[Show abstract][Hide abstract] ABSTRACT: In acute coronary syndromes, C-reactive protein (CRP) strongly relates to subsequent death, but surprisingly not to recurrent myocardial infarction. Other biomarkers may reflect different processes related to these outcomes. We assessed 8 inflammatory and vascular biomarkers and the risk of death and recurrent nonfatal cardiovascular events in the 16 weeks after an acute coronary syndrome.
We measured blood concentrations of CRP, serum amyloid A (SAA), interleukin-6 (IL-6), soluble intercellular adhesion molecule (ICAM), soluble vascular cell adhesion molecule (VCAM), E-selectin, P-selectin, and tissue plasminogen activator antigen (tPA) 24 to 96 hours after presentation with acute coronary syndrome in 2925 subjects participating in a multicenter study. Biomarkers were related to the risk of death, and recurrent nonfatal acute coronary syndromes (myocardial infarction or unstable angina) over 16 weeks using Cox proportional hazard models. On univariate analyses, baseline CRP (P=0.006), SAA (P=0.012), and IL-6 (P<0.001) were related to death, but not to recurrent nonfatal acute coronary syndromes. VCAM and tPA related to the risk of death (P<0.001, P=0.021, respectively) and to nonfatal acute coronary syndromes (P=0.021, P=0.049, respectively). Adjusting for significant covariates reduced the strength of the associations; however, CRP and SAA continued to relate to death.
In acute coronary syndromes, the CRP inflammatory axis relates to the risk of death and may reflect myocardial injury. VCAM and tPA may have greater specificity for processes reflecting inflammation and thrombosis in the epicardial arteries, which determine recurrent coronary events.
Journal of the American Heart Association. 12/2013; 2(1):e003103.
[Show abstract][Hide abstract] ABSTRACT: Current guidelines advocate primary percutaneous coronary intervention as the therapy of choice for ST-segment elevation myocardial infarction (STEMI) when available. Little is known about the outcomes of patients without a culprit lesion after referral for primary percutaneous coronary intervention for a presumed STEMI. Subjects were identified within a registry containing consecutive patients who underwent emergent angiography for a potential STEMI from October 2008 to July 2012. Vital status was obtained from the medical record and Social Security Death Index. Cox proportional hazards models were created to evaluate the relation between the angiographic findings and cardiovascular outcomes, including major adverse cardiovascular events (MACE) and mortality. Among 539 patients who underwent emergent angiography, 65 (12%) had no coronary artery disease (CAD), 110 (20%) had CAD without a culprit lesion, and 364 (68%) had a culprit lesion. Kaplan-Meier analysis of MACE demonstrated that patients with CAD who lack a culprit lesion had a similar rate of MACE to those with a culprit lesion (p = 0.64), and both groups had significantly increased risk compared with those with no CAD (hazard ratio [HR] 1.9, 95% confidence interval [CI] 1.01 to 3.41 and HR 2.0, 95% CI 1.15 to 3.54, respectively). Kaplan-Meier analysis of mortality illustrated a nonsignificant trend toward increased mortality in patients having a culprit lesion (HR 1.7, 95% CI 0.59 to 4.80) and those having CAD without a culprit lesion (HR 1.2, 95% CI 0.39 to 3.81) compared with those with no CAD. In conclusion, patients found to have CAD without a culprit lesion in emergent angiography after a presumptive STEMI diagnosis have similar long-term rates of MACE compared with those requiring emergent revascularization.
The American journal of cardiology 09/2013; · 3.58 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: With adoption of telemedicine, physicians are increasingly asked to diagnose ST-segment elevation myocardial infarctions (STEMIs) based on electrocardiograms (ECGs) with minimal associated clinical information. We sought to determine physicians' diagnostic agreement and accuracy when interpreting potential STEMI ECGs.
A cross-sectional survey was performed consisting of 36 deidentified ECGs that had previously resulted in putative STEMI diagnoses. Emergency physicians, cardiologists, and interventional cardiologists participated in the survey. For each ECG, physicians were asked, "based on the ECG above, is there a blocked coronary artery present causing a STEMI?" The reference standard for ascertaining the STEMI diagnosis was subsequent emergent coronary arteriography. Responses were analyzed with generalized estimating equations to account for nested and repeated measures. One hundred twenty-four physicians interpreted a total of 4392 ECGs. Among all physicians, interreader agreement (kappa) for ECG interpretation was 0.33, reflecting poor agreement. The sensitivity to identify "true" STEMIs was 65% (95% CI: 63 to 67) and the specificity was 79% (95% CI: 77 to 81). There was a 6% increase in the odds of accurate ECG interpretation for every 5 years of experience since medical school graduation (OR 1.06, 95% CI: 1.02 to 1.10, P=0.01). After adjusting for experience, there was no significant difference in the odds of accurate interpretation by specialty-Emergency Medicine (reference), General Cardiology (AOR 0.97, 95% CI: 0.79 to 1.2, P=0.80), or Interventional Cardiology physicians (AOR 1.24, 95% CI: 0.93 to 1.7, P=0.15).
There is significant physician disagreement in interpreting ECGs with features concerning for STEMI. Such ECGs lack the necessary sensitivity and specificity to act as a suitable "stand-alone" diagnostic test.
Journal of the American Heart Association. 08/2013; 2(5):e000268.
[Show abstract][Hide abstract] ABSTRACT: Prompt percutaneous coronary intervention is associated with improved survival in patients presenting with cardiac arrest. Few studies, however, have focused on patients with cardiac arrest not selected for coronary angiography. The aim of the present study was to evaluate the clinical characteristics and outcomes of patients with cardiac arrest denied emergent angiography. Patients with cardiac arrest were identified within a registry that included all catheterization laboratory activations from 2008 to 2012. Logistic regression and proportional-hazards models were created to assess the clinical characteristics and mortality associated with denying emergent angiography. Among 664 patients referred for catheterization, 110 (17%) had cardiac arrest, and 26 of these patients did not undergo emergent angiography. Most subjects (69%) were turned down for angiography for clinical reasons and a minority for perceived futility (27%). After multivariate adjustment, pulseless electrical activity as the initial arrest rhythm (adjusted odds ratio [AOR] 13.27, 95% confidence interval [CI] 1.76 to 100.12), <1.0 mm of ST-segment elevation (AOR 10.26, 95% CI 1.68 to 62.73), female gender (AOR 4.45, 95% CI 1.04 to 19.08), and advancing age (AOR 1.10 per year, 95% CI 1.04 to 1.16) were associated with increased odds of withholding angiography. The mortality rate was markedly higher for patients who were denied emergent angiography (hazard ratio 3.64, 95% CI 2.05 to 6.49), even after adjustment for medical acuity (hazard ratio 2.29, 95% CI 1.19 to 4.41). In conclusion, older subjects, women, and patients without ST-segment elevation were more commonly denied emergent angiography after cardiac arrest. Patients denied emergent angiography had increased mortality that persisted after adjustment for illness severity.
The American journal of cardiology 02/2013; · 3.58 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: AimsThe effect of resistant hypertension on outcomes in patients with atherothrombotic disease is currently unknown. Accordingly, we sought to determine the prevalence and outcomes of resistant hypertension in stable hypertensive outpatients with subclinical or established atherothombotic disease enrolled in the international Reduction of Atherothrombosis for Continued Health (REACH) registry.Methods and resultsResistant hypertension was defined as a blood pressure ≥140/90 mmHg at baseline (≥130/80 mmHg if diabetes/renal insufficiency) with the use of ≥3 antihypertensive medications, including a diuretic. The primary outcome was a composite of cardiovascular death, myocardial infarction, or stroke at 4 years. A total of 53 530 hypertensive patients were included. The prevalence of resistant hypertension was 12.7%; 6.2% on 3 antihypertensive agents, 4.6% on 4 agents, and 1.9% on ≥5 agents (mean: 4.7 ± 0.8). In addition to a diuretic, these patients were being treated mostly with ACE-inhibitors/angiotensin receptor blockers (90.1%), beta-blockers (67.0%), and calcium channel blockers (50.8%). Patients with resistant hypertension had a higher risk of the primary endpoint on multivariable analysis [hazard ratio (HR) 1.11, 95% confidence interval (CI) 1.02-1.20; P = 0.017], including an increased non-fatal stroke risk (HR: 1.26; 95% CI: 1.10-1.45; P = 0.0008). Hospitalizations due to congestive heart failure were higher (P < 0.0001). Patients on ≥5 agents had a higher adjusted risk for the primary endpoint when compared with those on ≤3 agents (P = 0.03).Conclusion
The presence of resistant hypertension identifies a subgroup of patients with hypertension and atherothrombosis who are at heightened risk for adverse long-term outcomes.
European Heart Journal 11/2012; · 14.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background- Little is known about the components of door-to-balloon time among patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. We assessed the role of time from hospital arrival to ST-segment elevation myocardial infarction diagnosis (door-to-activation time) on door-to-balloon time in contemporary practice and evaluated factors that influence door-to-activation times. Methods and Results- Registry data on 347 consecutive patients diagnosed with a ST-segment elevation myocardial infarction in the emergency department over 30 months at 2 urban primary percutaneous coronary intervention centers were analyzed. The primary study end point was the time from hospital arrival to catheterization laboratory activation by the emergency department physician, and we assessed factors associated with this period. Door-to-balloon time and its other components were secondary study end points. The median door-to-activation time was 19 minutes (interquartile range, 9-54). Variation in door-to-activation times explained 93% of the variation in door-to-balloon times and demonstrated the strongest correlation with door-to-balloon times (r=0.97). Achieving a door-to-activation time of ≤20 minutes resulted in an 89% chance of achieving a door-to-balloon time of ≤90 minutes compared with only 28% for patients with a door-to-activation time >20 minutes. Factors significantly associated with door-to-activation time include the following: prehospital ECG use (61% shorter, 95% confidence interval, -50 to -72%; P<0.001) and computed tomography scan use in the emergency department (245% longer, 95% confidence interval, +50 to +399%; P=0.001). Conclusions- The interval from hospital arrival to ST-segment elevation myocardial infarction diagnosis and catheterization laboratory activation (door-to-activation time) is a strong driver of overall door-to-balloon times. Achieving a door-to-activation time ≤20 minutes was key to achieving a door-to-balloon time ≤90 minutes. Delays in door-to-activation time are not associated with delays in other aspects of the primary percutaneous coronary intervention process.
[Show abstract][Hide abstract] ABSTRACT: Patients with electrocardiographic (ECG) left ventricular hypertrophy (LVH) have repolarization abnormalities of the ST segment that may be confused with an ischemic current of injury. We analyzed the ACTIVATE-SF database, a registry of consecutive emergency department ST-segment elevation (STE) myocardial infarction diagnoses from 2 medical centers. Univariate analysis was performed to identify ECG variables associated with presence of an angiographic culprit lesion. Recursive partitioning was then applied to identify a clinical decision-making rule that maximizes sensitivity and specificity for presence of an angiographic culprit lesion. Seventy-nine patients with ECG LVH underwent emergency cardiac catheterization for primary angioplasty. Patients with a culprit lesion had greater magnitude of STE (3.0 ± 1.8 vs 1.9 ± 1.0 mm, p = 0.005), more leads with STE (3.1 ± 1.6 vs 2.0 ± 1.8 leads, p = 0.002), and a greater ratio of STE to R-S-wave magnitude (median 25% vs 9.2%, p = 0.003). Univariate application of ECG criteria had limited sensitivity and a high false-positive rate for identifying patients with an angiographic culprit lesion. In patients with anterior territory STE, using a ratio of ST segment to R-S-wave magnitude ≥25% as a diagnostic criteria for STE myocardial infarction significantly improved specificity for an angiographic culprit lesion without decreasing sensitivity (c-statistic 0.82), with a net reclassification improvement of 37%. In conclusion, application of an ST segment to R-S-wave magnitude ≥25% rule may augment current criteria for determining which patients with ECG LVH should undergo primary angioplasty.
The American journal of cardiology 06/2012; 110(7):977-83. · 3.58 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Rapid activation of the cardiac catheterization laboratory for primary percutaneous coronary intervention (PCI) improves outcomes for ST-segment elevation myocardial infarction (STEMI), but selected emphasis on minimizing time to reperfusion may lead to a greater frequency of false-positive activations.
We analyzed consecutive patients referred for primary PCI for a possible STEMI at 2 centers from October 2008 to April 2011. "False-positive STEMI activation" was defined as lack of a culprit lesion by angiography or by assessment of clinical, electrocardiographic, and biomarker data in the absence of angiography. Clinical and electrocardiographic factors associated with false-positive activations were evaluated in a backward stepwise selection bootstrapped logistic regression model.
Of 411 STEMI activations by emergency physicians, 146 (36%) were deemed to be false-positive activations. Structural heart disease and heart failure were the most common diagnoses among false-positive activations. Electrocardiographic left ventricular hypertrophy (adjusted odds ratio [AOR], 3.15; 95% CI, 1.55-6.40; P=.001), a history of coronary disease (AOR, 1.93; 95% CI, 1.04-3.59; P=.04), or prior illicit drug abuse (AOR, 2.67; 95% CI, 1.13-6.26; P=.02) independently increased the odds of false-positive STEMI activations. Increasing body mass index decreased the odds of a false-positive activation (AOR, 0.91; 95% CI, 0.86-0.97; P=.004), as did angina at presentation (AOR, 0.28; 95% CI, 0.14-0.57; P < .001).
More than a third of patients referred for primary PCI from the emergency department did not have a STEMI. Multiple patient-level characteristics were significantly associated with an increased odds of false-positive STEMI activation.
Archives of internal medicine 05/2012; 172(11):864-71. · 11.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Patients presenting with suspected ST-segment elevation myocardial infarction (STEMI) may have important alternative diagnoses (e.g., aortic dissection, pulmonary emboli) or safety concerns for STEMI management (e.g., head trauma). Computed tomographic (CT) scanning may help in identifying these alternative diagnoses but may also needlessly delay primary percutaneous coronary intervention (PCI). We analyzed the ACTIVATE-SF Registry, which consists of consecutive patients with a clinical diagnosis of STEMI admitted to the emergency departments of 2 urban hospitals. Of 410 patients with a suspected diagnosis of STEMI, 45 (11%) underwent CT scanning before primary PCI. Presenting electrocardiograms, baseline risk factors, and presence of an angiographic culprit vessel were similar in those with and without CT scanning before PCI. Only 2 (4%) of these CT scans changed clinical management by identifying a stroke. Patients who underwent CT scanning had far longer door-to-balloon times (median 166 vs 75 minutes, p <0.001) and higher in-hospital mortality (20% vs 7.8%, p = 0.006). After multivariate adjustment, CT scanning in the emergency department before primary PCI remained independently associated with longer door-to-balloon times (100% longer, 95% confidence interval 60 to 160, p <0.001) but was no longer associated with mortality (odds ratio 1.4, p = 0.5). In conclusion, CT scanning before primary PCI rarely changed management and was associated with significant delays in door-to-balloon times. More judicious use of CT scanning should be considered.
The American journal of cardiology 04/2012; 110(3):345-9. · 3.58 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Patients with critical limb ischemia have higher rates of death and amputation after revascularization compared to patients with intermittent claudication. However, the differences in patency after percutaneous revascularization of the superficial femoral artery are uncertain and impact the long-term risk of amputation and function in critical limb ischemia. We identified 171 limbs from 136 consecutive patients who had angioplasty and/or stenting for superﬁcial femoral artery stenoses or occlusions from July 2003 through June 2007. Patients were followed for primary and secondary patency, death and amputation up to 2.5 years, and 111 claudicants were retrospectively compared to the 25 patients with critical limb ischemia. Successful percutaneous revascularization occurred in 128 of 142 limbs (90%) with claudication versus 25 of 29 limbs (86%) with critical limb ischemia (p = 0.51). Overall secondary patency at 2.5 years was 91% for claudication and 88% for critical limb ischemia. In Cox proportional hazards models, percutaneous revascularization for critical limb ischemia had similar long-term primary patency (adjusted hazard ratio = 1.1, 95% CI = 0.4, 2.6; p = 0.89) and secondary patency (adjusted hazard ratio = 1.1, 95% CI = 0.2, 6.0; p = 0.95) to revascularization for claudication. Patients with critical limb ischemia had higher mortality and death rates compared to claudicants, with prior statin use associated with less death (p = 0.034) and amputation (p = 0.010), and prior clopidogrel use associated with less amputation (p = 0.034). In conclusion, percutaneous superficial femoral artery revascularization is associated with similar long-term durability in both groups. Intensive treatment of atherosclerosis risk factors and surveillance for restenosis likely contribute to improving the long-term outcomes of both manifestations of peripheral artery disease.
Vascular Medicine 04/2012; 17(3):138-44. · 1.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Ultrasound imaging has been used in a range of cardiac interventions. We describe the use of intravascular ultrasound to assist in coronary sinus lead implantation in a patient where contrast venography was contraindicated. (PACE 2012;xx;e1-e3).
Pacing and Clinical Electrophysiology 04/2012; · 1.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Antihypertensive agents lower the risk of cardiovascular events, but whether they affect pathways important in inflammation and plaque remodeling in atherosclerosis is uncertain. We assessed whether 2 commonly used antihypertensive agents affected plasma biomarkers reflecting specific inflammatory and remodeling processes over 2 years in the Comparison of Amlodipine versus Enalapril to Limit Occurrences of Thrombosis (CAMELOT) study.
The study was a randomized controlled trial of 2 antihypertensives (amlodipine and enalapril) compared with placebo in patients with coronary artery disease and diastolic blood pressure less than 100 mm Hg. In 196 subjects who had baseline and 2-year intravascular coronary ultrasound examinations, we measured plasma interleukin 18, interleukin 1 receptor antagonist, matrix metalloproteinase 9, neopterin, and C-reactive protein. Results for both treatment groups were pooled and compared with placebo.
Antihypertensive treatment with either agent significantly lowered diastolic blood pressure (-4.7 vs placebo 1.3 mm Hg, P = .002) and progression of coronary atheroma (Δ percent atheroma volume 0.6 vs placebo 2.1, P = .031). Antihypertensive therapy did not affect plasma biomarkers of inflammation or plaque remodeling in the 135 subjects with baseline and 2-year biomarker samples. Progression in percent atheroma volume was significantly less in subjects taking statins at baseline (-2.5%, P = .0008).
In patients with coronary artery disease and well-controlled risk factors, antihypertensive therapy lowered blood pressure and progression of coronary atherosclerosis but did not affect plasma biomarkers of inflammation and remodeling. Antihypertensives may decrease atheroma progression by mechanisms other than those reflected by these plasma biomarkers.
American heart journal 04/2012; 163(4):735-40. · 4.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Vascular remodeling of distal pulmonary arterioles that promotes abnormal pulmonary vascular reactivity is a central mechanism in the pathogenesis of pulmonary arterial hypertension (PAH). In selected patients, invasive pulmonary vasoreactivity testing performed in the cardiac catheterization laboratory with inhaled nitric oxide, epoprostenol, or adenosine is useful for PAH diagnosis, risk stratification, and assessing patient appropriateness for PAH-specific treatment(s). Limited accessibility to inhaled nitric oxide and a suboptimal test sensitivity profile reported for adenosine has contributed to the selection of epoprostenol for pulmonary vasoreactivity testing in some pulmonary hypertension referral centers. However, standardized procedural protocols for administrating epoprostenol for this purpose are largely unavailable to the practicing clinical community. The current work aims to bridge this gap by providing a stepwise procedure for the safe administration of clinically indicated intravenous epoprostenol during pulmonary vasoreactivity testing.
Critical pathways in cardiology 03/2012; 11(1):40-2.
[Show abstract][Hide abstract] ABSTRACT: The clinical value of measuring C-reactive protein (CRP) to guide statin therapy is uncertain. It has no value in patients at high risk who would be treated regardless of CRP (eg, patients with coronary disease or of equivalent risk), in patients at low risk who do not warrant treatment, and those with other acute or chronic inflammatory conditions that amplify CRP. Drawbacks to the widespread clinical use of CRP include its small impact on risk prediction beyond other risk factors, and evidence from JUPITER and other trials that baseline CRP is unable to identify patients who obtain greater absolute benefits from statin therapy. Furthermore, the within-person variability of CRP is about the same as the reduction in CRP from intensive statin therapy, and this leads to many patients registering an increase in CRP with treatment. For these reasons, CRP has no clear role in determining who should receive statin therapy or for monitoring the success of treatment.
Current Atherosclerosis Reports 11/2011; 14(1):26-32. · 3.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Early in the course of ST-segment elevation myocardial infarction (STEMI), therapies that may harm patients who develop left ventricular (LV) dysfunction, such as β-blockers, are often administered. The investigators analyzed the ACTIVATE-SF database, a registry of consecutive STEMI activations presenting to 2 medical centers at the University of California, San Francisco. LV dysfunction was defined as an ejection fraction ≤40% on echocardiography. Of 211 patients included in the analysis, 66 (31%) had LV ejection fractions ≤40%. Patients with LV dysfunction were older (63 ± 15 vs 56 ± 13 years, p = 0.002). In multivariate regression models, decreased renal function (reference group, creatinine <1.0 mg/dl; adjusted odds ratio [AOR] creatinine >1.5 mg/dl 6.35, 95% confidence interval [CI] 1.66 to 24.31, p = 0.007), a history of coronary artery disease (AOR 3.12, 95% CI 1.26 to 7.71, p = 0.014), ST-segment elevation >2 mm on 12-lead electrocardiography (AOR 2.78, 95% CI 1.31 to 5.87, p = 0.008), and need for mechanical ventilation (AOR 3.98, 95% CI 1.41 to 11.19, p = 0.009) increased the odds of LV dysfunction. Inferior ST-segment elevations were associated with 88% decreased odds of LV dysfunction (AOR 0.12, 95% CI 0.06 to 0.35, p <0.001). A prediction score using these characteristics stratified patients into low-, intermediate-, and high-risk groups for LV dysfunction; positive likelihood ratios for LV dysfunction in these groups were 0.07, 1.14, and 4.93, respectively. In conclusion, 5 key predictors of in-hospital LV dysfunction after STEMI were identified; a risk score based on these predictors helps to quickly identify patients presenting with STEMI who are at the highest risk for developing significant LV dysfunction and could guide optimal therapeutic choices.
The American journal of cardiology 11/2011; 109(3):327-31. · 3.58 Impact Factor