American Heart Journal

A review of dyspnea in acute heart failure syndromes

2010-08-01

In acute heart failure syndrome (AHFS), dyspnea is one of the most common but least understood presenting symptoms for hospitalization. For this reason, dyspnea relief is increasingly becoming a focus in the development of therapies for the treatment of AHFS, and currently stands as an acceptable primary end point for regulatory approval by governmental agencies. This raises the question of how best to measure such a subjective symptom. In this review, we will describe the basis for dyspnea, provide a detailed description of the strengths and weaknesses of the current best tools used to measure it, and describe future directions for future development of dyspnea measurement in AHFS.

Intramyocardial injection of autologous bone marrow mononuclear cells for patients with chronic ischemic heart disease and left ventricular dysfunction (First Mononuclear Cells injected in the US [FOCUS]): Rationale and design

2010-08-01

Background: The increasing worldwide prevalence of coronary artery disease (CAD) continues to challenge the medical community. Management options include medical and revascularization therapy. Despite advances in these methods, CAD is a leading cause of recurrent ischemia and heart failure, posing significant morbidity and mortality risks along with increasing health costs in a large patient population worldwide.Trial Design: The Cardiovascular Cell Therapy Research Network (CCTRN) was established by the National Institutes of Health to investigate the role of cell therapy in the treatment of chronic cardiovascular disease. FOCUS is a CCTRN-designed randomized, phase II, placebo-controlled clinical trial that will assess the effect of autologous bone marrow mononuclear cells delivered transendocardially to patients with left ventricular (LV) dysfunction and symptomatic heart failure or angina. All patients need to have limiting ischemia by reversible ischemia on single-photon emission computed tomography assessment.Results: After thoughtful consideration of both statistical and clinical principles, we will recruit 87 patients (58 cell treated and 29 placebo) to receive either bone marrow–derived stem cells or placebo. Myocardial perfusion, LV contractile performance, and maximal oxygen consumption are the primary outcome measures.Conclusions: The designed clinical trial will provide a sound assessment of the effect of autologous bone marrow mononuclear cells in improving blood flow and contractile function of the heart. The target population is patients with CAD and LV dysfunction with limiting angina or symptomatic heat failure. Patient safety is a central concern of the CCTRN, and patients will be followed for at least 5 years.

The new high-sensitivity cardiac troponin T assay improves risk assessment in acute coronary syndromes

Bertil Lindahl, Per Venge, Stefan James — 2010-08-01

Background: Cardiac troponins are currently the markers of choice for diagnosis of acute myocardial infarction and risk assessment in acute coronary syndrome (ACS). With the introduction of the new high-sensitivity cardiac troponin T (hs-cTnT) assay, it has become possible to measure cTnT even in healthy subjects. However, how the hs-cTnT assay compares with the old cTnT assay for risk assessment in ACS is still unknown.Methods: Cardiac troponin T levels were measured with the new hs-cTnT assay and the old third-generation cTnT assay in serum samples collected 48 hours after randomization in 1,452 randomly selected ACS patients enrolled in the GUSTO-IV trial. During 30 days of follow-up, deaths and myocardial infarctions were recorded. At 12 months, only all-cause mortality was collected.Results: The 16% of the patients that had levels higher than the 99th percentile cutoff for hs-cTnT but less than for cTnT had a similar 1-year mortality as the 60% that were positive for both assays (9.2% vs 10.7%, P = .52) and a higher 1-year mortality compared with the 24% that were negative for both assays (9.2% vs 2.6%, P = .001). For death or acute myocardial infarction at 30 days, the group that was positive only for hs-cTnT had an intermediate risk compared with the groups negative or positive for both assays (2.4%, 5.2%, and 8.7%; P < .001).Conclusion: The new hs-cTnT assay, compared with the old cTnT assay, identified more patients with myocardial damage and who were at an increased risk for new cardiac events.

High burden of cardiovascular disease risk factors in Mexico: An epidemic of ischemic heart disease that may be on its way?

Benjamín Acosta-Cázares, Jorge Escobedo-de la Peña — 2010-08-01

Background: Whereas developed nations have witnessed a drop in the occurrence and mortality of ischemic heart disease, developing nations have recorded a constant rise. The burden of cardiovascular disease risk factors may explain this increase.Methods: We conducted a population-based cross-sectional survey to estimate the prevalence of cardiovascular risk factors in the population protected by the Mexican Social Security Institute. A total of 20,062 Mexicans, aged ≥20 years, 43.5% (8,727) male and 56.5% (11,335) female, randomly selected in a 4-stage stratified population-based sampling process were included.Results: The most prevalent cardiovascular risk factor in men was smoking (31.9%), whereas in women, it was obesity (26.6%) and central obesity (49.7%). A similar high age-adjusted prevalence was observed in women and men for hypertension (29.7% and 28.8%), diabetes (12.94% and 12.66%), and hypercholesterolemia (13.81% and 12.36%). There was a clear age effect on the prevalence of diabetes, hypertension, and hypercholesterolemia, with increasing prevalence with aging. Smoking also had an age effect, but its prevalence increases as age diminishes. More than half of the subjects in reproductive age (20-44 years old) have at least 1 cardiovascular risk factor, mainly smoking.Conclusions: Cardiovascular risk factors are highly prevalent in the Mexican population, which seems to be between the second and third stages of the tobacco epidemic. The increased prevalence of risk factors clustering indicates the need for comprehensive integrated management of cardiovascular risk factors in Mexicans, with special emphasis on individuals at younger ages.

Transcatheter aortic valve implantation for severe aortic stenosis—a new paradigm for multidisciplinary intervention: A prospective cohort study

2010-08-01

Background: Transcatheter aortic valve implantation (TAVI) is an alternative treatment option for patients with aortic stenosis deemed high risk or unsuitable for aortic valve replacement. The aim of this study was to assess the feasibility of TAVI in elderly patients, the delivery of this technology with a multidisciplinary approach, and the use of traditional surgical scoring systems.Methods: One hundred fifty-one consecutive patients (mean age 82.6 ± 7.3 years) with severe aortic stenosis underwent TAVI with the Edwards Lifesciences (Irvine, CA) Sapien bioprosthesis using the transapical (n = 84; 56%) or transfemoral (n = 67; 44%) approach from August 2007 to September 2009 at King's Health Partners, London, United Kingdom. We analyzed procedural outcome, complications, functional status, and midterm outcome of patients.Results: The multidisciplinary team comprised interventional cardiologists, cardiothoracic surgeons, imaging specialists, cardiac anesthetists, and specialist nurses. Seventy percent of patients were in New York Heart Association class III/IV, and logistic EuroSCORE was 21.6 ± 11.9. Procedural success was achieved in 98%. Postoperative complications included stroke (6%), complete atrioventricular block (5.3%), renal failure requiring hemofiltration (9.3%), and vascular injury (8.6%). Overall 30-day mortality was 9.9% (n = 15). The logistic EuroSCORE was a predictor of short-term mortality (logistic regression model, P < .05). Thirty-day mortality post-TAVI for patients with logistic EuroSCORE <20, 20 to 40, and >40 was 5.4%, 13.2%, and 22.2%, respectively.Conclusions: Transcatheter aortic valve implantation is a feasible treatment option in this patient group with promising short/medium-term results. Renal failure is the commonest short-term complication, and the incidence of vascular complications remains high. Risk prediction/case selection remains challenging, and a multidisciplinary team approach appears to be helpful in appropriate patient selection.

Application of appropriatenes criteria to stress single photon emission computed tomography sestamibi studies: A comparison of the 2009 revised appropriateness criteria to the 2005 original criteria

2010-08-01

Background: The 2005 appropriate use criteria (AUC) for stress single-photon emission computed tomographic myocardial perfusion imaging (SPECT MPI) were revised in 2009 to reflect changes in published evidence, clinical practice and experience with application of the 2005 AUC. The purpose of this study was to compare the 2009 AUC for SPECT MPI with the original 2005 criteria.Methods: Using the Mayo Rochester Nuclear Cardiology Laboratory database, we retrospectively examined 281 patients who underwent stress SPECT MPI at Mayo Clinic Rochester between May 1, 2005, and May 15, 2005, using the revised 2009 AUC and compared these findings to our previously published results in this same cohort using the 2005 AUC.Results: Compared to the 2005 AUC, the 2009 AUC resulted in a highly significant overall change (P < .001) in the classification of appropriateness. The 2009 AUC eliminated unclassified patients, reduced appropriate studies (59.8% vs 63.7%, P = .02), increased studies of uncertain appropriateness (16.0% vs 10.7%, P = .01), and increased inappropriate studies (24.2% vs 14.6%, P < .001).Conclusions: In this cohort of patients undergoing SPECT MPI, compared to our previous study using the original 2005 AUC, the 2009 AUC had a significant impact on the classification of appropriateness. The 2009 AUC eliminated unclassified patients, increased inappropriate studies and increased studies of uncertain appropriateness.

Joint effects of common genetic variants from multiple genes and pathways on the risk of premature coronary artery disease

2010-08-01

Objective: The aim of this study is to discover common variants in 6 lipid metabolic genes and construct and validate a genetic risk score (GRS) based on the joint effects of genetic variants in multiple genes from lipid and other pathobiologic pathways.Background: Explaining the genetic basis of coronary artery disease (CAD) is incomplete. Discovery and aggregation of genetic variants from multiple pathways may advance this objective.Methods: Premature CAD cases (n = 1,947) and CAD-free controls (n = 1,036) were selected from our angiographic registry. In a discovery phase, single nucleotide polymorphisms (SNPs) at 56 loci from internal discovery and external reports were tested for associations with biomarkers and CAD: 28 promising SNPs were then tested jointly for CAD associations, and a GRS consisting of SNPs contributing independently was constructed and validated in a replication set of familial cases and population-based controls (n = 1,320).Results: Five variants contributed jointly to CAD prediction in a multigenic GRS model: odds ratio 1.24 (95% CI 1.16-1.33) per risk allele, P = 8.2 × 10−11, adjusted OR 2.03 (1.53-2.70), fourth versus first quartile. 5-SNP genetic risk score had minor impact on area under the receiver operating characteristic curve (P > .05) but resulted in substantial net reclassification improvement: 0.16 overall, 0.28 in intermediate-risk patients (both P < .0001). GRS5 predicted familial CAD with similar magnitude in the validation set.Conclusions: The Intermountain Healthcare's Coronary Genetics study demonstrates the ability of a multigenic, multipathway GRS to improve discrimination of angiographic CAD. Genetic risk scores promise to increase understanding of the genetic basis of CAD and improve identification of individuals at increased CAD risk.

Economic analysis of a tailored behavioral intervention to improve blood pressure control for primary care patients

2010-08-01

Background: Few telemedicine programs have undergone cost analyses, impeding their implementation into practice. We report on the economic analysis of a nurse-administered intervention designed to improve blood pressure control among hypertensive veterans.Methods: We randomized hypertensive patients at the Durham Veterans Affairs Medical Center primary care clinic to behavioral (n = 294) or nonbehavioral (n = 294) interventions. Behavioral intervention patients received tailored information bimonthly for 2 years via telephone. To calculate intervention cost, we microcosted the nurse's labor cost and computer hardware and software costs, applied a direct-to-indirect cost ratio, and distributed the costs over an estimated cohort of patients. We analyzed data from the Veterans Affairs Decision Support System to assess whether the intervention impacted overall health care utilization and costs. We used life expectancy estimates from the literature to develop decision models to calculate cost per life-year saved.Results: The mean annual intervention cost was $112 (range $61-$259). During 2 years of follow-up, patients in the intervention group incurred $7,800 in inpatient costs and $9,741 in outpatient costs; the nonintervention group incurred $6,866 in inpatient costs and $9,599 in outpatient costs. The total cost difference was not statistically significant (P = .56). Cost-effectiveness of the behavioral intervention ranged from $42,457 per life-year saved for normal-weight women to $87,300 per life-year saved for normal-weight men.Conclusions: The study results suggest that a nurse-administered, tailored behavioral intervention can be implemented at nominal cost and be cost-effective; however, there was no apparent lowering of health care utilization and costs during the 2 years of follow-up.

Diuretic dose and long-term outcomes in elderly patients with heart failure after hospitalization

2010-08-01

Background: The array of outcomes according to longitudinal furosemide doses in heart failure (HF) have not been evaluated. We examined the relationship of dynamic furosemide dose with mortality and hospitalizations for cardiovascular disease and renal dysfunction.Methods: Among elderly patients with HF (≥65 years) newly discharged from hospital, dynamic furosemide exposure was determined by examining dose fluctuations up to 5 years of follow-up using the Ontario Drug Benefit pharmacare database. Dynamic furosemide exposures were classified as low dose (LD; 1-59 mg/d), medium dose (MD; 60-119 mg/d), or high dose (HD; ≥120 mg/d). Outcomes were assessed by modeling furosemide exposure as a time-dependent covariate.Results: Among 4,406 patients (78.4 ± 7.0 years; 50.5% male), 46% changed furosemide dose categories within 1 year, and 63% changed dose categories over the follow-up period. High-dose furosemide patients were younger, were mostly male, and exhibited more ischemic or valvular disease, diabetes, atrial fibrillation, hypotension, hyponatremia, and higher baseline creatinine than LD. Compared with LD, MD exposure was associated with increased mortality with adjusted hazard ratio 1.96 (95% CI 1.79-2.15), whereas HD exposure conferred greater mortality risk with hazard ratio 3.00 (95% CI 2.72-3.31) after multiple covariate adjustment (both P < .001). Adjusted risks of hospitalization for HF (MD: 1.24 [95% CI 1.12-1.38] and HD: 1.43 [95% CI 1.26-1.63]), renal dysfunction (MD: 1.56 [95% CI 1.38-1.76] and HD: 2.16 [95% CI 1.88-2.49]), and arrhythmias (MD: 1.15 [95% CI 1.03-1.30] and HD: 1.45 [95% CI 1.27-1.66]) were also higher with increasing furosemide exposure.Conclusion: Exposure to higher furosemide doses is associated with worsened outcomes and is broadly predictive of death and morbidity.

Predicting chronic left ventricular dysfunction 90 days after ST-segment elevation myocardial infarction: An Assessment of Pexelizumab in Acute Myocardial Infarction (APEX-AMI) Substudy

2010-08-01

Objectives: The purpose of this study was to determine predictors of 90-day left ventricular function following acute ST-segment elevation myocardial infarction (STEMI) using variables from clinical presentation, biomarker testing, and cardiovascular magnetic resonance imaging (CMR).Background: Identifying patients with acute STEMI who experience adverse remodeling and develop left ventricular dysfunction 3 months post-MI is a priority for guiding subsequent therapy.Methods: The Assessment of Pexelizumab in Acute Myocardial Infarction trial tested pexelizumab treatment in STEMI patients presenting within 6 hours of symptom onset who were to undergo primary percutaneous coronary intervention. We studied 64 patients within this trial according to a prespecified substudy that included paired core laboratory delayed-enhancement CMR at days 3 and 90 as well as plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP; in picograms per milliliter) measured at randomization and 24 hours. A multivariable model predicting day 90 left ventricular ejection fraction (LVEF) was developed from clinical, biomarker, and imaging findings.Results: Patients had a median age of 60 years (52-68), 89% were male, and 60% had anterior STEMI. Time from symptom onset to percutaneous coronary intervention was 3 hours. The median baseline LVEF was 48% (38%-56%) and was 50% (40%-54%) at 90 days: 7 patients (11%) had an LVEF <35% at 90 days. Patients with a lower 90-day LVEF (as a continuous variable) had a higher 24-hour NT-proBNP (P = .02) and a larger baseline infarct size by CMR (median 15% LV [8%-20% LV]) (P < .01). Microvascular obstruction (no reflow) was greater as measured by CMR (median 2.8% [1.4%-6.1%]) in patients with a lower 90-day LVEF (P < .01). Median baseline and 24-hour NT-proBNP levels were 94 pg/mL (54-292 pg/mL) and 1,448 pg/mL (958-2,599 pg/mL), respectively. In a multivariable model with clinical, biomarker, and imaging variables, only 3 variables independently predicted 90-day LVEF: 24-hour NT-proBNP, baseline CMR infarct size, and microvascular obstruction.Conclusions: Three key pathophysiologic variables of the post-STEMI myocardium measuring baseline infarct size and the extent of microvascular obstruction on CMR and wall tension (24-hour NT-proBNP) independently predicted 90-day LVEF. Further studies linking these measures with earlier use of clinical therapies may be warranted.

Serum albumin concentration and heart failure risk: The Health, Aging, and Body Composition Study

2010-08-01

Background: How serum albumin levels are associated with risk for heart failure (HF) in the elderly is unclear.Methods: We evaluated 2,907 participants without HF (age 73.6 ± 2.9 years, 48.0% male, 58.7% white) from the community-based Health ABC Study. The association between baseline albumin and incident HF was assessed with standard and competing risks proportional hazards models controlling for HF predictors, inflammatory markers, and incident coronary events.Results: During a median follow-up of 9.4 years, 342 (11.8%) participants developed HF. Albumin was a time-dependent predictor of HF, with significance retained for up to 6 years (baseline hazard ratio [HR] per −1 g/L 1.14, 95% CI 1.06-1.22, P < .001; annual rate of HR decline 2.1%, 95% CI 0.8%-3.3%, P = .001). This association persisted in models controlling for HF predictors, inflammatory markers, and incident coronary events (baseline HR per −1 g/L 1.13, 95% CI 1.05-1.22, P = .001; annual rate of HR decline 1.8%, 95% CI 0.5%-3.0%, P = .008) and when mortality was accounted for in adjusted competing risks models (baseline HR per −1 g/L 1.13, 95% CI 1.05-1.21, P = .001; annual rate of HR decline 1.9%, 95% CI 0.7%-3.1%, P = .002). The association of albumin with HF risk was similar in men (HR per −1 g/L 1.13, 95% CI 1.05-1.23, P = .002) and women (HR per −1 g/L 1.12, 95% CI 1.04-1.22, P = .005) and in whites and blacks (HR per −1 g/L 1.13, 95% CI 1.04-1.22, P< .01 for both races) in adjusted models.Conclusions: Low serum albumin levels are associated with increased risk for HF in the elderly in a time-dependent manner independent of inflammation and incident coronary events.

Prognostic value of osteoprotegerin in chronic heart failure: The GISSI-HF trial

2010-08-01

Background: Circulating levels of osteoprotegerin (OPG), a member of the tumor necrosis factor receptor superfamily, is predictive of death and hospitalization for heart failure after acute coronary syndrome. The association between OPG and outcome in patients with chronic heart failure (CHF) is unknown.Methods: Plasma OPG levels at baseline were assessed in 1,229 patients with CHF recruited from 51 clinical centers and included in the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-Heart Failure (GISSI-HF) trial. Patients were randomized to n-3 polyunsaturated fatty acids (1 g/d) or rosuvastatin (10 mg/d) versus placebo. Osteoprotegerin was analyzed by enzyme-linked immunosorbent assay. The association between OPG and outcome was assessed by Cox proportional hazards regression models.Results: During a median follow-up time of 3.9 years, 332 patients died; and 791 patients died or were hospitalized because of cardiovascular causes. By univariate analysis, baseline OPG levels were strongly associated with the incidence of death (hazard ratio {HR} [95% CI] 1.53 [1.40-1.67] per 1-SD increase in log OPG). After adjustment for conventional risk markers, OPG remained a significant predictor of death (HR [95% CI] 1.20 [1.06-1.35], P < .001). Similar findings were observed for the composite end point (HR [95% CI] 1.34 [1.07-1.69], P = .012).Conclusion: In patients with CHF, OPG is associated with the incidence of death independently of conventional cardiovascular risk factors.

Correlation of heart-type fatty acid–binding protein with mortality and echocardiographic data in patients with pulmonary embolism at intermediate risk

2010-08-01

Background: The management strategy in patients presenting with pulmonary embolism at intermediate risk still remains controversial. Our aim was to determine the role of heart-type fatty acid–binding protein (H-FABP) in this patient population.Methods: One hundred one consecutive patients with confirmed pulmonary embolism and echocardiographic signs of right ventricular overload but without evidence for hypotension or shock, referred to as pulmonary embolism at intermediate risk, were included in the study. Heart-type fatty acid–binding protein and other biomarkers were measured in all patients upon arrival in the emergency department.Results: Of the included 101 patients, 14 had positive H-FABP tests. Ten patients with positive H-FABP (71%) had clinical deterioration during the hospital course and required inotropic support and 8 of these patients died. None of the 87 patients with a negative test worsened or needed inotropic support or died during hospital stay (P < .005). In the H-FABP–positive group, right ventricular function on echocardiography was more impaired (tricuspid annular plane systolic excursion 13 ± 4 vs 18 ± 4 mm, RV/LV ratio 1.1 ± 0.2 vs 0.9 ± 0.2, presence of paradoxical septal movement 79% vs 46%, presence of McConnell sign 100% vs 60%, respectively, all P < .05) compared to the H-FABP–negative group. After adjusting for potential confounding parameters, in multivariate analysis, H-FABP was the only independent predictor of mortality.Conclusions: Heart-type fatty acid–binding protein significantly predicts mortality in patients with pulmonary embolism at intermediate risk. Furthermore, it is significantly associated with impaired right ventricular function and shows better correlation with mortality than troponin I. It may be a novel prognostic parameter enabling the optimization of management strategy in the very difficult population of pulmonary embolism at intermediate risk.

Prognostic value of exercise echocardiography in patients with left ventricular systolic dysfunction and known or suspected coronary artery disease

2010-08-01

Background: The prognostic value of exercise echocardiography (ExE) in patients with left ventricular systolic dysfunction (LVSD) has not been characterized. We sought to assess the value of ExE for predicting outcome in patients with LVSD and known/suspected coronary artery disease.Methods: This study is a retrospective analysis of a prospectively collected database of 1,107 patients who underwent treadmill ExE and had resting LVSD (left ventricular ejection fraction <50%). Ischemia was defined as an increase in wall motion score index from rest to exercise. The end points were all-cause mortality and major cardiac events (MACE).Results: Overall, 494 patients (44.6%) developed new or worsening wall motion abnormalities. During a mean follow-up of 4.1 ± 3.4 years, 301 patients died and 166 had a MACE. In patients with mild LVSD, the 5-year mortality rate was 8.8% in those without ischemia and 21% in those with ischemia (P < .001). For patients with moderate LVSD without ischemia, the 5-year mortality rate was 18.3%, whereas it was 29.2% when ischemia was present (P = .009). In those with severe LVSD, the 5-year mortality rate was 23.9% without ischemia and 35.7% with ischemia (P = .03). In the multivariate analysis, increase in wall motion score index was an independent predictor of mortality (hazard ratio 2.25, 95% CI 1.26-2.06, P = .001) and MACE (hazard ratio 2.60, 98% CI 1.34-5.04, P = .005). The addition of the ExE results to clinical, resting echocardiography and exercise variables provided significant incremental prognostic information for predicting mortality (P = .001) and MACE (P = .005).Conclusions: The ExE provides significant information for predicting outcome in patients with LVSD and known/suspected coronary artery disease.

Predictors of early readmission or death in elderly patients with heart failure

2010-08-01

Background: Contemporary heart failure (HF) patients are elderly and have a high rate of early rehospitalization or death, resulting in a high burden for both the patients and the health care system. Prior studies were focused on younger and less well-characterized patients. We aimed to identify predictors of early hospital readmission and death in elderly patients with HF.Methods: Patients with chronic HF taking part in the TIME-CHF study (n = 614, age 77 ± 8 years, 41% female, left ventricular ejection fraction 35% ± 13%) were evaluated with respect to predictors of hospital readmission or death 30 and 90 days after inclusion. Demographic, clinical, laboratory, echocardiographic, and social variables were obtained at baseline and included in a multivariable logistic regression analysis to identify predictors of early events.Results: The rate of hospital readmission or death was high at 30 (11%) and 90 days (26%). The reason for hospitalization was HF in 33%, other cardiovascular in 32%, and noncardiovascular in 45% of the cases, respectively. Predictors of readmission or death at 30 days were angina, lower systolic blood pressure, anemia, more extensive edema, higher creatinine levels, and dry cough; and at 90 days were coronary artery disease, prior pacemaker implantation, high jugular venous pressure, pulmonary rales, prior abdominal surgery, older age, and depressive symptoms.Conclusions: Early hospital readmission or death was frequent among elderly HF patients. A very large proportion of readmissions were due to noncardiovascular causes. In addition to clinical signs of HF, comorbidities are important predictors of early events in elderly HF patients.

Aortic dissection in young adults who abuse amphetamines

Arthur N. Westover, Paul A. Nakonezny — 2010-08-01

Background: Case reports suggest a relationship between amphetamine abuse/dependence and aortic dissection, but no population-based epidemiologic studies have examined this link. Our objective was to test the hypothesis that young adults with a diagnosis of amphetamine abuse/dependence would be at higher risk for aortic dissection after accounting for known risk factors.Methods: In this population-based case-control study of 30,922,098 discharges from the Healthcare Cost and Utilization Project Nationwide Inpatient Sample from 1995 to 2007, among persons aged 18 to 49 years, we identified 3,116 thoracic and thoracoabdominal aortic dissections using International Classification of Disease, Ninth Edition, Clinical Modification codes 441.01 and 441.03. The SURVEYLOGISTIC procedure in SAS 9.2 (SAS Institute, Cary, NC) was used to account for the Nationwide Inpatient Sample sampling methodology.Results: In a multiple logistic regression analysis, while controlling for known risk factors, amphetamine abuse/dependence was significantly associated with aortic dissection (adjusted odds ratio = 3.33, 95% CI = 2.37-4.69, P < .0001).Conclusions: This statistically significant association suggests that amphetamine abuse/dependence may play a role in aortic dissection in young adults in the United States.

Cost and health outcome of primary percutaneous coronary intervention versus thrombolysis in acute ST-segment elevation myocardial infarction—Results of the Swedish Early Decision reperfusion Study (SWEDES) trial

2010-08-01

Background: In ST-elevation myocardial infarction, primary percutaneous coronary intervention (PCI) has a superior clinical outcome, but it may increase costs in comparison to thrombolysis. The aim of the study was to compare costs, clinical outcome, and quality-adjusted survival between primary PCI and thrombolysis.Methods: Patients with ST-elevation myocardial infarction were randomized to primary PCI with adjunctive enoxaparin and abciximab (n = 101), or to enoxaparin followed by reteplase (n = 104). Data on the use of health care resources, work loss, and health-related quality of life were collected during a 1-year period. Cost-effectiveness was determined by comparing costs and quality-adjusted survival. The joint distribution of incremental costs and quality-adjusted survival was analyzed using a nonparametric bootstrap approach.Results: Clinical outcome did not differ significantly between the groups. Compared with the group treated with thrombolysis, the cost of interventions was higher in the PCI-treated group ($4,602 vs $3,807; P = .047), as well as the cost of drugs ($1,309 vs $1,202; P = .001), whereas the cost of hospitalization was lower ($7,344 vs $9,278; P = .025). The cost of investigations, outpatient care, and loss of production did not differ significantly between the 2 treatment arms. Total cost and quality-adjusted survival were $25,315 and 0.759 vs $27,819 and 0.728 (both not significant) for the primary PCI and thrombolysis groups, respectively. Based on the 1-year follow-up, bootstrap analysis revealed that in 80%, 88%, and 89% of the replications, the cost per health outcome gained for PCI will be <$0, $50,000, and $100,000 respectively.Conclusion: In a 1-year perspective, there was a tendency toward lower costs and better health outcome after primary PCI, resulting in costs for PCI in comparison to thrombolysis that will be below the conventional threshold for cost-effectiveness in 88% of bootstrap replications.

Preoperative angiotensin-blocking drug therapy is not associated with atrial fibrillation after cardiac surgery

Florian Rader, David R. Van Wagoner, A. Marc Gillinov, Eugene H. Blackstone — 2010-08-01

Background: Preoperative use of angiotensin-blocking drug therapy (ABDT) with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers and its link to occurrence of postoperative atrial fibrillation (POAF), a common marker of poor outcomes after cardiac surgery, remain controversial.Methods: From 1997 to 2003, 10,552 patients underwent coronary artery bypass grafting with or without valve surgery. To adjust for differences of clinical characteristics between patients who received ABDT within 24 hours before surgery compared with those who did not, propensity score analyses were conducted.Results: Angiotensin-blocking drug therapy was prescribed in 4,795 (45%) before surgery, of which 1,725 (36%) developed POAF before discharge versus 1,908 (33%) of 5,757 patients who did not receive ABDT (unadjusted odds ratio 1.13, 95% CI 1.05-1.25, P < .01). In 6,744 propensity score–matched patients with well-balanced comorbidity profiles, ABDT was not associated with POAF (odds ratio 1.05, CI 0.95-1.16, P = .38). Stratified analysis within quintiles of propensity score and propensity-adjusted logistic multivariable regression confirmed these findings.Conclusions: In this large observational study, we found no evidence of an association between preoperative angiotensin blockade and the occurrence of POAF. Adequately powered randomized studies are needed to clarify the best strategy of perioperative ABDT in patients with and without guideline-based indications.

Comparison of the clinical outcome after pulmonary vein isolation based on the appearance of adenosine-induced dormant pulmonary vein conduction

2010-08-01

Background: The elimination of transient pulmonary vein (PV) reconduction (dormant PV conduction) revealed by adenosine in addition to PV isolation reduced the atrial fibrillation (AF) recurrence after catheter ablation. The dormant PV conduction is induced in approximately half of the AF patients that undergo PV isolation. The present study compared the clinical outcome of AF ablation in patients whose dormant PV conduction was eliminated by additional radiofrequency applications with the outcome in patients without dormant conduction.Methods: A total of 233 consecutive patients (206 male, 54.2 ± 10.1 years) that underwent AF ablation were included in the present study. Dormant PV conduction was induced by the administration of adenosine triphosphate after PV isolation and was eliminated by supplemental radiofrequency application. All patients were followed up for >12 months (mean 903 days) after the first ablation.Results: Following PV isolation, dormant PV conduction was induced in 139 (59.7%) of 233 patients and was successfully eliminated in 98% (223/228) of those in the first ablation procedure. After the first procedure, 63.9% (149/233) of patients were free from AF recurrence events. The success rates of a single or final AF ablation in patients with the appearance of the dormant PV conduction were similar to those of patients without dormant conduction (P = .69 and P = .69, respectively).Conclusions: Dormant PV conduction was induced in over half of the patients with AF. After the elimination of adenosine triphosphate–induced reconnection, the clinical outcome of patients with the dormant PV conduction was equivalent to that of patients without conduction.

Adenosine diphosphate–induced platelet-fibrin clot strength: A new thrombelastographic indicator of long-term poststenting ischemic events

2010-08-01

Background: Poststenting ischemic events occur despite dual-antiplatelet therapy, suggesting that a “one size fits all” antithrombotic strategy has significant limitations. Ex vivo platelet function measurements may facilitate risk stratification and personalized antiplatelet therapy.Methods: We investigated the prognostic utility of the strength of adenosine diphosphate (ADP)–induced (MAADP) and thrombin-induced (MATHROMBIN) platelet-fibrin clots measured by thrombelastography and ADP-induced light transmittance aggregation (LTAADP) in 225 serial patients after elective stenting treated with aspirin and clopidogrel. Ischemic and bleeding events were assessed over 3 years.Results: Overall, 59 (26%) first ischemic events occurred. Patients with ischemic events had higher MAADP, MATHROMBIN, and LTAADP (P < .0001 for all comparisons). By receiver operating characteristic curve analysis, MAADP >47 mm had the best predictive value of long-term ischemic events compared with other measurements (P < .0001), with an area under the curve = 0.84 (95% CI 0.78-0.89, P < .0001). The univariate Cox proportional hazards model identified MAADP >47 mm, MATHROMBIN >69 mm, and LTAADP >34% as significant independent predictors of first ischemic events at the 3-year time point, with hazard ratios of 10.3 (P < .0001), 3.8 (P < .0001), and 4.8 (P < .0001), respectively. Fifteen bleeding events occurred. Receiver operating characteristic curve and quartile analysis suggests MAADP ≤31 as a predictive value for bleeding.Conclusion: This study is the first demonstration of the prognostic utility of MAADP in predicting long-term event occurrence after stenting. The quantitative assessment of ADP-stimulated platelet-fibrin clot strength measured by thrombelastography can serve as a future tool in investigations of personalized antiplatelet treatment designed to reduce ischemic events and bleeding.

Platelet response to clopidogrel and restenosis in patients treated predominantly with drug-eluting stents

2010-08-01

Background: Preclinical studies suggest a relationship between early thrombotic response after vascular injury and later development of restenosis. The aim of this study was to assess the impact of platelet response to clopidogrel on the risk of restenosis after drug-eluting stenting (DES).Methods: A total of 1,608 consecutive patients were previously enrolled in a study on the relation between platelet reactivity and outcomes after DES. All patients received a loading dose of 600 mg clopidogrel. Blood samples for the assessment of adenosine diphosphate–induced platelet aggregation with multiple electrode platelet aggregometry were drawn directly before percutaneous coronary intervention. Clopidogrel low response was defined as upper quintile of multiple electrode platelet aggregometry measurements. Accordingly, 323 patients (20%) were considered as low and 1,285 (80%) as normal responders. Primary end point of the present study was target lesion revascularization at 1 year. Secondary end points included binary angiographic restenosis and late lumen loss at 6- to 8-month angiography.Results: Target lesion revascularization rates were comparable in both groups (10.9% vs 9.5%, hazard rate [HR] 1.2, 95% CI 0.8-1.7, P = .441). Follow-up angiography revealed no difference in binary angiographic restenosis (13.9% vs 15.9%, P = .445) and late lumen loss (0.32 ± 0.64 vs 0.35 ± 0.63 mm, P = .477). Low responders had significantly more stent thromboses (2.5% vs 0.5%, HR 5.4, 95% CI 1.9-15.6, P = .002), Q wave myocardial infarctions (2.5% vs 0.6%, HR 4.0, 95% CI 1.5-10.7, P = .005), and ischemic strokes (1.3% vs 0.2%, HR 5.4, 95% CI 1.2-24.0, P = .028) at 1 year.Conclusion: Low platelet responsiveness to clopidogrel, a known predictor of thrombotic complications, does not have a significant impact on restenosis after DES.

Incidence and clinical relevance of anti–platelet factor 4/heparin antibodies before cardiac surgery

2010-08-01

Background: Heparin-induced thrombocytopenia (HIT) is caused by anti–platelet factor 4/heparin (PF4/H) immunoglobulin (Ig) G antibodies, which activate platelets. In some patients, anti-PF4/H antibodies are already detectable before cardiac surgery. Whether preoperative presence of antibodies confers adverse prognosis and which particular antibody classes (IgG, IgA, IgM) might be implicated are unknown.Methods: We prospectively screened 591 patients undergoing cardiopulmonary bypass surgery for heparin-dependent antibodies by PF4/H immunoassay (separately for IgG, IgA, and IgM) and platelet activation test at preoperative baseline and at days 6 and 10. All patients received heparin or low–molecular-weight heparin postsurgery regardless of antibody status and were followed for postoperative complications, frequency of HIT, length of hospital stay, and 30-day mortality.Results: Anti-PF4/H antibodies of any class were detected at preoperative baseline in 128 (21.7%) of 591 patients: IgG n = 44 (7.4%), IgA n = 36 (6.1%), and IgM n = 79 (13.4%); some patients had >1 antibody class. Neither IgG nor IgA was a risk factor for any adverse outcome parameter. However, preoperative presence of IgM antibodies was associated with an increased risk for nonthromboembolic complications (all complications combined: hazard ratio 1.73, 95% CI 1.15-2.61) and a longer in-hospital stay (P = .02), but without evidence for increased risk of thrombotic complications or subsequent HIT.Conclusions: Patients with preoperative anti-PF4/H antibodies of IgG and IgA class are not at increased risk for thrombotic or nonthrombotic adverse events, whereas those with baseline anti-PF4/H IgM had an increased risk of nonthrombotic adverse outcomes but not of subsequent HIT or thrombosis. Because IgM antibodies do not cause HIT, they could represent a surrogate marker for other heparin-independent risk factors.

Effectiveness and safety of drug-eluting stents in vein grafts: A meta-analysis

Eliano Pio Navarese, Antonino Buffon, Giuseppe De Luca, Stefano De Servi — 2010-08-01

We read with interest the study by Joyal et al titled “Effectiveness and safety of drug-eluting stents in vein grafts: A meta-analysis.” However, there are several methodological drawbacks that flawed the present analysis. First of all, literature research and inclusion process of the observational studies are incomplete for a meta-analysis largely driven by nonrandomized data. In particular, recent observational studies with >2000 patients enrolled were not included in the prespecified analysis for observational studies. In addition, selection as an end point of overall “MACEs” is incorrect because of different single clinical outcomes incorporated in MACE definition applied in several trials. Second issue of concern is that internal validity of studies included was not investigated. Meta-analyses of observational studies face the challenge of incorporating studies with various quality levels. Including studies of various quality levels can mask or reverse effect direction. The “Newcastle-Ottawa Scale” for assessing quality of nonrandomized studies in meta-analyses is quite comprehensive and has been recommended by the Cochrane Non-Randomized Studies Methods Working Group. Third issue is the “publication bias” that was not investigated in the study of Joyal et al; studies with negative results can take longer to be published, and results not conforming to the desired outcome may not even be reported. An investigation of this bias can be performed using a graphical test, such as a funnel plot, which is created by plotting the estimated treatment effect against the study size. Finally, significant heterogeneity was found in the analysis of data. However, no effort was made to explain it. Investigation of heterogeneity is a key issue when dealing with observational nonrandomized studies, where potential uncontrolled confounders might flaw pooled estimates of the meta-analysis.

Response to the letter regarding the article “Effectiveness and safety of drug-eluting stents in vein grafts: A meta-analysis“

Kristian B. Filion, Dominique Joyal, Mark J. Eisenberg — 2010-08-01

We thank Dr Navarese et al for their interest in our meta-analysis entitled “Effectiveness and safety of drug-eluting stents in vein grafts: A meta-analysis” and for the opportunity to clarify some of the methodological issues raised in their letter.

Low-molecular-weight heparin versus unfractionated heparin in acute ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention with drug-eluting stents

Wail Nammas, Khaled Hossam — 2010-08-01

With great interest, we read the article “Low-molecular-weight heparin versus unfractionated heparin in acute ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention with drug-eluting stents” by Li et al. Indeed, they are to be congratulated for their well-powered, multicenter, prospective, real-world study which concluded that antithrombotic therapy with subcutaneous enoxaparin plus periprocedural reduced-dose unfractionated heparin (UFH) (50 U/kg) in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention with drug-eluting stents showed a lower incidence of in-hospital cardiac and total death versus UFH alone. Eventually, this was translated into a reduction of 8-month mortality and major adverse cardiac events.

Response to the letter regarding the article “Low-molecular-weight heparin versus unfractionated heparin in acute ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention with drug-eluting stents”

2010-08-01

We thank Drs Nammas and Hossam for their interest in our article and for raising some concerns. They suggested that the rate of in-hospital death in the unfractionated heparin (UFH) group is quite high (cardiac and total death: 4.7% and 6.3%, respectively) and is far beyond the usual figures reported in literature and that the significantly higher death in this group at 8 months was chiefly driven by this unacceptably higher in-hospital mortality. We do understand their concerns about the high in-hospital mortality in the UFH group, but our study is different from the previously reported literature. The present study was derived from a prospectively designed registry reflecting the real-world clinical practice in the era of drug-eluting stents. In the present study, we even enrolled patients with worse baseline characteristics including patients with advanced heart failure (Killip grade IV: 6.4% in the UFH group and 6.8% in the low–molecular-weight heparin group), which might have caused the higher rate of in-hospital mortality as compared with other previous randomized studies. We totally agree with the opinion of Drs Nammas and Hossam that the criterion standard in trial design for the comparison between 2 strategies is the prospective, randomized, controlled trial. However, randomized trials are not always perfect because they usually have highly selected patients with relatively lower risk profiles treated in a nonroutine setting. Therefore, a multicenter registry study with larger study population such as our study may help to complete the picture gained from randomized trials.

Detection of elevated right atrial pressure using a simple bedside ultrasound measure

Viroj Wiwanitkit — 2010-08-01

I read the recent publication by Simon et al with a great interest. Simon et al concluded that “An increase in RIJV CSA >17% during Valsalva effectively rules out elevated RAP. This simple bedside technique may be useful to assess central venous pressure and reduce the need for invasive pressure measurement.” I agree that the bedside ultrasound measure might be an alternative noninvasive technique for assessment of right atrial pressure. However, there are some concerns on the report by Simon et al. The specificity of the test is poor, and the sensitivity is only fair. Hence, it is still questionable for the effectiveness of this alternative method for measurement of right atrial pressure. The problem of false-positive in the ultrasound for determining right heart stress is mentioned. Similar to a previous report on the use of pulsatile lower limb venous Doppler waveform determintation, a good correlation to the right atrial pressure might be derived from internal jugular ultrasonography, but the poor diagnostic property might make this imaging approach unable to be used to screen for right-sided heart failure.

Response to the letter regarding the article Detection of elevated right atrial pressure using a simple bedside ultrasound measure

2010-08-01

We appreciate the comments regarding our recent publication. With any test, there are pros and cons as to its effectiveness. This is particularly true of noninvasive estimates of pressure, which have been a vexing problem in cardiovascular imaging. As we reported, the value of this test is in its simplicity and clear relation to vascular physiology. Dr Wiwanitkit has interpreted our conclusion that “An increase in RIJV CSA >17% during Valsalva rules out elevated RAP” means “specificity.” However, we are in fact referring to the negative predictive value, which, at 94%, is very powerful. We are uncertain as to how 90% sensitivity can be classified as only fair and 74% specificity as poor, but clearly this is open to interpretation. Test characteristics are a function of the cutoff value used; and for our report, there were actually very few false positives (Figure 3, right quadrant defined by right atrial pressure >12 mm Hg and RIJV CSA >17%) because we felt it important to err on the side of more false negatives and less false positives. Therefore, this test appears to be an advance from those mentioned by Dr Wiwanitkit. We are continuing to evaluate this technique and hope to provide more data for discussion soon.

2010-08-01

Editorial Board

2010-08-01

Information for Readers

2010-08-01

American Heart Journal

A review of dyspnea in acute heart failure syndromes

Intramyocardial injection of autologous bone marrow mononuclear cells for patients with chronic ischemic heart disease and left ventricular dysfunction (First Mononuclear Cells injected in the US [FOCUS]): Rationale and design

The new high-sensitivity cardiac troponin T assay improves risk assessment in acute coronary syndromes

High burden of cardiovascular disease risk factors in Mexico: An epidemic of ischemic heart disease that may be on its way?

Transcatheter aortic valve implantation for severe aortic stenosis—a new paradigm for multidisciplinary intervention: A prospective cohort study

Application of appropriatenes criteria to stress single photon emission computed tomography sestamibi studies: A comparison of the 2009 revised appropriateness criteria to the 2005 original criteria

Joint effects of common genetic variants from multiple genes and pathways on the risk of premature coronary artery disease

Economic analysis of a tailored behavioral intervention to improve blood pressure control for primary care patients

Diuretic dose and long-term outcomes in elderly patients with heart failure after hospitalization

Predicting chronic left ventricular dysfunction 90 days after ST-segment elevation myocardial infarction: An Assessment of Pexelizumab in Acute Myocardial Infarction (APEX-AMI) Substudy

Serum albumin concentration and heart failure risk: The Health, Aging, and Body Composition Study

Prognostic value of osteoprotegerin in chronic heart failure: The GISSI-HF trial

Correlation of heart-type fatty acid–binding protein with mortality and echocardiographic data in patients with pulmonary embolism at intermediate risk

Prognostic value of exercise echocardiography in patients with left ventricular systolic dysfunction and known or suspected coronary artery disease

Predictors of early readmission or death in elderly patients with heart failure

Aortic dissection in young adults who abuse amphetamines

Cost and health outcome of primary percutaneous coronary intervention versus thrombolysis in acute ST-segment elevation myocardial infarction—Results of the Swedish Early Decision reperfusion Study (SWEDES) trial

Preoperative angiotensin-blocking drug therapy is not associated with atrial fibrillation after cardiac surgery

Comparison of the clinical outcome after pulmonary vein isolation based on the appearance of adenosine-induced dormant pulmonary vein conduction

Adenosine diphosphate–induced platelet-fibrin clot strength: A new thrombelastographic indicator of long-term poststenting ischemic events

Platelet response to clopidogrel and restenosis in patients treated predominantly with drug-eluting stents

Incidence and clinical relevance of anti–platelet factor 4/heparin antibodies before cardiac surgery

Effectiveness and safety of drug-eluting stents in vein grafts: A meta-analysis

Response to the letter regarding the article “Effectiveness and safety of drug-eluting stents in vein grafts: A meta-analysis“

Low-molecular-weight heparin versus unfractionated heparin in acute ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention with drug-eluting stents

Response to the letter regarding the article “Low-molecular-weight heparin versus unfractionated heparin in acute ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention with drug-eluting stents”

Detection of elevated right atrial pressure using a simple bedside ultrasound measure

Response to the letter regarding the article Detection of elevated right atrial pressure using a simple bedside ultrasound measure

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