Autonomic dysfunction in early breast cancer: Incidence, clinical importance, and underlying mechanisms.

Autonomic dysfunction represents a loss of normal autonomic control of the cardiovascular system associated with both sympathetic nervous system overdrive and reduced efficacy of the parasympathetic nervous system. Autonomic dysfunction is a strong predictor of future coronary heart disease, vascular disease, and sudden cardiac death. In the current review, we will discuss the clinical importance of autonomic dysfunction as a cardiovascular risk marker among breast cancer patients. We will review the effects of antineoplastic therapy on autonomic function, as well as discuss secondary exposures, such as psychological stress, sleep disturbances, weight gain/metabolic derangements, and loss of cardiorespiratory fitness, which may negatively impact autonomic function in breast cancer patients. Lastly, we review potential strategies to improve autonomic function in this population. The perspective can help guide new therapeutic interventions to promote longevity and cardiovascular health among breast cancer survivors.

Risk factors and the effect of cardiac resynchronization therapy on cardiac and non-cardiac mortality in MADIT-CRT.

AIMS: To understand modes of death and factors associated with the risk for cardiac and non-cardiac deaths in patients with cardiac resynchronization therapy with implantable cardioverter-defibrillator (CRT-D) vs. implantable cardioverter-defibrillator (ICD) therapy, which may help clarify the action and limitations of cardiac resynchronization therapy (CRT) in relieving myocardial dysfunction. METHODS AND RESULTS: In Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy (MADIT-CRT), during 4 years of follow-up, 169 (9.3%) of 1820 patients died of known causes, 108 (63.9%) deemed cardiac, and 61 (36.1%) non-cardiac. In multivariate analysis, increased baseline creatinine was significantly associated with both cardiac and non-cardiac deaths [hazard ratio (HR) 2.97, P < 0.001; HR 1.80, P = 0.035, respectively], as was diabetes (HR 1.79, P = 0.006; HR 1.73, P = 0.038, respectively), and the worst New York Heart Association Class > II more than 3 months prior to enrolment (HR 1.90, P = 0.012; HR 2.46, P = 0.010, respectively). Baseline left atrial volume index was significantly associated only with cardiac mortality (HR 1.28 per 5 unit increase, P < 0.001). Ischaemic cardiomyopathy was associated only with non-cardiac death (HR 3.54, P = 0.001). CRT-D vs. an ICD-only was associated with a reduced risk for cardiac death in patients with left bundle branch block (LBBB) (HR 0.56, P = 0.029) but was associated with an increased risk for non-cardiac death in non-LBBB patients (HR 3.48, P = 0.048). CONCLUSIONS: In MADIT-CRT, two-thirds of the deaths were cardiac and one-third non-cardiac. Many of the same risk factors were associated with both cardiac and non-cardiac mortalities. CRT-D was associated with a reduced risk for cardiac death in LBBB but an increased risk for non-cardiac death in non-LBBB. CLINICAL TRIAL REGISTRATION: Information for the MADIT-CRT main study http://www.clinicaltrials.gov, NCT00180271.

Clinical and angiographic risk stratification and differential impact on treatment outcomes in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial.

BACKGROUND: The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial assigned patients with type 2 diabetes mellitus to prompt coronary revascularization plus intensive medical therapy versus intensive medical therapy alone and reported no significant difference in mortality. Among patients selected for coronary artery bypass graft surgery, prompt coronary revascularization was associated with a significant reduction in death/myocardial infarction/stroke compared with intensive medical therapy. We hypothesized that clinical and angiographic risk stratification would affect the effectiveness of the treatments overall and within revascularization strata. METHODS AND RESULTS: An angiographic risk score was developed from variables assessed at randomization; independent prognostic factors were myocardial jeopardy index, total number of coronary lesions, prior coronary revascularization, and left ventricular ejection fraction. The Framingham Risk Score for patients with coronary disease was used to summarize clinical risk. Cardiovascular event rates were compared by assigned treatment within high-risk and low-risk subgroups. Overall, no outcome differences between the intensive medical therapy and prompt coronary revascularization groups were seen in any risk stratum. The 5-year risk of death/myocardial infarction/stroke was 36.8% for intensive medical therapy compared with 24.8% for prompt coronary revascularization among the 381 coronary artery bypass graft surgery-selected patients in the highest angiographic risk tertile (P=0.005); this treatment effect was amplified in patients with both high angiographic and high Framingham risk (47.3% intensive medical therapy versus 27.1% prompt coronary revascularization; P=0.010; hazard ratio=2.10; P=0.009). Treatment group differences were not significant in other clinical-angiographic risk groups within the coronary artery bypass graft surgery stratum, or in any subgroups within the percutaneous coronary intervention stratum. CONCLUSION: Among patients with diabetes mellitus and stable ischemic heart disease, a strategy of prompt coronary artery bypass graft surgery significantly reduces the rate of death/myocardial infarction MI/stroke in those with extensive coronary artery disease or impaired left ventricular function. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00006305.

Quality of life in patients with non-CAD chest pain: associations to fear of pain and psychiatric disorder severity.

Chest pain in the absence of identified cardiac cause, or non-cardiac chest pain (NCCP), is a common condition that may result in impaired quality of life. Theories of NCCP put forward that patients who react to cardiopulmonary sensations with fear may avoid activities that elicit cardiac sensations. Co-morbid psychiatric disorders, which are prevalent in this population, may predispose individuals to be more vigilant to physiological sensations, including cardiac-related symptoms. The daily impact of avoiding cardiopulmonary cues may limit quality of life. This study examined psychiatric disorders, fear of pain, and quality of life in 30 non-coronary artery disease (CAD) chest pain patients. Psychiatric disorder severity was independently associated with mental health related quality of life and fear of pain was independently associated with physical health related quality of life. This research adds understanding to contributory factors to impaired quality of life among patients with non-CAD chest pain.

Appropriateness of percutaneous coronary intervention.

CONTEXT: Despite the widespread use of percutaneous coronary intervention (PCI), the appropriateness of these procedures in contemporary practice is unknown. OBJECTIVE: To assess the appropriateness of PCI in the United States. DESIGN, SETTING, AND PATIENTS: Multicenter, prospective study of patients within the National Cardiovascular Data Registry undergoing PCI between July 1, 2009, and September 30, 2010, at 1091 US hospitals. The appropriateness of PCI was adjudicated using the appropriate use criteria for coronary revascularization. Results were stratified by whether the procedure was performed for an acute (ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction, or unstable angina with high-risk features) or nonacute indication. MAIN OUTCOME MEASURES: Proportion of acute and nonacute PCIs classified as appropriate, uncertain, or inappropriate; extent of hospital-level variation in inappropriate procedures. RESULTS: Of 500,154 PCIs, 355,417 (71.1%) were for acute indications (ST-segment elevation myocardial infarction, 103,245 [20.6%]; non-ST-segment elevation myocardial infarction, 105,708 [21.1%]; high-risk unstable angina, 146,464 [29.3%]), and 144,737 (28.9%) for nonacute indications. For acute indications, 350,469 PCIs (98.6%) were classified as appropriate, 1055 (0.3%) as uncertain, and 3893 (1.1%) as inappropriate. For nonacute indications, 72,911 PCIs (50.4%) were classified as appropriate, 54,988 (38.0%) as uncertain, and 16,838 (11.6%) as inappropriate. The majority of inappropriate PCIs for nonacute indications were performed in patients with no angina (53.8%), low-risk ischemia on noninvasive stress testing (71.6%), or suboptimal (≤1 medication) antianginal therapy (95.8%). Furthermore, although variation in the proportion of inappropriate PCI across hospitals was minimal for acute procedures, there was substantial hospital variation for nonacute procedures (median hospital rate for inappropriate PCI, 10.8%; interquartile range, 6.0%-16.7%). CONCLUSIONS: In this large contemporary US cohort, nearly all acute PCIs were classified as appropriate. For nonacute indications, however, 12% were classified as inappropriate, with substantial variation across hospitals.

Cardiac Amyloidosis for the Primary Care Provider: A Practical Review to Promote Earlier Recognition of Disease.

Cardiac amyloidosis is increasingly recognized as an underdiagnosed cause of heart failure. Diagnostic delays of up to 3 years from symptom onset may occur, and patients may be evaluated by more than 5 specialists prior to receiving the correct diagnosis. Newly available therapies improve clinical outcomes by preventing amyloid fibril deposition and are usually more effective in early stages of disease, making early diagnosis essential. Better awareness among primary care providers of the clinical presentation and modern treatment landscape is essential to improve timely diagnosis and early treatment of this disease. In this review, we provide practical guidance on the epidemiology, clinical manifestations, diagnostic evaluation, and treatment of transthyretin and light chain cardiac amyloidosis to promote earlier disease recognition among primary care providers.

Interim Analysis of the Phase II Study: Noninferiority Study of Doxorubicin with Upfront Dexrazoxane plus Olaratumab for Advanced or Metastatic Soft-Tissue Sarcoma.

PURPOSE: To report the interim analysis of the phase II single-arm noninferiority trial, testing the upfront use of dexrazoxane with doxorubicin on progression-free survival (PFS) and cardiac function in soft-tissue sarcoma (STS). PATIENTS AND METHODS: Patients with metastatic or unresectable STS who were candidates for first-line treatment with doxorubicin were deemed eligible. An interim analysis was initiated after 33 of 65 patients were enrolled. Using the historical control of 4.6 months PFS for doxorubicin in the front-line setting, we tested whether the addition of dexrazoxane affected the efficacy of doxorubicin in STS. The study was powered so that a decrease of PFS to 3.7 months would be considered noninferior. Secondary aims included cardiac-related mortality, incidence of heart failure/cardiomyopathy, and expansion of cardiac monitoring parameters including three-dimensional echocardiography. Patients were allowed to continue on doxorubicin beyond 600 mg/m2 if they were deriving benefit and were not demonstrating evidence of symptomatic cardiac dysfunction. RESULTS: At interim analysis, upfront use of dexrazoxane with doxorubicin demonstrated a PFS of 8.4 months (95% confidence interval: 5.1-11.2 months). Only 3 patients were removed from study for cardiotoxicity, all on > 600 mg/m2 doxorubicin. No patients required cardiac hospitalization or had new, persistent cardiac dysfunction with left ventricular ejection fraction remaining below 50%. The median administered doxorubicin dose was 450 mg/m2 (interquartile range, 300-750 mg/m2). CONCLUSIONS: At interim analysis, dexrazoxane did not reduce PFS in patients with STS treated with doxorubicin. Involvement of cardio-oncologists is beneficial for the monitoring and safe use of high-dose anthracyclines in STS.See related commentary by Benjamin and Minotti, p. 3809.

Effect of omega-3 fatty acids on heart rate variability in depressed patients with coronary heart disease.

OBJECTIVE: To determine whether omega-3 fatty acid (FA) increases the natural log of very low frequency (lnVLF) power, an index of heart rate variability (HRV), and reduces 24-hour heart rate (HR) in depressed patients with coronary heart disease (CHD). Low intake of omega-3 FAs is associated with depression and with low HRV, and all three are associated with an increased risk of death in patients with CHD. METHODS: Thirty-six depressed patients with CHD randomized to receive 50 mg of sertraline and 2 g of omega-3/day, and 36 randomized to sertraline and a placebo, had 24-hour HRV measured at baseline and after 10 weeks of treatment. RESULTS: There was a significant treatment × time interaction for covariate adjusted lnVLF (p = .009), for mean 24-hour HR (p = .03), and for 1-minute resting HR (p = .02). The interaction was not significant for three other measures of HRV. LnVLF did not change over time in the omega-3 arm but decreased in the placebo arm (p = .002), suggesting that omega-3 may have prevented or slowed deterioration in cardiac autonomic function. CONCLUSIONS: The effects of omega-3 FAs on lnVLF and HR, although modest, were detected after only 10 weeks of treatment with 2 g per day of omega-3. Whether a longer course of treatment or a higher dose of omega-3 would further decrease HR, improve other indices of HRV, or reduce mortality in depressed CHD patients should be investigated.

Impact of ethnicity and gender differences on angiographic coronary artery disease prevalence and in-hospital mortality in the American College of Cardiology-National Cardiovascular Data Registry.

BACKGROUND: Although populations referred for coronary angiography are increasingly diverse, there is limited information on coronary artery disease (CAD) prevalence and in-hospital mortality other than for predominately white male patients. METHODS AND RESULTS: We examined gender and ethnic differences in CAD prevalence and in-hospital mortality in a prospective cohort of patients referred for angiographic evaluation of stable angina (n=375,886) or acute coronary syndromes (ACS; unstable angina or myocardial infarction, n=450,329) at 388 US hospitals participating in the American College of Cardiology-National Cardiovascular Data Registry, an angiographic registry. Univariable and multivariable (with covariates that included risk factors, symptoms, and comorbidities) logistic regression models were used to estimate significant CAD, defined as > or = 70% stenosis, and in-hospital mortality. Within stable angina and ACS cohorts, 7% of patients were black, 2% were Hispanic, 0.3% were Native American, 1% were Asian, and 90% were white, respectively. In stable angina, the risk-adjusted OR for significant CAD was 0.34 for women compared with men (P<0.0001), with black women having the lowest risk-adjusted odds (P<0.0001) compared with other females. Among ACS patients, the risk-adjusted OR of significant CAD was 0.47 for women compared with men (P<0.0001); similarly, black women had the lowest risk-adjusted odds (P<0.0001) compared with other females. Higher in-hospital mortality was reported for white women presenting with stable angina (P<0.00001). White women had a 1.34-fold (95% CI 1.21 to 1.48) higher risk-adjusted odds ratio for mortality than white men with stable angina (P<0.0001), with higher rates noted for white women who were older or had significant CAD (both P<0.0001). Lower utilization of elective coronary revascularization, aspirin, and glycoprotein IIb/IIIa inhibitors (all P<0.0001) may have contributed to higher in-hospital mortality for white women. In ACS, higher in-hospital mortality was reported for Hispanic (P=0.015) and white (P<0.0001) women; however, neither white (P=0.51) or Hispanic (P=0.13) women had higher in-hospital risk-adjusted mortality. CONCLUSIONS: The likelihood for significant CAD at coronary angiography and for in-hospital mortality varied significantly by ethnicity and gender. Future clinical practice guidelines should be tailored to gender subsets of the population, in particular for black women, to improve the efficient use of angiographic laboratories and to target at-risk populations of women and men.

Risk-adjusted mortality analysis of percutaneous coronary interventions by American College of Cardiology/American Heart Association guidelines recommendations.

An American College of Cardiology (ACC)/American Heart Association (AHA) task force on practice guidelines in 2001 published evidence-based recommendations for performing percutaneous coronary interventions (PCIs). These guidelines grouped the indications for PCI into 4 classes (I, IIa, IIb, and III) based on analyses of risks and benefits. In a previous study, we found that clinical success and in-hospital adverse events varied by indications class. However, no adjustment for risk was used in those comparisons. The ACC/National Cardiovascular Data Registry (ACC-NCDR) previously developed a risk-adjustment model for the adverse event of in-hospital PCI mortality. We investigated how the 14 individual risk factors in the ACC-NCDR PCI mortality model might differ across the 4 indications classes and whether estimated mortality for each class approximated the observed mortality for that class. We analyzed the ACC-NCDR PCI database for January 1, 2001 to December 31, 2004. We excluded procedures performed for treatment of acute ST-segment elevation myocardial infarction; all others were included, yielding 559,273 procedures for analysis. An algorithm derived from the 2001 guidelines was used to assign procedures to an indications class. Increasing frequencies of risk components were observed across classes I, IIa, IIb, and III. Expected mortalities for each class calculated by the risk-adjustment model were close to observed values (expected 0.52%, 0.59%, 1.72%, and 1.96%, respectively; observed 0.49%, 0.63%, 1.88%, and 1.60%, respectively). In conclusion, the ACC-NCDR risk-adjusted mortality model can be linked to the ACC/AHA PCI guidelines, and together these produce mortality risk estimates by indications classes that are close to actual observed values. With further refinement, these methods should be able to be used as powerful analytic tools for quality assurance and appropriateness purposes.

Utilization of distal embolic protection in saphenous vein graft interventions (an analysis of 19,546 patients in the American College of Cardiology-National Cardiovascular Data Registry).

In clinical trials, the use of a distal embolic protection device (EPD) during saphenous vein graft (SVG) percutaneous intervention (PCI) decreases the incidence of major adverse events. However, the frequency of EPD use during SVG PCI in clinical practice is unknown. We evaluated 19,546 SVG PCI procedures in the American College of Cardiology-National Cardiovascular Data Registry from January 1, 2004, through March 30, 2006. EPD use was the primary outcome. Univariate and multivariable analyses were used to assess for characteristics associated with EPD use and to determine the association between EPD use and 2 outcomes: no-reflow and in-hospital mortality. EPDs were used in 22% of patients who underwent SVG PCI. Characteristics independently associated with EPD use were age (odds ratio [OR] 1.04, p = 0.03), male gender (OR 1.12, p = 0.02), older grafts (p <0.001 for the group), longer lesions (OR 1.16, p <0.001), and American College of Cardiology/American Heart Association class C lesions (OR 1.41, p <0.001). Patients were less likely to receive an EPD if they had class <3 grade flow according to Thrombolysis in Myocardial Infarction classification (p <0.001) or previously treated lesions (OR 0.55, p <0.001). There was a weak correlation between annual hospital PCI volume and EPD use (r = 0.2, p <0.001). Nineteen percent of centers did not use EPDs and 41% used them in <10% of cases. EPD use was independently associated with a lower incidence of no-reflow (OR 0.68, p = 0.032), but not in-hospital mortality (1.0% vs 0.9%, p = NS). In conclusion, in current practice, EPDs are used in <25% of SVG PCI procedures.

Relationship between procedure indications and outcomes of percutaneous coronary interventions by American College of Cardiology/American Heart Association Task Force Guidelines.

BACKGROUND: An American College of Cardiology/American Heart Association (ACC/AHA) Task Force periodically revises and publishes guidelines with evidence-based recommendations for appropriate use of percutaneous coronary intervention (PCI). Some studies have suggested that closer adherence to guidelines can reduce variations in care, can improve quality, and may ultimately result in better outcomes, but this finding is incompletely understood. Guidelines themselves must change to be responsive to continuously evolving clinical practice. Our goal here was to investigate whether any relationship existed between the most recent ACC/AHA recommended indications for PCI and short term in-hospital outcomes. METHODS AND RESULTS: We analyzed the ACC National Cardiovascular Data Registry for the period of January 1, 2001, through March 31, 2004. We excluded PCI procedures performed for acute myocardial infarction (ST-segment elevation myocardial infarction); all others were grouped by their indications according to the standard ACC/AHA scheme: Class I, evidence and/or agreement that PCI is useful and effective; Class IIa, conflicting evidence and/or divergent opinions, weight is in favor; Class IIb, usefulness/efficacy is less well established; and Class III, evidence and/or agreement that PCI is not useful or effective and may be harmful. Clinical success was defined as angiographic success (<20% residual stenosis) at all lesions attempted without the adverse events of myocardial infarction, same-admission bypass surgery, or death. There were 412 617 PCI procedures included in the analysis. Frequency of indications was as follows: Class I, 64%; Class IIa, 21%; Class IIb, 7%; and Class III, 8%. Clinical success declined across the indications classes (92.8%, 91.7%, 89%, and 85.5%, respectively; P<0.001), whereas adverse events increased. CONCLUSIONS: In this large survey of contemporary PCI practice, most procedures were performed for Class I indications. A significant relationship between evidence-based indications recommended by the ACC/AHA Task Force and in-hospital outcomes was noted.

Patterns and outcomes of drug-eluting coronary stent use in clinical practice.

OBJECTIVE: To determine patterns and outcomes of drug-eluting stents (DES) use in clinical practice. BACKGROUND: DES are technology associated with superior outcomes. The initial limited availability and high cost of DES had the potential to influence their use. METHODS: Data from the American College of Cardiology-National Cardiovascular Data Registry were examined to describe the patterns of DES use in 408,033 percutaneous coronary intervention (PCI) procedures at 383 sites. Predictors of DES use were determined, and inhospital outcomes were examined. RESULTS: From April 2003 through December 2004, the proportion of procedures using DES increased from 19.7% to 78.2%. DES use increased across all patient groups and hospital types, but adoption was slower among older patients and those without health insurance. DES use varied among hospitals such that use was lower at rural and low-volume hospitals. Multivariable regression demonstrated a progressive decrease in the odds of DES use as age increased. White race, female sex, presence of insurance, diabetes mellitus, PCI of de novo lesion, PCI at a high volume center, and PCI at a suburban hospital were significant predictors of DES use. The availability of a second DES product did not influence the adoption patterns. Inhospital outcomes with DES were excellent. CONCLUSIONS: Access to DES was influenced by demographic, socioeconomic, and hospital characteristics. Further study is needed to determine if the availability of another DES platform or increased overall availability of DES impacts favorably on PCI practice patterns.

A contemporary overview of percutaneous coronary interventions. The American College of Cardiology-National Cardiovascular Data Registry (ACC-NCDR).

The American College of Cardiology (ACC) established the National Cardiovascular Data Registry (ACC-NCDR) to provide a uniform and comprehensive database for analysis of cardiovascular procedures across the country. The initial focus has been the high-volume, high-profile procedures of diagnostic cardiac catheterization and percutaneous coronary intervention (PCI). Several large-scale multicenter efforts have evaluated diagnostic catheterization and PCI, but these have been limited by lack of standard definitions and relatively nonuniform data collection and reporting methods. Both clinical and procedural data, and adverse events occurring up to hospital discharge, were collected and reported according to uniform guidelines using a standard set of 143 data elements. Datasets were transmitted quarterly to a central facility for quality-control screening, storage and analysis. This report is based on PCI data collected from January 1, 1998, through September 30, 2000.A total of 139 hospitals submitted data on 146,907 PCI procedures. Of these, 32% (46,615 procedures) were excluded because data did not pass quality-control screening. The remaining 100,292 procedures (68%) were included in the analysis set. Average age was 64 +/- 12 years; 34% were women, 26% had diabetes mellitus, 29% had histories of prior myocardial infarction (MI), 32% had prior PCI and 19% had prior coronary bypass surgery. In 10% the indication for PCI was acute MI < or =6 h from onset, while in 52% it was class II to IV or unstable angina. Only 5% of procedures did not have a class I indication by ACC criteria, but this varied by hospital from a low of 0 to a high of 38%. A coronary stent was placed in 77% of procedures, but this varied by hospital from a low of 0 to a high of 97%. The frequencies of in-hospital Q-wave MI, coronary artery bypass graft surgery and death were 0.4%, 1.9% and 1.4%, respectively. Mortality varied by hospital from a low of 0 to a high of 4.2%. This report presents the first data collected and analyzed by the ACC-NCDR. It portrays a contemporary overview of coronary interventional practices and outcomes, using uniform data collection and reporting standards. These data reconfirm overall acceptable results that are consistent with other reported data, but also confirm large variations between individual institutions.

Development of a risk adjustment mortality model using the American College of Cardiology-National Cardiovascular Data Registry (ACC-NCDR) experience: 1998-2000.

OBJECTIVES: We sought to develop and evaluate a risk adjustment model for in-hospital mortality following percutaneous coronary intervention (PCI) procedures using data from a large, multi-center registry. BACKGROUND: The 1998-2000 American College of Cardiology-National Cardiovascular Data Registry (ACC-NCDR) dataset was used to overcome limitations of prior risk-adjustment analyses. METHODS: Data on 100,253 PCI procedures collected at the ACC-NCDR between January 1, 1998, and September 30, 2000, were analyzed. A training set/test set approach was used. Separate models were developed for presentation with and without acute myocardial infarction (MI) within 24 h. RESULTS: Factors associated with increased risk of PCI mortality (with odds ratios in parentheses) included cardiogenic shock (8.49), increasing age (2.61 to 11.25), salvage (13.38) urgent (1.78) or emergent PCI (5.75), pre-procedure intra-aortic balloon pump insertion (1.68), decreasing left ventricular ejection fraction (0.87 to 3.93), presentation with acute MI (1.31), diabetes (1.41), renal failure (3.04), chronic lung disease (1.33); treatment approaches including thrombolytic therapy (1.39) and non-stent devices (1.64); and lesion characteristics including left main (2.04), proximal left anterior descending disease (1.97) and Society for Cardiac Angiography and Interventions lesion classification (1.64 to 2.11). Overall, excellent discrimination was achieved (C-index = 0.89) and application of the model to high-risk patient groups demonstrated C-indexes exceeding 0.80. Patient factors were more predictive in the MI model, while lesion and procedural factors were more predictive in the analysis of non-MI patients. CONCLUSIONS: A risk adjustment model for in-hospital mortality after PCI was successfully developed using a contemporary multi-center registry. This model is an important tool for valid comparison of in-hospital mortality after PCI.

Mortality after emergent percutaneous coronary intervention in cardiogenic shock secondary to acute myocardial infarction and usefulness of a mortality prediction model.

Although percutaneous coronary intervention (PCI) in the setting of cardiogenic shock has a high in-hospital mortality rate, it has been shown to decrease the mortality rate in certain subgroups. The identity and relative importance of variables that are predictive of in-hospital mortality rate after PCI for cardiogenic shock are uncertain. Accordingly, we examined data of >300,000 patients in the American College of Cardiology-National Cardiovascular Data Registry (ACC-NCDR) that were collected from 1998 to 2002 and evaluated the outcomes in 483 consecutive patients who underwent emergency PCI for cardiogenic shock. Patients' mean age was 65 +/- 13 years, with men predominating (61%). All underwent emergency/salvage PCI in the setting of cardiogenic shock after acute myocardial infarction. Mean left ventricular ejection fraction was 30 +/- 16%. Stents were placed in 64% of patients, and thrombolytic agents were administered in 26%. Although PCI was angiographically successful in 79% of patients, the in-hospital mortality rate was 59.4%. Length of stay after PCI was 7.2 +/- 8 days. Logistic regression using all available variables identified 6 multivariate predictors of death: age (odds ratio [OR] 2.34, 95% confidence interval [CI] 1.68 to 3.28, p <0.001) for each 10-year increment, female gender (OR 1.55, 95% CI 1.00 to 2.41, p <0.001), baseline renal insufficiency (creatinine >2.0 mg/dl; OR 4.69, 95% CI 1.96 to 11.23, p <0.001), total occlusion in the left anterior descending artery (OR 1.99, 95% confidence interval 1.28 to 3.09, p <0.01), no stent used (OR 2.55, 95% CI 1.63 to 3.96, p <0.01), and no glycoprotein IIb/IIIa inhibitor used during PCI (OR 1.96, 95% CI 1.30 to 2.98, p <0.01). In a second analysis using only variables known to the clinician at the time of initial presentation, gender, age, renal insufficiency, and total occlusion of the left anterior descending coronary artery were significant. In conclusion, analysis of patients from the ACC-NCDR who underwent emergency PCI for acute myocardial infarction in the presence of cardiogenic shock shows an in-hospital mortality rate of approximately 60% when PCI is attempted.

Atherosclerotic risk genotypes and recurrent coronary events after myocardial infarction.

The association of a group of prespecified atherosclerotic risk genotypes with recurrent coronary events (coronary-related death, nonfatal myocardial infarction, or unstable angina) was investigated in a cohort of 1,008 patients after infarction during an average follow-up of 28 months. We used a carrier-ship approach with time-dependent survivorship analysis to evaluate the average risk of each carried genotype. Contrary to expectation, the hazard ratio for recurrent coronary events per carried versus noncarried genotype was 0.89 (95% confidence interval 0.80 to 0.99, p = 0.03) after adjustment for relevant genetic, clinical, and environmental covariates. This hazard ratio, derived from the 7 prespecified genotypes, indicated an average 11% reduction in the risk of recurrent coronary events per carried versus noncarried genotype. At 1 year after hospital discharge, the cumulative probability of recurrent coronary events was 26% in those who carried < or =1, 20% for those with 2 to 4, and 13% for those with > or =5 of these genotypes (p = 0.02). This unexpected risk reversal is a likely consequence of changes in the mix of risk factors in pre- and postinfarction populations. In conclusion, this under appreciated, population-based, risk-reversal phenomenon may explain the inconsistent associations of genetic risk factors with outcome events in previous reports involving coronary populations with different risk attributes.

Relationship between intermittent claudication, inflammation, thrombosis, and recurrent cardiac events among survivors of myocardial infarction.

BACKGROUND: Among coronary disease patients, concomitant peripheral arterial disease is a potent risk factor for future cardiac events and mortality. We sought to determine clinical and biochemical markers that might better elucidate the relationship between coronary and peripheral arterial disease. METHODS: Two months after an index myocardial infarction, 1045 patients provided detailed medical histories and underwent blood testing for selected hemostatic, lipid, and inflammatory markers. Patients were then followed up prospectively for a mean of 26 months. RESULTS: Compared with individuals without intermittent claudication (n = 966), those with claudication (n = 78) (information was unavailable for 1 individual) were significantly older and demonstrated an increased frequency of diabetes mellitus, tobacco use, prior cardiac and cerebrovascular events, and depressed left ventricular function. Individuals with claudication were less likely to receive beta-blocker therapy after the index infarction. Individuals with claudication had evidence of enhanced procoagulant and proinflammatory states manifested by relative elevations in plasma fibrinogen, D-dimer, C-reactive protein, and serum amyloid A concentrations. During follow-up, the presence of claudication was associated with an independent 2-fold increase in the combined end point of death or nonfatal cardiac event (38.5% vs 17.8%, P =.001) and a 5-fold increase in cardiac mortality (19.2% vs 3.6%, P =.001). Patients with intermittent claudication who were not treated with beta-blockers had a significant 3-fold mortality excess relative to those receiving beta-blockers. CONCLUSIONS: Following myocardial infarction, the added presence of intermittent claudication is associated with heightened procoagulant and proinflammatory states and an underuse of beta-blocker therapy and is a strong independent predictor of recurrent cardiovascular events.