Heparin Does Not Regulate Circulating Human PCSK9 (Proprotein Convertase Subtilisin-Kexin Type 9) in a General Population-Brief Report.

BACKGROUND: PCSK9 (proprotein convertase subtilisin-kexin type 9) chaperones the hepatic LDLR (low-density lipoprotein receptor) for lysosomal degradation, elevating serum LDL (low-density lipoprotein) cholesterol and promoting atherosclerotic heart disease. Though the major effect on the hepatic LDLR comes from secreted PCSK9, the details of PCSK9 reuptake into the hepatocyte remain unclear. In both tissue culture and animal models, HSPGs (heparan sulfate proteoglycans) on hepatocytes act as co-receptors to promote PCSK9 reuptake. We hypothesized that if this PCSK9:HSPG interaction is important in humans, disrupting it with unfractionated heparin (UFH) would acutely displace PCSK9 from the liver and increase plasma PCSK9. METHODS: We obtained remnant plasma samples from 160 subjects undergoing cardiac catheterization before and after administration of intravenous UFH. PCSK9 levels were determined using a commercial enzyme-linked immunosorbent assay. RESULTS: Median plasma PCSK9 was 113 ng/mL prior to UFH and 119 ng/mL afterward. This difference was not significant (P=0.83 [95% CI, -6.23 to 6.31 ng/mL]). Equivalence testing provided 95% confidence that UFH would not raise plasma PCSK9 by > 4.7%. Among all subgroups, only subjects with the lowest baseline PCSK9 concentrations exhibited a response to UFH (8.8% increase, adj. P=0.044). A modest correlation was observed between baseline plasma PCSK9 and the change in plasma PCSK9 due to UFH (RS=-0.3634; P<0.0001). CONCLUSIONS: Administration of UFH does not result in a clinically meaningful effect on circulating PCSK9 among an unselected population of humans. The results cast doubt on the clinical utility of disrupting the PCSK9:HSPG interaction as a general therapeutic strategy for PCSK9 inhibition. However, the observations suggest that in selected populations, disrupting the PCSK9:HSPG interaction could still affect PCSK9 reuptake and offer a therapeutic benefit.

Angiographically confirmed stent thrombosis in contemporary practice: insights from intravascular ultrasound.

OBJECTIVE: We hypothesized that patients presenting with stent thrombosis (ST) have a high prevalence of stent underexpansion and malapposition when assessed by intravascular ultrasound (IVUS). BACKGROUND: IVUS can provide mechanistic insight into mechanical factors, including stent underexpansion, malapposition, and fracture that may predispose to ST. METHODS: All consecutive cases of angiographically confirmed ST from a multicenter registry (from 2005 to 2010) were reviewed. All IVUS images were reviewed off-line for the presence of stent underexpansion, malapposition, and fracture. Kaplan-Meier analysis was used to determine whether use of IVUS at the time of ST was associated with long-term mortality and major adverse cardiovascular events. RESULTS: IVUS was performed in 32 of 173 subjects with ST (18%). Stent underexpansion was present in 82% of cases and in all cases of early ST, with a mean stent expansion of 0.7 ± 0.23 by MUSIC criteria. Stent malapposition was most frequently observed in very late ST (40%). In-hospital mortality was similar between subjects who had IVUS performed at the time of ST when compared with the non-IVUS group (3.2% vs. 4.3%, P = 0.8). Subjects who had IVUS performed at the time of ST had lower rates of mortality (HR 0.4, 95% CI 0.1-1.6, P =0.2) and major adverse cardiovascular events (HR 0.5, 95% CI 0.2-1.4, P =0.2) at follow-up, but these values were not statistically significant. CONCLUSIONS: There is a high prevalence of stent underexpansion in early ST, while the prevalence of malapposition is higher in very late ST. Use of IVUS during treatment for ST may identify mechanisms underlying the development of ST.

Procedural success and long-term outcomes of aspiration thrombectomy for the treatment of stent thrombosis.

BACKGROUND: Stent thrombosis (ST) is associated with a significant burden of coronary thrombus and potential microvascular obstruction. Aspiration thrombectomy may decrease the extent of microvascular obstruction in patients with acute myocardial infarction but its role in the treatment of ST is uncertain. The present study sought to evaluate the association between aspiration thrombectomy, procedural success and long-term outcomes among patients presenting with ST. METHODS: In a multicenter cohort of patients with definite ST, procedural success, long-term mortality, and major adverse cardiovascular events (death, stroke, re-infarction, revascularization) were ascertained. Propensity weighting was used to determine the association between aspiration thrombectomy and long-term outcomes. RESULTS: A total of 205 patients with ST were identified. Among these, 115 (56%) patients underwent adjunctive aspiration thrombectomy during percutaneous coronary intervention. Patients undergoing aspiration thrombectomy were more likely to present with ST-elevation myocardial infarction (75% vs. 52%, P < 0.003) and require hemodynamic support (19% vs. 10%, P = 0.07). Aspiration thrombectomy was associated with improved procedural outcomes including postprocedural TIMI 3 flow, resulting in higher angiographic and procedural success (each 96% vs. 83%, P < 0.001). Despite improved angiographic outcomes, the use of aspiration thrombectomy was not associated with a difference in long-term mortality (adjusted HR 0.99, 95% CI 0.44-2.24) or major adverse cardiovascular events (adjusted HR 1.06, 95% CI 0.45-2.48). CONCLUSIONS: Aspiration thrombectomy is associated with improved coronary flow and procedural success but is not associated with improved long-term outcomes among patients undergoing percutaneous intervention for definite ST. CLINICAL TRIAL REGISTRATION: NCT00931502 (http://www.clinicaltrials.gov/ct2/show/NCT00931502)

Contemporary clinical characteristics, treatment, and outcomes of angiographically confirmed coronary stent thrombosis: results from a multicenter California registry.

OBJECTIVES: To describe the contemporary treatment and outcomes for patients with angiographically confirmed (definite) stent thrombosis (ST). BACKGROUND: Limited data are available on contemporary treatment patterns and outcomes of patients with ST in the United States. METHODS: In this multicenter California registry, consecutive cases of definite ST over 5 years were identified. Clinical characteristics, in-hospital outcomes, and long-term survival are reported. RESULTS: One hundred and sixty five consecutive episodes of ST were identified in 153 patients from January 2005 to February 2010. The distribution of acute (≤24 hr), subacute (24 hr to 30 days), late (30 days to 1 year), and very late (≥1 year) ST was 3.9%, 21.8%, 17.6%, and 50.3%, respectively. Only 41.2% of patients were on dual antiplatelet therapy at the time of presentation, while 22.4% of patients were on none. Of the 61.4% of patients treated with restenting, 71.1% of them received a drug-eluting stent. Procedural success was 88.1%, and in-hospital death, stroke, and CABG occurred in 5.5%, 0.6%, and 6.1% of subjects, respectively. All-cause mortality at 1 year was 14.3%. Although female gender, diabetes mellitus (DM), bifurcation disease, ejection fraction <40%, and cardiogenic shock at the time of presentation were associated with an increased risk of in-hospital mortality, only DM (P = 0.047) and bifurcation disease (P = 0.027) remained independent predictors of in-hospital death. CONCLUSION: In-hospital mortality from definite ST is lower than previously reported, but long-term mortality remains high. DM and bifurcation disease, but not type of percutaneous therapy, are independently associated with in-hospital mortality.

Pregnancy-Associated Chest Pain: A Case of Spontaneous Coronary Artery Dissection.

Spontaneous Coronary Artery Dissection (SCAD) is an important cause of myocardial infarction that typically affects women without traditional cardiovascular risk factors. It is the most common cause of myocardial infarction in pregnant and postpartum women. SCAD is often underdiagnosed due to the lack of clinician familiarity, and patients with pregnancy-associated SCAD often have more severe clinical presentations than those without. We present a case of SCAD in a multiparous woman who presented with acute chest pain in the postpartum period.

Echocardiographic determination of pulmonary arterial capacitance.

A growing body of evidence has demonstrated that pulmonary arterial capacitance (PAC) is the strongest hemodynamic predictor of clinical outcomes across a wide spectrum of cardiovascular disease, including pulmonary hypertension and heart failure. We hypothesized that a ratio of right ventricular stroke volume (RVOT VTI) to the associated peak arterial systolic pressure (PASP) could function as a reliable non-invasive surrogate for PAC. We performed a prospective study of patients undergoing simultaneous transthoracic echocardiography and right heart catheterization (RHC) for various clinical indications. Measurements of the RVOT VTI/PASP ratio from echocardiographic measurements were compared against PAC calculated from RHC measurements. Correlation coefficients and Bland-Altman analysis compared the RVOT VTI/PASP ratio with PAC. Forty-five subjects were enrolled, 38% were female and mean age was 54 years (SD 13 years). The reason for referral to RHC was most commonly post-heart transplant surveillance (40%), followed by heart failure (22%), and pulmonary hypertension (18%). Pre-capillary pulmonary hypertension was present in 18%, isolated post-capillary pulmonary hypertension was present in 13%, and combined pre-and post-capillary pulmonary hypertension was present in 29%. The RVOT VTI/PASP ratio was obtainable in the majority of patients (78%), and Pearson's correlation demonstrated moderately-strong association between PAC and the RVOT VTI/PASP ratio, r = 0.75 (P < 0.001). Bland-Altman analysis demonstrated good agreement between measurements without suggestion of systematic bias and a mean difference in standardized units of - 0.133. In a diverse population of patients and hemodynamic profiles, we validated that the ratio of RVOT VTI/PASP to be a reliably-obtained non-invasive marker associated with PAC.

Endothelin-1 Predicts Hemodynamically Assessed Pulmonary Arterial Hypertension in HIV Infection.

BACKGROUND: HIV infection is an independent risk factor for PAH, but the underlying pathogenesis remains unclear. ET-1 is a robust vasoconstrictor and key mediator of pulmonary vascular homeostasis. Higher levels of ET-1 predict disease severity and mortality in other forms of PAH, and endothelin receptor antagonists are central to treatment, including in HIV-associated PAH. The direct relationship between ET-1 and PAH in HIV-infected individuals is not well described. METHODS: We measured ET-1 and estimated pulmonary artery systolic pressure (PASP) with transthoracic echocardiography (TTE) in 106 HIV-infected individuals. Participants with a PASP ≥ 30 mmHg (n = 65) underwent right heart catheterization (RHC) to definitively diagnose PAH. We conducted multivariable analysis to identify factors associated with PAH. RESULTS: Among 106 HIV-infected participants, 80% were male, the median age was 52 years and 77% were on antiretroviral therapy. ET-1 was significantly associated with higher values of PASP [14% per 0.1 pg/mL increase in ET-1, p = 0.05] and PASP ≥ 30 mmHg [PR (prevalence ratio) = 1.24, p = 0.012] on TTE after multivariable adjustment for PAH risk factors. Similarly, among the 65 individuals who underwent RHC, ET-1 was significantly associated with higher values of mean pulmonary artery pressure and PAH (34%, p = 0.003 and PR = 2.43, p = 0.032, respectively) in the multivariable analyses. CONCLUSIONS: Higher levels of ET-1 are independently associated with HIV-associated PAH as hemodynamically assessed by RHC. Our findings suggest that excessive ET-1 production in the setting of HIV infection impairs pulmonary endothelial function and contributes to the development of PAH.

Clinical features of acute coronary syndromes in patients with human immunodeficiency virus infection.

BACKGROUND: Patients with HIV infection exhibit increased rates of coronary events; however, the clinical features of acute coronary syndromes (ACS) in HIV-infected patients have not been well defined. METHODS AND RESULTS: Between 1993 and 2003, 68 HIV-infected patients were hospitalized with ACS. We compared the clinical features and outcome of these patients with those of 68 randomly selected control patients with ACS without HIV. HIV patients were on average more than a decade younger than controls and more likely to be male and current smokers and to have low HDL cholesterol. They were less likely than controls to have diabetes or hyperlipidemia, and their TIMI (Thrombolysis In Myocardial Infarction) risk scores on admission were significantly lower. At coronary angiography, the number of vessels with >50% stenosis was 1.3+/-1.0 in HIV patients and 1.9+/-1.2 in controls (P=0.007). Restenosis developed in 15 of 29 HIV patients who underwent percutaneous coronary intervention compared with 3 of 21 controls (52% versus 14%, P=0.006). CONCLUSIONS: HIV patients with ACS are younger and more likely to be males and current smokers and to have low HDL cholesterol levels compared with other ACS patients. Their TIMI risk scores are lower, and they are more likely to have single-vessel disease; however, their restenosis rates after percutaneous coronary intervention are unexpectedly high.

Long-term outcomes of angiographically confirmed coronary stent thrombosis: results from a multicentre California registry.

AIMS: Limited data exist on long-term outcomes of patients with stent thrombosis (ST). Our aim was to describe the long-term outcomes after angiographically confirmed ST. METHODS AND RESULTS: In this multicentre registry, consecutive cases of definite ST were identified between 2005 and 2013. Clinical and procedural characteristics, in-hospital outcomes and long-term survival up to five years were compared between those with and those without adverse cardiovascular and cerebrovascular events (MACCE), defined as all-cause mortality, myocardial infarction and stroke. Two hundred and twenty-one patients with 239 stent thrombosis events were identified. Patients who developed MACCE were older, less likely to be men, and less likely to have hypertension. Angiographic characteristics were similar. Patients who had a MACCE event showed a trend towards a lower likelihood of procedural success (86% vs. 91%, p=0.05). MACCE rates were 22% at one year and 41% at five years. All-cause mortality was 13% at one year and 24% at five years. On multivariable analysis, age, diabetes mellitus, active smoking and ST at a bifurcation were independently associated with the occurrence of MACCE up to five years. CONCLUSIONS: Age, active smoking, diabetes mellitus and bifurcation disease are independently associated with long-term MACCE over a five-year follow-up period.

Increased levels of asymmetric dimethylarginine are associated with pulmonary arterial hypertension in HIV infection.

OBJECTIVE: To examine the relationship between asymmetric dimethylarginine (ADMA) and HIV-associated pulmonary arterial hypertension (PAH). DESIGN: HIV infection is an independent risk factor for PAH, but the underlying pathogenesis remains unclear. Chronic inflammation resulting in nitric oxide-mediated endothelial dysfunction is a key mechanism underlying other types of PAH. ADMA is an endogenous inhibitor of endothelial nitric oxide synthase. Among uninfected individuals, ADMA is associated with PAH and predicts disease-related mortality. METHODS: We measured ADMA, high sensitivity C-reactive protein, interleukin-6 (IL-6), D-dimer, and pulmonary artery systolic pressure (PASP) using echocardiography in HIV-infected individuals. Right heart catheterization (RHC) was performed in individuals with a PASP at least 30  mmHg. We performed multivariable analysis to identify factors associated with high PASP by echocardiogram and PAH by RHC. RESULTS: Among 214 HIV-infected individuals, the median age was 50 years, 82% were men, 71% were on antiretroviral therapy, and 4.2% carried a prior diagnosis of PAH. ADMA and IL-6 were associated with increased values of PASP following multivariable adjustment (7.2% per 0.1 µmol/l, P = 0.0049 and 3.9% per doubling, P = 0.027, respectively). In adjusted analysis among the 85 participants who underwent RHC, ADMA and IL-6 were associated with higher values of mean PAP (14.2% per 0.1 µmol/l, P = 0.0014 and 5.8% per doubling, P = 0.038, respectively). However, only ADMA was associated with PAH (prevalence ratio = 1.74, P = 0.029). CONCLUSION: Elevated levels of ADMA are independently associated with PAH among HIV-infected individuals. Our findings suggest that chronic HIV-associated inflammation leading to an accumulation of ADMA and subsequent nitric oxide-mediated endothelial dysfunction may represent a novel mechanism for HIV-associated PAH.

Predictors and outcomes of recurrent stent thrombosis: results from a multicenter registry.

OBJECTIVES: The aim of this study was to determine the incidence, predictors, and outcomes of recurrent stent thrombosis (rST). BACKGROUND: Patients who had an initial stent thrombosis (ST) develop may be at high risk of rST. METHODS: We analyzed a multicenter California registry of angiographic definite ST at 5 academic hospitals from 2005 to 2013. A detailed review of the angiogram and procedure was performed of patients with and without rST. RESULTS: Among 221 patients with a median follow-up of 3.3 years, definite or probable rST developed in 29, including 19 with angiographic definite rST. The cumulative hazard ratio (HR) of definite or probable rST was 16% at 1 year and 24% at 5 years, whereas the cumulative HR of angiographic definite rST was 11% at 1 year and 20% at 5 years. Despite similar angiographic results, patients who had rST develop had significantly greater peak creatine kinase at the time of initial ST (mean, 2,655 mg/dl vs. 1,654 mg/dl; p = 0.05) than those without rST. The 3-year rate of major adverse cardiovascular events was 50% for patients with rST compared with 22% for patients with a single ST (p = 0.01). After multivariable adjustment, independent predictors of definite/probable rST were age (HR: 1.4; 95 confidence interval [CI]: 1.1 to 1.8 per 10 years), bifurcation ST (HR: 4.4; 95% CI: 1.8 to 10.9), and proximal vessel diameter (HR: 1.8; 95% CI: 1.1 to 3.2 per millimeter). CONCLUSIONS: rST represents an important cause of long-term morbidity and mortality after an initial ST. Bifurcation ST and a larger proximal reference vessel diameter are independently associated with an increased risk of rST.

Comparison of procedural success and long-term outcomes of stent thrombosis in coronary bypass grafts versus native coronary arteries.

Percutaneous coronary intervention within bypass grafts accounts for a significant percentage of total interventions. Bypass graft interventions are associated with an increased risk for stent thrombosis (ST), a condition that leads to significant morbidity and mortality. Despite this, the procedural characteristics and long-term outcomes of patients with bypass-graft ST have not been reported. The aim of the present study was to evaluate the procedural success and long-term outcomes of patients presenting with ST of coronary bypass grafts. Clinical and procedural characteristics of 205 ST cases at 5 academic hospitals were reviewed. Long-term mortality and major adverse cardiovascular events (stroke, reinfarction, and revascularization) were ascertained through review of medical records and the Social Security Death Index. Kaplan-Meier analysis was used to determine the association between ST in a bypass graft and long-term outcomes. Thirteen patients (6%) in the cohort presented with ST of a coronary bypass graft. Patients with bypass-graft ST had less severe presentations with a lower proportion of ST-segment elevation myocardial infarction (23% vs 69%, p <0.001). Despite this, ST of a bypass graft was associated with a trend toward reduced postprocedural Thrombolysis In Myocardial Infarction (TIMI) flow grade (p = 0.09), leading to lower angiographic (58% vs 92%, p <0.001) and procedural (62% vs 92%, p <0.001) success. After multivariate adjustment, bypass-graft ST was associated with increased long-term mortality (hazard ratio 3.3, 95% confidence interval 1.0 to 10.7) and major adverse cardiovascular events (hazard ratio 2.7, 95% confidence interval 1.1 to 6.9). In conclusion, ST in coronary bypass grafts is associated with reduced angiographic and procedural success as well as increased long-term major adverse cardiovascular events compared to ST in native coronary vessels.

Impact of door-to-activation time on door-to-balloon time in primary percutaneous coronary intervention for ST-segment elevation myocardial infarctions: a report from the Activate-SF registry.

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.

Angiographic stent thrombosis at coronary bifurcations: short- and long-term prognosis.

OBJECTIVES: This study sought to describe the presentation, management, and outcomes of patients presenting with angiographic definite stent thrombosis (ST) at coronary bifurcations. BACKGROUND: The development of drug-eluting stents has made it increasingly feasible to treat bifurcation lesions percutaneously. However, ST at coronary bifurcations may be associated with greater mortality than ST elsewhere. METHODS: We analyzed a multicenter California registry comprising all cases of angiographic definite ST at 5 academic hospitals from 2005 to 2010. Stenting was defined as occurring at a bifurcation if the main vessel stent crossed a side branch ≥2.0 mm in diameter (provisional single-stent approach), or if there was a prior 2-stent bifurcation approach. RESULTS: Among 173 cases of angiographic definite ST, we identified 20 cases of ST at coronary bifurcations. Nine of 20 bifurcation ST (45%) occurred with a stent present in both the parent and branch vessel. Eight cases had thrombus present in both the parent and side branch vessels. In-hospital mortality was much higher for subjects with bifurcation ST than ST at a nonbifurcation site (20% vs. 2%, p < 0.0001). During a median follow-up of 2.3 years, ST at a coronary bifurcation was associated with increased long-term mortality (hazard ratio [HR]: 3.3, 95% confidence interval [CI]: 1.4 to 7.7, p = 0.007) and a significantly higher risk for major adverse cardiovascular events (HR: 2.2, 95% CI: 1.04 to 4.8, p = 0.04) relative to ST at a nonbifurcation site. CONCLUSIONS: ST at coronary bifurcations is associated with a higher in-hospital and long-term mortality than ST at nonbifurcation lesions. (Stent Thrombus in Acute Coronary Syndromes; NCT00931502).

Predictors of depressed left ventricular function in patients presenting with ST-elevation myocardial infarction.

Early in the course of ST-segment elevation myocardial infarction (STEMI), therapies that may harm patients who develop left ventricular (LV) dysfunction, such as ß-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.

Electrocardiographic criteria for ST-elevation myocardial infarction in patients with left ventricular hypertrophy.

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.

Delaying primary percutaneous coronary intervention for computed tomographic scans in the emergency department.

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.

Doppler echocardiography does not accurately estimate pulmonary artery systolic pressure in HIV-infected patients.

Doppler echocardiography is used to screen for HIV-related pulmonary arterial hypertension (HRPAH). We studied patients with HIV infection to determine the accuracy of Doppler echocardiography-estimated pulmonary artery systolic pressure (PASP) compared with PASP measured during right heart catheterization. Doppler echocardiography-estimated PASP was inaccurate in 19.7% of cases. Using Doppler echocardiography-estimated PASP, one in three patients with HRPAH was missed. Doppler echocardiography estimates of PASP are not accurate in patients with HIV.

Prevalence and factors associated with false-positive ST-segment elevation myocardial infarction diagnoses at primary percutaneous coronary intervention­capable centers: a report from the Activate-SF registry.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.