cleveland Clinic, Cleveland, Ohio from 2003 through 2007 (n = 1,874) were included. In-hospital and long-term mortalities were assessed. Cox proportional hazards models were constructed to study the influence of gender on mortality. Interactions with age and biomarker status were examined. Women were older and had a higher incidence of co-morbid conditions compared to men. They had a smaller reference vessel diameter compared to men. Despite these characteristics there was no overall difference in in-hospital (1.4% vs 1.6%) or long-term (14.6% vs 15.8%) mortality between men and women. However, there was evidence of a significant effect modification by age (p = 0.012) and troponin status (p = 0.0073) for long-term mortality such that women <60 years of age, especially those who were troponin negative, had more than a twofold increase in long-term mortality compared to men (p = 0.007). In conclusion, although overall mortality rates are similar between men and women undergoing PCI for NSTE-ACS, women <60 years old with negative biomarkers have a higher mortality than their men peers.

Diabetes Mellitus, Myocardial Reperfusion, and Outcome in Patients With Acute ST-Elevation Myocardial Infarction Treated With Primary Angioplasty (from HORIZONS AMI) - Corrected Proof

2012-01-16

Diabetes mellitus (DM) increases mortality in acute ST-segment elevation myocardial infarction (STEMI) but the responsible mechanism is not fully elucidated. We compared the rate of successful myocardial reperfusion measured by tissue myocardial perfusion grade (TMPG) and outcomes in patients with and without DM undergoing primary percutaneous coronary intervention (PCI) for STEMI. Patients enrolled in the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS AMI) trial were analyzed according to presence of DM with respect to TMPG after PCI and outcomes at 30 days and 3 years. Multivariable logistic regression was performed to identify the independent contribution to mortality of DM and TMPG and the interaction between the 2 was assessed. Complete data were available for 3,265 patients, of whom 533 (16.3%) had DM. Diabetic patients were significantly older and heavier and had more risk factors for coronary disease and more previous MI, revascularization, and heart failure. There were no differences in rates of Thrombolysis In Myocardial Infarction grade 3 flow after PCI in the infarct artery or TMPG 2/3 between patients with and without DM. Compared to nondiabetics, mortality was significantly higher at 30 days and at 3 years in the DM group (1.8% vs 4.5%, p = 0.0002 and 5.4% vs 11.0%, p <0.0001, respectively). DM and TMPG were significantly associated with 3-year mortality, but there was no statistical interaction between DM and TMPG (p = 0.70). In conclusion, DM is associated with a significantly higher risk of death but this association is not mediated by impaired epicardial or myocardial reperfusion.

Comparison of Percutaneous Coronary Intervention Safety Before and During the Establishment of a Transradial Program at a Teaching Hospital - Corrected Proof

2012-01-16

This study sought to examine the safety of percutaneous coronary intervention (PCI) before and during de novo establishment of a transradial (TR) program at a teaching hospital. TR access remains underused in the United States, where cardiology fellowship programs continue to produce cardiologists with little TR experience. Establishment of TR programs at teaching hospitals may affect PCI safety. Starting in July 2009 a TR program was established at a teaching hospital. PCI-related data for academic years 2008 to 2009 (Y1) and 2009 to 2010 (Y2) were prospectively collected and retrospectively analyzed. Of 1,366 PCIs performed over 2 years, 0.1% in Y1 and 28.7% in Y2 were performed by TR access. No major complications were identified in 194 consecutive patients undergoing TR PCI, and combined bleeding and vascular complication rates were lower in Y2 versus Y1 (0.7% vs 2.0%, p = 0.05). Patients treated in Y2 versus Y1 and by TR versus transfemoral approach required slightly more fluoroscopy but similar contrast volumes and had similar procedural durations, lengths of stay, and predischarge mortality rates. PCI success rates were 97% in Y1, 97% in Y2, and 98% in TR cases. TR PCIs were performed by 13 cardiology fellows and 9 attending physicians, none of whom routinely performed TR PCI previously. In conclusion, de novo establishment of a TR program improved PCI safety at a teaching hospital. TR programs are likely to improve PCI safety at other teaching hospitals and should be established in all cardiology fellowship training programs.

Effect of Embolic Particles During Coronary Interventional Procedures on Regional Wall Motion in Patients With Stable Angina Pectoris - Corrected Proof

2012-01-16

Microembolization during percutaneous coronary intervention (PCI) causes minor myocardial injury, and a Doppler guidewire can detect embolic particles as high-intensity transient signals (HITS). The present study investigated the effect of microembolization during PCI on regional wall motion using a Doppler guidewire and myocardial strain analysis. We performed PCI to the left anterior descending coronary artery in 25 patients (18 men and 7 women, 68 ± 8 years old) with stable angina pectoris. Coronary flow spectrums were obtained with a Doppler guidewire to count the total number of HITS throughout the PCI procedures. On the days before and after PCI, we recorded echocardiography and measured the longitudinal peak systolic strain, peak strain rate, and early diastolic strain rate in the left anterior descending territory using a 2-dimensional speckle tracking method. PCI was successfully performed, and 10 ± 6 HITS (range 0 to 22, median 9) were recognized during PCI. The echocardiographic study showed no visible wall motion abnormalities in the left anterior descending territory either after or before PCI. In cases in which the total number of HITS was ≥10, the peak systolic strain, peak strain rate, and early diastolic strain rate worsened on the day after PCI compared with those on the day before PCI (p <0.01). The rates of change in peak systolic strain and early diastolic strain rate, defined as the ratios of those parameters after PCI to those before PCI, had modest to strong inverse correlations with the total number of HITS (R2 = 0.35 and R2 = 0.46, respectively). In conclusion, periprocedural microembolization during PCI reduces subclinical cardiac function in patients with stable angina pectoris.

Relation Between Estimated Glomerular Filtration Rate and Composition of Coronary Arterial Atherosclerotic Plaques - Corrected Proof

2012-01-16

It is well known that chronic kidney disease is a risk factor for atherosclerosis. The present study was conducted to identify any relation between the estimated glomerular filtration rate (eGFR) and coronary plaque characteristics using integrated backscatter intravascular ultrasound (IB–IVUS), which can detect coronary plaque composition. We performed IB–IVUS for 201 consecutive patients undergoing percutaneous coronary intervention, and they were divided into 3 groups according to the eGFR values (group 1 [n = 20], ≥90 ml/min/1.73 m2; group 2 [n = 123], 60 to 90 ml/min/1.73 m2; and group 3 [n = 58], <60 ml/min/1.73 m2). Coronary plaques in nonculprit lesions on 3-dimensional analysis were evaluated using IB–IVUS. The baseline characteristics were similar, except for older age and a greater prevalence of men in group 3. IB–IVUS showed a percentage of lipid volume of 44.7 ± 5.0% in group 1, 53.6 ± 6.2% in group 2, and 63.5 ± 6.2% in group 3 (p <0.01), with a corresponding percentage of fibrous volume of 53.9 ± 4.9%, 45.1 ± 6.0%, and 35.3 ± 6.1%, respectively (p <0.01). The eGFR correlated significantly with both parameters (r = −0.68, p <0.001 and r = 0.68, p <0.001, respectively). In conclusion, lower eGFR levels were associated with greater lipid and lower fibrous contents, contributing to coronary plaque vulnerability.

Meta-Analysis of Randomized Controlled Trials Comparing Intracoronary and Intravenous Administration of Glycoprotein IIb/IIIa Inhibitors in Patients With ST-Elevation Myocardial Infarction - Corrected Proof

Yongshi Wang, Boting Wu, Xianhong Shu — 2012-01-16

Glycoprotein IIb/IIIa receptor inhibitors (GPIs) have been widely adopted as an adjuvant regimen during primary percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction, but whether intracoronary administration of these potent antiplatelet agents conveys better efficacy and safety over the intravenous route has not been well addressed. A meta-analysis was performed by a systematic search of the published research for randomized controlled trials comparing intracoronary versus intravenous administration of GPIs in patients with ST-segment elevation myocardial infarction. Eight studies involving 686 patients in the intracoronary arm and 660 in the intravenous arm met the inclusion criteria. Postprocedural Thrombolysis In Myocardial Infarction (TIMI) grade 3 flow (odds ratio [OR] 1.46, 95% confidence interval [CI] 1.08 to 1.98, p <0.05) and myocardial reperfusion grade 2 or 3 (OR 1.78, 95% CI 1.29 to 2.46, p <0.001) were markedly more often achieved in patients who received intracoronary boluses of GPIs than those receiving the intravenous strategy. Intracoronary administration resulted in a reduced incidence of mortality (OR 0.44, 95% CI 0.21 to 0.92, p <0.05), target vessel revascularization (OR 0.53, 95% CI 0.29 to 0.99, p <0.05), and the composite end point of major adverse cardiac events (OR 0.48, 95% CI 0.31 to 0.76, p <0.005) at 30-day follow-up. No significant difference was found in terms of major or minor bleeding (OR 1.14, p = 0.71, and OR 0.86, p = 0.47 respectively). In conclusion, intracoronary administration of GPIs yielded favorable outcomes in postprocedural blood flow restoration and 30-day clinical prognosis in patients with ST-segment elevation myocardial infarction. The intracoronary use of GPIs can be recommended as a preferred regimen during primary percutaneous coronary intervention.

Six Year Follow-Up After Catheter Ablation of Atrial Fibrillation: A Palliation More Than a True Cure - Corrected Proof

Antonio Sorgente, Patricia Tung, Jack Wylie, Mark E. Josephson — 2012-01-16

Long-term outcomes after pulmonary vein isolation for atrial fibrillation (AF) remain uncertain. In particular, the influence of rigorous arrhythmia monitoring on outcomes is not yet clear. In this study, 103 patients with symptomatic AF who underwent catheter ablation at a single academic medical center from 2002 to 2006 were evaluated, with a median follow-up time of 6 years. The primary end point was the success rate of catheter ablation, defined as the absence of any atrial arrhythmia recurrence lasting >10 seconds at the clinical visit and electrocardiographic or long-term cardiac rhythm recording after a single procedure and after the last procedure. In all, 153 procedures were performed, with a median of 1 (interquartile range 1 to 2) per patient as follows: 61 had 1, 35 had 2, 6 had 3, and 1 had 4 catheter ablations. Freedom from all atrial arrhythmias was present in 23% of patients at 6 years after a single procedure and in 39% of patients after the last procedure. No clinical predictors of AF recurrence were recognized after a single procedure, whereas after the last procedure, in univariate and multivariate Cox regression analysis, only nonparoxysmal AF (hazard ratio 1.92, 95% confidence interval 1.07 to 3.47, p = 0.02) was a predictor of recurrence. In conclusion, AF recurrence at 6-year follow-up after catheter ablation in a selected group of patients with symptomatic drug-refractory AF was relatively high, with 2/3 of AF relapses occurring in the first year of follow-up. Strict clinical surveillance after catheter ablation should be considered to help guide clinical decisions.

United States National Prevalence of Electrocardiographic Abnormalities in Black and White Middle-Age (45- to 64-Year) and Older (≥65-Year) Adults (from the Reasons for Geographic and Racial Differences in Stroke Study) - Corrected Proof

2012-01-16

A United States national sample of 20,962 participants (57% women, 44% blacks) from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study provided general population estimates for electrocardiographic (ECG) abnormalities among black and white men and women. The participants were recruited from 2003 to 2007 by random selection from a commercially available nationwide list, with oversampling of blacks and those from the stroke belt, with a cooperation rate of 49%. The measurement of risk factors and 12-lead electrocardiograms (centrally coded using Minnesota code criteria) showed 28% had ≥1 major ECG abnormality. The prevalence of abnormalities was greater (≥35%) for those ≥65 years old, with no differences between blacks and whites. However, among men <65 years, blacks had more major abnormalities than whites, most notably for atrial fibrillation, major Q waves, and left ventricular hypertrophy. Men generally had more ECG abnormalities than women. The most common ECG abnormalities were T-wave abnormalities. The average heart rate-corrected QT interval was longer in women than in men, similar in whites and blacks, and increased with age. However, the average heart rate was greater in women than in men and in blacks than in whites and decreased with age. The prevalence of ECG abnormalities was related to the presence of hypertension, diabetes, blood pressure, and age. In conclusion, black men and women in the United States have a significantly greater prevalence of ECG abnormalities than white men and women at age 45 to 64 years; however, these proportions, although larger, tended to equalize or reverse after age 65.

Cardiologist in the Land of the Thunder Dragon: A Medical Mission to Bhutan - Corrected Proof

John Davis Cantwell — 2012-01-16

In recent years, I have been intrigued by reading about Bhutan (), the Shangri-La Himalayan kingdom wedged between India and China. When an opportunity arose to join the Flying Doctors of America medical mission there, I promptly volunteered, along with my wife, Marilyn.

Use and Outcomes of Multivessel Percutaneous Coronary Intervention in Patients With Acute Myocardial Infarction Complicated by Cardiogenic Shock (from the EHS-PCI Registry) - Corrected Proof

2012-01-12

The value of multivessel percutaneous coronary intervention (MV-PCI) in patients with cardiogenic shock (CS) and multivessel disease (MVD) is still unclear because randomized controlled trials are missing. Therefore, we sought to evaluate the impact of MV-PCI on in-hospital outcomes of patients with MVD presenting with CS: 336 patients with acute myocardial infarction complicated by CS and ≥70% stenoses in ≥2 major epicardial vessels were included in this analysis of the Euro Heart Survey PCI registry. Patients undergoing MV-PCI (n = 82, 24%) were compared to those with single-vessel PCI (n = 254, 76%). The rate of 3-vessel disease (60% vs 57%, p = 0.63) was similar in the 2 cohorts. Presentation with resuscitation (48 vs 46%, p = 0.76) and ST-segment elevation myocardial infarction (83 vs 87%, p = 0.31) was frequent in patients with MV-PCI and single-vessel PCI. Patients with ventilation were more likely to receive MV-PCI (30% vs 19%, p = 0.05). There was a tendency toward a higher hospital mortality in patients with MV-PCI (48.8% vs 37.4%, p = 0.07). After adjustment for confounding variables, no significant difference for in-hospital mortality (odd ratio [OR] 1.28, 95% confidence interval [CI] 0.72 to 2.28) could be observed between the 2 groups. Age (OR 1.41, 95% CI 1.13 to 1.77), 3-vessel disease (OR 1.78, 95% CI 1.04 to 3.03), ventilation (OR 3.01, 95% CI 1.59 to 5.68), and previous resuscitation (OR 2.55, 95% CI 1.48 to 4.39) were independent predictors of hospital death. In conclusion, MV-PCI is currently used in only 1/4 of patients with CS and MVD. An additional nonculprit PCI was not associated with a survival benefit in these high risk patients.

Comparison of the Diamond-Forrester Method and Duke Clinical Score to Predict Obstructive Coronary Artery Disease by Computed Tomographic Angiography - Corrected Proof

2012-01-12

We sought to evaluate the ability of the Diamond and Forrester method (DFM) and the Duke Clinical Score (DCS) to predict obstructive coronary artery disease (CAD) on coronary computed tomographic angiography (CCTA) and the effect of these different risk scores on the appropriateness level using the 2010 Appropriate Use Criteria. Consecutive symptomatic patients who underwent CCTA for evaluation of CAD (n = 114) were classified as having a low, intermediate, or high pretest probability using the DFM and DCS. Using the Appropriate Use Criteria, the indications for CCTA were classified according to the pretest probability and previous testing. The CCTA results were classified as revealing obstructive (≥70% stenosis), nonobstructive (<70%), or no CAD. When the patients' risk was classified using the DFM, 18% were low, 65% intermediate, and 17% high risk. When using the DCS, 53% of patients had a reclassification of their risk, most of whom changed from intermediate to either low or high risk (50% low, 19% intermediate, 35% high risk). The net reclassification improvement for the prediction of obstructive CAD was 51% (p = 0.01). Of the 37 patients who were reclassified as low risk, 36 (97%) lacked obstructive CAD. Appropriateness for CCTA was reclassified for 13% of patients when using the DCS instead of the DFM, and the number of appropriate examinations was significantly fewer (68% vs 55%, p <0.001). In conclusion, reclassification of risk using the DCS instead of the DFM resulted in improved prediction of obstructive CAD on CCTA, especially in low-risk patients. More patients were categorized as having a high pretest probability of CAD, resulting in reclassification of their examination indications as uncertain or inappropriate. These results identify the need for improved pretest risk scores for noninvasive tests such as CCTA and suggest that the method of risk assessment could have important implications for patient selection and quality assurance programs.

Comparison of Bleeding and In-Hospital Mortality in Asian-Americans Versus Caucasian-Americans With ST-Elevation Myocardial Infarction Receiving Reperfusion Therapy - Corrected Proof

2012-01-05

Concern has been raised that Asian-Americans may have a higher bleeding risk than Caucasian-Americans when treated with fibrinolytic and antithrombotic agents. To date there is limited evidence to support or refute this hypothesis or evaluate bleeding risk and its related outcomes in Caucasian-Americans versus Asian-Americans with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary interventions (PPCI). We evaluated Asian-Americans and Caucasian-Americans with STEMI receiving reperfusion therapy in the National Registry of Myocardial Infarction (NRMI) 4 and 5 (n = 90,317). We studied risk-adjusted major bleeding and in-hospital mortality. Major bleeding rates after fibrinolysis were similar in Asian-Americans (n = 705) and Caucasian-Americans (n = 42,243, 11.1% vs 10.3%, adjusted odds ratio [OR] 0.97, 95% confidence interval [CI] 0.69 to 1.36, p = 0.5002). Although the observed major bleeding rate was higher in Asian-Americans (n = 1,037) compared to Caucasian-Americans (n = 46,332) treated with PPCI (10.3% vs 7.8%, p = 0.0036), these rates differed only marginally after adjusting for baseline clinical variables (OR 1.24, 95% CI 0.97 to 1.59). Overall adjusted mortality was similar in Asian-Americans and Caucasian-Americans when treated with fibrinolysis (OR 0.96, 95% CI 0.56 to 1.65) or with PPCI (OR 1.35, 95% CI 0.85 to 2.13). Major bleeding after PPCI or fibrinolysis was associated with similar increased risks for mortality in these ethic groups. In conclusion, despite suggestions to the contrary, Asian-Americans with STEMI treated with fibrinolysis or PPCI had similar bleeding and bleeding-related mortality risks compared to Caucasian-Americans. Given the genotypic and phenotypic differences between the 2 cohorts, similar studies in the rapidly growing Asian-American population are needed to confirm our findings and to understand the safety and effectiveness of newer potent antiplatelet and antithrombotic agents in patients with coronary syndromes.

Meta-Analysis of Long-Term Outcomes for Drug-Eluting Stents Versus Bare-Metal Stents in Primary Percutaneous Coronary Interventions for ST-Segment Elevation Myocardial Infarction - Corrected Proof

2012-01-05

The use of drug-eluting stents (DESs) in primary percutaneous coronary intervention (PPCI) has shown early benefit over bare-metal stents (BMSs) in decreasing adverse cardiac events. However, there are concerns regarding the increased risk of late and very late stent thrombosis (ST) after DES use. With the paucity of ST events individual trials may have been underpowered to detect significant differences. We sought to perform a meta-analysis to evaluate the available literature examining the outcomes of DESs and BMSs in PPCI after ≥3 years of follow-up. We analyzed 8 randomized clinical trials (RCTs) and 5 observational studies comparing DESs to BMSs in PPCI. Clinical end-point data were analyzed for RCTs and observational studies separately using random-effect models. RCTs included 5,797 patients in whom first-generation DESs (sirolimus- or paclitaxel-eluting stents) were compared to BMS control arms. Patients receiving DESs had a significantly lower risk of target lesion revascularization (odds ratio [OR] 0.48, confidence interval [CI] 0.37 to 0.61), target vessel revascularization (OR 0.53, CI 0.42 to 0.66), and accordingly major adverse cardiac events (OR 0.69; CI 0.56 to 0.84). Incidence of ST was not different between groups (OR 1.02, CI 0.76 to 1.37). There was no significant difference in mortality (OR 0.88, CI 0.68 to 1.12) or recurrent myocardial infarction (OR 0.97; CI 0.61 to 1.54). Among observational studies (n = 4,650) fewer studies reported on target lesion revascularization and target vessel revascularization, but the trend remained in favor of DESs. A small but statistically significant increase in ST was noted with DES use (OR 1.62, CI 1.18 to 2.21) at ≥3 years of follow up, without evidence of recurrent myocardial infarction. Those receiving DESs had a significantly lower mortality compared to those receiving BMSs (OR, 0.65, 95% CI 0.53 to 0.80, p <0.001). In conclusion, this meta-analysis of RCTs examining the long-term outcomes of first-generation DESs versus BMSs in PPCI, DES use resulted in decreased repeat revascularization with no increase in ST, mortality, or recurrent myocardial infarction.

Coronary Artery Disease in Patients With Psoriasis Referred for Coronary Angiography - Corrected Proof

2012-01-05

Patients with psoriasis may have an increased risk of cardiovascular disease and myocardial infarction. The aim of this study was to investigate whether psoriasis is associated with an increased prevalence of coronary artery disease (CAD) independent of established cardiovascular risk factors in patients undergoing coronary angiography. A retrospective cohort analysis was performed by linking records of all patients undergoing coronary angiography from 2004 through 2009 with dermatology medical records. From an overall cohort of 9,473 patients, we identified 204 patients (2.2%) with psoriasis before coronary angiography. Patients with psoriasis had higher body mass index (31.3 ± 8.1 vs 29.3 ± 7.1 kg/m2, p <0.001) but the prevalence of other risk factors was similar. Median duration of psoriasis before cardiac catheterization was 8 years (interquartile range 2 to 24). Patients with psoriasis were more likely to have CAD (84.3% vs 75.7%, p = 0.005) at coronary angiography. After adjusting for established cardiovascular risk factors, psoriasis was independently associated with presence of angiographically confirmed CAD (adjusted odds ratio 1.8, 95% confidence interval 1.2 to 2.8, p = 0.006). In patients with psoriasis, duration of psoriasis >8 years was also independently associated with angiographically confirmed CAD after adjusting for established cardiovascular risk factors (adjusted odds ratio 3.5, 95% confidence interval 1.3 to 9.6, p = 0.02). In conclusion, patients with psoriasis and especially those with psoriasis for >8 years have a higher prevalence of CAD than patients without psoriasis undergoing coronary angiography.

Predictors of Ten-Year Event-Free Survival in Patients With Acute Myocardial Infarction (from the Adria, Bassano, Conegliano, and Padova Hospitals [ABC] Study on Myocardial Infarction) - Corrected Proof

2012-01-05

The long-term event-free survival (EFS) after acute myocardial infarction (AMI) is largely uninvestigated. We analyzed noninvasive clinical variables in association with long-term EFS after AMI. The present prospective study included 504 consecutive patients with AMI at 3 hospitals from 1995 to 1998 (Adria, Bassano, Conegliano, and Padova Hospitals [ABC] study). Thirty-seven variables were examined, including demographics, cardiovascular risk factors, in-hospital characteristics, and blood components. The end point was 10-year EFS. Logistic and Cox regression models were used to identify the predictive factors. We compared 3 predictive models according to the goodness of fit and C-statistic analyses. At enrollment, the median age was 67 years (interquartile range 58 to 75), 29% were women, 38% had Killip class >1, and the median left ventricular ejection fraction was 51% (interquartile range 43% to 60%). The 10-year EFS rate was 19%. Both logistic and Cox analyses identified independent predictors, including young age (hazard ratio 1.2, 95% confidence interval 1.1 to 1.3, p = 0.0006), no history of angina (hazard ratio 1.4, 95% confidence interval 1.1 to 1.8, p = 0.009), no previous myocardial infarction (hazard ratio 1.4, 95% confidence interval 1.1 to 1.7, p = 0.01), high estimated glomerular filtration rate (hazard ratio 0.8, 95% confidence interval 0.7 to 0.9, p = 0.001), low albumin/creatinine excretion ratio (hazard ratio 1.2, 95% confidence interval 1.1 to 1.3, p <0.0001), and high left ventricular ejection fraction (hazard ratio 0.8, 95% confidence interval 0.7 to 0.9, p = 0.006). These variables had greater predictive power and improved the predictive power of 2 other models, including Framingham cardiovascular risk factors and the recognized predictors of acute heart damage. In conclusion, 10-year EFS was strongly associated with 4 factors (ABC model) typically neglected in studies of AMI survival, including estimated glomerular filtration rate, albumin/creatinine excretion ratio, a history of angina, and previous myocardial infarction. This model had greater predictive power and improved the power of 2 other models using traditional cardiovascular risk factors and indicators of heart damage during AMI.

Relations Between QRS|T Angle, Cardiac Risk Factors, and Mortality in the Third National Health and Nutrition Examination Survey (NHANES III) - Corrected Proof

2012-01-05

On the surface electrocardiogram, an abnormally wide QRS|T angle reflects changes in the regional action potential duration profiles and in the direction of the repolarization sequence, which is thought to increase the risk of ventricular arrhythmia. We investigated the relation between an abnormal QRS|T angle and mortality in a nationally representative sample of subjects without clinically evident heart disease. We studied 7,052 participants ≥40 years old in the third National Health and Nutrition Examination Survey with 12-lead electrocardiograms. Those with self-reported or electrocardiographic evidence of a previous myocardial infarction, QRS duration of ≥120 ms, or history of heart failure were excluded. Borderline and abnormal spatial QRS|T angles were defined according to gender-specific 75th and 95th percentiles of frequency distributions. All-cause (1,093 women and 1,191 men) and cardiovascular (462 women and 455 men) mortality during the 14-year period was assessed through linkage with the National Death Index. On multivariate analyses, an abnormal spatial QRS|T angle was associated with an increased hazard ratio (HR) for cardiovascular mortality in women (HR 1.82, 95% confidence interval 1.05 to 3.14) and men (HR 2.21, 95% confidence interval 1.32 to 3.68). Also, the multivariate adjusted HR for all-cause mortality associated with an abnormal QRS|T angle was 1.30 (95% confidence interval 0.95 to 1.78) for women and 1.87 (95% confidence interval 1.29 to 2.7) for men. A borderline QRS|T angle was not associated with an increased risk of all-cause or cardiovascular mortality. In conclusion, an abnormal QRS|T angle, as measured on a 12-lead electrocardiogram, was associated with an increased risk of cardiovascular and all-cause mortality in this population-based sample without known heart disease.

Relation of the Utility of Exercise Testing for Risk Assessment in Pediatric Patients With Ventricular Preexcitation to Pathway Location - Corrected Proof

David S. Spar, Eric S. Silver, Allan J. Hordof, Leonardo Liberman — 2012-01-05

The gradual loss of ventricular preexcitation during exercise stress testing (EST) has an unclear risk of an association with life-threatening arrhythmia and could be related to the accessory pathway (AP) location. We compared the loss of preexcitation during EST with the risk assessment during invasive electrophysiology testing and determined whether the loss of preexcitation correlates with the AP location. We retrospectively reviewed patients aged ≤21 years with ventricular preexcitation who had undergone both EST and an electrophysiology study. The patients were divided into 3 groups: sudden loss (SL), gradual loss (GL), or no loss (NL) of preexcitation during EST. A total of 76 patients were included, with 11 (14%) in the SL group, 18 (24%) in the GL group, and 47 (62%) in the NL group. The SL group demonstrated a longer cycle length with 1-to-1 conduction by way of the AP during incremental atrial pacing compared with the NL group (375 ± 135 ms vs 296 ± 52 ms, p = 0.002), with no difference between the GL and NL groups (325 ± 96 vs 296 ± 52 ms, p = NS). Of the patients with 1-to-1 AP conduction of <270 ms, none (0 of 11) were in the SL group compared to 18 of 47 in the NL group (p = 0.0017), with no significant difference in the GL group (5 of 18) compared to the NL group (p = NS). The patients in the GL group were more likely to have a left-sided AP (14 of 18) than the NL group (17 of 47, p = 0.002) and the SL group (3 of 11, p = 0.002). In conclusion, a sudden loss of preexcitation during an EST predicted a long cycle length with 1-to-1 conduction by way of the AP. Also, the AP conduction characteristics in patients with GL compared to those with NL did not differ, and the GL of preexcitation was more frequently seen in patients with a left-sided AP.

Cardiorespiratory Fitness and Metabolic Risk - Corrected Proof

2012-01-05

The present study sought to evaluate the relation between cardiovascular risk factors and cardiorespiratory fitness (CRF) in a large population. Low CRF has been associated with increased total mortality and cardiovascular mortality. The mechanisms underlying greater cardiovascular mortality have not yet been determined. A series of cardiovascular risk factors were measured in 59,820 men and 22,192 women who had undergone determinations of CRF with maximal exercise testing. The risk factor profiles were segregated into 5 quintiles of CRF. With decreasing CRF, increases occurred in obesity, triglycerides, non–high-density lipoprotein cholesterol, triglyceride/high-density lipoprotein ratios, blood pressure, metabolic syndrome, diabetes, and cigarette smoking. Self-reported physical activity declined with decreasing levels of CRF. In conclusion, it appears likely that the enrichment of cardiovascular risk factors, especially metabolic risk factors, account for a portion of the increased cardiovascular mortality in low-fitness subjects. The mechanisms responsible for this enrichment in subjects with a low CRF represent a challenge for future research.

Height and Risk of Heart Failure in the Physicians' Health Study - Corrected Proof

2012-01-05

Although previous studies have reported an association between height and cardiovascular disease, it is unclear whether height is associated with the risk of heart failure (HF). We hypothesized that height would be inversely associated with HF risk. We used prospective data from 22,042 male physicians (mean age 53.8 years) from the Physicians' Health Study. Height was self-reported at baseline. Incident HF was ascertained using follow-up questionnaires and validated through review of the medical records in a subsample. The Cox proportional hazard model was used to compute the hazard ratio (HR) and corresponding 95% confidence interval (CI). The mean height ± SD was 1.78 ± 0.07 m. A total of 1,444 HF cases occurred during a mean follow-up of 22.3 years. Compared to subjects in the lowest height category (1.40 to 1.73 m), the HR for HF was 0.86 (95% CI 0.74 to 0.99), 0.82 (95% CI 0.70 to 0.95), and 0.76 (95% CI 0.63 to 0.91) for the height categories of 1.74 to 1.78 m, 1.79 to 1.83 m, and 1.84 to 2.08 m, respectively, after adjustment for age, weight, hypertension, and diabetes mellitus (p for trend = 0.0023). The HR per SD increment in height was 0.92 (95% CI 0.86 to 0.98) in a fully adjusted model. The exclusion of those with prevalent atrial fibrillation, left ventricular hypertrophy, valvular heart disease, and a history of coronary artery bypass grafting yielded similar results (HR per SD 0.88, 95% CI 0.83 to 0.94). In conclusion, our data demonstrated an inverse association between height and incident HF in United States male physicians. Additional studies to elucidate the underlying biologic mechanisms are warranted.

Follow-Up with Exercise Test of Effort-Induced Ventricular Arrhythmias Linked to Ryanodine Receptor Type 2 Gene Mutations - Corrected Proof

2012-01-05

The aim of this study was to assess exercise test results and efficacy of therapy with a β blocker (acebutolol) in ryanodine receptor type 2 (RyR2) mutation carriers with documented ventricular arrhythmias (VAs) and long-term follow-up. Twenty RyR2 mutation carriers belonging to 8 families and regularly followed at our center were analyzed using a study protocol involving electrocardiography, exercise tests off and on β-blocker therapy, 2-dimensional echocardiography, and signal-averaged electrocardiography. Off-therapy exercise testing triggered the onset of VAs at different heart rates (mean 132 ± 13 beats/min) with various patterns that worsened while exercising and disappeared immediately after stopping. The most severe VAs detected were nonsustained ventricular tachycardia in 35% and ventricular couplets in 35%. In the remaining subjects single ventricular premature beats were recorded. In 15% of patients single monomorphic ventricular premature beats were detected and identified to be linked to RyR2 mutations owing to the presence of sudden deaths of their family members and subsequent family screening. Acebutolol made the VAs disappear completely in 20% of subjects and decreased their complexity in 50%, whereas it did not change VAs appreciably in 30% of patients with less complex VAs. After 11 ± 8 years of follow-up 2 patients developed syncope. In conclusion, exercise testing was a fundamental tool for assessing the clinical phenotype and efficacy of therapy in RyR2 mutation carriers and therapy with acebutolol led in most subjects to a decreased complexity of the arrhythmic pattern or to complete suppression.

Cost–Effectiveness of Clopidogrel Plus Aspirin for Stroke Prevention in Patients With Atrial Fibrillation in Whom Warfarin Is Unsuitable - Corrected Proof

2012-01-05

Guidelines for atrial fibrillation (AF) recommend clopidogrel plus aspirin as an alternative stroke prevention strategy in patients in whom warfarin is unsuitable. A Markov model was conducted from a Medicare prospective using data from the Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events–A (ACTIVE-A) trial and other published studies. Base-case analysis evaluated patients 65 years old with AF, a CHADS2 (congestive heart failure, 1 point; hypertension defined as blood pressure consistently >140/90 mm Hg or antihypertension medication, 1 point; age ≥75 years, 1 point; diabetes mellitus, 1 point; previous stroke or transient ishemic attack, 2 points) score of 2, and a lower risk for major bleeding. Patients received clopidogrel 75 mg/day plus aspirin or aspirin alone. Patients were followed for up to 35 years. Outcomes included quality-adjusted life-years (QALYs), costs (in 2011 American dollars), and incremental cost–effectiveness ratios. Quality-adjusted life expectancy and costs were 9.37 QALYs and $88,751 with clopidogrel plus aspirin and 9.01 QALYs and $79,057 with aspirin alone. Incremental cost–effectiveness ratio for clopidogrel plus aspirin was $26,928/QALY. With 1-way sensitivity analysis using a willingness-to-pay threshold of $50,000/QALY, clopidogrel plus aspirin was no longer cost effective when the CHADS2 score was ≤1, major bleeding risk with aspirin was ≥2.50%/patient-year, the relative risk decrease for ischemic stroke with clopidogrel plus aspirin versus aspirin alone was <25%, and the utility of being healthy with AF on combination therapy decreased to 0.95. Monte Carlo simulation demonstrated that clopidogrel plus aspirin was cost effective in 55% and 73% of 10,000 iterations assuming willingness-to-pay thresholds of $50,000 and $100,000/QALY. In conclusion, clopidogrel plus aspirin appears cost-effective compared to aspirin alone for stroke prevention in patients with AF with a CHADS2 of ≥2 and a lower risk of bleeding.

Relation of Impaired Coronary Microcirculation to Increased Urine Albumin Excretion in Patients With Systemic Hypertension and No Epicardial Coronary Arterial Narrowing - Corrected Proof

2012-01-05

Coronary flow reserve (CFR) is impaired and urinary albumin excretion is increased in patients with essential hypertension. Our aim was to investigate the associations between CFR and cardiac and renal damage in hypertensives. For this purpose we studied 37 never-treated hypertensives (57.9 years old, 16 men) without chest pain but with a positive ischemia stress test result and normal coronary arteries on coronary angiogram. CFR was calculated by a 0.014-inch Doppler guidewire (Flowire, Volcano, San Diego) in the left anterior descending artery in response to bolus intracoronary administration of adenosine (60 μg) as the ratio of hyperemic to basal average peak velocity of the distal vessel. All participants underwent complete echocardiographic study including left ventricular diastolic function evaluation by tissue Doppler imaging (peak early diastolic velocity/peak atrial systolic velocity) and determination of the albumin-to-creatinine ratio (ACR). Hypertensives with low CFR (<2.5, n = 22) compared to those with high CFR (n = 15) exhibited a larger left ventricular mass index by 10.9 g/m2 (p = 0.045) and ACR values by 10 mg/g (p <0.001). CFR was negatively correlated with logACR (r = −0.511, p = 0.001). LogACR (beta −0.792, p <0.001), male gender (beta 0.313, p = 0.005), left ventricular mass index (beta −0.329, p = 0.007), and peak early diastolic velocity/peak atrial systolic velocity (beta 0.443, p <0.001) were the only independent predictors of CFR in linear regression analysis (adjusted R2 = 0.672). In conclusion, never-treated asymptomatic hypertensives who exhibit impaired CFR and angiographically normal epicardial arteries are characterized by intrarenal vascular damage as reflected by increased ACR. These findings suggest a plausible role of ACR estimation in the identification of hypertensive subjects with early coronary microvascular dysfunction.

Computerized Tomographic Quantification of Chronic Obstructive Pulmonary Disease as the Principal Determinant of Frontal P Vector - Corrected Proof

Lovely Chhabra, Pooja Sareen, Amit Gandagule, David Spodick — 2012-01-05

Verticalization of the P-wave axis is characteristic of chronic obstructive pulmonary disease (COPD). We studied the correlation of P-wave axis and computerized tomographically quantified emphysema in patients with COPD/emphysema. Individual correlation of P-wave axis with different structural types of emphysema was also studied. High-resolution computerized tomographic scans of 23 patients >45 years old with known COPD were reviewed to assess the type and extent of emphysema using computerized tomographic densitometric parameters. Electrocardiograms were then independently reviewed and the P-wave axis was calculated in customary fashion. Degree of the P vector (DOPV) and radiographic percent emphysematous area (RPEA) were compared for statistical correlation. The P vector and RPEA were also directly compared to the forced expiratory volume at 1 second. RPEA and the P vector had a significant positive correlation in all patients (r = +0.77, p <0.0001) but correlation was very strong in patients with predominant lower lobe emphysema (r = +0.89, p <0.001). Forced expiratory volume at 1 second and the P vector had almost a linear inverse correlation in predominantly lower lobe emphysema (r = −0.92, p <0.001). DOPV positively correlated with radiographically quantified emphysema. DOPV and RPEA were strong predictors of qualitative lung function in patients with predominantly lower lobe emphysema. In conclusion, a combination of high DOPV and predominantly lower lobe emphysema indicates severe obstructive lung dysfunction in patients with COPD.

Comparison of the Effect on Long-Term Outcomes in Patients With Thoracic Aortic Aneurysms of Taking Versus Not Taking a Statin Drug - Corrected Proof

2012-01-05

The potential of medical therapy to influence the courses and outcomes of patients with thoracic aortic aneurysms is not known. The aim of this study was to determine whether statin intake is associated with improved long-term outcomes in these patients. A total of 649 patients with thoracic aortic aneurysms were studied, of whom 147 were taking statins at their first presentation and 502 were not. After a median follow-up period of 3.6 years, 30 patients (20%) taking statins had died, compared with 167 patients (33%) not taking statins (hazard ratio 0.68, 95% confidence interval 0.46 to 1, p = 0.049); 87 patients (59%) taking statins reached the composite end point of death, rupture, dissection, or repair compared with 378 patients (75%) not taking statins (hazard ratio 0.72, 95% confidence interval 0.57 to 0.91, p = 0.006). After adjustments for co-morbidities, the association between statin therapy and the composite end point was driven mainly by a reduction in aneurysm repairs (hazard ratio 0.57 95% confidence interval 0.4 to 0.83, p = 0.003). On Kaplan-Meier analysis, the survival rate of patients taking statins was significantly better (p = 0.047). In conclusion, the intake of stains was associated with an improvement in long-term outcomes in this cohort of patients with thoracic aortic aneurysms. This was driven mainly by a reduction in aneurysm repairs.

Comparison of Pro-Atrial Natriuretic Peptide and Atrial Remodeling in Marathon Versus Non-Marathon Runners - Corrected Proof

Matthias Wilhelm, Jean-Marc Nuoffer, Jean-Paul Schmid, Ilca Wilhelm, Hugo Saner — 2012-01-05

Long-term endurance sports are associated with atrial remodeling and an increased risk for atrial fibrillation (AF) and atrial flutter. Pro–atrial natriuretic peptide (pro-ANP) is a marker of atrial wall tension and elevated in patients with AF. The aim of this study was to test the hypothesis that atrial remodeling would be perpetuated by repetitive episodes of atrial stretching during strenuous competitions, reflected by elevated levels of pro-ANP. A cross-sectional study was performed on nonelite runners scheduled to participate in the 2010 Grand Prix of Bern, a 10-mile race. Four hundred ninety-two marathon and nonmarathon runners applied for participation, 70 were randomly selected, and 56 entered the final analysis. Subjects were stratified according to former marathon participations: a control group (nonmarathon runners, n = 22), group 1 (1 to 4 marathons, n = 16), and group 2 (≥5 marathons, n = 18). Results were adjusted for age, training years, and average weekly endurance training hours. The mean age was 42 ± 7 years. Compared to the control group, marathon runners in groups 1 and 2 had larger left atria (25 ± 6 vs 30 ± 6 vs 34 ± 7 ml/m2, p = 0.002) and larger right atria (27 ± 7 vs 31 ± 8 vs 35 ± 5 ml/m2, p = 0.024). Pro-ANP levels at baseline were higher in marathon runners (1.04 ± 0.38 vs 1.42 ± 0.74 vs 1.67 ± 0.69 nmol/L, p = 0.006). Pro-ANP increased significantly in all groups after the race. In multiple linear regression analysis, marathon participation was an independent predictor of left atrial (β = 0.427, p <0.001) and right atrial (β = 0.395, p = 0.006) remodeling. In conclusion, marathon running was associated with progressive left and right atrial remodeling, possibly induced by repetitive episodes of atrial stretching. The altered left and right atrial substrate may facilitate atrial arrhythmias.

Relation of Systemic-to-Pulmonary Artery Collateral Flow in Single Ventricle Physiology to Palliative Stage and Clinical Status - Corrected Proof

2012-01-05

Systemic–to–pulmonary collateral arteries (SPCs) are common in patients with single-ventricle physiology, but their impact on clinical outcomes is unclear. The aim of this study was to use retrospective cardiac magnetic resonance data to determine the relation between SPC flow and palliative stage and clinical status in single-ventricle physiology. Of 116 patients, 78 were after Fontan operation (median age 19 years) and 38 were at an earlier palliative stage (median age 2 years). SPC flow was quantified as aortic flow minus total caval flow or total pulmonary vein flow minus total branch pulmonary artery flow. Median SPC flow/body surface area (BSA) was higher in the pre-Fontan group (1.06 vs 0.43 L/min/m2, p <0.0001) and decreased nonlinearly with increasing age after the Fontan operation (r2 = 0.17, p <0.0001). In the Fontan group, patients in the highest quartile of SPC flow had larger ventricular end-diastolic volume/BSA (p <0.0001) and were older at the time of Fontan surgery (p = 0.04), but SPC flow/BSA was not associated with heart failure symptoms, atrial or ventricular arrhythmias, atrioventricular valve regurgitation, the ventricular ejection fraction, or peak oxygen consumption. In multivariate analysis of all patients (n = 116), higher SPC flow was independently associated with pre-Fontan status, unilateral branch pulmonary artery stenosis, a diagnosis of hypoplastic left-heart syndrome, and previous catheter occlusion of SPCs (model r2 = 0.37, p <0.0001). In conclusion, in this cross-sectional study of single-ventricle patients, BSA-adjusted SPC flow was highest in pre-Fontan patients and decreased after the Fontan operation with minimal clinical correlates aside from ventricular dilation.