Sex differences in long-term outcomes of patients across the spectrum of coronary artery disease.

BACKGROUND: Patients with nonobstructive coronary artery disease (CAD) have worse outcomes compared with those without CAD; however, few studies have compared the intermediate- and long-term impact of CAD severity as a function of patient sex. METHODS: We evaluated 5-year and long-term all-cause mortality of women and men undergoing elective coronary angiography at a single center by degree of CAD: no CAD (1%-24% stenosis), nonobstructive CAD (25%-69% epicardial stenosis or 25%-49% left main stenosis), or obstructive CAD (epicardial stenosis ≥70% or left main stenosis ≥50%), both overall and after adjusting for baseline clinical risk factors using Cox proportional-hazards models. RESULTS: Between January 1986 and July 2010, 8,766 women and 11,638 men underwent angiography and were followed for a median of 9.2 years. The majority (67%) of women had no CAD or nonobstructive CAD, whereas the majority of men had obstructive CAD (56%, P < .001). In both sexes, increasing CAD was associated with increased 5-year risk of mortality. Risk-adjusted hazard ratios (vs no CAD) for women were 1.36 (95% CI, 1.16-1.60) and 1.86 (1.61-2.16) for nonobstructive and obstructive CAD, respectively; corresponding hazard ratios for men were 1.24 (1.06-1.45) and 1.38 (1.20-1.59). After risk adjustment, 5-year mortality risk was higher in men than in women at all levels of CAD severity. The relationships between severity of CAD and mortality risk during long-term follow-up in women and men were similar to the 5-year relationships above. CONCLUSIONS: Although women undergoing elective catheterization have less severe CAD than men, nonobstructive CAD is prevalent in both sexes and carries a worse prognosis than no CAD. These data suggest a need for further investigation to establish optimal therapies for this at-risk group of patients with nonobstructive CAD.

Association between surgical indications, operative risk, and clinical outcome in infective endocarditis: a prospective study from the International Collaboration on Endocarditis.

BACKGROUND: Use of surgery for the treatment of infective endocarditis (IE) as related to surgical indications and operative risk for mortality has not been well defined. METHODS AND RESULTS: The International Collaboration on Endocarditis-PLUS (ICE-PLUS) is a prospective cohort of consecutively enrolled patients with definite IE from 29 centers in 16 countries. We included patients from ICE-PLUS with definite left-sided, non-cardiac device-related IE who were enrolled between September 1, 2008, and December 31, 2012. A total of 1296 patients with left-sided IE were included. Surgical treatment was performed in 57% of the overall cohort and in 76% of patients with a surgical indication. Reasons for nonsurgical treatment included poor prognosis (33.7%), hemodynamic instability (19.8%), death before surgery (23.3%), stroke (22.7%), and sepsis (21%). Among patients with a surgical indication, surgical treatment was independently associated with the presence of severe aortic regurgitation, abscess, embolization before surgical treatment, and transfer from an outside hospital. Variables associated with nonsurgical treatment were a history of moderate/severe liver disease, stroke before surgical decision, and Staphyloccus aureus etiology. The integration of surgical indication, Society of Thoracic Surgeons IE score, and use of surgery was associated with 6-month survival in IE. CONCLUSIONS: Surgical decision making in IE is largely consistent with established guidelines, although nearly one quarter of patients with surgical indications do not undergo surgery. Operative risk assessment by Society of Thoracic Surgeons IE score provides prognostic information for survival beyond the operative period. S aureus IE was significantly associated with nonsurgical management.

PROspective Multicenter Imaging Study for Evaluation of chest pain: rationale and design of the PROMISE trial.

BACKGROUND: Suspected coronary artery disease (CAD) is one of the most common, potentially life-threatening diagnostic problems clinicians encounter. However, no large outcome-based randomized trials have been performed to guide the selection of diagnostic strategies for these patients. METHODS: The PROMISE study is a prospective, randomized trial comparing the effectiveness of 2 initial diagnostic strategies in patients with symptoms suspicious for CAD. Patients are randomized to either (1) functional testing (exercise electrocardiogram, stress nuclear imaging, or stress echocardiogram) or (2) anatomical testing with ≥64-slice multidetector coronary computed tomographic angiography. Tests are interpreted locally in real time by subspecialty certified physicians, and all subsequent care decisions are made by the clinical care team. Sites are provided results of central core laboratory quality and completeness assessment. All subjects are followed up for ≥1 year. The primary end point is the time to occurrence of the composite of death, myocardial infarction, major procedural complications (stroke, major bleeding, anaphylaxis, and renal failure), or hospitalization for unstable angina. RESULTS: More than 10,000 symptomatic subjects were randomized in 3.2 years at 193 US and Canadian cardiology, radiology, primary care, urgent care, and anesthesiology sites. CONCLUSION: Multispecialty community practice enrollment into a large pragmatic trial of diagnostic testing strategies is both feasible and efficient. The PROMISE trial will compare the clinical effectiveness of an initial strategy of functional testing against an initial strategy of anatomical testing in symptomatic patients with suspected CAD. Quality of life, resource use, cost-effectiveness, and radiation exposure will be assessed.

Impact of choice of imaging modality accompanying outpatient exercise stress testing on outcomes and resource use after revascularization for acute coronary syndromes.

BACKGROUND: Exercise stress testing is commonly obtained after percutaneous coronary intervention (PCI) performed for acute coronary syndromes (ACS). We compared the relationships between exercise echocardiography and nuclear testing after ACS-related PCI on outcomes and resource use. METHODS: Longitudinal observational study using fee-for-service Medicare claims to identify patients undergoing outpatient exercise stress testing with imaging within 15 months after PCI performed for ACS between 2003 and 2004. RESULTS: Of 63,100 patients undergoing stress testing 3 to 15 months post-PCI, 31,731 (50.3%) underwent an exercise stress test with imaging. Among 29,279 patients undergoing exercise stress testing with imaging, 15.5% received echocardiography. Echocardiography recipients had higher rates of repeat stress testing (adjusted hazard ratio [HR] 2.60, CI 2.19-3.10) compared with those undergoing nuclear imaging in the 90 days after testing, but lower rates of revascularization (adjusted HR 0.87, CI 0.76-0.98) and coronary angiography (adjusted HR 0.88, CI 0.80-0.97). None of these differences persisted subsequent to 90 days after stress testing. Rates of death and readmission for myocardial infarction rates were similar. Total Medicare payments were lower initially after echocardiography (incremental difference $498, CI 488-507), an effect attributed primarily to lower reimbursement for the stress test itself, but not significantly different after 14 months after testing. CONCLUSIONS: In this study using administrative data, echocardiography recipients initially had fewer invasive procedures but higher rates of repeat testing than nuclear testing recipients. However, these differences between echo and nuclear testing did not persist over longer time frames.

Use of stress testing and diagnostic catheterization after coronary stenting: association of site-level patterns with patient characteristics and outcomes in 247,052 Medicare beneficiaries.

OBJECTIVES: The aim of this study was to determine diagnostic testing patterns after percutaneous coronary intervention (PCI). BACKGROUND: Little is known about patterns of diagnostic testing after PCI in the United States or the relationship of these patterns to clinical outcomes. METHODS: Centers for Medicare and Medicaid Services inpatient and outpatient claims were linked to National Cardiovascular Data Registry CathPCI Registry data from 2005 to 2007. Hospital quartiles of the cumulative incidence of diagnostic testing use within 12 and 24 months after PCI were compared for patient characteristics, repeat revascularization, acute myocardial infarction, and death. RESULTS: A total of 247,052 patients underwent PCI at 656 institutions. Patient and site characteristics were similar across quartiles of testing use. There was a 9% and 20% higher adjusted risk for repeat revascularization in quartiles 3 and 4 (highest testing rate), respectively, compared with quartile 1 (lowest testing rate) (p = 0.020 and p < 0.0001, respectively). The adjusted risk for death or acute myocardial infarction did not differ among quartiles. CONCLUSIONS: Although patient characteristics were largely independent of rates of post-PCI testing, higher testing rates were not associated with lower risk for myocardial infarction or death, but repeat revascularization was significantly higher at these sites. Additional studies should examine whether increased testing is a marker for improved quality of post-PCI care or simply increased health care utilization.

Patterns of stress testing and diagnostic catheterization after coronary stenting in 250 350 medicare beneficiaries.

BACKGROUND: Patterns of noninvasive stress test (ST) and invasive coronary angiography (CA) utilization after percutaneous coronary intervention (PCI) are not well described in older populations. METHODS AND RESULTS: We linked National Cardiovascular Data Registry CathPCI Registry data with longitudinal Medicare claims data for 250 350 patients undergoing PCI from 2005 to 2007 and described subsequent testing and outcomes. Between 60 days post-PCI and end of follow-up (median 24 months), 49% (n=122 894) received ST first, 10% (n=25 512) underwent invasive CA first, and 41% (n=101 944) had no testing. Several clinical risk factors at time of index PCI were associated with decreased likelihood of downstream testing (ST or CA, P<0.05 for all), including older age (hazard ratio [HR] 0.784 per 10-year increase), male sex (HR 0.946), heart failure (HR 0.925), diabetes mellitus (HR 0.954), smoking (HR 0.804), and renal failure (HR 0.880). Fifteen percent of patients with ST first proceeded to subsequent CA within 90 days of testing (n=18 472/122 894) [corrected]; of these, 48% (n=8831) underwent revascularization within 90 days, compared with 53% (n=13 316) of CA first patients (P<0.0001). CONCLUSIONS: In this descriptive analysis, ST and invasive CA were common in older patients after PCI. Paradoxically, patients with higher risk features at baseline were less likely to undergo post-PCI testing. The revascularization yield was low on patients referred for ST after PCI, with only 7% [corrected] undergoing revascularization within 90 days.

Patterns and predictors of stress testing modality after percutaneous coronary stenting: data from the NCDR(®).

OBJECTIVES: We evaluated temporal trends and geographic variation in choice of stress testing modality after percutaneous coronary intervention (PCI), as well as associations between modality and procedure use after testing. BACKGROUND: Stress testing is frequently performed post-PCI, but the choices among available modalities (electrocardiography only, nuclear, or echocardiography; pharmacological or exercise stress) and consequences of such choices are not well characterized. METHODS: CathPCI Registry(®) data were linked with identifiable Medicare claims to capture stress testing use between 60 and 365 days post-PCI and procedures within 90 days after testing. Testing rates and modality used were modeled on the basis of patient, procedure, and PCI facility factors, calendar quarter, and Census Divisions using Poisson and logistic regression. Post-test procedure use was assessed using Gray's test. RESULTS: Among 284,971 patients, the overall stress testing rate after PCI was 53.1 per 100 person-years. Testing rates declined from 59.3 in quarter 1 (2006) to 47.1 in quarter 4 (2008), but the relative use of modalities changed little. Among exercise testing recipients, adjusted proportions receiving electrocardiography-only testing varied from 6.8% to 22.8% across Census Divisions; and among exercise testing recipients having an imaging test, the proportion receiving echocardiography (versus nuclear) varied from 9.4% to 34.1%. Post-test procedure use varied among modalities; exercise electrocardiography-only testing was associated with more subsequent stress testing (13.7% vs. 2.9%; p < 0.001), but less catheterization (7.4% vs. 14.1%; p < 0.001) than imaging-based tests. CONCLUSIONS: Modest reductions in stress testing after PCI occurring between 2006 and 2008 cannot be ascribed to trends in use of any single modality. Additional research should assess whether this trend represents better patient selection for testing or administrative policies (e.g., restricted access for patients with legitimate testing needs). Geographic variation in utilization of stress modalities and differences in downstream procedure use among modalities suggest a need to identify optimal use of the different test modalities in individual patients.

Downstream testing and subsequent procedures after coronary computed tomographic angiography following coronary stenting in patients ≥65 years of age.

Limited data are available on the use of coronary computed tomographic angiography (CCTA) in patients who have received percutaneous coronary intervention (PCI). To evaluate patterns of cardiac testing including CCTA after PCI, we created a retrospective observational dataset linking National Cardiovascular Data Registry CathPCI Registry baseline data with longitudinal inpatient and outpatient Medicare claims data for patients who received coronary stenting from November 1, 2005 through December 31, 2007. In 192,009 patients with PCI (median age 74 years), the first test after coronary stenting was CCTA for 553 (0.3%), stress testing for 89,900 (46.8%), and coronary angiography for 22,308 (11.6%); 79,248 (41.3%) had no further testing. Patients referred to CCTA first generally had similar or lower baseline risk than those referred for stress testing or catheterization first. Compared to patients with stress testing first after PCI, patients who underwent CCTA first had higher unadjusted rates of subsequent noninvasive testing (10% vs 3%), catheterization (26% vs 15%), and revascularization (13% vs 8%) within 90 days of initial testing after PCI (p <0.0001 for all comparisons). In conclusion, despite similar or lesser-risk profiles, patients initially evaluated with CCTA after PCI had more downstream testing and revascularization than patients initially evaluated with stress testing. It is unclear whether these differences derive from patient selection, performance of CCTA compared to other testing strategies, or the association of early adoption of CCTA with distinct patterns of care.

Downstream procedures and outcomes after stress testing for chest pain without known coronary artery disease in the United States.

BACKGROUND: Millions of Americans with suspected coronary artery disease undergo noninvasive cardiac stress testing annually. Downstream procedures and subsequent outcomes among symptomatic patients without known coronary disease referred for stress testing are not well characterized in contemporary community practice. METHODS: We examined administrative insurance billing data from a national insurance provider from November 2004 through June 2007. After excluding patients with prior cardiac disease or chest pain evaluation, we identified 80,676 people age 40 to 64 years with outpatient cardiac stress testing within 30 days after an office visit for chest pain. We evaluated rates of invasive coronary angiography, coronary revascularization, and cardiovascular events after stress testing. RESULTS: Within 60 days, only 8.8% of stress test patients underwent cardiac catheterization and only 2.7% underwent revascularization; within 1 year, only 0.5% died and had myocardial infarction or stroke. There were marked geographic variations in 1-year rates of catheterization (3.8%-14.8%) and revascularization (1.2%-3.0%) across 20 hospital referral regions. CONCLUSIONS: In this large national cohort of middle-aged patients without previously coded cardiac diagnosis who were referred for stress testing after outpatient chest pain evaluation, few proceeded to invasive angiography or revascularization, and subsequent cardiovascular events were infrequent.

Changes in glycoprotein IIb/IIIa inhibitor excess dosing with site-specific safety feedback in the Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines (CRUSADE) initiative.

BACKGROUND: Glycoprotein (GP) IIb/IIIa inhibitors can improve outcomes in patients with non-ST-segment elevation acute coronary syndromes but raise the risk of bleeding, particularly if dosed in excess. The impact of GP IIb/IIIa dosing feedback on safety and major bleeding is unknown. METHODS: Glycoprotein IIb/IIIa dosing feedback was added to the CRUSADE quarterly site reports in the first quarter of 2006. We describe GP IIb/IIIa use and dosing among 25,641 patients with non-ST-segment elevation acute coronary syndromes from the fourth quarter of 2005 to the fourth quarter of 2006. RESULTS: Eleven thousand eight hundred forty-six patients received GP IIb/IIIa inhibitors, including 4,031 women and 2,609 elderly patients (age, ≥75 years). Among GP IIb/IIIa-treated patients, unadjusted rates of excess GP IIb/IIIa dosing declined overall (26.4%-22.4%, Ptrend=.01) and among the elderly (65.6%-52.1%, Ptrend<.001). After adjustment, declines in excess dosing remained significant only for the elderly, although more than half of GP IIb/IIIa-treated elderly patients continued to receive excess dosing at the end of the study period (64.1%-51.3%, Ptrend<.001). There were concurrent declines in unadjusted major bleeding rates overall (9.6%-8.0%, Ptrend=.02), but declines among women (14.4%-11.5%, Ptrend=.08) and the elderly (17.1%-11.0%, Ptrend=.05) did not reach statistical significance. After adjustment for baseline characteristics and excess dosing, declines in major bleeding rates were no longer significant overall or for any subgroup. CONCLUSION: Within 9 months of initiating a safety feedback program, we observed early decreases in excess GP IIb/IIIa dosing among the elderly but minimal changes in excess dosing overall. Further work is needed to promote safe and effective medication use in vulnerable patients who are most at risk of harm.

Intraoperative device closure of postinfarction ventricular septal defects.

Postinfarction ventricular septal defects (VSDs) are associated with high mortality and typically these are treated urgently with surgery for exclusion patch repair. Percutaneous closure of postinfarction VSDs using occlusion devices is feasible in some patients, but in some cases device deployment may not be possible due to VSD anatomy or valvular apparatus interference. We report the novel technique of deploying Amplatzer VSD devices in the operating room under direct vision through a right atriotomy with and without aortotomy in 2 patients with large inferobasal VSDs after myocardial infarction.

Does myocardial perfusion imaging provide incremental prognostic information to left ventricular ejection fraction?

Cardiac nuclear imaging studies such as gated single photon emission computed tomography can offer assessment of myocardial perfusion and ventricular function. These two types of data can provide valuable information for the diagnosis of coronary artery disease, prognosis, and optimal treatment strategies. Ejection fraction and other measures of ventricular function generally are the best predictors of mortality, whereas perfusion parameters and estimates of ischemic burden are often the best predictors of nonfatal cardiac events and response to revascularization; the combination of both can provide increased sensitivity and specificity for diagnosis of significant coronary disease, and increased predictive power for outcomes. Recent data show that together they also add incremental value in predicting sudden cardiac death. Less commonly used modalities such as positron emission tomography may offer additional tools for quantification of perfusion and function at rest and at stress, with important clinical implications.

Poor validity of self-reported hepatitis B virus infection and vaccination status among young drug users.

Self-reported hepatitis B virus (HBV) infection status and immunization status were compared with HBV serological markers among 324 young injection drug users (IDUs) and noninjection drug users (NIDUs). The overall validity of self-reported status was poor; 52% claiming to be vaccinated were actually susceptible to HBV. There was no difference in validity of self-reported HBV status between IDUs and NIDUs. Clinicians should adopt a "Don't Ask, Vaccinate" vaccination policy for young drug users.

Spontaneous renal artery dissection: treatment with coil embolization.

A 47-year-old man presented with nonspecific left flank pain and severe hypertension as a result of a spontaneous dissection of an accessory renal artery. Because of the progressive increase in the size of the dissection flap and uncontrollable hypertension, treatment with segmental embolization of the true and false lumen of the accessory renal artery was performed with successful clinical outcome. This case report will address the salient clinical features of spontaneous renal artery dissections and treatment options.

Imbalance between xanthine oxidase and nitric oxide synthase signaling pathways underlies mechanoenergetic uncoupling in the failing heart.

Inhibition of xanthine oxidase (XO) in failing hearts improves cardiac efficiency by an unknown mechanism. We hypothesized that this energetic effect is due to reduced oxidative stress and critically depends on nitric oxide synthase (NOS) activity, reflecting a balance between generation of nitric oxide (NO) and reactive oxygen species. In dogs with pacing-induced heart failure (HF), ascorbate (1000 mg) mimicked the beneficial energetic effects of allopurinol, increasing both contractility and efficiency, suggesting an antioxidant mechanism. Allopurinol had no additive effect beyond that of ascorbate. Crosstalk between XO and NOS signaling was assessed. NOS inhibition with N(G)-monomethyl-L-arginine (L-NMMA; 20 mg/kg) had no effect on basal contractility or efficiency in HF, but prevented the +26.2+/-3.5% and +66.5+/-17% enhancements of contractility and efficiency, respectively, observed with allopurinol alone. Similarly, improvements in contractility and energetics due to ascorbate were also inhibited by L-NMMA. Because of the observed NOS-XO crosstalk, we predicted that in normal hearts NOS inhibition would uncover a depression of energetics caused by XO activity. In normal conscious dogs, L-NMMA increased myocardial oxygen consumption (MVO2) while lowering left ventricular external work, reducing efficiency by 31.1+/-3.8% (P<0.005). Lowered efficiency was reversed by XO inhibition (allopurinol, 200 mg) or by ascorbate without affecting cardiac load or systemic hemodynamics. Single-cell immunofluorescence detected XO protein in cardiac myocytes that was enhanced in HF, consistent with autocrine signaling. These data show that both NOS and XO signaling systems participate in the regulation of myocardial mechanical efficiency and that upregulation of XO relative to NOS contributes to mechanoenergetic uncoupling in heart failure.