Comparison of Framingham risk score and chest-CT identified coronary artery calcification in breast cancer patients to predict cardiovascular events.

BACKGROUND: In breast cancer patients, coincidental detection of CAC at chest CT may be important in determining cardiovascular (CV) outcomes and facilitate CV disease primary prevention strategies. METHODS: 408 consecutive breast cancer patients referred to cardiac oncology clinic were included in the study. 256 patients without a prior history of coronary artery disease had undergone a chest CT. CT images were reviewed to detect CAC. Framingham risk score (FRS) was calculated and patient electronic medical records were interrogated to document the incidence of a composite clinical end point of all-cause mortality and cardiac events (coronary revascularization, heart failure hospitalization and de novo atrial fibrillation). Prevalence of statin prescribing was also collected. RESULTS: Patients were followed for a median of 6.5 years. 112 clinical events occurred. Clinical follow up was 98%. CAC was found in 26% of patients. On multivariable analysis, CAC and advance cancer stage, but not FRS predicted the composite clinical end point (OR for CAC 2.59, p < 0.01). CAC but not FRS also predicted the incidence of cardiac events (OR for CAC 4.90, p < 0.01). CAC was present in 7.3% of patients with low FRS; none had been prescribed a statin. In patients with CAC and FRS ≥ 10%, 45% were not on a statin. CONCLUSION: CAC is a common coincidental finding at CT chest in breast cancer patients referred to cardiac oncology. CAC but not FRS was predictive of composite clinical events and cardiac events. Detection of CAC at chest CT could alter the prescribing of primary prevention strategies to help prevent future cardiac events in breast cancer patients.

Paging the eCardiologist: insights into referral behaviour of primary care physicians from qualitative analysis of a cardiology eConsult service.

OBJECTIVE: The purpose of this study is to investigate determinants of primary care physician cardiology referrals by performing qualitative analysis of questions asked by primary care physicians in cardiology electronic consultation services (eConsults). SETTING: A health region in eastern Ontario, Canada, where primary care providers have had access to an eConsult service since 2010. PARTICIPANTS: We included all consecutive cardiology eConsults initiated by registered primary care provider users of our eConsult service and who initiated one or more eConsult between July 2014 and January 2015. We excluded eConsults in which the primary care provider attached a document without asking a question. A convenience sample of 100 consecutive eConsults initiated by 61 primary care providers was analysed after excluding 14 eConsults.Primary and secondary outcome measures: Primary care provider eConsult questions are categorised into thematic categories based on the constant comparison method of qualitative analysis with external validation by content experts. Secondary outcomes include sample primary care provider eConsult questions to illustrate each theme and any emergent subthemes. RESULTS: Thematic saturation occurred after analysis of 30 eConsults. An additional 70 eConsults were coded with no new emergent themes. Themes include exceptions to clinical guidelines (n=13), non-cardiac treatment in a cardiac patient (n=13), specific investigation/management (n=18), interpretation of diagnostic testing (n=46), clinical concerns despite normal testing (n=4) and screening for positive family history (n=6). Subthemes include multiple comorbidities and mild abnormalities on cardiac tests. CONCLUSIONS: We report categories of clinical questions that drive primary care provider cardiology eConsults. Multimorbidity leads to cardiology eConsults as primary care providers try to apply treatment guidelines in medically complex patients. Mild test abnormalities unrelated to clinical problems commonly lead to cardiology eConsult requests. Further research is needed to determine how guidelines can better account for multimorbidity, and how cardiologists can better communicate with primary care providers to put cardiac test results in clinical context.

Sex-Specific Trends in Incidence and Mortality for Urban and Rural Ambulatory Patients with Heart Failure in Eastern Ontario from 1994 to 2013.

BACKGROUND: Differences in outcomes have previously been reported between urban and rural settings across a multitude of chronic diseases. Whether these discrepancies have changed over time, and how sex may influence these findings is unknown for patients with ambulatory heart failure (HF). We examined the temporal incidence and mortality trends by geography in these patients. METHODS AND RESULTS: We conducted a retrospective cohort study of 36,175 eastern Ontario residents who were diagnosed with HF in an outpatient setting from 1994 to 2013. The primary outcome was 1-year mortality. We examined temporal changes in mortality risk factors with the use of multivariable Cox proportional hazard models. The incidence of HF decreased in women and men across both rural and urban settings. Age-standardized mortality rates also decreased over time in both sexes but remained greater in rural men compared with rural women. CONCLUSIONS: The incidence of HF in the ambulatory setting was greater for men than women and greater in rural than urban areas, but mortality rates remained higher in rural men compared with rural women. Further research should focus on ways to reduce this gap in the outcomes of men and women with HF.

Sex differences in outcomes of heart failure in an ambulatory, population-based cohort from 2009 to 2013.

BACKGROUND: Heart failure remains a substantial cause of morbidity and mortality in women. We examined the sex differences in heart failure incidence, mortality and hospital admission in a population-based cohort. METHODS: All Ontario residents who were diagnosed with heart failure in an ambulatory setting between Apr. 1, 2009, and Mar. 31, 2014, were included in this study. Incident cases of heart failure were captured through physician billing using a validated algorithm. Outcomes were mortality and hospital admission for heart failure within 1 year of the diagnosis. Probability of death and hospital admission were calculated using the Kaplan-Meier method. The hazard of death was assessed using a multivariable Cox proportional hazard model. RESULTS: A total of 90 707 diagnoses of heart failure were made in an ambulatory setting during the study period (47% women). Women were more likely to be older and more frail, and had different comorbidities than men. The incidence of heart failure decreased during the study period in both sexes. The mortality rate decreased in both sexes, but remained higher in women than men. The female age-standardized mortality rate was 89 (95% confidence interval [CI] 80-100) per 1000 in 2009 and 85 (95% CI 75-95) in 2013, versus male age-standardized mortality rates of 88 (95% CI 80-97) in 2009 and 83 (95% CI 75-91) in 2013. Conversely, the rates of incident heart failure hospital admissions after heart failure diagnosis decreased in men and increased in women. INTERPRETATION: Despite decreases in overall heart failure incidence and mortality in ambulatory patients, mortality rates remain higher in women than in men, and rates of hospital admission for heart failure increased in women and declined in men. Further studies should focus on sex differences in health-seeking behaviour, medical therapy and response to therapy to provide guidance for personalized care.

Reporting of coronary artery calcification on chest CT studies in breast cancer patients at high risk of cancer therapy related cardiac events.

BACKGROUND: The identification of coronary artery calcification (CAC) detected coincidentally on chest CT exams could assist in cardiovascular risk assessment but may not be reported consistently on clinical studies. Cardiovascular risk factor stratification is important to predict short term cardiac events during cancer therapy and long term cardiac event free survival in cancer patients. We sought to determine the prevalence of CAC and clinical reporting rates in a cohort of cancer patients at high risk of cancer therapy related cardiac events. METHODS: 408 Breast cancer patients who were referred to a cardiac oncology clinic were screened. Inclusion criteria included having had a CT chest and the absence of known coronary disease. Among those screened 263 patients were included in the study. RESULTS: CAC was identified in 70 patients (26%). CAC was reported in 18% of studies. The reporting rates of CAC increased with the extent of coronary calcification (p < 0.01) and increased during the period of the study (p < 0.05). CONCLUSIONS: CAC was commonly detected on chest CT studies in this observational study of breast cancer patients at high risk of cardiac oncology events. The presence of CAC was often not reported clinically but reporting rates have increased over time. Recent SCCT/STR guidelines recommend reporting the presence of CAC on routine chest CT scans in recognition of the importance of CAC as a predictor of cardiovascular events. Reporting of CAC on chest CTs may help to further risk stratify breast cancer patients and improve cardiovascular outcomes in this vulnerable population.

The State of Affairs for Cardiovascular Health Research in Indigenous Women in Canada: A Scoping Review.

Cardiovascular disease (CVD) is the leading cause of death among Indigenous peoples in Canada. As rates of CVD rise, the impacts among the growing population of Indigenous women will emerge as an important health issue. The objective of this scoping review was to advance the state of knowledge about cardiovascular health research in Indigenous women in Canada. Five databases and grey literature (non-peer reviewed works) were searched to identify all studies that reported on the prevalence, pathophysiology, diagnosis, treatment, or interventions for CVD among adult Indigenous women in Canada, including First Nations, Métis, and Inuit. Searching identified 3194 potential articles; 61 of which were included. The most commonly researched topics were the prevalence of CVD, hypertension, and dyslipidemia. Rates of CVD and associated mortality among Indigenous women appear to have surpassed those of their nonindigenous counterparts. Very little research has examined the pathophysiology, diagnosis, and treatment of CVD. Gaps in the research identified the need for sex-based analyses, comparison with nonindigenous women, comprehensive longitudinal data, assessment of diagnosis criteria, development and evaluation of cardiovascular health interventions, and a better understanding of the role of culture and traditions in the prevention and treatment of CVD among Indigenous women. Although comprehensive CVD data are lacking, rates of CVD among Indigenous women in Canada are rising and are nearing or surpassing those of nonindigenous women. This review serves as a call to action to seek further research on the pathophysiology, diagnosis, and treatment of CVD among Indigenous women from across Canada.

Women's Heart Health: Knowledge, Beliefs, and Practices of Canadian Physicians.

BACKGROUND: Heart disease is a leading cause of morbidity and mortality in women. To date, the majority of knowledge regarding heart disease is based on research conducted in men. As a result, a male-oriented model of heart disease constitutes the basis for diagnostic and therapeutic strategies for both sexes. This article reports findings from the first survey of Canadian physicians to examine their knowledge, beliefs, and practices regarding heart disease in women. MATERIALS AND METHODS: This cross-sectional survey, adapted from an instrument used in the United States, was undertaken in the spring of 2015. A sample of 504 physicians from a randomly selected sample of online responses was produced. RESULTS: Overall, physician responses demonstrate a general lack of awareness regarding the prevalence and approaches to the identification of, and treatments for, heart disease in women. In addition, physicians did not provide high ratings of their own effectiveness in supporting female patients to prevent or manage heart disease. The barriers that physicians face and the strategies to support them in improving women's heart health were explored. CONCLUSIONS: There is a clear need to educate physicians about heart disease in women and its prevention and management. More female-specific research, prevention, and clinical programs will enhance our ability to significantly improve cardiovascular health in Canadian women.

Right heart function deteriorates in breast cancer patients undergoing anthracycline-based chemotherapy.

BACKGROUND: Cardiotoxicity from anthracycline-based chemotherapy is an important cause of early and late morbidity and mortality in breast cancer patients. Left ventricular (LV) function is assessed for patients receiving anthracycline-based chemotherapy to identify cardiotoxicity. However, animal studies suggest that right ventricular (RV) function may be a more sensitive measure to detect LV dysfunction. The purpose of this pilot study was to determine if breast cancer patients undergoing anthracycline-based chemotherapy experience RV dysfunction. METHODS: Forty-nine breast cancer patients undergoing anthracycline-based chemotherapy at the Ottawa Hospital between November 2007 and March 2013 and who had 2 echocardiograms performed at least 3months apart were retrospectively identified. Right atrial area (RAA), right ventricular fractional area change (RV FAC) and RV longitudinal strain of the free wall (RV LSFW) were evaluated according to the American Society of Echocardiography guidelines. RESULTS: The majority (48/49) of patients were females with an average age of 53.4 (95% CI: 50.1-56.7years). From baseline to follow-up study, average LV ejection fraction (LVEF) decreased from 62.22 (95% CI: 59.1-65.4) to 57.4% (95% CI: 54.0-60.9) (P=0.04). During the same time period, the mean RAA increased from 12.1cm(2) (95% CI: 11.1-13.0cm(2)) to 13.8cm(2) (95% CI: 12.7-14.9cm(2)) (P=0.02), mean RV FAC decreased (P=0.01) from 48.3% (95% CI: 44.8-51.74) to 42.1% (95% CI: 38.5-45.6%), and mean RV LSFW worsened from -16.2% (95% CI: -18.1 to -14.4%) to -13.81% (95% CI: -15.1 to -12.5%) (P=0.04). CONCLUSION: This study demonstrates that breast cancer patients receiving anthracycline-based chemotherapy experience adverse effects on both right atrial size and RV function. Further studies are required to determine the impact of these adverse effects on right heart function and whether this represents an earlier marker of cardiotoxicity.

An International Survey of Health Care Providers Involved in the Management of Cancer Patients Exposed to Cardiotoxic Therapy.

Cardiotoxicity is the second leading cause of morbidity and mortality in cancer survivors. The objective of this international cardiac oncology survey was to gain a better understanding of current knowledge and practice patterns among HCPs involved in the management of cancer patients exposed to potentially cardiotoxic drugs. Between 2012 and 2013, we conducted an email-based survey of HCPs involved in the management of cardiac disease in cancer patients. 393 survey responses were received, of which 77 were from Canadian respondents. The majority of respondents were cardiologists (47%), followed closely by medical oncologists. The majority of respondents agreed that cardiac issues are important to cancer patients (97%). However, only 36% of total respondents agreed with an accepted definition of cardiotoxicity. While 78% of respondents felt that cardiac medications are protective during active cancer treatment, only 51% would consider prescribing these medications up-front in cancer patients. Although results confirm a high level of concern for cardiac safety, there continues to be a lack of consensus on the definition of cardiotoxicity and a discrepancy in clinical practice between cardiologists and oncologists. These differences in opinion require resolution through more effective research collaboration and formulation of evidence-based guidelines.

Clinical Experience of Patients Referred to a Multidisciplinary Cardiac Oncology Clinic: An Observational Study.

Cardiotoxicity is the second leading cause of long-term morbidity and mortality among cancer survivors. The purpose of this retrospective observational study is to report on the clinical and cardiac outcomes in patients with early stage and advanced cancer who were referred to our multidisciplinary cardiac oncology clinic (COC). A total of 428 patients were referred to the COC between October 2008 and January 2013. The median age of patients at time of cancer diagnosis was 60. Almost half of patients who received cancer therapy received first-line chemotherapy alone (169, 41.7%), of which 84 (49.7%) were exposed to anthracyclines. The most common reasons for referral to the cardiac oncology clinic were decreased LVEF (34.6%), prechemotherapy assessment (11.9%), and arrhythmia (8.4%). A total of 175 (40.9%) patients referred to the COC were treated with cardiac medications. The majority (331, 77.3%) of patients were alive as of January 2013, and 93 (21.7%) patients were deceased. Through regular review of cardiac oncology clinic referral patterns, management plans, and patient outcomes, we aim to continuously improve delivery of cardiac care to our patient population and optimize cardiac health.

Acute cardiogenic shock induced by infusional 5-Fluorouracil.

A 49-year-old patient with metastatic carcinoma of the bladder and no prior history of heart disease presented with diffuse ST elevation, elevated troponins, and biventricular dysfunction requiring intensive care unit admission and inotropic support after receiving her first course of infusional 5-fluorouracil (5-FU). Over the course of several days, the patient's cardiac function and clinical status returned to baseline. A follow-up echocardiogram performed 5 days after initial presentation revealed an ejection fraction of 59 percent, with no evidence of wall motion abnormalities. Subsequent 5-FU chemotherapy was discontinued, and the patient went on to receive second-line chemotherapy.

Heart disease as a risk factor for dementia.

As life expectancy lengthens, dementia is becoming a significant human condition in terms of its prevalence and cost to society worldwide. It is important in that context to understand the preventable and treatable causes of dementia. This article exposes the link between dementia and heart disease in all its forms, including coronary artery disease, myocardial infarction, atrial fibrillation, valvular disease, and heart failure. This article also explores the cardiovascular risk factors and emphasizes that several of them are preventable and treatable. In addition to medical therapies, the lifestyle changes that may be useful in retarding the onset of dementia are also summarized.

The experience of a multidisciplinary clinic in the management of early-stage breast cancer patients receiving trastuzumab therapy: an observational study.

Background. We established a dedicated cardiac oncology clinic in 2008 for the rapid diagnosis and treatment of cardiotoxicity related to cancer therapy. In this retrospective observational study, we report on clinical outcomes in women with early-stage breast cancer (EBC) referred to this clinic. Methods. Patients with EBC treated with chemotherapy/trastuzumab and referred between October 2008 and December 2010. Data included patient demographics, staging, cancer treatment/completion, dose delays, left ventricular ejection fraction (LVEF) and cardiac treatment. Results. Forty eight patients: median age 55.5 years, stage I/II disease (77%) and HER-2 positive (98%). The majority of women (n = 32) were referred for decreases in LVEF (from baseline). Overall, 37 (77%) patients experienced at least one drop in LVEF while on treatment, of which 22 patients (59%) experienced a ≥10 percentage point drop. The majority of patients (30/37; 81%) experienced declines in LVEF while on trastuzumab. Interventions included trastuzumab delays (n = 16/48; 33%) and cardiac medication (12/48: 25%). A total of 81% of patients completed ≥90% of trastuzumab therapy and 15% of patients discontinued therapy due to cardiotoxicity. Conclusion. The majority of patients referred to our clinic completed therapy. Further studies are needed to determine the impact of this multidisciplinary approach on treatment completion and cardiac outcomes.

Interactions of commonly used dietary supplements with cardiovascular drugs: a systematic review.

BACKGROUND: The objective of this systematic review was to examine the benefits, harms and pharmacokinetic interactions arising from the co-administration of commonly used dietary supplements with cardiovascular drugs. Many patients on cardiovascular drugs take dietary supplements for presumed benefits and may be at risk for adverse supplement-drug interactions. METHODS: The Allied and Complementary Medicine Database, the Cochrane Library, EMBASE, International Bibliographic Information on Dietary Supplements and MEDLINE were searched from the inception of the review to October 2011. Grey literature was also reviewed.Two reviewers independently screened records to identify studies comparing a supplement plus cardiovascular drug(s) with the drug(s) alone. Reviewers extracted data using standardized forms, assessed the study risk of bias, graded the strength of evidence and reported applicability. RESULTS: Evidence was obtained from 65 randomized clinical trials, 2 controlled clinical trials and 1 observational study. With only a few small studies available per supplement, evidence was insufficient for all predefined gradable clinical efficacy and harms outcomes, such as mortality and serious adverse events. One long-term pragmatic trial showed no benefit from co-administering vitamin E with aspirin on a composite cardiovascular outcome. Evidence for most intermediate outcomes was insufficient or of low strength, suggesting no effect. Incremental benefits were noted for triglyceridemia with omega-3 fatty acid added to statins; and there was an improvement in levels of high-density lipoprotein cholesterol with garlic supplementation when people also consumed nitrates CONCLUSIONS: Evidence of low-strength indicates benefits of omega-3 fatty acids (plus statin, or calcium channel blockers and antiplatelets) and garlic (plus nitrates or warfarin) on triglycerides and HDL-C, respectively. Safety concerns, however, persist.

Primary percutaneous coronary angioplasty with and without eptifibatide in ST-segment elevation myocardial infarction: a safety and efficacy study of integrilin-facilitated versus primary percutaneous coronary intervention in ST-segment elevation myocardial infarction (ASSIST).

BACKGROUND: Primary percutaneous coronary intervention, if performed promptly, is the preferred strategy to restore flow to the infarct-related artery in patients with ST-segment elevation myocardial infarction. We sought to determine whether eptifibatide, a platelet glycoprotein IIb/IIIa inhibitor, given before catheterization would improve clinical outcomes in patients referred for primary percutaneous coronary intervention. METHODS AND RESULTS: We randomly assigned a total of 400 patients with ST-segment elevation myocardial infarction referred for primary percutaneous coronary intervention to treatment initiated before cardiac catheterization, with either heparin plus eptifibatide (201 patients) or heparin alone (199 patients), in addition to oral aspirin (160 mg) and high-dose clopidogrel (600 mg). The primary end point was a composite of death from any cause, recurrent myocardial infarction, or recurrent severe ischemia during the first 30 days after randomization. At 30 days, the primary end point was reached by 13 patients (6.47%) assigned to heparin plus eptifibatide and by 11 patients (5.53%) assigned to heparin alone (relative risk, 1.18; 95% CI, 0.52 to 2.70; P=0.69). The rates of major or minor bleeding were higher in patients assigned to heparin plus eptifibatide than that in patients assigned to heparin alone (22.4% versus 14.6%; relative risk, 1.69; 95% CI, 1.01 to 2.83; P=0.04). CONCLUSIONS: In patients pretreated with high-dose clopidogrel who were referred for primary PCI, treatment with heparin plus eptifibatide, when compared with heparin alone, did not improve clinical outcomes and was associated with more bleeding complications.

Effect of long-term aspirin use on embolic events in infective endocarditis.

BACKGROUND: In a recent clinical trial, aspirin therapy was initiated approximately 34 days after the onset of symptoms but did not reduce the risk of embolism in patients with endocarditis. However, it is possible that aspirin used early in the course of the disease may be beneficial. The purpose of the study is to assess the effect of long-term daily aspirin use on the risk of embolic events in patients with infective endocarditis. METHODS: The clinical characteristics and outcomes of patients excluded from the Multi-Centre Aspirin Trial in Infective Endocarditis because of long-term aspirin use (n = 84) were compared with the data for patients randomized to the placebo arm (n = 55). The former patients took aspirin before and during the early stages of infective endocarditis, whereas the latter patients were not exposed to aspirin before and during the entire hospitalization. Logistic modeling was used to assess the effect of long-term aspirin use on embolism and bleeding. RESULTS: There was a trend toward excess bleeding in long-term aspirin recipients, compared with placebo recipients (P = .065). Logistic modeling revealed that long-term aspirin use may be associated with excess bleeding (unadjusted odds ratio, 2.35 [P = .059]; adjusted odds ratio, 2.08 [P = .118]), but it had no impact on the risk of embolic events in either model. CONCLUSIONS: In patients with endocarditis, long-term daily use of aspirin does not reduce the risk of embolic events but may be associated with a higher risk of bleeding. In the acute phase of endocarditis, aspirin should be used with caution.

Canadian Consensus Conference on menopause, 2006 update.

OBJECTIVE: To provide guidelines for health care providers on the management of menopause in asymptomatic healthy women as well as in women presenting with vasomotor symptoms, urogenital, sexual, and mood and memory concerns and on specific medical considerations, and cardiovascular and cancer issues. OUTCOMES: Prescription medications, complementary and alternative medicine (CAM), and lifestyle interventions are presented according to their efficacy in treating menopausal symptoms. EVIDENCE: MEDLINE and the Cochrane database were searched for articles from March 2001 to April 2005 in English on subjects related to menopause, menopausal symptoms, urogenital and sexual health, mood and memory, hormone therapy, CAM, and on specific medical considerations that affect the decision of which intervention to choose. VALUES: The quality of evidence is rated using the criteria described in the report of the Canadian Task Force on the Periodic Health Examination. Recommendations for practice are ranked according to the method described in this report (see Table 1). SPONSORS: The development of this consensus guideline was supported by unrestricted educational grants from Berlex Canada Inc, Lilly Canada, Merck Frosst, Novartis, Novogen, Novo Nordisk, Proctor and Gamble, Schering Canada, and Wyeth Canada.

Comparison of mortality patterns in patients with ST-elevation myocardial infarction arriving by emergency medical services versus self-transport (from the prospective Ottawa Hospital STEMI Registry).

Emergency medical services (EMSs) play a key role in the recognition and treatment of ST-elevation of myocardial infarction (STEMI). We sought to determine contemporary use of EMS in patients with STEMI and its relation to treatment, morbidity, and mortality patterns. Patients who arrived by EMS were compared with those who arrived by self-transport. Among 401 patients, 59.9% arrived by EMS and 40.1% by self-transport. Patients who arrived by EMS were older (p <0.001) and had higher Killip's scores (p <0.001). Door-to-needle and door-to-balloon intervals were shorter in patients who arrived by EMS (42 vs 57 minutes, p <0.001, and 124 vs 154 minutes, p <0.001, respectively). In-hospital mortality was higher in patients who used EMS (13.3% vs 5.0%, p <0.001). Patients who arrived by EMS also had higher mortality within the first hour of hospital arrival (4.2% vs 0%, p = 0.007). Multivariate analysis showed that only age and systolic blood pressure were predictors of mortality. Despite faster onset of reperfusion therapy in patients who arrived by EMS, mortality was higher. Almost 33% of these deaths occurred in the early in-hospital period, which was due to older and sicker patients having the tendency to come by EMS. Our results suggest that regional approaches are needed to trigger earlier reperfusion therapy in patients with STEMI who use EMS.

Combined angioplasty and pharmacological intervention versus thrombolysis alone in acute myocardial infarction (CAPITAL AMI study).

OBJECTIVES: We compared a strategy of tenecteplase (TNK)-facilitated angioplasty with one of TNK alone in patients presenting with high-risk ST-segment elevation myocardial infarction (STEMI). BACKGROUND: Previous trials show that thrombolysis followed by immediate angioplasty for the treatment of STEMI does not improve ischemic outcomes compared with thrombolysis alone and is associated with excessive bleeding complications. Since the publication of these trials, however, significant pharmacological and technological advances have occurred. METHODS: We randomized 170 patients with high-risk STEMI to treatment with TNK alone (84 patients) or TNK-facilitated angioplasty (86 patients). The primary end point was a composite of death, reinfarction, recurrent unstable ischemia, or stroke at six months. RESULTS: At six months, the incidence of the primary end point was 24.4% in the TNK-alone group versus 11.6% in the TNK-facilitated angioplasty group (p = 0.04). This difference was driven by a reduction in the rate of recurrent unstable ischemia (20.7% vs. 8.1%, p = 0.03). There was a trend toward a lower reinfarction rate with TNK-facilitated angioplasty (14.6% vs. 5.8%, p = 0.07). No significant differences were observed in the rates of death or stroke. Major bleeding was observed in 7.1% of the TNK-alone group and in 8.1% of the TNK-facilitated angioplasty group (p = 1.00). CONCLUSIONS: In patients presenting with high-risk STEMI, TNK plus immediate angioplasty reduced the risk of recurrent ischemic events compared with TNK alone and was not associated with an increase in major bleeding complications.

Impending paradoxical embolus: a case report and review of the literature.

A case of a 43-year-old man with impending paradoxical embolism (IPE) is described. The patient initially presented with pulmonary embolism and was diagnosed with an IPE on transthoracic and transesophageal echocardiography. He was subsequently treated with heparin and thrombolysis. A comprehensive review of the English literature over the past 20 years identified 60 previously reported cases of IPE. This report discusses the main clinical features, the diagnostic role of echocardiography and the outcome of medical and surgical treatment strategies in patients with IPE. Based on the literature to date, we recommend that patients with impending paradoxical embolism be treated with initial systemic heparinization followed by emergent surgical embolectomy if the surgical risks are acceptable.