American Journal of Cardiology - Articles in Press

Safety of “Bridging” With Eptifibatide for Patients With Coronary Stents Before Cardiac and Non-Cardiac Surgery - Corrected Proof

2012-05-16

Patients with previously implanted coronary stents are at risk for stent thrombosis if dual-antiplatelet therapy is prematurely discontinued. Bridging with a glycoprotein IIb/IIIa inhibitor has been advocated as an alternative, with few supporting data. The aim of this study was to determine the safety of such a strategy by retrospectively analyzing bleeding in 100 consecutive patients with previously implanted coronary stents who were bridged to surgery with eptifibatide after discontinuing thienopyridine therapy. A propensity-matched control comparison was performed for a subgroup of 71 patients who underwent cardiovascular surgery. Blood transfusions were required in 65% in the bridged group versus 66% in the control group (p = 0.86). The mean numbers of units transfused were 4.84 ± 6.93 and 3.65 ± 7.46, respectively (p >0.25). Rates of return to the operating room for bleeding or tamponade were 10% and 2.9%, respectively (p = 0.085). Increased rates of transfusion were noted for patients who received concomitant aspirin and/or intravenous heparin infusion. In conclusion, there does not appear to be any increase in the need for blood transfusions or rate of return to the operating room for patients being bridged with eptifibatide when thienopyridines are discontinued in the perioperative period, but concomitant use of additional antiplatelet or anticoagulant agents may increase transfusions and delays to surgery. Clinicians who are considering this strategy must weigh the risks of stent thrombosis versus bleeding.

Meta-Analysis of Cytochrome P450 2C19 Polymorphism and Risk of Adverse Clinical Outcomes Among Coronary Artery Disease Patients of Different Ethnic Groups Treated With Clopidogrel - Corrected Proof

2012-05-16

Loss-of-function (LOF) variants of cytochrome P450 2C19 (CYP2C19) have been hypothesized to be associated with lesser degrees of platelet inhibition and increased risk for recurrent ischemic events in patients with coronary artery disease on clopidogrel therapy; however, studies from Western countries have yielded mixed results. We aimed to assess the impact of CYP2C19 LOF variants on clinical outcomes from different ethnic groups. Sixteen prospective cohort studies including 7,035 patients carrying ≥1 CYP2C19 LOF allele and 13,750 patients with the wild-type genotype were included in this meta-analysis. Carriers of ≥1 CYP2C19 LOF allele were at significantly higher risk for adverse clinical events compared to noncarriers during clopidogrel therapy (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.13 to 1.78). The summary OR showed a significant association between CYP2C19 LOF variants and an increased risk of cardiac death (OR 2.18, 95% CI 1.37 to 3.47), myocardial infarction (OR 1.42, 95% CI 1.12 to 1.81), and stent thrombosis (OR 2.41, 95% CI 1.76 to 3.30). Stratified analysis by ethnicity of study population suggested higher odds of adverse clinical events in the Asian population with LOF variants of CYP2C19 (OR 1.89, 95% CI 1.32 to 2.72) compared to Western populations (OR 1.28, 95% CI 1.00 to 1.64). In conclusion, carrier status for LOF CYP2C19 is associated with an increased risk of adverse clinical events in patients with coronary artery disease on clopidogrel therapy despite differences in clinical significance according to ethnicity.

Predictors of Atrial Fibrillation Termination and Clinical Success of Catheter Ablation of Persistent Atrial Fibrillation - Corrected Proof

2012-05-16

The termination of persistent atrial fibrillation (AF) during catheter ablation has been associated in some, but not all, studies with reduced arrhythmia during clinical follow-up. We sought to determine the rate of persistent AF termination achievable with a stepwise ablation strategy, the predictors of AF termination, and the clinical outcomes associated with termination and nontermination. A total of 143 consecutive patients (age 62 ± 9 years, AF duration 5.7 ± 5.2 years) with persistent and longstanding persistent AF resistant to antiarrhythmic medication who presented in AF for catheter ablation were studied. Ablation was done with a stepwise approach, including pulmonary vein isolation, followed by complex fractionated atrial electrogram ablation and ablation of resultant atrial tachycardias. Clinical follow-up was then performed after a 2-month blanking period to assess arrhythmia recurrence, defined as AF or atrial tachycardia lasting ≥30 seconds. AF termination by ablation was achieved in 95 (66%) of the 143 patients. Multivariate predictors of AF termination included longer baseline AF cycle length (p <0.001) and smaller left atrial size (p = 0.002). AF termination by ablation was associated with both a lower incidence of arrhythmia recurrence after a single procedure without antiarrhythmic drugs (p = 0.01) and overall clinical success (single or multiple procedures, with or without antiarrhythmic drugs; p = 0.005). On multivariate analysis, the predictors of overall clinical success included AF termination by ablation (p = 0.001), a shorter ablation duration (p = 0.002), younger age (p = 0.02), male gender (p = 0.03), and the presence of hypertension (p = 0.03). In conclusion, among patients with persistent AF, termination of AF by ablation can be achieved in most patients and is associated with reduced recurrence of arrhythmia.

Cardiac Transplantation in Patients With Hypertrophic Cardiomyopathy - Corrected Proof

2012-05-16

Cardiac transplantation is a treatment option for patients with hypertrophic cardiomyopathy (HC) who developed refractory heart failure and/or intractable arrhythmia. However, the pretransplant characteristics and post-transplant prognosis for patients with nondilated idiopathic HC has not yet fully elucidated. Therefore, we retrospectively reviewed 813 consecutive transplant recipients undergoing cardiac transplantation at Columbia University Medical Center from 1999 to 2010 and compared the clinical course of 41 patients with idiopathic HC with that of 373 patients with ischemic heart disease and 398 patients with other heart disease. The patients with HC were younger than those with ischemic heart disease (47.8 ± 14.0 vs 57.1 ± 9.4 years; p <0.0001). The proportion of patients undergoing ventricular assist devise surgery for bridge-to-transplant was lower in patients with HC than in those with ischemic heart disease or other heart disease (14.6% vs 31.1% vs 35.7%, all p <0.01). The post-transplant survival of those with HC was better than that for those with ischemic heart disease (90.1% vs 85.8% and 83.9% vs 67.1% at 1 and 5 years, respectively; p = 0.0359), although it was not significantly different from those with other heart disease. Proportional hazards analysis revealed that the subjects with HC had reduced post-transplant mortality (hazard ratio 0.4760, 95% confidential interval 0.1889 to 0.9762; p = 0.042) on univariate, but not multivariate, analysis. Most patients with HC had nondilated left ventricles (left ventricular end-diastolic dimension ≤55 mm; n = 27), and post-transplant survival did not differ from that for those with dilated left ventricles (left ventricular end-diastolic dimension >55 mm; n = 14). In conclusion, the post-transplant survival of those with HC did not differ from those of the subjects who underwent transplant for other non-HC indications.

Outcome of Noncardiac and Nonvascular Surgery in Patients With Mechanical Heart Valves - Corrected Proof

2012-05-16

There is a tendency to avoid noncardiac surgery in patients with mechanical heart valves (MHVs) owing to the increased risk of perioperative thromboembolism, infective endocarditis, and bleeding. We aimed to determine the risk of cardiac and noncardiac complications in patients with MHVs who underwent noncardiothoracic, nonvascular surgery. A total of 140 patients with MHVs (77 aortic, 46 mitral, and 17 double valve) and 1,200 patients with native valves (control group) were prospectively followed up for a minimum of 3 months after noncardiothoracic and nonvascular surgery. Patients with bioprostheses were excluded. Those patients aged >18 years who underwent an elective, non-outpatient, open surgical procedure were enrolled. Subcutaneous enoxaparin 1 mg/kg, twice daily, was used as bridging anticoagulation. The demographics, co-morbidities, and preoperative (medications, echocardiographic findings, laboratory results) and postoperative data were evaluated for their association with the occurrence of perioperative adverse events. The incidence of perioperative adverse cardiovascular (10.8% vs 10.7%, p = 0.985) and noncardiovascular (11.9% vs 11.4%, p = 0.989) events was similar in those patients with and without MHVs. Bleeding (18.6% vs 14.2%, p = 0.989), thromboembolism (3.6% vs 2%, p = 0.989), and mortality at 3 months (1.4% vs 1.3%, p = 0.825) were also similar for the 2 groups. In conclusion, with close follow-up and strict adherence to the guidelines, patients with MHVs and patients with native heart valves undergoing noncardiac and nonvascular surgery have a similar risk of mortality and morbidity.

Meta-Analysis Comparing Bivalirudin Versus Heparin Monotherapy on Ischemic and Bleeding Outcomes After Percutaneous Coronary Intervention - Corrected Proof

2012-05-16

With femoral access, bivalirudin decreases risks of major bleeding after percutaneous coronary intervention (PCI) and provides better net clinical benefit compared to unfractionated heparin (UFH) plus planned glycoprotein IIb/IIIa inhibitors. Whether this benefit exists compared to UFH monotherapy is less clear. We performed a systematic review and meta-analysis to compare outcomes in patients undergoing transfemoral PCI with UFH or bivalirudin. Randomized trials (n = 3) and observational studies (n = 13) comparing bivalirudin to UFH monotherapy were reviewed. Primary outcomes were 30-day rates of major adverse cardiovascular events (MACEs) including death, myocardial infarction (MI), urgent revascularization, as well as all-cause mortality, MI, major bleeding, and blood transfusion. We collected data from 16 studies involving 32,492 patients undergoing PCI. Most observational studies were performed in the United States, whereas all randomized trials were done in Europe. Compared to UFH monotherapy, bivalirudin was associated with similar risk of MACEs (odds ratios [OR] 0.92, 95% confidence interval [CI] 0.75 to 1.12), a substantial 45% relative decrease in major bleeding (OR 0.55, 95% CI 0.43 to 0.72), and a trend in the decrease of transfusion (OR 0.87, 95% CI 0.70 to 1.08). A decrease in mortality was seen in observational studies (OR 0.62, 95% CI 0.45 to 0.85) but remained inconclusive in randomized trials (OR 0.63, 95% CI 0.20 to 2.01). MI rate was similar with the 2 anticoagulants. In conclusion, in patients undergoing transfemoral PCI, the benefit of bivalirudin over UFH monotherapy is driven by a significant decrease in major bleeding with similar rates of MACE. As PCI practice moves toward other bleeding-avoidance strategies such as the radial approach, future studies should focus on the interaction between anticoagulant strategy and access-site choice.

Importance of Physical Fitness on Predictive Effect of Body Mass Index and Weight Gain on Incident Atrial Fibrillation in Healthy Middle-Age Men - Corrected Proof

2012-05-14

The incidence of both atrial fibrillation (AF) and obesity is increasing in the community, and lifestyle intervention is recommended. We aimed to test whether the predictive effect of body mass index (BMI) and weight change from age 25 years to midlife on incident AF were influenced by physical fitness. In 1972 to 1975, 2,014 healthy middle-age men conducted a bicycle exercise electrocardiographic test as a part of a cardiovascular survey program, defining physical fitness as work performed divided by body weight. During 35 years of follow-up, 270 men developed AF, documented by scrutiny of the health files in all Norwegian hospitals. Risk estimation was analyzed using Cox proportional hazard models and tested for age-adjusted physical fitness above and below the median. The mean BMI of 24.6 kg/m2 defined a lean baseline cohort. The men with a baseline BMI of ≥28 kg/m2 (11%) compared to a BMI <28 kg/m2 had a 1.68-fold risk of AF (95% confidence interval 1.14 to 2.40) and men reporting weight gain of ≥10 kg (24%) compared to weight loss (11%) of 1.66-fold (95% confidence interval 1.00 to 2.89), respectively. The dichotomy into men with age-adjusted physical fitness above and below the median, demonstrated statistically significant risk associations only for men with low fitness. The overall risk of AF was reduced by 23% in the fit men. In conclusion, within our lean baseline cohort of healthy middle-age men, a BMI of ≥28 kg/m2 and weight gain of ≥10 kg from age 25 to midlife were long-term predictors of incident AF in men with physical fitness below the population median. The fit men had an overall slightly reduced risk of AF.

Comparison of Safety and Efficacy of Bivalirudin Versus Unfractionated Heparin in High-Risk Patients Undergoing Percutaneous Coronary Intervention (from the Anti-Thrombotic Strategy for Reduction of Myocardial Damage During Angioplasty–Bivalirudin vs Heparin Study)† - Corrected Proof

2012-05-14

Bivalirudin, a direct thrombin inhibitor, is as effective as unfractionated heparin (UFH), with decreased bleeding in patients with acute coronary syndromes who undergo percutaneous coronary intervention (PCI). The aim of this study was to evaluate the effectiveness of bivalirudin versus UFH in selected PCI patients at high bleeding risk. Four hundred one consecutive patients who underwent PCI fulfilling ≥1 enrollment criterion (age >75 years, chronic renal failure, and diabetes mellitus) were randomized to bivalirudin (bolus 0.75 mg/kg followed by infusion during the procedure; n = 198) or UFH (75 IU/kg; n = 203). In the overall population, 39% were aged >75 years, 22% had renal failure, 63% had diabetes, and 29% had acute coronary syndromes. The primary efficacy end point was the 30-day incidence of major adverse cardiac events (cardiac death, myocardial infarction, stent thrombosis, or target vessel revascularization). The primary safety end point was the occurrence of any bleeding or entry-site complications after PCI. All patients were preloaded with clopidogrel 600 mg. Glycoprotein IIb/IIIa inhibitors were used at the operators' discretion. Thirty-day major adverse cardiac event rates were 11.1% in the bivalirudin group and 8.9% in the UFH group (p = 0.56); the primary efficacy end point was reached mainly because of periprocedural myocardial infarction; 1 patient in the bivalirudin group had stent thrombosis. Occurrence of the primary safety end point was 1.5% in the bivalirudin group and 9.9% in the UFH group (p = 0.0001); this benefit was essentially driven by the prevention of entry-site hematomas >10 cm (0.5% vs 6.9%, p = 0.002). In conclusion, Anti-Thrombotic Strategy for Reduction of Myocardial Damage During Angioplasty–Bivalirudin vs Heparin (ARMYDA-7 BIVALVE) indicates that bivalirudin, compared with UFH, causes significantly lower bleeding and has a similar incidence of major adverse cardiac events in patients with older age, diabetes mellitus, or chronic renal failure who undergo PCI.

Relation Between Angiographic Lesion Severity, Vulnerable Plaque Morphology and Future Adverse Cardiac Events (from the Providing Regional Observations to Study Predictors of Events in the Coronary Tree Study) - Corrected Proof

2012-05-14

Previous angiographic studies have suggested that the future risk for major adverse cardiovascular events (MACEs) is related to coronary stenosis severity. The aim of this study was to use the grayscale and virtual histology (VH)–intravascular ultrasound (IVUS) data from the Providing Regional Observations to Study Predictors of Events in the Coronary Tree (PROSPECT) study to identify underlying lesion morphologic characteristics that might explain these findings. In PROSPECT, patients presenting with acute coronary syndromes in whom percutaneous coronary intervention was successful underwent 3-vessel grayscale and VH-IVUS and were followed for a median of 3.4 years for the incidence of MACEs. Overall, 3,115 nonculprit lesions detected by IVUS were divided into quartiles according to baseline angiographic diameter stenosis. From the first to fourth quartiles, there were increases in the prevalence of lesions with IVUS minimum luminal areas ≤4 mm2, IVUS plaque burden ≥70%, and VH-IVUS thin-cap fibroatheroma (13.4%, 22.0%, 24.2%, and 30.3%, respectively, p <0.001), along with an increased frequency of plaque ruptures and greater necrotic core volumes. The incidence of lesions with plaque burden ≥70%, minimum luminal area ≤4 mm2, and VH thin-cap fibroatheroma was highest in the fourth quartile (0%, 0.4%, 0.4%, and 2.8% in the first through fourth quartiles, respectively, p <0.001). Three-year MACE rates were also highest in the fourth quartile (0.3%, 0.7%, 1.3%, and 5.1%, respectively, p <0.001). In conclusion, increasing angiographic diameter stenosis was associated with an increased frequency of grayscale and VH-IVUS lesion morphologic features that have been associated with adverse events and that may, in part, explain why future MACEs were related to baseline lesion severity.

Influence of Resting Heart Rate on Mortality in Patients Undergoing Coronary Angiography (from the Ludwigshafen Risk and Cardiovascular Health [LURIC] Study) - Corrected Proof

2012-05-14

Several epidemiologic studies have reported an association between elevated heart rate (HR) at rest and reduced survival. The usefulness of HR at rest in predicting end points in high-risk patients is yet to be definitively established. The purpose of this study was to clarify the relation between HR at rest with total and cardiovascular mortality in patients who underwent coronary angiography. A total of 3,316 Caucasian patients with available coronary angiograms were prospectively followed from 2001 to 2011 (median 9.9 years). The effect of HR at rest on total and cardiovascular mortality was explored, while correcting for a number of confounders. Patients in the highest quartile (HR at rest ≥84 beats/min) had survival times reduced by 1.2 and 1.4 years for overall and cardiovascular mortality, respectively. Likewise, these patients had significantly elevated adjusted risk for total (hazard ratio 1.39, 95% confidence interval 1.17 to 1.67, p for trend <0.001) and cardiovascular mortality (hazard ratio 1.38, 95% confidence interval 1.08 to 1.78, p for trend = 0.004). In conclusion, HR at rest is an inexpensive, easily measured, and modifiable predictor of mortality.

Comparison of Frequency of Complications With On-Label Versus Off-Label Use of Rotational Atherectomy - Corrected Proof

2012-05-14

Although rotational atherectomy (RA) is used for complex lesions in percutaneous coronary intervention, there are several contraindications and precautions. The purpose of our study was to compare complications between off-label and on-label use of RA. We identified 250 consecutive patients who underwent RA. Off-label characteristics included saphenous vein graft lesions, presence of thrombus, unprotected left main stenosis, coronary artery dissection, acute myocardial infarction (MI), left ventricular dysfunction, 3-vessel disease, long lesion (≥25 mm), or angulated lesion (≥45°). Patients who had ≥1 off-label characteristic were assigned to the off-label group (156 patients), and patients who had no off-label characteristics were assigned to the on-label group (94 patients). Occurrence of slow flow or periprocedural MI in the off-label group was higher than that in the on-label group (slow flow 30% vs 18%, p = 0.06; MI 8.8% vs 2.1%, p = 0.04), whereas severe complications such as burr entrapment, transection of the guidewire, or perforation were rare in the 2 groups. In conclusion, compared to the on-label group, the off-label group had a higher incidence of slow flow and periprocedural MI. Severe complications such as burr entrapment, transection of the guidewire, or perforation were rare in the 2 groups.

Early Readmissions After Percutaneous Coronary Intervention in a Rural Tertiary Care Center (from the Guthrie Health Off-Label Stent [GHOST] Registry) - Corrected Proof

Kishore J. Harjai, Maninder Singh, Judy Boura — 2012-05-14

Early readmissions (ERs) impose a huge cost to the health care system, lower patients' quality of life, and may be an indicator of quality of initial care. We performed this single-center study to assess the incidence, predictors, and implications of 30-day readmission after percutaneous coronary intervention (PCI) in a tertiary care rural setting. In 4,262 consecutive patients who underwent PCI, we evaluated 30-day readmission rates and assessed demographic, clinical, and angiographic correlates of ER. Using Cox regression analyses, we estimated the multivariable impact of an ER on 1-year all-cause mortality and major adverse events (MACEs; death, myocardial infarction, target vessel revascularization, stent thrombosis). ER occurred in 486 patients (11.4%) including 366 (8.6%) for cardiac reasons and 120 (2.8%) for noncardiac reasons. Multivariable models predicting any readmission, cardiac readmission, and noncardiac readmission had c-statistic values of 0.63, 0.63, and 0.68, respectively. One-year mortality and MACEs were higher in the readmitted versus not readmitted patients (7.9% vs 3.2%, 18 vs 9.7%, p <0.0001 for the 2 comparisons). ER had a significant and independent impact on 1-year mortality (adjusted hazards ratio 2.2, 95% confidence interval 1.4 to 3.4) and MACEs (hazards ratio 2.2, 95% confidence interval 1.8 to 2.8). In conclusion, readmission within 30 days after PCI is common and frequently related to cardiac causes. Patients who require an ER after PCI have higher 1-year mortality and MACEs.

Epicardial Adipose Tissue as a Predictor of Coronary Artery Disease in Asymptomatic Subjects - Corrected Proof

Gil N. Bachar, Dror Dicker, Ran Kornowski, Eli Atar — 2012-05-14

This study sought to elucidate the relation between epicardial adipose tissue (EAT) thickness measured by multidetector computed tomography and presence of coronary artery atherosclerosis. Recent studies have suggested that fat disposition in visceral organs and epicardial tissue could serve as a predictor of coronary artery disease (CAD). The sample included 190 asymptomatic subjects with ≥1 cardiovascular risk factor who were referred for cardiac computed tomographic angiography. Body mass index, blood pressure, fasting glucose level, and lipid profile were measured. Multidetector computed tomographic results were analyzed for atherosclerosis burden, calcium Agatston score, and EAT thickness: mean EAT values were 3.54 ± 1.59 mm in patients with atherosclerosis and 1.85 ± 1.28 mm in patients without atherosclerosis (p <0.001). On receiver operating characteristic analysis, an EAT value ≥2.4 mm predicted the presence of significant (>50% diameter) coronary artery stenosis. There was a significant difference in EAT values between patients with and without metabolic syndrome (2.58 ± 1.63 vs 2.04 ± 1.46 mm, p <0.05) and between patients with a calcium score >400 and <400 (3.38 ± 1.58 vs 2.02 ± 1.42 mm, p <0.0001). In conclusion, asymptomatic patients with CAD have significantly more EAT than patients without CAD. An EAT thickness of 2.4 mm is the optimal cutoff for prediction of presence of significant CAD.

Comparison of Coronary Calcium Screening Versus Broad Statin Therapy for Patients at Intermediate Cardiovascular Risk - Corrected Proof

2012-05-14

Net reclassification has become widely accepted as a method to demonstrate whether new diagnostic technologies add significantly to the discrimination of risk. However, more accurate categorization of risk does not necessarily result in a better clinical outcome. This study examined whether coronary artery calcium, a technology that improves net reclassification in patients at intermediate risk for cardiovascular events, is superior to a strategy that calls for broader intervention with statin therapy in these patients. To do so, the clinical impact and costs of 2 intervention regimens on outcome in the Multi-Ethnic Study of Atherosclerosis (MESA) were calculated based on the known efficacy of statins. Intervention 1 involved treatment of all subjects at conventional intermediate risk with moderate-dose stain, whereas intervention 2 involved moderate- and high-dose statin therapy, respectively, of those remaining at intermediate risk and those reassigned to high risk after reclassification by coronary artery calcium. The 2 strategies would decrease clinical events by 23% and would produce net savings. However, these would be greater with the broad statin prevention strategy than with the coronary calcium reclassification strategy ($732,152 vs $288,336, respectively). In conclusion, even in the short term, the broad statin prevention strategy would be at least as effective in decreasing clinical events but with greater net savings than a prevention strategy using coronary calcium screening.

Red Blood Cell Membrane Concentration of cis-Palmitoleic and cis-Vaccenic Acids and Risk of Coronary Heart Disease - Corrected Proof

Luc Djoussé, Nirupa R. Matthan, Alice H. Lichtenstein, John M. Gaziano — 2012-05-14

Although previous studies have suggested associations between plasma palmitoleic acid and coronary heart disease (CHD) risk factors, including blood pressure, inflammation, and insulin resistance, little is known about the relation of palmitoleic acid and CHD. This ancillary study of the Physicians' Health Study was designed to examine whether red blood cell (RBC) membrane cis-palmitoleic acid and cis-vaccenic acid—2 fatty acids that can be synthesized endogenously—are associated with CHD risk. We used a risk set sampling method to prospectively select 1,000 incident CHD events and 1,000 matched controls. RBC membrane fatty acids were measured using gas chromatography. The CHD cases were ascertained using an annual follow-up questionnaire and validated by an End Point Committee through a review of the medical records. In a conditional logistic regression analysis adjusting for demographics, anthropometric, lifestyle factors, and co-morbidity, the odds ratios and 95% confidence intervals (CIs) for CHD were 1.0 (referent), 1.29 (95% CI 0.95 to 1.75), 1.08 (95% CI 0.78 to 1.51), 1.25 (95% CI 0.90 to 1.75), and 1.48 (95% CI 1.03 to 2.14) across consecutive quintiles of RBC membrane cis-palmitoleic acid (p for trend = 0.041). The odds ratio associated with each SD higher RBC membrane cis-palmitoleic acid level was 1.19 (95% CI 1.06 to 1.35) in a multivariate-adjusted model. Finally, RBC membrane cis-vaccenic acid was inversely associated with CHD risk (odds ratio 0.79, 95% CI 0.69 to 0.91, per SD increase). In conclusion, our data showed a positive association between RBC membrane cis-palmitoleic acid and CHD risk in male physicians. Furthermore, RBC membrane cis-vaccenic acid was inversely related to CHD.

Comparison of Outcomes of Illicit Drug Users and Nonusers Hospitalized With Heart Failure - Corrected Proof

Ahmad M. Slim, Hillary Thomas, Roy Parish, Ishak Mansi — 2012-05-14

The long-term effects of illicit drug use (IDU) on the clinical outcome of patients with heart failure (HF) are not well described. The objective of the present study was to describe the characteristics of patients with HF who used illicit drugs and to determine the effects of IDU on the clinical outcomes such as in-hospital mortality and hospital readmission for HF. A retrospective cohort study was conducted that included all patients admitted with HF from June 2003 to September 2004 and followed up until 2008 at a university hospital serving an at-risk population. The patients were divided into 2 groups: IDU and non-IDU according to self-reported use or positive laboratory results. The outcome measures were in-hospital mortality, HF readmission rate, interval to readmission for HF, and average brain natriuretic peptide and troponin levels throughout the follow-up period. Of 646 reviewed records, 542, representing 357 patients, were included in the present analysis. Of the 357 patients, 53 patients were in the IDU group and 304 were in the non-IDU group. Kaplan-Meier log-rank analysis and Cox proportional hazard analysis showed that IDU was associated with a shorter interval to readmission for HF (hazard ratio 3.8, 95% confidence interval 2.3 to 10.7, p <0.0001) but not with in-hospital mortality (hazard ratio 0.7, 95% confidence interval 0.3 to 1.7, p = 0.4). Multiple linear regression analysis identified IDU as an independent variable for the HF readmission rate (p = 0.0001) but not for average brain natriuretic peptide or average troponin levels. In conclusion, the results of the present study have demonstrated that IDU was associated with a decreased interval to readmission for HF and greater HF readmission rates.

Prediction of Outcome by Highly Sensitive Troponin T in Outpatients With Chronic Systolic Left Ventricular Heart Failure - Corrected Proof

2012-05-14

Our aim was to assess the prognostic impact of a high-sensitivity cardiac troponin T (hs-cTnT) assay in an outpatient population with chronic systolic left ventricular heart failure (HF). Four hundred sixteen patients with chronic HF and left ventricular ejection fraction ≤45% were enrolled in a prospective cohort study. In addition to hs-cTnT, plasma amino-terminal pro–B-type natriuretic peptide was measured at baseline. Mean age was 71 years, 29% were women, 62% had coronary artery disease (CAD), mean left ventricular ejection fraction was 31%, and 57% had abnormal level of hs-cTnT. During 4.4 years of follow-up, 211 (51%) patients died. In multivariate Cox regression models, hs-cTnT was categorized as quartiles or dichotomized by the 99th percentile of a healthy population. Adjusted hazard ratios for all-cause mortality for quartiles 2 to 4, with quartile 1 as reference, were 1.4 (95% confidence interval 0.9 to 2.4, p = 0.16) for quartile 2, 1.7 (0.9 to 2.5, p = 0.12) for quartile 3, and 2.6 (1.6 to 4.4, p <0.001) for quartile 4 and 1.7 (1.2 to 2.5, p = 0.003) for abnormal versus normal level of hs-cTnT. In patients without CAD, quartile 4 of hs-cTnT was associated with an adjusted hazard ratio of 6.8. In conclusion, hs-cTnT is increased in most outpatients with chronic systolic HF and carries prognostic information beyond clinical parameters and amino-terminal pro–B-type natriuretic peptide. Increased hs-cTnT indicated a particularly deleterious prognosis in patients without CAD.

Cardiac Troponins in Young Marathon Runners - Corrected Proof

Natthapon Traiperm, Hannes Gatterer, Maria Wille, Martin Burtscher — 2012-05-14

Cardiac troponin increases are common in adult marathon finishers. However, data on troponin values for young marathon runners are scarce. Forty young runners (20 healthy male and 20 female) 13 to 17 years old participated in this study. Blood samples were taken before, immediately after, and 24 hours after the race for determination of cardiac troponin T (cTnT) and troponin I (cTnI). Thirty-seven runners completed the race with a mean finishing time of 4 hours 53 minutes. No participant developed an adverse medical event during or after the race. In 30 of 37 participants, levels of cTnT and/or cTnI exceeded upper reference limits of 0.01 and 0.1 ng/ml immediately after the race, and in 3 participants these levels were even higher than the reference range for acute myocardial infarction (>0.1 and >0.5 ng/ml for cTnT and cTnI, respectively). Twenty-four hours after the race no participant had troponin levels exceeding the upper reference limits. Average increases of troponin levels did not differ between sexes. In conclusion, this is the first study to show that cardiac troponin levels increase to a similar extent in male and female adolescent marathon runners as observed in adults. Rapid recovery of troponin levels after a race is indicative of a physiologic rather than a pathologic response.

Acute and Long-Term Outcomes of Catheter Ablation Using Remote Magnetic Navigation in Patients With Congenital Heart Disease - Corrected Proof

2012-05-10

The aim of the present study was to assess the feasibility, safety, and long-term results of remote magnetic navigation in arrhythmias associated with complex congenital heart disease (CHD). The improved outcomes for CHD resulted in an increased number of complex arrhythmias requiring distinctive ablation techniques. Thirty-six patients with CHD (age 35 ± 19 years, 21 male) were divided into 3 complexity groups and underwent 43 radiofrequency catheter ablation procedures using the magnetic navigation system (including 7 redo ablations) in combination with the CARTO RMT system. A total of 59 tachyarrhythmias were identified. Most patients had surgical scar-related tachycardia (25 focal, including 4 microreentrant atrial tachycardia, and 27 macroreentrant atrial tachycardia). Four accessory pathways and three ventricular tachycardias were diagnosed and treated. In 31 patients, ablation was successful, with an end point of noninducibility (86%). The success rate for CHD complexity of type I, II, and III was 50%, 88%, and 89%, respectively. The mean procedure and fluoroscopy time was 216 ± 101 minutes and 40 ± 34 minutes, respectively. The number of radiofrequency applications was 42 ± 47. No major complications related to the procedures occurred. Of the patients, 67% remained free of recurrence during a mean follow-up of 26 ± 4 months. Recurrence developed in 0%, 16%, and 45% of patients with CHD type I, II, and III, respectively. In conclusion, the magnetic navigation system is feasible to treat arrhythmias with reasonable success rates and good long-term outcomes in adult patients with CHD. The use of the magnetic navigation system offers advantages in complex anatomic situations.

Impact of Drug Eluting Stent Length on Outcomes of Percutaneous Coronary Intervention (from the EVENT Registry) - Corrected Proof

2012-05-07

In randomized trials, longer drug-eluting stent (DES) length has been associated with adverse clinical events. We used data from the EVENT registry to examine the impact of DES length on outcomes in routine clinical practice. We identified 5,425 unselected consecutive patients from the EVENT registry who had a single vessel treated with DES for nonemergency indications from 2004 through 2007. The association between stented length and short- and long-term outcomes was analyzed in ordinal categories (<15, 15 to 19, 20 to 24, and >24 mm) and as a continuous variable. There were few differences in baseline characteristics across categories. At 1 year, there was a stepwise increase in major adverse cardiac events (composite of death, myocardial infarction [MI], and target lesion revascularization [TLR]) with increasing stent length (8.0%, 10.1%, 11.8%, and 14.8%, p <0.001) and a similar relation with TLR (3.0%, 3.1%, 3.3%, and 5.0%, p = 0.02). After adjusting for demographic, clinical, angiographic, and treatment characteristics, longer stent length remained associated with 1-year major adverse cardiac events (adjusted hazard ratio 1.17 per 10-mm increase stent length) and TLR (hazard ratio 1.20 per 10 mm), but not with stent thrombosis. In conclusion, longer DES length is associated with increased adverse events, predominantly periprocedural MI, but also an increased rate of TLR.

Serum High-Density Lipoprotein Cholesterol Levels as a Prognostic Indicator in Patients With Idiopathic Pulmonary Arterial Hypertension - Corrected Proof

2012-05-07

High-density lipoprotein (HDL) cholesterol levels are a strong, independent inverse predictor of cardiovascular disease. The present study aimed to determine whether serum HDL cholesterol levels correlated with disease severity and clinical outcomes in patients with idiopathic pulmonary arterial hypertension (IPAH). The serum HDL cholesterol levels were measured in 76 Chinese patients with IPAH and 45 healthy controls, together with other clinical variables. Univariate and multivariate Cox proportional hazards analysis was performed to assess the prognostic value of HDL cholesterol and event-free survival. Event-free survival was estimated using the Kaplan-Meier method. Serum HDL cholesterol levels were significantly decreased in patients with IPAH compared with controls (1.0 ± 0.3 vs 1.5 ± 0.3 mmol/L; p <0.001). The serum HDL cholesterol levels decreased in proportion to the severity of World Health Organization functional class. Compared to the high HDL cholesterol group, the low HDL cholesterol group demonstrated a significantly lower 6-minute walking distance, cardiac index, mixed venous saturation, and arterial carbon dioxide pressure but significantly greater pulmonary vascular resistance and serum uric acid levels. The serum HDL cholesterol levels correlated positively with the cardiac index (r = 0.42; p = 0.002) and negatively with the pulmonary vascular resistance (r = −0.25; p = 0.04). Serum HDL cholesterol was independently related to event-free survival on multivariate Cox proportional hazards analysis. Kaplan-Meier survival curves according to the median HDL cholesterol value showed that lower HDL cholesterol levels were associated with lower event-free survival. In conclusion, serum HDL cholesterol levels might serve as an indicator of disease severity and prognosis in patients with IPAH.

Usefulness of Left Ventricular End-Systolic Dimension by Echocardiography to Predict Reverse Remodeling in Patients With Newly Diagnosed Severe Left Ventricular Systolic Dysfunction - Corrected Proof

Pradeep K. Bhat, Mahi L. Ashwath, David S. Rosenbaum, Ottorino Costantini — 2012-05-03

In many patients with left ventricular (LV) systolic dysfunction, the LV ejection fraction (LVEF)—a surrogate for reverse remodeling—fails to improve despite optimal medical therapy. The early identification of such patients would allow instituting aggressive treatment, including early therapy with implantable cardioverter defibrillators. We sought to establish the predictors of reverse remodeling in patients with LV systolic dysfunction receiving optimal medical therapy. Patients (n = 568) with newly documented LVEF of ≤0.35, who had ≥1 follow-up echocardiogram after ≥3 months, were evaluated. Reverse remodeling was defined as improvement in LVEF to >0.35. The clinical, laboratory, and echocardiographic data were compared between patients with (n = 263) and without (n = 305) reverse remodeling. The mean follow-up was 27 ± 16 months. Patients who demonstrated reverse remodeling had a significantly greater mean follow-up LVEF (0.51 ± 0.09 vs 0.25 ± 0.08; p <0.001). On multivariate analysis, the baseline LV end-systolic diameter index was the strongest predictor of reverse remodeling (odds ratio 5.79; 95% confidence interval 1.82 to 18.46; p <0.001). Other independent predictors of reverse remodeling were female gender (odds ratio 1.88; 95% confidence interval 1.19 to 2.98; p = 0.007), and nonischemic cardiomyopathy (odds ratio 1.65; 95% confidence interval 1.05 to 2.58; p = 0.03). Baseline LVEF was not an independent predictor of reverse remodeling. In conclusion, among patients with newly diagnosed LV systolic dysfunction, the LV end-systolic diameter index, but not the LVEF, at diagnosis, was a strong predictor of reverse remodeling. Patients with a low likelihood of reverse remodeling might benefit from more aggressive heart failure therapy, including the possible early use of implantable cardioverter defibrillators.

Effect of Glycemic Control on Response to Antiplatelet Therapy in Patients With Diabetes Mellitus and ST-Segment Elevation Myocardial Infarction - Corrected Proof

2012-05-01

Impaired glycemic control (GC) is a troubling clinical condition with an unclear prognostic value that is frequent in diabetics, especially in the setting of acute coronary syndrome. Residual platelet reactivity can be also affected by GC. We evaluated the relation between response to dual antiplatelet therapy and GC in diabetics with STEMI treated with primary coronary angioplasty (PCI). Sixty diabetic patients were prospectively enrolled in the study. All patients were treated with clopidogrel and aspirin. Platelet reactivity (whole blood aggregation and phosphorylation of vasodilator-stimulated phosphoprotein, VASP) were assessed serially before and 24 hours, 7 days, and 30 days after the PCI. Blood glucose >8.5 mmol/L on admission was an independent predictor of a impaired clopidogrel response measured with platelet reactivity index (PRI) >50% on admission (OR 7.8, 95% CI 1.4-17.7, p<0.02) and 24 hours after PCI (OR 13.1, 95% CI 3.4-28.1, p<0.01). In conclusion, diabetic patients with STEMI and glycemia >8.5 mmol/L on admission is related to a poorer response to clopidogrel. There were no interaction between glycated hemoglobin level or glycemia on admission and platelet reactivity measured with collagen, arachidonic acid or thrombin receptor agonist peptide-induced aggregation. Further clinical studies of the role of GC in the efficacy of antiplatelet agents are warranted.

Meta-Analysis of Accuracy of Left Ventricular Mass Measurement by Three-Dimensional Echocardiography - Corrected Proof

Yuichi J. Shimada, Takahiro Shiota — 2012-04-30

Left ventricular (LV) hypertrophy is a fundamental prognostic factor in a variety of cardiac diseases. Three-dimensional echocardiography (3DE) has achieved better estimation of LV mass than 2-dimensional echocardiography. However, significant underestimation has often been reported, and no previous study has synthesized these data. The aim of this meta-analysis was to investigate if there has been improvement in the accuracy in LV mass measurement by 3DE over time. Studies comparing LV mass between 3DE and magnetic resonance imaging were eligible. A cumulative meta-analysis was performed to investigate improvement in accuracy, followed by subgroup and meta-regression analysis to reveal factors affecting the bias. A total of 25 studies including 671 comparisons were analyzed. Studies published in or before 2004 showed high heterogeneity (I2 = 69%) and significant underestimation of LV mass by 3DE (−5.7 g, 95% confidence interval −11.3 to −0.2, p = 0.04). Studies published from 2005 to 2007 were still heterogenous (I2 = 60%) but showed less systematic bias (−0.5 g, 95% confidence interval −2.5 to 1.5, p = 0.63). In contrast, studies published in or after 2008 were highly homogenous (I2 = 3%) and showed excellent accuracy (−0.1 g, 95% confidence interval −2.2 to 1.9, p = 0.90). Investigation of factors affecting the bias revealed that evaluation of cardiac patients compared to healthy volunteers led to larger bias (p <0.05). In conclusion, this meta-analysis elucidates the underestimation of LV mass by 3DE, its improvement over the past decade, and factors affecting the bias. These data provide a more detailed basis for improving the accuracy of 3DE, an indispensable step toward further clinical application.

Therapeutic Hypothermia for Acute Myocardial Infarction and Cardiac Arrest - Corrected Proof

2012-04-30

This report focuses on cardioprotection and describes the advantages and disadvantages of various methods of inducing therapeutic hypothermia (TH) with regard to neuroprotection and cardioprotection for patients with cardiac arrest and ST-segment elevation myocardial infarction (STEMI). TH is recommended in cardiac arrest guidelines. For patients resuscitated after out-of-hospital cardiac arrest, improvements in survival and neurologic outcomes were observed with relatively slow induction of TH. More rapid induction of TH in patients with cardiac arrest might have a mild to modest incremental impact on neurologic outcomes. TH drastically reduces infarct size in animal models, but achievement of target temperature before reperfusion is essential. Rapid initiation of TH in patients with STEMI is challenging but attainable, and marked infarct size reductions are possible. To induce TH, a variety of devices have recently been developed that require additional study. Of particular interest is transcoronary induction of TH using a catheter or wire lumen, which enables hypothermic reperfusion in the absence of total-body hypothermia. At present, the main methods of inducing and maintaining TH are surface cooling, endovascular heat-exchange catheters, and intravenous infusion of cold fluids. Surface cooling or endovascular catheters may be sufficient for induction of TH in patients resuscitated after out-of-hospital cardiac arrest. For patients with STEMI, intravenous infusion of cold fluids achieves target temperature very rapidly but might worsen left ventricular function. More widespread use of TH would improve survival and quality of life for patients with out-of-hospital cardiac arrest; larger studies with more rapid induction of TH are needed in the STEMI population.

Use and Misuse of Serum Troponin Assays in Pediatric Practice - Corrected Proof

Kirk Liesemer, T. Charles Casper, Kent Korgenski, Shaji C. Menon — 2012-04-27

Cardiac troponin (cTn) is instrumental in screening and diagnosing myocardial ischemia in adults. However, the role of cTn screening in the pediatric population is less clear. The purpose of this study was to evaluate the current clinical practice, diagnostic and prognostic value, and resource utilization associated with cTn assays in the pediatric population. A multicenter, retrospective review of all cTn assays performed on patients aged ≤18 years from January 2003 to December 2010 in the Intermountain Healthcare system was conducted. Data collected included patient demographics, location, presenting symptoms, provisional and discharge diagnoses, additional tests, clinical outcomes (hospitalization days, ventilation, and death), and patient charges. During the study period, cTn assays were performed on 3,497 pediatric patients. The most common presenting diagnoses were chest pain (40%), trauma (11%), and poisoning or drug overdose (9%). Irrespective of diagnosis, elevated cTn was associated with an increased rate of hospitalization, ventilation, and death. Overall, 12% of patients had elevated cTn. Of the patients with chest pain, 4% had elevated cTn, 53% of whom were diagnosed with myopericarditis. In the myopericarditis group, 66% presented with fever, and 98% had abnormal electrocardiographic findings. For patients presenting with chest pain, approximately $162,000 was spent per positive result. In conclusion, cTn screening has strong prognostic value in pediatric patients, even in noncardiac diagnoses such as trauma or drug overdose. However, cTn screening in pediatric patients with chest pain provides minimal benefits and is associated with increased resource utilization, unless patients have constitutional symptoms, such as fever and/or electrocardiographic abnormalities.

Effect of Weight Loss After Bariatric Surgery on Left Ventricular Mass and Ventricular Repolarization in Normotensive Morbidly Obese Patients - Corrected Proof

2012-04-27

To assess the effect of weight loss on ventricular repolarization in morbidly obese patients, 39 normotensive subjects whose baseline body mass indexes were ≥40 kg/m2 before weight loss from bariatric surgery were studied. All patients were free of underlying organic heart disease, heart failure, and conditions that might affect ventricular repolarization. Twelve-lead electrocardiography and transthoracic echocardiography were performed just before surgery and at the nadir of postoperative weight loss. The corrected QT interval (QTc) was derived using Bazett's formula. QTc dispersion was calculated by subtracting the minimum from the maximum QTc on the 12-lead electrocardiogram. Echocardiographic left ventricular (LV) mass was indexed to height2.7. The mean body mass index decreased from 42.8 ± 2.1 to 31.9 ± 2.2 kg/m2 (p <0.0005). For the entire group, weight loss was associated with significant reductions in mean QTc (from 428.7 ± 18.5 to 410.5 ± 11.9 ms, p <0.0001) and mean QTc dispersion (from 44.1 ± 11.2 to 33.2 ± 3.3 ms, p <0.0005). Mean QTc and QTc dispersion decreased significantly with weight loss in patients with LV hypertrophy but not in subjects without LV hypertrophy. Multivariate analysis identified pre–weight loss LV mass/height2.7 as the most important predictor of pre–weight loss QTc and QTc dispersion and also identified weight loss–induced change in LV mass/height2.7 as the most important predictor of weight loss–induced changes in QTc and QTc dispersion. In conclusion, LV hypertrophy is a key determinant of QTc and QTc dispersion in normotensive morbidly obese patients. Regression of LV hypertrophy associated with weight loss decreases QTc and QTc dispersion.

Meta-Analysis of Efficacy and Safety of New Oral Anticoagulants (Dabigatran, Rivaroxaban, Apixaban) Versus Warfarin in Patients With Atrial Fibrillation - Corrected Proof

2012-04-27

New oral anticoagulants, including apixaban, dabigatran, and rivaroxaban, have been developed as alternatives to warfarin, the standard oral anticoagulation therapy for patients with atrial fibrillation (AF). A systematic review and meta-analysis of randomized controlled trials was performed to compare the efficacy and safety of new oral anticoagulants to those of warfarin in patients with AF. The published research was systematically searched for randomized controlled trials of >1 year in duration that compared new oral anticoagulants to warfarin in patients with AF. Random-effects models were used to pool efficacy and safety data across randomized controlled trials. Three studies, including 44,563 patients, were identified. Patients randomized to new oral anticoagulants had a decreased risk for all-cause stroke and systemic embolism (relative risk [RR] 0.78, 95% confidence interval [CI] 0.67 to 0.92), ischemic and unidentified stroke (RR 0.87, 95% CI 0.77 to 0.99), hemorrhagic stroke (RR 0.45, 95% CI 0.31 to 0.68), all-cause mortality (RR 0.88, 95% CI 0.82 to 0.95), and vascular mortality (RR 0.87, 95% CI 0.77 to 0.98). Randomization to a new oral anticoagulant was associated with a lower risk for intracranial bleeding (RR 0.49, 95% CI 0.36 to 0.66). Data regarding the risks for major bleeding (RR 0.88, 95% CI 0.71 to 1.09) and gastrointestinal bleeding (RR 1.25, 95% CI 0.91 to 1.72) were inconclusive. In conclusion, the new oral anticoagulants are more efficacious than warfarin for the prevention of stroke and systemic embolism in patients with AF. With a decreased risk for intracranial bleeding, they appear to have a favorable safety profile, making them promising alternatives to warfarin.

Cardiologist Concordance With the American College of Cardiology Appropriate Use Criteria for Cardiac Testing in Patients With Coronary Artery Disease - Corrected Proof

2012-04-26

The American College of Cardiology Appropriate Use Criteria (AUC) were developed to guide use of myocardial perfusion single-photon emission computed tomography (MPS), stress echocardiography, and cardiac computed tomographic angiography (CCTA). To date, cardiologist application of AUC from a patient-based multiprocedure perspective has not been evaluated. A Web-based survey of 15 clinical vignettes spanning a wide spectrum of indications for MPS, STE, and CCTA in coronary artery disease was administered to cardiologists who rated the ordered test as appropriate, inappropriate, or uncertain by AUC application and suggested a preferred alternative imaging procedure, if any. In total 129 cardiologists responded to the survey (mean age 49.5 years, board certification for MPS 65%, echocardiography 39%, CCTA 32%). Cardiologists agreed with published AUC ratings 65% of the time, with differences in all categories (appropriate, 50% vs 53%; inappropriate, 42% vs 20%; uncertain, 9% vs 27%, p <0.0001 for all comparisons). Physician age, practice type, or board certification in MPS or echocardiography had no effect on concordance with AUC ratings, with slightly higher agreement for those board certified in CCTA (68% vs 64%, p = 0.04). Cardiologist procedure preference was positively associated with active clinical interpretation of MPS and CCTA (p = 0.03 for the 2 comparisons) but not for ownership of the respective imaging equipment. In conclusion, cardiologist agreement with published AUC ratings is generally high, although physicians classify more uncertain indications as inappropriate. Active clinical interpretation of a procedure contributes most to increased procedure preference.

Clopidogrel Response Up to Six Months After Acute Myocardial Infarction - Corrected Proof

2012-04-26

High on-treatment platelet reactivity (HTPR) despite clopidogrel therapy is associated with adverse cardiac events after acute myocardial infarction (AMI). Most studies to date have assessed clopidogrel response at a single time point before or after percutaneous coronary intervention (PCI). It is unclear, however, whether the HTPR phenotype is stable over time. Therefore, we aimed to examine response to clopidogrel in patients with AMI treated with PCI over a 6-month period. Patients (n = 57) with AMI treated with PCI were assessed for response to clopidogrel at 3 time points: in hospital, 30 days, and 6 months after index hospitalization. Response to clopidogrel was determined by the VerifyNow P2Y12 assay (reported as P2Y12 response units) and multiple electrode aggregometry (MEA; reported as aggregation units). HTPR was defined as ≥235 P2Y12 response units or ≥47 aggregation units. Patients' mean age was 54.5 ± 10.9 years, 91% were men, 19% had diabetes, and 74% were admitted with ST-segment elevation MI. HTPR based on MEA was observed in 22.8% of patients in hospital, 26.3% at 30 days, and 17.5% at 6 months (p = NS). HTPR based on the VerifyNow assay was observed in 38.6% of patients in hospital, 28.1% at 30 days, and 33.3% at 6 months (p = NS). Individual HTPR phenotypic assignment at baseline was stable in 73.7% (based on MEA) and 70.2% (based on VerifyNow) of patients at 6-month follow-up. In conclusion, this is the first study evaluating the stability of clopidogrel response over time after AMI. Rates of HTPR to clopidogrel therapy appear to be relatively stable up to 6 months after AMI.

Delaying Primary Percutaneous Coronary Intervention for Computed Tomographic Scans in the Emergency Department - Corrected Proof

2012-04-26

Patients presenting with suspected ST-segment elevation myocardial infarction (STEMI) may have important alternative diagnoses (e.g., aortic dissection, pulmonary emboli) or safety concerns for STEMI management (e.g., head trauma). Computed tomographic (CT) scanning may help in identifying these alternative diagnoses but may also needlessly delay primary percutaneous coronary intervention (PCI). We analyzed the ACTIVATE-SF Registry, which consists of consecutive patients with a clinical diagnosis of STEMI admitted to the emergency departments of 2 urban hospitals. Of 410 patients with a suspected diagnosis of STEMI, 45 (11%) underwent CT scanning before primary PCI. Presenting electrocardiograms, baseline risk factors, and presence of an angiographic culprit vessel were similar in those with and without CT scanning before PCI. Only 2 (4%) of these CT scans changed clinical management by identifying a stroke. Patients who underwent CT scanning had far longer door-to-balloon times (median 166 vs 75 minutes, p <0.001) and higher in-hospital mortality (20% vs 7.8%, p = 0.006). After multivariate adjustment, CT scanning in the emergency department before primary PCI remained independently associated with longer door-to-balloon times (100% longer, 95% confidence interval 60 to 160, p <0.001) but was no longer associated with mortality (odds ratio 1.4, p = 0.5). In conclusion, CT scanning before primary PCI rarely changed management and was associated with significant delays in door-to-balloon times. More judicious use of CT scanning should be considered.

Changes in Left Ventricular Morphology and Function After Mitral Valve Surgery - Corrected Proof

2012-04-26

Degenerative mitral valve disease is the leading cause of mitral regurgitation in North America. Surgical intervention has hinged on the symptoms and ventricular changes that develop as compensatory ventricular remodeling occurs. In the present study, we sought to characterize the temporal response of left ventricular (LV) morphology and function to mitral valve surgery for degenerative disease and to identify the preoperative factors that influence reverse remodeling. From 1986 to 2007, 2,778 patients with isolated degenerative mitral valve disease underwent valve repair (n = 2,607 [94%]) or replacement (n = 171 [6%]) and had ≥1 postoperative transthoracic echocardiogram; 5,336 transthoracic echocardiograms were available for analysis. Multivariate longitudinal repeated-measures analysis was performed to identify the factors associated with reverse remodeling. The LV dimensions decreased in the first year after surgery (end-diastolic from 5.7 ± 0.80 to 4.9 ± 1.4 cm; end-systolic from 3.4 ± 0.71 to 3.1 ± 1.4 cm). The LV mass index decreased from 139 ± 44 to 112 ± 73 g/m2. The reduction in LV hypertrophy was less pronounced in patients with greater preoperative left heart enlargement (p <0.0001) and a greater preoperative LV mass (p <0.0001). The postoperative LV ejection fraction initially decreased from 58 ± 7.0% to 53 ± 20%, increased slightly during the first postoperative year, and was negatively influenced by preoperative heart failure symptoms (p <0.0001) and a lower preoperative LV ejection fraction (p <0.0001). The risk-adjusted response of LV morphology and function to valve repair and replacement was similar (p >0.2). In conclusion, a positive response toward normalization of LV morphology and function after mitral valve surgery is greatest in the first year. The best response occurs when surgery is performed before left heart dilation, LV hypertrophy, or LV dysfunction develop.

Comparison of Usefulness of Sokolow and Cornell Criteria for Left Ventricular Hypertrophy in Subjects Aged <20 Years Versus >30 Years - Corrected Proof

Alon Grossman, Alex Prokupetz, Nira Koren-Morag, Ehud Grossman, Ari Shamiss — 2012-04-26

The use of electrocardiography in sports or military screening is considered an effective tool for diagnosing potentially fatal conditions. The present study was designed to compare the yield of electrocardiographic criteria for left ventricular hypertrophy (LVH) criteria for the diagnosis of LVH and hypertrophic obstructive cardiomyopathy in subjects aged <20 years and >30 years. The association between the electrocardiographic (ECG) criteria for LVH (ECG-LVH) and echocardiographic findings was compared in 4 groups of air force academy candidates: (1) young candidates undergoing echocardiography because of ECG-LVH findings (n = 666); (2) young candidates without ECG-LVH findings undergoing routine echocardiography (n = 4,043); (3) older designated aviators undergoing echocardiography because of ECG-LVH findings (n = 196); and (4) older designated aviators undergoing routine echocardiography without ECG-LVH findings (n = 1,098). The predictive value of ECG-LVH findings for echocardiographic LVH, left ventricular mass, posterior wall thickness, and interventricular septal thickness were compared among the 4 groups. The ECG criteria in young subjects correlated with the left ventricular mass and posterior wall thickness but not with the interventricular septal thickness. In older subjects, these criteria correlated with left ventricular mass, interventricular septal, and posterior wall thickness. The positive and negative predictive value of ECG-LVH findings for the echocardiographic diagnosis of LVH in young subjects was 6.0% and 99.0%, respectively. In older subjects the positive and negative predictive value of ECG-LVH findings was 34% and 93%, respectively. In conclusion, ECG criteria are probably a useful tool for exclusion of LVH in young and older subjects; however, their low positive predictive value would probably lead to unnecessary echocardiographic tests, particularly in young subjects.

One-Year Results of Health-Related Quality of Life Among Patients Undergoing Transcatheter Aortic Valve Implantation - Corrected Proof

2012-04-23

Recently, it has been demonstrated that transcatheter aortic valve implantation (TAVI) can result in significant improvement in patients' quality of life (QOL) in the short term. At present, however, little is known about the long-term improvements in QOL after TAVI. Thus, our aim was to prospectively assess the 1-year QOL outcome of patients undergoing TAVI. We performed a prospective analysis of 186 patients with symptomatic severe aortic valve stenosis ineligible for conventional aortic valve replacement, who underwent TAVI with either the Medtronic CoreValve or Edwards Sapien device. A total of 106 patients completed the 1-year follow-up protocol. The QOL was measured using the Medical Outcomes Study 36-item short-form health survey questionnaire at baseline and at 3 months and 1 year of follow-up. At 1 year of follow-up, significant improvements in the Medical Outcomes Study 36-item short-form health survey questionnaire scores for physical functioning (baseline 34.6 ± 2.3 vs 1 year of follow-up 45.6 ± 2.7; p <0.001), role physical (20 ± 3.0 vs 34.2 ± 4.4; p <0.001), bodily pain (59.9 ± 3 vs 70 ± 2.7; p <0.01), general health (47.3 ± 1.5 vs 55.2 ± 2.1, p <0.001), vitality (35.9 ± 2 vs 48.5 ± 2; p <0.001), and mental health (62.2 ± 2.2 vs 67.3 ± 1.8; p <0.05) were observed compared to baseline. No significant improvement could be detected for social functioning (75.4 ± 2.5 vs 76.5 ± 2.6; p = 0.79) and role emotional (61.1 ± 4.3 vs 66.5 ± 4.7; p = 0.29). At 1 year of follow-up, the various physical and mental scores were comparable to an age-matched standard population. In conclusion, the present study has demonstrated that TAVI can improve the QOL status of high-surgical risk patients with severe aortic valve stenosis that can be maintained for ≤1 year postproceduraly in survivors. Although the mental subscales improved slightly, the mental component summary score failed to reach statistical significance in our study population.

Effect of New Versus Known Versus No Atrial Fibrillation on 30-Day and 10-Year Mortality in Patients With Acute Coronary Syndrome - Corrected Proof

2012-04-23

Coronary artery disease promotes the development of atrial fibrillation (AF). The aim of this study was to determine short- and long-term mortality in patients with acute coronary syndromes (ACS) and AF, depending on the AF presentation. A total of 2,335 consecutive patients with ACS were included. AF was classified as known persistent or permanent AF, known paroxysmal AF, new AF at admission, and new AF during hospitalization for ACS. Four hundred forty-two patients had any AF: 54 with known persistent or permanent AF, 150 with known paroxysmal AF, 54 with new AF at admission, and 184 with new AF during hospitalization. Statistically significant differences among subgroups related to previous heart failure (p <0.0001), stroke (p = 0.04), myocardial infarction (p <0.0001), angina pectoris (p <0.0001), hypercholesterolemia (p = 0.007), coronary artery bypass grafting (p <0.0001), and percutaneous coronary intervention (p = 0.03) were observed. Thirty-day mortality differed among the subgroups (p = 0.02) and was lowest in patients with known paroxysmal AF (7.3%). Ten-year mortality ranged from 53% to 78% among the subgroups. There were 5 predictors of long-term mortality across the subgroups: age (hazard ratio [HR] 1.06, 95% confidence interval [CI] 1.04 to 1.09, p <0.0001), previous myocardial infarction (HR 1.4, 95% CI 1.0 to 1.8, p = 0.04), heart failure (HR 1.8, 95% CI 1.3 to 2.4, p = 0.0002), diabetes (HR 1.7, 95% CI 1.2 to 2.2, p = 0.0005), and smoking (HR 1.7, 95% CI 1.2 to 2.3, p = 0.001). In conclusion, patient characteristics and 30-day mortality differed significantly among the subgroups, but long-term mortality did not. Any AF associated with ACS almost doubled the long-term mortality risk. AF in patients with ACS should therefore be regarded as an important risk factor irrespective of its presentation.

One-Year Consumption of a Grape Nutraceutical Containing Resveratrol Improves the Inflammatory and Fibrinolytic Status of Patients in Primary Prevention of Cardiovascular Disease - Corrected Proof

2012-04-23

The search for complementary treatments in primary prevention of cardiovascular disease (CVD) is a high-priority challenge. Grape and wine polyphenol resveratrol confers CV benefits, in part by exerting anti-inflammatory effects. However, the evidence in human long-term clinical trials has yet to be established. We aimed to investigate the effects of a dietary resveratrol-rich grape supplement on the inflammatory and fibrinolytic status of subjects at high risk of CVD and treated according to current guidelines for primary prevention of CVD. Seventy-five patients undergoing primary prevention of CVD participated in this triple-blinded, randomized, parallel, dose–response, placebo-controlled, 1-year follow-up trial. Patients, allocated in 3 groups, consumed placebo (maltodextrin), a resveratrol-rich grape supplement (resveratrol 8 mg), or a conventional grape supplement lacking resveratrol, for the first 6 months and a double dose for the next 6 months. In contrast to placebo and conventional grape supplement, the resveratrol-rich grape supplement significantly decreased high-sensitivity C-reactive protein (−26%, p = 0.03), tumor necrosis factor-α (−19.8%, p = 0.01), plasminogen activator inhibitor type 1 (−16.8%, p = 0.03), and interleukin-6/interleukin-10 ratio (−24%, p = 0.04) and increased anti-inflammatory interleukin-10 (19.8%, p = 0.00). Adiponectin (6.5%, p = 0.07) and soluble intercellular adhesion molecule-1 (−5.7%, p = 0.06) tended to increase and decrease, respectively. No adverse effects were observed in any patient. In conclusion, 1-year consumption of a resveratrol-rich grape supplement improved the inflammatory and fibrinolytic status in patients who were on statins for primary prevention of CVD and at high CVD risk (i.e., with diabetes or hypercholesterolemia plus ≥1 other CV risk factor). Our results show for the first time that a dietary intervention with grape resveratrol could complement the gold standard therapy in the primary prevention of CVD.

Alcohol and Vagal Tone as Triggers for Paroxysmal Atrial Fibrillation - Corrected Proof

2012-04-23

Alcohol and vagal activity may be important triggers for paroxysmal atrial fibrillation (PAF), but it remains unknown if these associations occur more often than would be expected by chance alone because of the lack of a comparator group in previous studies. We compared self-reported frequency of these triggers in patients with PAF to those with other supraventricular tachycardias (SVTs). Consecutive consenting patients presenting for electrophysiology procedures at a single university medical center underwent a structured interview regarding arrhythmia triggers. Two hundred twenty-three patients with a documented arrhythmia (133 with PAF and 90 with SVT) completed the survey. After multivariable adjustment, patients with PAF had a 4.42 greater odds (95% confidence interval [CI] 1.35 to 14.44) of reporting alcohol consumption (p = 0.014) and a 2.02 greater odds (95% CI 1.02 to 4.00) of reporting vagal activity (p = 0.044) as an arrhythmia trigger compared to patients with SVT. In patients with PAF, drinking primarily beer was associated with alcohol as a trigger (odds ratio [OR] 4.49, 95% CI 1.41 to 14.28, p = 0.011), whereas younger age (OR 0.68, 95% CI 0.49 to 0.95, p = 0.022) and a family history of AF (OR 5.73, 95% CI 1.21 to 27.23, p = 0.028) each were independently associated with having vagal activity provoke an episode. Patients with PAF and alcohol triggers were more likely to have vagal triggers (OR 10.32, 95% CI 1.05 to 101.42, p = 0.045). In conclusion, alcohol consumption and vagal activity elicit PAF significantly more often than SVT. Alcohol and vagal triggers often were found in the same patients with PAF, raising the possibility that alcohol may precipitate AF by vagal mechanisms.

Meta-Analysis of Randomized Trials of Angioedema as an Adverse Event of Renin–Angiotensin System Inhibitors - Corrected Proof

2012-04-23

Angioedema is a rare, potentially life-threatening adverse event of renin–angiotensin system inhibitors. The objective of the present study was to determine the risk of angioedema from randomized clinical trials. A PubMed/CENTRAL/EMBASE search was made for randomized clinical trials from 1980 to October 2011 in patients on angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or direct renin inhibitor (DRI). Trials with a total number of patients ≥100 and a duration of ≥8 weeks were included for analysis. Incidence of angioedema was pooled by weighing the incident rate of each trial by the inverse of the variance. Twenty-six trials with 74,857 patients in the ACE inhibitor arm with 232,523 person-years of follow-up, 19 trials with 35,479 patients on ARB with 122,293 person-years of follow-up, and 2 trials with 5,141 patients on DRI with 1,735 person-years of follow-up met the inclusion criteria and were included in the analysis. In head-to-head comparison in 7 trials, risk of angioedema with ACE inhibitors was 2.2 times higher than with ARBs (95% confidence interval [CI] 1.5 to 3.3). With ACE inhibitors and ARBs, incidence of angioedema was higher in heart failure trials compared to hypertension or coronary artery disease trials without heart failure (p <0.0001). Weighted incidence of angioedema with ACE inhibitors was 0.30% (95% CI 0.28 to 0.32) compared to 0.11% (95% CI 0.09 to 0.13) with ARBs, 0.13% (95% CI 0.08 to 0.19) with DRIs, and 0.07% with placebo (95% CI 0.05 to 0.09). In conclusion, incidence of angioedema with ARBs and DRI was <1/2 than that with ACE inhibitors and not significantly different from placebo. Incidence of angioedema was higher in patients with heart failure compared to those without heart failure with ACE inhibitors and ARBs.

Relation of Systemic Blood Pressure to Sudden Cardiac Death - Corrected Proof

2012-04-23

The role of systolic blood pressure (SBP) as an independent risk factor for sudden cardiac death (SCD) is not well defined in a general population. Thus, we assessed the association between BP at rest and risk of SCD. BP and other risk factors were measured in a representative population-based sample of 2,666 Finnish men (42 to 61 years of age). During an average follow-up period of 18.9 years (interquartile range 17.9 to 22.6), 213 SCDs occurred. Each increment 10-mm Hg of SBP at rest was associated with an increased risk of SCD (relative hazard 1.15, 95% confidence interval 1.07 to 1.25, p <0.001) after adjustment for age, alcohol consumption, cigarette smoking, serum low-density lipoprotein cholesterol, type 2 diabetes, body mass index, left ventricular hypertrophy, previous myocardial infarction, family history of coronary heart disease, and use of antihypertensive medications. Men with increased SBP of >145 mm Hg had a 2.04-fold (95% confidence interval 1.23 to 2.52, p = 0.003) adjusted risk for SCD compared to those with SBP <123 mm Hg. In conclusion, this study emphasizes the importance of the definition of SBP at rest because it provides a valuable prognostic measurement for SCD.

Usefulness of Risk Scores to Estimate the Risk of Cardiovascular Disease in Patients With Rheumatoid Arthritis - Corrected Proof

2012-04-23

Patients with rheumatoid arthritis (RA) have an excess burden of cardiovascular (CV) disease (CVD). CV risk scores for the general population may not accurately predict CV risk for patients with RA. A population-based inception cohort of patients who fulfilled 1987 American College of Rheumatology criteria for RA from 1988 to 2007 was followed until death, migration, or December 31, 2008. CV risk factors and CVD (myocardial infarction, CV death, angina, stroke, intermittent claudication, and heart failure) were ascertained by medical record review. Ten-year predicted CVD risk was calculated using the general Framingham and the Reynolds risk scores. Standardized incidence ratios were calculated to compare observed and predicted CVD risks. The study included 525 patients with RA aged ≥30 years without previous CVD. The mean follow-up period was 8.4 years, during which 84 patients developed CVD. The observed CVD risk was 2-fold higher than the Framingham risk score predicted in women and 65% higher in men, and the Reynolds risk score revealed similar deficits. Patients aged ≥75 years had observed CVD risk >3 times the Framingham-predicted risk. Patients with positive rheumatoid factor or persistently elevated erythrocyte sedimentation rates also experienced more CVD events than predicted. In conclusion, the Framingham and Reynolds risk scores substantially underestimated CVD risk in patients with RA of both genders, especially in older ages and in patients with positive rheumatoid factor. These data underscore the need for more accurate tools to predict CVD risk in patients with RA.

Association Between Retinopathy and Cardiovascular Disease in Patients With Chronic Kidney Disease (from the Chronic Renal Insufficiency Cohort [CRIC] Study) - Corrected Proof

2012-04-20

Patients with chronic kidney disease experience co-morbid illnesses, including cardiovascular disease (CVD) and retinopathy. The purpose of the present study was to assess the association between retinopathy and self-reported CVD in a subgroup of the participants in the Chronic Renal Insufficiency Cohort study. For this observational, ancillary investigation, 2,605 Chronic Renal Insufficiency Cohort participants were invited to participate in the present study, and nonmydriatic fundus photographs in both eyes were obtained for 1,936 subjects. The photographs were reviewed in a masked fashion at a central photograph reading center. The presence and severity of retinopathy (diabetic, hypertensive, or other) and vessel diameter caliber were assessed using standard protocols by trained graders who were masked to the information about the study participants. A history of self-reported CVD was obtained using a medical history questionnaire. Kidney function measurements and traditional and nontraditional risk factors for CVD were obtained from the Chronic Renal Insufficiency Cohort study. A greater severity of retinopathy was associated with a greater prevalence of any CVD, and this association persisted after adjustment for the traditional risk factors for CVD. The presence of vascular abnormalities usually associated with hypertension was also associated with increased prevalence of CVD. We found a direct relation between CVD prevalence and mean venular caliber. In conclusion, the presence of retinopathy was associated with CVD, suggesting that retinovascular pathology might indicate macrovascular disease, even after adjustment for renal dysfunction and traditional CVD risk factors. This would make the assessment of retinal morphology a valuable tool in CKD studies of CVD outcomes.

Usefulness of Desirable Lifestyle Factors to Attenuate the Risk of Heart Failure Among Offspring Whose Parents Had Myocardial Infarction Before Age 55 Years - Corrected Proof

Owais Khawaja, Gregory Kotler, John Michael Gaziano, Luc Djoussé — 2012-04-20

Heart failure (HF) is one of the leading causes of hospitalization and death in the United States and throughout Europe. Although a higher risk for HF with antecedent myocardial infarction (MI) has been reported in offspring whose parents had MIs before age 55 years, it is unclear whether adherence to healthful behaviors can mitigate that risk. The aim of the present study was therefore to prospectively examine if adherence to healthy weight, regular exercise, moderate alcohol consumption, and abstinence from smoking can attenuate such increased HF risk. Information on parental history of MI and lifestyle factors was collected using questionnaires. Subjects adhering to ≥3 healthy lifestyle factors were classified as having good versus poor lifestyle scores. Incident HF was assessed via yearly follow-up questionnaires and validated in a subsample. During an average follow up of 21.7 ± 6.5 years, 1,323 new HF cases (6.6%), of which 190 (14.4%) were preceded by MI, occurred. Compared to subjects with good lifestyle scores and no parental histories of premature MI, multivariate adjusted hazard ratios for incident HF with antecedent MI were 3.21 (95% confidence interval 1.74 to 5.91) for subjects with good lifestyle score and parental histories of premature MI, 1.52 (95% confidence interval 1.12 to 2.07) for those with poor lifestyle score and no parental histories of premature MI, and 4.60 (95% confidence interval 2.55 to 8.30) for those with poor lifestyle scores and parental histories of premature MI. In conclusion, our data suggest that even in subjects at higher risk for HF because of genetic predisposition, adherence to healthful lifestyle factors may attenuate such an elevated HF risk.

Bleeding Risk and Major Adverse Events in Patients With Previous Ulcer on Oral Anticoagulation Therapy - Corrected Proof

2012-04-20

Bleeding is the major concern for patients receiving oral anticoagulation therapy (OAT), especially those with histories of gastrointestinal ulcer. The aim of this study was to evaluate the efficacy and safety of OAT in patients with nonvalvular atrial fibrillation with histories of ulcer. A composite end point, including major adverse cardiac events or major bleeding, was compared between patients with AF with previous ulcers who were (OAT+; n = 200) and were not (OAT− n = 230) receiving OAT. During the follow-up period of 3.3 ± 2.7 years, 28 (14%) and 66 (29%) OAT+ and OAT− patients, respectively, had major adverse cardiac events (p = 0.001). Major bleeding occurred in 46 OAT+ patients (23%) and 25 OAT− patients (11%) (p = 0.001). There was no significant difference in the composite end point between OAT+ and OAT− patients (29% vs 36%, p = 0.08). The incidence of major bleeding was significantly lower, decreasing from 30% to 14%, when OAT began after endoscopic confirmation of ulcer healing (p = 0.02). OAT+ patients who achieved time in the therapeutic range ≥60% for international normalized ratio (2.0 to 3.0) demonstrated better cumulative survival free from the composite end point than OAT− patients (p = 0.01). In conclusion, OAT in patients with nonvalvular AF with histories of gastrointestinal ulcer made no difference in the composite end point compared to absence of OAT. In OAT+ patients, maintaining an optimal international normalized ratio reduced the composite end point, and the confirmation of ulcer healing reduced the incidence of bleeding.

Relation of the Severity of Obstructive Sleep Apnea in Response to Anti-Arrhythmic Drugs in Patients With Atrial Fibrillation or Atrial Flutter - Corrected Proof

2012-04-20

Atrial fibrillation (AF) is more common in those with obstructive sleep apnea (OSA) than in unaffected subjects and recurs more frequently in the presence of severe OSA after electrical cardioversion and AF ablation. However, it is unknown whether the severity of OSA influences the efficacy of antiarrhythmic drug (AAD) therapy in patients with OSA and AF. The aim of this study was to examine the impact of OSA severity on the treatment of patients with symptomatic AF using AADs. Sixty-one patients (mean age 62 ± 15 years, 21 women) treated with AADs for symptomatic AF who underwent overnight polysomnography were studied. Rhythm control was prospectively defined as successful if a patient remained on the same AAD therapy for ≥6 months with ≥75% reduction in symptomatic AF burden. Twenty-four patients (40%) had severe OSA. Thirty patients (49%) were rhythm controlled with AADs. Nonresponders to AADs were more likely to have severe OSA than milder disease (52% vs 23%, p <0.05); those with severe OSA were less likely to respond to AADs than participants with nonsevere OSA (39% vs 70%, p = 0.02). Nonresponders had higher apnea-hypopnea indexes than responders (34 ± 25 vs 22 ± 18 events/hour, p = 0.05), but there were no differences between these groups in minimum oxygen saturation or percentage of time spent in rapid eye movement sleep. In conclusion, patients with severe OSA are less likely to respond to AAD therapy for AF than those with milder forms of OSA.

Performance of the Seattle Heart Failure Model in Implantable Defibrillator Patients Treated With Cardiac Resynchronization Therapy - Corrected Proof

2012-04-20

The Seattle Heart Failure Model (SHFM) is a validated multivariate risk prediction model for mortality in patients with heart failure, using widely available clinical variables. The aim of this study was to assess the performance of the SHFM when applied to patients with heart failure who received cardiac resynchronization therapy devices with defibrillation. A total of 413 patients were identified from 2 prospective implantable cardioverter-defibrillator registries who received cardiac resynchronization therapy devices with defibrillation for the primary prevention of sudden death. Baseline laboratory and clinical data were entered in the SHFM to calculate predicted survival. The end point was all-cause mortality. During a median follow-up period of 2.8 years, 78 patients died and 9 underwent heart transplantation. Observed versus predicted 5-year mortality rates were 11.6% versus 11.4%, 21.5% versus 22.1%, and 41.4% versus 46.1% by ascending tertile of Seattle Heart Failure Score, respectively. No systematic or substantial errors of risk estimation were observed. Discrimination was excellent; the C-statistic ranged from 0.78 at 1-year follow-up to 0.70 at 5-year follow-up, and the Hosmer-Lemeshow chi-square statistic was 0.87 (p = 0.65). In conclusion, in patients with heart failure who received cardiac resynchronization therapy devices with defibrillation, the SHFM offers adequate discrimination of risk for all-cause mortality and estimation of mortality risk without substantial or systematic errors.

Long-Term Compliance With Nonpharmacologic Treatment of Patients With Heart Failure - Corrected Proof

2012-04-20

The aim of this study was to examine long-term compliance with nonpharmacologic treatment of patients with heart failure (HF) and its associated variables. Data from 648 hospitalized patients with HF (mean age 69 ± 12 years, 38% women, mean left ventricular ejection fraction 33 ± 14%) were analyzed. Compliance was assessed by means of self-report at baseline and 1, 6, 12, and 18 months after discharge. Patients completed questionnaires on depressive symptoms, HF knowledge, and physical functioning at baseline. Logistic regression analyses were performed to examine independent associations with low long-term compliance. From baseline to 18-month follow-up, long-term compliance with diet and fluid restriction ranged from 77% to 91% and from 72% to 89%, respectively. In contrast, compliance with daily weighing (34% to 85%) and exercise (48% to 64%) was lower. Patients who were in New York Heart Association functional class II were more often noncompliant with fluid restriction (odds ratio [OR] 1.97, 95% confidence interval [CI] 1.25 to 3.08). A lower level of knowledge on HF was independently associated with low compliance with fluid restriction (OR 0.78, 95% CI 0.71 to 0.86) and daily weighing (OR 0.86, 95% CI 0.79 to 0.94). Educational support improved compliance with these recommendations. Female gender (OR 1.91, 95% CI 1.26 to 2.90), left ventricular ejection fraction ≥40% (OR 1.55, 95% CI 1.03 to 2.34), a history of stroke (OR 3.55, 95% CI 1.54 to 8.16), and less physical functioning (OR 0.99, 95% CI 0.98 to 0.99) were associated with low compliance with exercise. In conclusion, long-term compliance with exercise and daily weighing was lower than long-term compliance with advice on diet and fluid restriction. Although knowledge on HF and being offered educational support positively affected compliance with weighing and fluid restriction, these variables were not related to compliance with exercise. Therefore, new approaches to help patients with HF stay physically active are needed.

Prognostic Usefulness of Clinical and Subclinical Peripheral Arterial Disease in Men With Stable Coronary Heart Disease - Corrected Proof

2012-04-19

The prognostic value of symptomatic peripheral arterial disease (PAD) in patients with coronary heart disease (CHD) is well documented, but few reports differentiating between symptomatic and asymptomatic forms of PAD are available. We investigated the respective prognostic effect of clinical and subclinical PAD on long-term all-cause mortality in patients with stable CHD. We analyzed 710 patients with stable CHD referred for hospitalization for CHD evaluation and management. As a part of the study, they completed questionnaires on medical history, underwent a standardized clinical examination, including ankle-brachial index (ABI) measurement, and provided a fasting blood sample. Three groups of patients were individualized: no PAD (no history of PAD and ABI >0.9 but ≤1.4); subclinical PAD (no history of PAD but abnormal ABI [i.e., ≤0.9 or >1.4); and clinical PAD (history of claudication, peripheral arterial surgery, or amputation due to PAD). Clinical and subclinical PAD was present in 83 (11.7%) and 181 (25.5%) patients, respectively. After a median follow-up of 7.2 years, 130 patients died. On multivariate analysis adjusted for age, hypertension, diabetes, dyslipidemia, smoking, left ventricular ejection fraction, CHD duration, heart rate, history of stroke or transient ischemic attack, and coronary revascularization, previous clinical PAD (hazard ratio 2.11, 95% confidence interval 1.28 to 3.47) and subclinical PAD (hazard ratio 1.65, 95% confidence interval 1.11 to 2.44) were significantly associated with increased all-cause mortality. In conclusion, our study has demonstrated that the detection of subclinical PAD by ABI in patients with stable CHD provides additional information for long-term mortality risk evaluation.

Therapeutic Ranges of Serum Digoxin Concentrations in Patients With Heart Failure - Corrected Proof

Zachary D. Goldberger, Ary L. Goldberger — 2012-04-16

Evidence-based medicine is an evolutionary process, intended to foster and disseminate the best practice guidelines from an ongoing critical analysis of available data. An underaddressed challenge relates to detecting and correcting delays where the evidence supports, but fails to effect, a timely change in practice. An example pertains to serum digoxin concentrations (SDCs) in the treatment of chronic heart failure (HF) because (1) the widely disseminated and used “therapeutic” SDCs for treating HF are not consistently aligned with considerably lower evidence-based values and (2) this discrepancy—a variant of the “clinical inertia” syndrome—may lead to unnecessary exposure of patients to potentially life-threatening toxicities.

Plasma Free Fatty Acids and Risk of Atrial Fibrillation (from the Cardiovascular Health Study) - Corrected Proof

2012-04-16

Atrial fibrillation (AF) is a highly prevalent cardiac arrhythmia in clinical practice, affecting approximately 2.3 million residents of the United States and 4.5 million residents of the European Union. It is unclear whether plasma free fatty acids (FFAs) influence the risk of AF in older adults. The aim of this study was to prospectively examine the association between plasma FFAs and incident AF in a prospective cohort of 4,175 men and women ≥65 years old from the Cardiovascular Health Study. Plasma concentrations of FFAs were measured 2 times during the 1992 to 1993 examination. Incident AF was ascertained based on study electrocardiographic and hospitalization records during follow-up. We used Cox regression to estimate relative risks of AF. Average age at baseline was 74.6 ± 5.1 years. During a mean follow-up of 10.0 years, 1,041 new cases of AF occurred. Crude incidence rates of AF were 23.7, 23.3, 23.9, and 29.7 cases/1,000 person-years across consecutive quartiles of plasma FFAs. There was a positive association between plasma FFAs and risk of AF. Multivariable adjusted hazard ratios (95% confidence intervals) for incident AF were 1.00 (referent), 1.02 (0.85 to 1.21), 1.05 (0.88 to 1.26), and 1.29 (1.08 to 1.55) from the lowest to highest quartiles of FFAs, respectively. In a secondary analysis restricted to the first 5 years of follow-up, this association persisted. In conclusion, our data show an increased risk of AF with higher plasma FFAs in community-dwelling older adults.

Role of CHADS2 Score in Evaluation of Thromboembolic Risk and Mortality in Patients With Atrial Fibrillation Undergoing Direct Current Cardioversion (from the ACUTE Trial Substudy) - Corrected Proof

2012-04-16

The CHADS2 (congestive heart failure, hypertension, age >75 years, diabetes mellitus, stroke or transient ischemic attack [2 points]) scoring scheme has been found to be a good predictor of stroke risk in patients with nonvalvular atrial fibrillation (AF). However, the value of the CHADS2 scoring system in the risk stratification of patients with AF who undergo direct-current cardioversion has not yet been specifically investigated. In this study, a subgroup of 541 patients from the Assessment of Cardioversion Using Transesophageal Echocardiography (ACUTE) study who had AF for >48 hours and planned to undergo transesophageal echocardiography before direct-current cardioversion were enrolled. Each patient had a CHADS2 score calculated. Of the patients with CHADS2 scores of 0, 14 (10%) were found to have left atrial appendage thrombi on transesophageal echocardiography. After 6 months of follow up, patients with CHADS2 scores of 3 to 6 showed a significantly higher mortality rate in comparison with patients with lower CHADS2 scores (4.3% vs 0.5%, p = 0.004), despite their similar prevalence of left atrial appendage thrombus and stroke (thrombus: 13.4% vs 11.6%, p = 0.60; stroke: 0% vs 0.3%, p = 0.70). In conclusion, the CHADS2 scoring system may be useful for predicting short-term mortality risk in patients with AF receiving elective direct-current cardioversion. However, in the preprocedural risk assessment of these patients, the CHADS2 scoring system is not reliable in predicting risk for left atrial appendage thrombus formation, especially in patients with low CHADS2 scores.