American Journal of Cardiology

Low-Density Lipoprotein and Noncalcified Coronary Plaque Composition in Patients With Newly Diagnosed Coronary Artery Disease on Computed Tomographic Angiography

2010-02-08

We sought to determine significant relations between atherogenic lipoproteins and the contribution of calcified plaque (CP), mixed plaque (MP), and noncalcified plaque (NCP) to the total plaque (TP) burden in patients without previous coronary artery disease. From 823 adult patients without previously established coronary artery disease (52% receiving statin therapy, 34% asymptomatic) but with visible coronary plaque on coronary computed tomographic angiography, we obtained segmental CP, MP, NCP, and TP counts from contrast-enhanced, electrocardiographic-gated computed tomography. Multivariate linear regression analysis was used to determine the associations of clinical factors and lipoprotein levels to CP, MP, and NCP counts and CP/TP, MP/TP, and NCP/TP count ratios. Age, male gender, diabetes, smoking, and statin therapy were significantly associated with the CP count (p <0.001, p <0.001, p = 0.049, p = 0.016, and p = 0.003, respectively). Low-density lipoprotein (LDL) cholesterol was significantly associated with MP and NCP counts (all p values ≤0.002). LDL cholesterol was also the only variable to demonstrate significant concurrent relations with CP/TP, MP/TP, and NCP/TP ratios, including an inverse association with CP/TP (p = 0.008) and a positive association with MP/TP (p = 0.032). Analyses using non–high-density lipoprotein cholesterol in place of LDL cholesterol yielded similar results. In conclusion, among the traditional clinical factors used to estimate cardiovascular event risk, LDL cholesterol is associated with an increased MP and NCP burden and is the sole variable that independently predicted relative predominance of CP, MP, and NCP, suggesting a potentially important role for lipoprotein levels in modulating the type of detectable coronary arterial plaque.

Evaluation of Contraindications and Efficacy of Oral Beta Blockade Before Computed Tomographic Coronary Angiography

2010-02-08

Multidetector computed tomographic coronary angiography (CTA) image quality is inversely related to the heart rate (HR). As a result beta-blocking medication is routinely administered before investigation. In the present study, the use, contraindications, and efficacy of prescan beta blockade with regard to HR reduction and CTA image quality were assessed. In 537 patients referred for CTA, the baseline HR and blood pressure were measured on arrival, and contraindications for beta blockade were noted. Unless contraindicated, a single dose of metoprolol was administered orally 1 hour before data acquisition in patients with a HR of ≥65 beats/min according to a predefined medication protocol. After 1 hour, the HR was remeasured. A total of 283 patients (53%) had a HR of ≥65 beats/min. In this group, beta blockade was contraindicated in 46 patients (16%). Metoprolol was administered to the remaining 237 patients. However, 26 patients (11%) received suboptimal (lower dose than prescribed by protocol) beta blockade because of contraindications. Of the 211 patients receiving optimal beta blockade, 57 (27%) did not achieve the target HR. Of the patients with contraindications to beta blockade, 43 (60%) did not achieve the target HR. Compared to patients with optimal HR control, those receiving no or suboptimal beta blockade because of contraindications had significantly fewer examinations of good image quality (40% vs 74%, p <0.001), and significantly more examinations of poor image quality (20% vs 6%, p <0.001). In conclusion, most patients require HR reduction before CTA. Contraindications to beta blockade are present in a substantial proportion of patients. This results in suboptimal HR control and image quality, indicating the need for alternative approaches for HR reduction.

Comparison of Usefulness of Exercise Testing Versus Coronary Computed Tomographic Angiography for Evaluation of Patients Suspected of Having Coronary Artery Disease

2010-02-08

In patients suspected of having coronary artery disease (CAD), we compared the diagnostic sensitivity and specificity of exercise testing using ST-segment changes alone and ST-segment changes, angina pectoris, and hemodynamic variables compared to coronary computed tomographic angiography (CTA). Quantitative invasive coronary angiography was the reference method (>50% coronary lumen reduction). A positive exercise test was defined as the development of significant ST-segment changes (≥1 mV measured 80 ms from the J-point), and the occurrence of one or more of the following criteria: ST-segment changes ≥1 mV measured 80 ms from the J-point, angina pectoris, ventricular arrhythmia (the occurrence of ≥3 premature ventricular beats), and ≥20 mm Hg decrease in systolic blood pressure during the test. Positive results on CTA were defined as a coronary lumen reduction of ≥50%. In 100 patients (61 ± 9 years old, 50% men, and 29% prevalence of significant CAD), the diagnostic sensitivity and specificity of exercise testing using ST-segment changes was 45% (95% confidence interval 53% to 87%) and 63% (95% confidence interval 61% to 84%), respectively. However, the inclusion of all test variables yielded a sensitivity of 72% (95% confidence interval 53% to 87%) and a specificity of 37% (95% confidence interval 26% to 49%). The diagnostic sensitivity of 97% (95% confidence interval 82% to 100%) and specificity of 80% (95% confidence interval 69% to 89%) for CTA, however, were superior to any of the exercise test analysis strategies. In conclusion, in patients suspected of having CAD, the diagnostic sensitivity of exercise testing significantly improves if all test variables are included compared to using ST-segment changes exclusively. Furthermore, the superior diagnostic performance of CTA for the detection and exclusion of significant CAD might favor CTA as the first-line diagnostic test in patients suspected of having CAD.

Prognostic Value of an Exaggerated Exercise Blood Pressure Response in Patients With Diabetes Mellitus and Known or Suspected Coronary Artery Disease

2010-03-15

The prognostic value of an exaggerated exercise systolic blood pressure response (EESBPR) remains controversial. Our aim was to assess whether an EESBPR is associated with the long-term outcome in patients with diabetes mellitus and known or suspected coronary artery disease (CAD). From an initial population of 22,262 patients with known or suspected CAD who underwent treadmill exercise electrocardiography or exercise echocardiography at our institution, 2,591 patients with a history of diabetes mellitus were selected for the present study. EESBPR was defined as systolic blood pressure >220 mm Hg during exercise. The end points were all-cause mortality and hard events (ie, death or myocardial infarction). A total of 236 patients (9.1%) developed an EESBPR during the tests. During a mean follow-up of 6.5 ± 3.9 years, 484 patients died and 646 experienced hard events. The 10-year mortality rate was 16.6% in patients with an EESBPR compared to 30.9% in those without an EESBPR (p <0.001). The 10-year hard event rate was also lower in patients with an EESBPR (23.2% vs 38.9% in patients without an EESBPR; p <0.001). On multivariate analysis, an EESBPR remained independently associated with a lower risk of all-cause mortality (hazard ratio 0.53, 95% confidence interval 0.36 to 0.78, p = 0.001) and hard events (hazard ratio 0.57, 95% confidence interval 0.41 to 0.79; p <0.001). These results remained consistent in the subgroup of patients without a known history of CAD. In conclusion, an EESBPR was associated with improved survival and a lower rate of death or myocardial infarction in patients with diabetes mellitus and known or suspected CAD.

Comparison of Evidence-Based Versus Non–Evidence-Based Pharmacotherapy on the Risk of Cardiovascular Hospitalization and All-Cause Mortality Among Patients With Established Cardiovascular Disease

Gregory A. Nichols, Fang Wang, Kathryn L. Pedula — 2010-02-08

Landmark studies have proved that several therapies reduce cardiovascular disease (CVD) risk; however, the rates of secondary CVD in the context of therapies delivered according to current guidelines are largely unknown. Therefore, we sought to estimate the incidence of secondary CVD hospitalizations and all-cause mortality among patients who did and did not receive guideline-level pharmacotherapy. For the 12,278 patients added to the Kaiser Permanente, Northwest CVD registry in 2000 to 2005, we used the pharmacy records to define guideline-level care (GLC) as at least one dispense of aspirin/antiplatelets, statins, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and β blockers within 6 months after registry enrollment. We followed patients until they died, experienced a CVD hospitalization, or June 30, 2008. We compared the age- and gender-adjusted incidence rates per 1,000 person-years of CVD hospitalization, death, and the composite, and estimated the hazard ratios using Cox regression analysis. During a mean follow-up of 45.8 ± 22.8 months, 25% of the study sample experienced the composite outcome. The age- and gender-adjusted incidence per 1,000 person-years of the composite outcome was significantly lower among GLC patients (hazard ratio 50.3, 95% confidence interval [CI] 46.6 to 54.3) versus non-GLC patients (hazard ratio 60.7, 95% CI 58.1 to 63.4). The difference was driven by lower mortality rates (hazard ratio 18.1, 95% CI 16.1 to 20.4 vs hazard ratio 28.1, 95% CI 26.3 to 30.0). The incidence of CVD hospitalizations did not differ significantly between the 2 groups (hazard ratio 29.2, 95% CI 26.4 to 32.2 vs hazard ratio 27.7, 95% CI 26.0 to 29.5). Multivariate adjustment resulted in a marginally significant 8% lower risk of the composite outcome among GLC recipients (hazard ratio 0.92, 95% CI 0.83 to 1.01, p = 0.067). In conclusion, treatment according to current guidelines was significantly associated with reduced mortality but not the risk of secondary hospitalizations.

Endothelial Nitric Oxide Synthase T-786C Mutation, A Reversible Etiology of Prinzmetal's Angina Pectoris

Charles J. Glueck, Jitender Munjal, Ayub Khan, Muhammad Umar, Ping Wang — 2010-02-08

Because the endothelial nitric oxide synthase (eNOS) T-786C polymorphism is associated with reduced nitric oxide production and coronary artery spasm in Japanese patients, we speculated that it might be reversibly associated with Prinzmetal's variant angina in white Americans. Polymerase chain reaction analyses of eNOS T-786C and stromelysin 5A6A polymorphisms were done in 31 women and 12 men (42 white and 1 black American, median age 50 years), with well-documented Prinzmetal's variant angina. We matched each case with 1 healthy control by race and gender. Of the 43 cases, 21 (49%) were homozygous for wild-type normal eNOS, 19 (44%) were T-786C heterozygotes, and 3 (7%) were T-786C homozygotes. Of the 43 controls, 31 (72%) were homozygous for wild-type normal eNOS, 12 (28%) were T-786C heterozygotes, and 0 (0%) were T-786C homozygotes (p = .013). The mutant eNOS T-786C allele frequency in patients was 25 (29%) of 86 vs 12 (14%) of 86 in the controls (p = 0.016). Patients did not differ from controls for the distribution of the stromelysin 6A mutation (p = 0.66) or for the mutant 6A allele frequency (53% in cases, 50% in controls; p = 0.65). Nineteen patients took nitric oxide-elevating l-arginine (9.2 g/day, orally). Of these 19 patients, 10 (53%) became free of angina, 3 (16%) were improved but not angina free, and 6 (32%) had no change in their angina. Using l-arginine, the physical ability score (Seattle Angina Questionnaire) increased from a median of 42 to 72 of a total possible score of 100 (p = 0.011), satisfaction with symptom reduction increased from 53 to 61 (p = 0.004), and the perception of quality of life as acceptable increased from 29 to 50 (p = 0.001). In conclusion, the eNOS T-786C mutation appears to be a reversible etiology of Prinzmetal's variant angina in white Americans whose angina might be ameliorated by l-arginine.

Usefulness of Soluble Fas Levels for Improving Diagnostic Accuracy and Prognosis for Acute Coronary Syndromes

2010-03-15

Although both inflammation and apoptosis occur in acute coronary syndromes (ACSs), previous studies have not tested the diagnostic and prognostic utility of an approach that measures circulating markers of these pathways. The aim of the present study was to assess whether measuring soluble Fas (sFas) and high-sensitivity C-reactive protein (hs-CRP), as markers of apoptosis and inflammation, improve ACS diagnostic and prognostic accuracy. In a prospective cohort of consecutive subjects admitted to the hospital for suspicion of ACS, we measured sFas, hs-CRP, and troponin T in those who had a final noncardiac chest pain diagnosis (n = 100), those who had an ACS diagnosis and experienced (n = 218) or did not experience (n = 170) recurrent cardiac events during 1 year of follow-up. sFas was strongly and independently associated with a discharge diagnosis of an ACS versus noncardiac chest pain during the index hospitalization (odds ratio 16.16 for the second vs first tertile, 95% confidence interval [CI] 7.07 to 36.91; and odds ratio 25.40 for the third vs first tertile, 95% CI 9.38 to 68.75). However, hs-CRP was not. sFas significantly improved the diagnostic accuracy for ACSs (C statistic increased from 0.85 to 0.93, difference +0.08, 95% CI for the difference 0.05 to 0.11). The sFas levels were high and did not vary with time in the subjects having early versus late measurements (β 0.00 ln pg/ml/hour, 95% CI −0.01 to 0.01). In contrast, troponin increased with time since the beginning of the symptoms (β 0.07 ln μg/L/hour, 95% CI 0.04 to 0.10). Baseline sFas and hs-CRP did not predict recurrent cardiac events. In conclusion, our results suggest that in suspected ACS cases, sFas, but not hs-CRP, helps to improve the diagnostic accuracy and timeliness over and above standard diagnostic criteria.

Results of Intracoronary Stem Cell Therapy After Acute Myocardial Infarction

2010-02-08

To assess the effect of autologous bone-marrow cell (BMC) therapy in patients with acute myocardial infarction in a rigorous double-blind, randomized, placebo-controlled trial. Patients with reperfusion >6 hours after symptom onset were randomly assigned in a 2:1 ratio to receive intracoronary BMC or placebo therapy 5 to 7 days after symptom onset. The patients were stratified according to age, acute myocardial infarction localization, and left ventricular (LV) function. Rigorous double-blinding was ensured using autologous erythrocytes for the placebo preparation that was visually indistinguishable from the active treatment. Serial cardiac magnetic resonance imaging studies were performed before study therapy and after 1, 3, and 6 months. The primary end point was the difference in the LV ejection fraction from baseline to 6 months. The secondary end points included changes in the LV end-diastolic and end-systolic volume indexes and infarct size. A total of 42 patients were enrolled (29 in the BMC group and 13 in the placebo group) in the integrated pilot phase. A mean of 381 × 106 mononuclear BMCs were administered. The baseline clinical and cardiac magnetic resonance imaging parameters did not differ. Compared to baseline, the difference in LV ejection fraction for the placebo group versus BMC group was 1.7 ± 6.4% versus −0.9 ± 5.5% at 1 month, 3.1 ± 6.0% versus 1.9 ± 4.3% at 3 months, and 5.7 ± 8.4% versus 1.8 ± 5.3% at 6 months (primary end point; not significant). No difference was found in the secondary end points between the 2 groups, including changes in infarct size or LV end-diastolic and end-systolic volume indexes. In conclusion, in this rigorous double-blind, randomized, placebo-controlled trial, we did not observe an evidence for a positive effect for intracoronary BMC versus placebo therapy with respect to LV ejection fraction, LV volume indexes, or infarct size.

Comparison of Outcomes Between Zotarolimus- and Sirolimus-Eluting Stents in Patients With ST-Segment Elevation Acute Myocardial Infarction

2010-03-15

Zotarolimus-eluting stents (ZESs) demonstrated greater in-segment late luminal loss and in-segment binary restenosis rates compared to sirolimus-eluting stents (SESs) in several studies. However, no data are available in direct comparison between the clinical outcomes of the 2 stents in unselected patients with ST-segment elevation acute myocardial infarction (STEMI). The aim of the present study was to compare the clinical outcomes of ZESs and SESs in real-world patients with STEMI. A total of 873 patients with STEMI (306 patients in the ZES group and 567 patients in the SES group) were enrolled in a nationwide prospective Korea Acute Myocardial Infarction Registry (KAMIR) from January 2007 to January 2008. The primary end points were major adverse cardiac events, a composite of all causes of death, myocardial infarction, and target lesion revascularization during a 12-month clinical follow-up. During 1 year of follow-up, the primary end points occurred in 140 patients (16.0%). The use of glycoprotein IIb/IIIa inhibitors and the occurrence of multivessel disease were more common in the SES group. The SES group had a significantly lower incidence of major adverse cardiac events (hazard ratio [HR] 1.52, 95% confidence interval [CI] 1.07 to 2.16, p = 0.02), target lesion revascularization (HR 2.16, 95% CI 1.01 to 4.59, p = 0.046), and target vessel revascularization (HR 2.24, 95% CI 1.18 to 4.24, p = 0.013). However, no significant differences were found in death or myocardial infarction (HR 1.37, 95% CI 0.91 to 2.05, p = 0.129). In conclusion, SESs provided superior angiographic outcomes, translating into better clinical outcomes and negating any change in STEMI patient safety profiles compared to ZESs.

Outcomes in Diabetic Versus Nondiabetic Patients Who Present With Acute Myocardial Infarction and Are Treated With Drug-Eluting Stents

2010-02-08

Patients with diabetes mellitus (DM) are at a greater risk of mortality and cardiovascular events after percutaneous coronary intervention than those without DM. We aimed to determine whether differences exist in the long-term mortality of patients with versus without DM who present with acute myocardial infarction and receive drug-eluting stents. Data were collected on 161 patients with and 395 without DM referred for primary percutaneous coronary intervention for acute myocardial infarction and treated with drug-eluting stents. The patients with cardiac arrest or cardiogenic shock were excluded. The 1-year major cardiac event (MACE) rates, defined as death, Q-wave myocardial infarction, or target lesion revascularization, were compared between the 2 groups. The patients with DM were sicker at baseline. The MACE rates at 1 year were significantly increased in those with DM compared to those without DM. This was primarily driven by all-cause mortality. No differences in Q-wave myocardial infarction, target lesion revascularization, stent thrombosis, type of drug-eluting stents used, or procedure-related renal failure were seen. No differences were found in death or MACE rates at 1 year after adjusting for age, gender, race, systemic hypertension, peripheral artery disease, and a history of chronic renal failure between the 2 groups (weighted log-rank statistic, p = 0.37 and p = 0.37, respectively). In patients presenting with acute myocardial infarction, those with DM were sicker than those without DM. In conclusion, after correction for co-morbid conditions, no difference was seen in the 1-year MACE or death rates between those with and without DM who presented with acute myocardial infarction and were treated with drug-eluting stents.

Long-Term Prognostic Value of Preprocedural C-Reactive Protein After Drug-Eluting Stent Implantation

2010-03-15

C-reactive protein (CRP) elevation is associated with an adverse cardiovascular prognosis after bare metal stent implantation. Data have suggested a similar association between preprocedural CRP and adverse events after drug-eluting stent (DES) implantation. The present study was designed to address whether such a relation exists after DES placement. After excluding patients presenting with an acute coronary syndrome with troponin I elevation, we analyzed the data from 936 consecutive patients who had undergone DES implantation from 2003 to 2007 and had a preprocedural CRP measurement. The patients were divided into 3 groups according to the preprocedural CRP level (<1.31, 1.31–3.76, and >3.76 mg/L). The primary end point was the composite of death and Q-wave myocardial infarction (QWMI) at 2 years of follow-up. Target vessel revascularization was also assessed. The rate of death/QWMI was not significantly different statistically among the CRP tertiles during the in-hospital period (0.6% vs 0.0% vs 0.6%, p = 0.5) or at 1 year of follow-up (1.9% vs 2.9% vs 4.5%, p = 0.2). At 2 years, death/QWMI had occurred in 2.9% of patients in the lowest, 5.2% in the middle, and 8.8% in the highest tertile (p = 0.006). The incidence of target vessel revascularization was similar in the 3 groups at 2 years of follow-up (13.2% vs 14.9% vs 16.9%, p = 0.5). On multivariate analysis, the upper tertile of CRP was an independent predictor of death/QWMI at 2 years (hazard ratio 2.5, 95% confidence interval 1.1 to 5.4, tertile 3 vs tertile 1, p = 0.006). In conclusion, high preprocedural CRP levels are associated with an increased risk of death and QWMI after DES implantation at long-term follow-up but not acutely. The CRP levels were not related to target vessel revascularization. Thus, an elevated CRP level in this population appears to be more of a marker of global cardiovascular risk than a predictor of post–DES-related complications.

Relation of Proton Pump Inhibitor Use After Percutaneous Coronary Intervention With Drug-Eluting Stents to Outcomes

2010-02-08

Recent evidence has shown that clopidogrel and proton pump inhibitors (PPIs) are metabolized by the same pathway and that patients taking both drugs have greater levels of platelet reactivity and more adverse outcomes than patients taking only clopidogrel. We sought to examine the effect of a PPI at discharge from the hospital after percutaneous coronary intervention with drug-eluting stents on the incidence of major adverse cardiac events (MACE) at 1 year. We compared 502 patients who were not prescribed a PPI at discharge and 318 patients who were prescribed a PPI. All patients were taking clopidogrel. We followed patients for 1 year with regard to MACE, including death, Q-wave myocardial infarction, target vessel revascularization, and stent thrombosis. We performed multivariate Cox regression to adjust for confounding variables, including compliance with clopidogrel, to assess the effect of a PPI at discharge on the 1-year outcomes. The baseline characteristics of patients discharged with a PPI were similar to those of patients discharged without a PPI. Univariate survival analysis of the outcomes showed a greater rate of MACE (13.8% vs 8.0%, p = 0.008) and overall mortality (4.7% vs 1.8%, p = 0.02) in the PPI group. After multivariate analysis, the adjusted MACE hazard ratio for PPI at discharge was 1.8 (95% confidence interval 1.1 to 2.7, p = 0.01). In conclusion, in patients undergoing percutaneous coronary intervention with drug-eluting stents and receiving clopidogrel, the prescription of a PPI at discharge was associated with a greater rate of MACE at 1 year.

Blunting of the Heart Rate Response to Adenosine and Regadenoson in Relation to Hyperglycemia and the Metabolic Syndrome

Fadi G. Hage, Gilbert Perry, Jaekyeong Heo, Ami E. Iskandrian — 2010-03-15

Adenosine and regadenoson cause an increase in heart rate (HR) during myocardial perfusion imaging (MPI). It has been shown that patients with diabetes mellitus have a blunted HR response due to cardiac autonomic dysfunction. It is not known whether the HR response is related to hyperglycemia and the metabolic syndrome (MS). HR changes were assessed in 2,000 patients (643 with diabetes mellitus [DM]) in the Adenoscan Versus Regadenoson Comparative Evaluation for Myocardial Perfusion Imaging (ADVANCE MPI 1 and ADVANCE MPI 2) trials in relation to MS status and blood sugar level on the day of MPI. The HR response was lower in patients with MS (32.43 ± 0.52% vs 36.15 ± 0.71%, p <0.001). An increase in the number of features of MS was associated with a stepwise decrease in the HR response (−0.92% per MS criterion, p <0.05), irrespective of the presence of DM. Increasing blood sugar levels resulted in blunting of the HR response even after controlling for DM and MS (0.60 ± 0.08% per 10 mg/dl, p <0.001). MS was independently related to the HR response on top of DM, renal function, left ventricular function, gender, age, baseline HR, blood pressure, and β-blocker use. The overall model was highly associated with the HR response (p <0.001) and able to explain 30% of its variation. In conclusion, the HR response to adenosine and regadenoson is blunted in patients with hyperglycemia and in those with MS. These results suggest that factors that precede the development of DM may be associated with cardiac autonomic neuropathy and may help explain the contribution of hyperglycemia and MS to cardiovascular risk.

Dietary Fish Intake and Incident Atrial Fibrillation (from the Women's Health Initiative)

2010-02-08

Experimental and clinical trial data have suggested an association between fish oil intake and atrial fibrillation (AF). However, previous observational studies have reported conflicting results regarding this association. Thus, we sought to compare the association between dietary fish intake and incident AF in a large sample of older, postmenopausal women. We included 44,720 participants from the Women's Health Initiative clinical trials who were not enrolled in the dietary modification intervention arm and without AF at baseline. The dietary intake of nonfried fish and omega-3 fatty acid intake was estimated from a Food Frequency Questionnaire at study entry. Incident AF was determined by follow-up electrocardiography at years 3 and 6. The baseline characteristics and rates of incident AF were compared across the quartiles of fish intake. Adjusted logistic regression models were used to evaluate the association between dietary nonfried fish intake and incident AF. A total of 378 incident cases of AF occurred during the follow-up period. In the age-adjusted models, no association was found between dietary nonfried fish intake and incident AF (odds ratio 1.17, 95% confidence interval 0.88 to 1.57 for quartile 4 vs quartile 1 of dietary fish intake). Similar findings were observed in the multivariate models and in the subgroup analyses. In conclusion, in a large cohort of healthy women, we found no evidence of an association between fish or omega-3 fatty acid intake and incident AF.

Current Status of Dual Renin Angiotensin Aldosterone System Blockade for the Treatment of Cardiovascular Diseases

Steven G. Chrysant — 2010-02-08

Clinical and experimental studies have shown that the initial suppression of angiotensin II after the administration of angiotensin-converting enzyme (ACE) inhibitors is later reversed and returns almost to pretreatment levels. This raised the hypothesis of the “escape phenomenon,” which was strengthened by the discovery that angiotensin II can also be generated through non-ACEs. Therefore, the addition of angiotensin receptor blockers to ACE inhibitors would produce additional benefits by blocking all angiotensin II at the angiotensin II receptor type 1 level and in addition allowing angiotensin II to stimulate the unoccupied angiotensin II receptor type 2, causing additional vasodilation and antiremodeling effects. However, analysis of various studies including hypertension, heart failure, and renal disease has demonstrated that the gain is modest when combining ACE inhibitors, angiotensin receptor blockers, or the renin blocker aliskiren. In conclusion, on the basis of the results of this analysis, dual blockade of the renin-angiotensin-aldosterone system should not be used for the treatment of hypertension, heart failure, and renal disease, with perhaps the exception of diabetic nephropathy with albuminuria, until additional information is provided from ongoing studies.

Circulating Matrix Metalloproteinase-3 and Metalloproteinase-9 and Tissue Doppler Measures of Diastolic Dysfunction to Risk Stratify Patients With Systolic Heart Failure

2010-02-08

Abnormal matrix metalloproteinase (MMP) activity and diastolic dysfunction may affect left ventricular (LV) remodeling and prognosis, but it is not known whether the combined evaluation of MMP-3 and MMP-9 and variables of diastolic dysfunction are useful for the risk stratification of patients with systolic heart failure (HF). Therefore, this study was designed to assess the value of combining circulating levels of MMPs and tissue Doppler measures of LV diastolic dysfunction to risk-stratify patients with systolic HF. Consecutive patients with systolic HF due to either ischemic or nonischemic cardiomyopathy (n = 134) and LV ejection fractions <45% were submitted to complete echocardiographic and Doppler examinations. The ratio of mitral E peak velocity and averaged e′ velocity (E/e′) was calculated. Plasma levels of MMP-3 and MMP-9 were measured at the time of index echocardiography. All-cause mortality was defined as the end point. The mean LV ejection fraction was 28 ± 9%. There was a total of 32 deaths during follow-up (24 ± 14 months). Several clinical, biochemical, Doppler, and echocardiographic parameters were associated with the outcome on univariate Cox regression analysis. After statistical adjustment for the potentially confounding factors by multivariate analysis, E/e′ (hazard ratio 1.11, p = 0.0028), ejection fraction (hazard ratio 0.92, p = 0.017), and MMP-9 (hazard ratio 1.01, p = 0.027) remained significant independent predictors of the end point. Kaplan-Meier curves showed that survival was worse in patients with E/e′ ratios ≥13 and MMP-9 levels >89.9 ng/mL (p <0.0001). In conclusion, the assessment of circulating MMP levels and tissue Doppler measures of LV diastolic dysfunction may improve the prognostic stratification of patients with systolic HF.

Clinical Profile, Treatment Assignment and Clinical Outcome of Patients With Severe Aortic Stenosis Not Eligible to Participate in a Clinical Trial of Percutaneous Aortic Valve Replacement

2010-02-08

Patients with severe aortic stenosis and considered at high surgical risk or inoperable, and not eligible for a randomized clinical trial evaluating percutaneous aortic valve replacement (PAVR), were studied. Many of the patients referred to the study did not meet the inclusion criteria and/or had conditions listed in the exclusion criteria. These patients were then deferred to other treatment modalities. The study cohort consisted of 285 patients with severe aortic stenosis referred to participate in a clinical trial of PAVR. Patients were screened for eligibility on the basis of the protocol inclusion and exclusion criteria and deferred to other treatment modalities if they did not meet the enrollment criteria. Those patients were followed clinically by telephone contact or office visits. Of the 285 patients referred for PAVR, 216 (75.8%) were not included. The leading reasons for lack of eligibility were significant peripheral vascular disease in 50 (23.1%), Society of Thoracic Surgeons score <10% in 48 (22.9%), aortic valve area >0.8 cm2 in 30 (13.9%), significant coronary artery disease in 25 (11.6%), and renal failure in 22 (10.2%). Sixty-nine of these patients (31.9%) were treated medically, 102 (47.2%) with balloon aortic valvuloplasty, and 45 (20.9%) with surgical aortic valve replacement. Major baseline characteristics were similar. Society of Thoracic Surgeons scores were lower in the surgical group compared with the medical and balloon aortic valvuloplasty groups (10.2 ± 2.5 vs 12.8 ± 3.3 vs 13.7 ± 3.3, respectively, p <0.001). During a median follow-up period of 175.5 days (range 55.7 to 344.75), the mortality rate was higher in the balloon aortic valvuloplasty group compared with the medical and surgical aortic valve replacement groups (46 [45.1%] vs 22 [31.9%] vs 10 [22.2%], respectively, p = 0.01). In conclusion, high-risk patients with severe aortic stenosis who are deferred from PAVR often do poorly and incur high mortality rates, especially when treated with balloon valvuloplasty or medical therapy, while a loss of quality of life is apparent in those treated surgically.

Calcium Metabolism in Adults With Severe Aortic Valve Stenosis and Preserved Renal Function

2010-02-08

Data suggest a link of aortic stenosis (AS) with calcium and bone metabolism. To further investigate this, the following parameters were analyzed in 38 patients with severe AS and in 38 age- and gender-matched controls, without obstructive coronary artery disease and with preserved renal function: calcium, phosphate, 1,25(OH2)-vitamin D3, intact parathyroid hormone (iPTH), and osteoprotegerin. Patients with AS had significantly higher serum levels of calcium (2.63 ± 0.28 vs 2.48 ± 0.23 mmol/L, p <0.01) and phosphate (1.56 ± 0.33 vs 1.38 ± 0.26 mmol/L, p <0.01) and increased calcium-phosphorus products (4.16 ± 1.13 vs 3.44 ± 0.89 mmol/L2, p = 0.003). Notably, the iPTH concentration in the AS group was lower, and significantly more patients in the AS group had levels less than the study median of 60 ng/L. Osteoprotegerin was elevated in patients with AS, confirming reports in other populations (9.94 ± 5.96 vs 6.73 ± 4.28 pmol/L, p = 0.009). The relations of several parameters to iPTH were also altered (AS vs controls): calcium and iPTH, 0.071 ± 0.034 versus 0.046 ± 0.023, p <0.0001; phosphate and iPTH, 0.042 ± 0.020 versus 0.025 ± 0.013, p <0.0001; vitamin D and iPTH, 0.99 ± 0.61 versus 0.63 ± 0.46, p = 0.006; and osteoprotegerin and iPTH, 0.24 ± 0.15 versus 0.12 ± 0.09, p <0.0001. In conclusion, these data support a hypothesis connecting (severe) AS to altered calcium and bone homeostasis.

Mortality After Total Cavopulmonary Connection in Children With the Down Syndrome

2010-03-15

A total cavopulmonary connection (Fontan surgery) is rarely performed in a child with trisomy 21 (Down syndrome) for a univentricular heart, and the outcomes after surgery are not well defined, but the incidence of mortality has been reported to be higher. To determine the mortality rate and contributing factors after Fontan surgery in children with Down syndrome, mortality data after Fontan surgery from the Pediatric Cardiac Care Consortium Registry were evaluated. Among Fontan procedures (n = 2,853), all patients with Down syndrome (n = 17) were selected, of whom 13 had hemodynamic data available. Thirteen children without chromosomal aberrations were then selected as a control group, matched 1 to 1 for gender, age, weight, lesion, and type of Fontan procedure. The following variables were evaluated: pulmonary artery pressure and vascular resistance, weight, hemoglobin, degree of atrioventricular regurgitation, previous Glenn operation, fenestration, and length of stay in the hospital. In children with Down syndrome, mortality after the Glenn operation was 28%. Mortality after the Fontan operation was increased significantly (p = 0.001) in children with Down syndrome (35%) compared with those without Down syndrome (10%). Between patients with Down syndrome and controls, there were no significant differences in the perioperative parameters evaluated. Almost all mortality was in the early postoperative period in children with Down syndrome. The relative risk ratio of mortality was 2.5 (95% confidence interval 0.63 to 10). In conclusion, Down syndrome was found to be an independent parameter associated with a significantly higher risk for mortality in the early postoperative period after Fontan surgery.

Usefulness of Natriuretic Peptide Levels to Predict Mortality in Adults With Congenital Heart Disease

2010-02-08

Neurohormonal activation is prevalent in adults with congenital heart disease, but its relation to outcome remains unknown. B-type natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) were measured prospectively in 49 patients with adult congenital heart disease, who were followed up for a median of 7.9 years (interquartile range 7.7 to 8.2). Cox proportional hazards regression analysis was used to determine the relation of BNP and ANP concentrations to all-cause mortality. The mean age at baseline was 33.9 ± 11.3 years, and 46.9% of patients were men. Most patients (77.5%) were symptomatic (20.4% had New York Heart Association class III), 10 (20.4%) were cyanotic, and 28 (57.1%) had systemic ventricular dysfunction (moderate or severe in 18.4%). The median concentration of BNP was 52.7 pg/ml (interquartile range 39.1 to 115.4) and of ANP was 47.4 pg/ml (interquartile range 19.7 to 112.8). Of the 49 patients, 11 (22.4%) died during the follow-up period. Both BNP and ANP were strong predictors of mortality (hazard ratio per 100-pg/ml increase 1.80, 95% confidence interval 1.38 to 2.34, p <0.0001; and hazard ratio per 100-pg/ml increase 1.21, 95% confidence interval 1.12 to 1.32, p <0.0001, respectively). A BNP value >78 pg/ml predicted death with a sensitivity of 100% and specificity of 76.3% (area under the curve 0.91, p = 0.0001). An ANP value of >146 pg/ml predicted death with a sensitivity of 72.7% and specificity 94.7% (area under the curve 0.89, p = 0.0001). No patients with a BNP level <78 pg/ml died during the follow-up period. In conclusion, the BNP and ANP levels strongly predicted death in symptomatic ambulatory patients with adult congenital heart disease during mid-term follow-up and could be used as a simple clinical marker for risk stratification in this population.

Long-Term Outcomes of Patients With Cardiovascular Abnormalities and Williams Syndrome

R. Thomas Collins, Paige Kaplan, Grant W. Somes, Jonathan J. Rome — 2010-02-08

Williams syndrome (WS) is a congenital disorder affecting the vascular, connective tissue, and central nervous systems of 1 in 8,000 live births. Previous reports have reported high frequencies of cardiovascular abnormalities (CVAs) in small numbers of patients with WS. A retrospective review was undertaken of patients with WS evaluated at our institution from January 1, 1980 through December 31, 2007. WS was diagnosed by an experienced medical geneticist and/or by fluorescence in situ hybridization. CVAs were diagnosed using echocardiography, cardiac catheterization, or computed tomographic angiography. Freedom from intervention was determined using Kaplan-Meier analysis. The study group was 270 patients with WS. The age at presentation was 3.3 ± 5.9 years with follow-up of 8.9 ± 9.0 years (range 0 to 56.9). CVAs were present in 82% of the patients. The most common lesions were supravalvar aortic stenosis in 45% and peripheral pulmonary stenosis in 37%; 20% had both. Other common lesions included mitral valve prolapse and regurgitation in 15%, ventricular septal defect in 13%, and supravalvar pulmonary stenosis in 12%. Surgical or catheter-based interventions were performed in 21%. The rate of freedom from intervention was 91%, 81%, 78%, 72%, and 62% at 1, 5, 10, 20, and 40 years. Eight patients died. In conclusion, CVAs are common in patients with WS, but supravalvar aortic stenosis and peripheral pulmonary stenosis occurred less frequently in this large cohort than previously reported. In patients with WS and CVAs, interventions are common and usually occur by 5 years of age. Most patients with WS do not require intervention during long-term follow-up, and the overall mortality has been low.

Unusual Features of Apical Hypertrophic Cardiomyopathy

Tommy Chung, John Yiannikas, Saul Ben Freedman, Leonard Kritharides — 2010-03-15

Apical hypertrophic cardiomyopathy (HC) is commonly regarded as a relatively benign condition of young to middle-aged Japanese men. Apical HC in a predominantly Caucasian population is not well characterized. The cardiovascular characteristics, morbidity, and mortality of a series of elderly, predominantly Caucasian subjects with apical HC are described. Thirty-two consecutive patients with apical HC (mean age 71 years, 15 men) were identified from a teaching hospital without a specialized HC clinic. Twenty-three subjects were Caucasian, 8 were Asian, and none Japanese. Twenty-two patients had coexistent hypertension. Six patients had documented late evolution of apical HC on electrocardiography and echocardiography up to 5 years after previous documented normal left ventricular morphology on echocardiography. The diagnosis of apical HC was initially missed in 7 patients because of inadequate image quality of the left ventricular apex and a lack of awareness of the condition. The correct diagnosis was assigned to all 7 patients after repeat echocardiography. Six of 13 patients who underwent coronary angiography had associated coronary artery fistulae. One patient required an implantable defibrillator for exertional syncope. Ten of the patients developed atrial fibrillation, 6 of whom had complicating thromboembolic events. Of the 6 deaths in the cohort, 2 followed atrial fibrillation–related hemiplegic strokes, and 2 followed progressive heart failure. In conclusion, apical HC in a teaching hospital without a specialized HC clinic and in a predominantly Caucasian population is a disease of the elderly. Documented late morphologic evolution is not uncommon, with a high incidence of coronary fistulae and morbid atrial fibrillation.

Prevalence and Clinical Characteristics of Nondilated Cardiomyopathy and the Effect of Atrial Fibrillation

Alexander Doumas, Timothy S. Draper, Edgar C. Schick, William H. Gaasch — 2010-02-08

The treatment of patients with chronic heart failure and those with asymptomatic left ventricular (LV) dysfunction has focused primarily on patients with LV enlargement and a low ejection fraction (EF). Little attention has been paid to those with a normal chamber size and a low EF. We sought to examine the LV geometry and clinical characteristics in such patients with nondilated cardiomyopathy. Of 3,350 transthoracic echocardiograms performed during a 6-month period, 696 showed an EF of ≤0.45. The patients with an end-diastolic diameter of >56 mm, regional wall motion abnormalities, or valvular disease were excluded. Of the 696 patients, 98 met these criteria, and their medical records were reviewed. The average age was 71 ± 14 years, and 56% were men. Common co-morbidities included hypertension in 52% and atrial fibrillation (AF) in 43%. Only 22% had disabling cardiac symptoms (functional class III or greater). The average end-diastolic dimension was 49 ± 5 mm, and the EF was 34 ± 8%. LV hypertrophic remodeling was present in 53%. A second echocardiogram (422 ± 177 days after the baseline study) was available for 54 patients. The chamber size was unchanged, but the EF had increased from 33 ± 8% to 40 ± 14% (p <0.01). The improvement in EF was seen in the group with AF (33 ± 6% to 44 ± 15%, p <0.01) but not in those with normal sinus rhythm (33 ± 9% to 37 ± 12%, p = NS). In conclusion, 14% of patients with an EF of ≤0.45 had nondilated cardiomyopathy, often with LV hypertrophic remodeling and/or AF. An improvement in LV function can be expected in many patients with nondilated cardiomyopathy, particularly those with AF.

Nomograms for Aortic Root Diameters in Children Using Two-Dimensional Echocardiography

2010-02-08

The evaluation of aortic root dilation is of major importance for the diagnosis and follow-up of patients with diverse diseases, including the Marfan syndrome. However, we noted that the available nomograms suggested a lower aortic root dilation rate in adults (75%) than in children (90%), when the opposite would have been expected. To establish new nomograms, we selected a population of 353 normal children. We took transthoracic echocardiographic measurements of the aortic root diameters at the level of the aortic annulus, sinuses of Valsalva, sinotubular junction, and ascending aorta according to the American Society of Echocardiography recommendations. All diameters correlated well with the height, weight, body surface area, and age (r = 0.75 to 0.84, p <0.0001). Covariance analysis adjusting for body surface area showed slightly larger diameters at the level of the sinuses of Valsalva in male children than in female children (+1 mm, p = 0.0002). Equations and derived nomograms were developed, giving the upper limit of normal (allowing simple recognition of aortic dilation) and the Z score (allowing fine quantification of dilation and differentiation of normal growth from pathologic dilation) for all 4 aortic root diameters (ie, aortic annulus, sinuses of Valsalva, sinotubular junction, and proximal ascending aorta) according to body surface area and gender. We applied the nomograms to 282 children with confirmed Marfan syndrome, of whom 65.2% presented with dilation of the sinuses of Valsalva. In conclusion, we propose equations to calculate the upper limit of normal and Z-score for aortic root diameters measured by 2-dimensional echocardiography, which should be useful tools for the diagnosis and follow-up of aortic root aneurysms in children.

Relation of Infra-Renal Abdominal Aortic Calcific Deposits and Cardiovascular Events in Patients With Peripheral Artery Disease

Adam Parr, Petra Buttner, Anwar Shahzad, Jonathan Golledge — 2010-02-08

In patients with peripheral artery disease, aortic calcific deposits are a common finding. The aim of this study was to assess the association of infrarenal abdominal aortic calcific deposits with prospective cardiovascular events in patients with peripheral artery disease. A consecutive series of 213 patients who presented for investigation of abdominal aortic aneurysm or intermittent claudication were assessed using computed tomographic angiography. Infrarenal abdominal aortic calcific deposits were estimated using a previously defined highly reproducible semiautomated program. Patients were followed prospectively for a median of 2.8 years (interquartile range 1.7 to 3.6), and cardiovascular events were recorded. Kaplan-Meier and Cox proportional-hazards analysis were used to examine the association of calcific deposits with cardiovascular events. A total of 45 cardiovascular events occurred during follow-up, including nonfatal myocardial infarction (n = 23), coronary revascularization (n = 6), stroke (n = 3), below-knee amputation (n = 2), and cardiovascular death (n = 11). The incidence of cardiovascular events was 21.7%, 33.0%, and 36.9% for patients with mild (<400 mm3), intermediate (400 to 1,700 mm3), and severe (>1,700 mm3) abdominal aortic calcific deposits, respectively (p = 0.039). Calcific deposit volume >400 mm3 (relative risk 2.8, 95% confidence interval 1.2 to 6.6) and coronary artery disease (relative risk 2.8, 95% confidence interval 1.4 to 5.6) were independently associated with increased cardiovascular events during follow-up. In conclusion, abdominal aortic calcific deposits are prognostic for cardiovascular events in patients with peripheral artery disease.

ObamaCare

Ralph J. DiLibero, George A. Diamond — 2010-03-15

On July 22, 2009, President Barack Obama held a nationally televised press conference that focused on his health care reform proposal. When asked by Steve Koff, a correspondent for the Cleveland Plain Dealer, if his proposed public insurance option would “guarantee that the government will never deny any services,” the president said, “Right now, doctors, a lot of times, are forced to make decisions based on the fee payment schedule that's out there. So if they're looking…and…and you come in and you've got a bad sore throat…or your child has a bad sore throat…or has repeated sore throats…the doctor may look at the reimbursement system and say to himself, 'You know what? I make a lot more money if I take this kid's tonsils out.'”

Effect of Air Pollution and Traffic on T-Wave Alternans

John E. Madias — 2010-03-15

Zanobetti et al, in their contribution in the September 1, 2009, issue of The American Journal of Cardiology, showed that air pollution and traffic caused increases in the magnitude of T-wave alternans (TWA) detected on 24-hour Holter electrocardiographic monitoring (HEM) in 48 patients with various manifestations of coronary artery disease. The investigators, using time-domain modifying moving average analysis of HEM, reported maximum TWA magnitude (TWA-MAX) in each 30-minute interval of the 24-hour HEM period, using data only from modified lead V5. Increases in TWA-MAX were associated with the previous 2-hour ambient black carbon level and with being in traffic in the previous 2 hours, thus revealing an impact of air pollution on TWA.

Vegetarians from Latin America

Julio Acosta Navarro, Bruno Caramelli — 2010-03-15

Ferdowsian and Barnard have presented important information about populations following plant-based diets, particularly vegetarian (VEG) and vegan, suggesting that they are at lower risk for ischemic heart disease mortality.

Relation of Multivessel Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction to Outcome and/or Non-Infarct Artery Intervention of a Chronic Total Occlusion

2010-03-15

We read with interest the recent report by Cavender et al, questioning the guidelines and use of multivessel percutaneous coronary intervention (PCI) in the setting of ST elevation myocardial infarction (STEMI). The investigators concluded that multivessel primary PCI for STEMI does not improve in-hospital outcomes, even in patients with cardiogenic shock.

Left Ventricular Remodeling and Heart Failure After Myocardial Infarction in Elderly Patients

Christophe Bauters, Pierre V. Ennezat, Nicolas Lamblin, Pascal de Groote — 2010-03-15

We read with interest the recent report by Carraba et al on the effect of age on left ventricular remodeling (LVR) and heart failure (HF) in patients treated by primary angioplasty for myocardial infarction (MI). The study demonstrated that despite very few differences in LVR, elderly patients had a much greater risk of HF at long-term follow-up. As noted by the authors, their study was, however, performed in a selected population as patients receiving lytic treatment or patients with clinical signs of HF during the first week after MI were excluded.

Editorial Board

2010-03-15

American Journal of Cardiology

Low-Density Lipoprotein and Noncalcified Coronary Plaque Composition in Patients With Newly Diagnosed Coronary Artery Disease on Computed Tomographic Angiography

Evaluation of Contraindications and Efficacy of Oral Beta Blockade Before Computed Tomographic Coronary Angiography

Comparison of Usefulness of Exercise Testing Versus Coronary Computed Tomographic Angiography for Evaluation of Patients Suspected of Having Coronary Artery Disease

Prognostic Value of an Exaggerated Exercise Blood Pressure Response in Patients With Diabetes Mellitus and Known or Suspected Coronary Artery Disease

Comparison of Evidence-Based Versus Non–Evidence-Based Pharmacotherapy on the Risk of Cardiovascular Hospitalization and All-Cause Mortality Among Patients With Established Cardiovascular Disease

Endothelial Nitric Oxide Synthase T-786C Mutation, A Reversible Etiology of Prinzmetal's Angina Pectoris

Usefulness of Soluble Fas Levels for Improving Diagnostic Accuracy and Prognosis for Acute Coronary Syndromes

Results of Intracoronary Stem Cell Therapy After Acute Myocardial Infarction

Comparison of Outcomes Between Zotarolimus- and Sirolimus-Eluting Stents in Patients With ST-Segment Elevation Acute Myocardial Infarction

Outcomes in Diabetic Versus Nondiabetic Patients Who Present With Acute Myocardial Infarction and Are Treated With Drug-Eluting Stents

Long-Term Prognostic Value of Preprocedural C-Reactive Protein After Drug-Eluting Stent Implantation

Relation of Proton Pump Inhibitor Use After Percutaneous Coronary Intervention With Drug-Eluting Stents to Outcomes

Blunting of the Heart Rate Response to Adenosine and Regadenoson in Relation to Hyperglycemia and the Metabolic Syndrome

Dietary Fish Intake and Incident Atrial Fibrillation (from the Women's Health Initiative)

Current Status of Dual Renin Angiotensin Aldosterone System Blockade for the Treatment of Cardiovascular Diseases

Circulating Matrix Metalloproteinase-3 and Metalloproteinase-9 and Tissue Doppler Measures of Diastolic Dysfunction to Risk Stratify Patients With Systolic Heart Failure

Clinical Profile, Treatment Assignment and Clinical Outcome of Patients With Severe Aortic Stenosis Not Eligible to Participate in a Clinical Trial of Percutaneous Aortic Valve Replacement

Calcium Metabolism in Adults With Severe Aortic Valve Stenosis and Preserved Renal Function

Mortality After Total Cavopulmonary Connection in Children With the Down Syndrome

Usefulness of Natriuretic Peptide Levels to Predict Mortality in Adults With Congenital Heart Disease

Long-Term Outcomes of Patients With Cardiovascular Abnormalities and Williams Syndrome

Unusual Features of Apical Hypertrophic Cardiomyopathy

Prevalence and Clinical Characteristics of Nondilated Cardiomyopathy and the Effect of Atrial Fibrillation

Nomograms for Aortic Root Diameters in Children Using Two-Dimensional Echocardiography

Relation of Infra-Renal Abdominal Aortic Calcific Deposits and Cardiovascular Events in Patients With Peripheral Artery Disease

ObamaCare

Effect of Air Pollution and Traffic on T-Wave Alternans

Vegetarians from Latin America

Relation of Multivessel Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction to Outcome and/or Non-Infarct Artery Intervention of a Chronic Total Occlusion

Left Ventricular Remodeling and Heart Failure After Myocardial Infarction in Elderly Patients

Editorial Board

Contents