Kathleen Stergiopoulos

Risk of hypertension and renal dysfunction with an angiogenesis inhibitor sunitinib: Systematic review and meta-analysis

Background. Sunitinib is a multitargeted tyrosine kinase inhibitor used in the treatment of metastatic renal cell carcinoma (RCC) and gastrointestinal stromal tumor (GIST), and undergoing evaluation for other malignancy. Hypertension is one of its major side effects with a substantial variation in the reported incidences among clinical studies. We here performed a systematic review and meta-analysis of published clinical trials to determine its overall risk. Methods. Relevant studies were searched and identified in MEDLINE (OVID 1966 to July, 2007), Web of Science, and abstracts presented at the American Society of Clinical Oncology annual meetings from 2004 through 2007. Eligible studies were prospective clinical trials that had described events of hypertension for patients who received single agent sunitinib. The incidence of hypertension and relative risk (RR) were calculated using the random-effects or the fixed-effects model. Results. A total of 4, 999 patients with RCC and other malignancies from 13 clinical trials were included for analysis. Among patients receiving sunitinib, the incidence of all-grade and high-grade hypertensions were 21.6% (95% CI: 18.7–24.8%) and 6.8% (95% CI: 5.3–8.8%) respectively. The risk may vary with tumor type and the dosing schedule of sunitinib. Sunitinib was associated with a significantly increased risk of high-grade hypertension (RR=22.72, 95% CI: 4.48 to 115.29, p<0.001) and renal dysfunction (RR: 1.36, 95% CI: 1.20 to 1.54, p<0.001) in comparison with controls. Conclusions. There is a significant risk of developing hypertension and renal dysfunction among patients receiving sunitinib. Adequate monitoring and treatment of hypertension is recommended.

Initial coronary stent implantation with medical therapy vs medical therapy alone for stable coronary artery disease: meta-analysis of randomized controlled trials.

BACKGROUND Prior meta-analyses have yielded conflicting results regarding the outcomes of treatment of stable coronary artery disease (CAD) with initial percutaneous coronary intervention (PCI) vs medical therapy. However, most of the studies in prior systematic reviews used balloon angioplasty as well as medical therapies that do not reflect current interventional or medical practices. We therefore performed a meta-analysis of all randomized clinical trials comparing initial coronary stent implantation with medical therapy to determine the effect on death, nonfatal myocardial infarction (MI), unplanned revascularization, and persistent angina. METHODS Prospective randomized trials were identified by searches of the MEDLINE database from 1970 to September 2011. Trials in which stents were used in less than 50% of PCI procedures were excluded. Data were extracted from each study, and summary odds ratios (ORs) were obtained using a random effects model. RESULTS Eight trials enrolling 7229 patients were identified. Three trials enrolled stable patients after MI, whereas 5 studies enrolled patients with stable angina and/or ischemia on stress testing. Mean weighted follow-up was 4.3 years. The respective event rates for death with stent implantation and medical therapy were 8.9% and 9.1% (OR, 0.98; 95% CI, 0.84-1.16); for nonfatal MI, 8.9% and 8.1% (OR, 1.12; 95% CI, 0.93-1.34); for unplanned revascularization, 21.4% and 30.7% (OR, 0.78; 95% CI, 0.57-1.06); and for persistent angina, 29% and 33% (OR, 0.80; 95% CI, 0.60-1.05). CONCLUSION Initial stent implantation for stable CAD shows no evidence of benefit compared with initial medical therapy for prevention of death, nonfatal MI, unplanned revascularization, or angina.

Percutaneous Coronary Intervention Outcomes in Patients With Stable Obstructive Coronary Artery Disease and Myocardial Ischemia: A Collaborative Meta-analysis of Contemporary Randomized Clinical Trials

IMPORTANCE Myocardial ischemia in patients with stable coronary artery disease (CAD) has been repeatedly associated with impaired survival. However, it is unclear if revascularization with percutaneous coronary intervention (PCI) to relieve ischemia improves outcomes compared with medical therapy (MT). OBJECTIVE The objective of this study was to compare the effect of PCI and MT with MT alone exclusively in patients with stable CAD and objectively documented myocardial ischemia on clinical outcomes. DATA SOURCES MEDLINE, Cochrane, and PubMed databases from 1970 to November 2012. Unpublished data were obtained from investigators. STUDY SELECTION Randomized clinical trials of PCI and MT vs MT alone for stable coronary artery disease in which stents and statins were used in more than 50% of patients. DATA EXTRACTION For studies in which myocardial ischemia diagnosed by stress testing or fractional flow reserve was required for enrollment, descriptive and quantitative data were extracted from the published report. For studies in which myocardial ischemia was not a requirement for enrollment, authors provided data for only those patients with ischemia determined by stress testing prior to randomization. The outcomes analyzed included death from any cause, nonfatal myocardial infarction (MI), unplanned revascularization, and angina. Summary odds ratios (ORs) were obtained using a random-effects model. Heterogeneity was assessed using the Q statistic and I2. RESULTS In 5 trials enrolling 5286 patients, myocardial ischemia was diagnosed in 4064 patients by exercise stress testing, nuclear or echocardiographic stress imaging, or fractional flow reserve. Follow-up ranged from 231 days to 5 years (median, 5 years). The respective event rates for PCI with MT vs MT alone for death were 6.5% and 7.3% (OR, 0.90 [95% CI, 0.71-1.16); for nonfatal MI, 9.2% and 7.6% (OR, 1.24 [95% CI, 0.99-1.56]); for unplanned revascularization, 18.3% and 28.4% (OR, 0.64 [95% CI, 0.35-1.17); and for angina, 20.3% and 23.3% (OR, 0.91 [95% CI, 0.57-1.44]). CONCLUSIONS AND RELEVANCE In patients with stable CAD and objectively documented myocardial ischemia, PCI with MT was not associated with a reduction in death, nonfatal MI, unplanned revascularization, or angina compared with MT alone.

Genotype-Guided vs Clinical Dosing of Warfarin and Its Analogues: Meta-analysis of Randomized Clinical Trials

IMPORTANCE Significant variations in dose requirements of warfarin and its analogues (acenocoumarol and phenprocoumon) make selecting the appropriate dose for an individual patient difficult. Genetic factors account for approximately one-third of the variation in dose requirement. The clinical usefulness of genotype-guided dosing of warfarin has been previously assessed in randomized clinical trials that were limited by lack of power and inconsistent results. OBJECTIVE To compare genotype-guided initial dosing of warfarin and its analogues with clinical dosing protocols. DATA SOURCES AND STUDY SELECTION MEDLINE (inception to December 31, 2013), EMBASE (inception to December 31, 2013), and the Cochrane Library Central Register of Controlled Trials (inception to December 31, 2013) were searched for randomized clinical trials comparing genotype-guided warfarin dosing vs clinical dosing for adults with indications for anticoagulation. DATA EXTRACTION AND SYNTHESIS Two investigators extracted data independently on trial design, baseline characteristics, and outcomes. High-quality studies were considered those that described an appropriate method of randomization, allocation concealment, blinding, and completeness of follow-up. MAIN OUTCOMES AND MEASURES The outcomes analyzed included the percentage of time that the international normalized ratio (INR) was within the therapeutic range, the percentage of patients with an INR greater than 4, and the incidence of major bleeding and thromboembolic events. Summary standardized differences in means (or Mantel-Haenszel risk ratios) were obtained using a random-effects model. RESULTS In 9 trials, 2812 patients were randomized to receive warfarin, acenocoumarol, or phenprocoumon according to a genotype-guided algorithm or a clinical dosing algorithm. Follow-up ranged from 4 weeks to 6 months (median, 12 weeks). The standardized difference in means of the percentage of time that the INR was within the therapeutic range was 0.14 (95% CI, -0.10 to 0.39) in the genotype-guided dosing cohort (P = .25). The risk ratio for an INR greater than 4 was 0.92 (95% CI, 0.82 to 1.05) for genotype-guided dosing vs clinical dosing. The risk ratios for major bleeding and thromboembolic events were 0.60 (95% CI, 0.29 to 1.22) and 0.97 (95% CI, 0.46 to 2.05), respectively, for genotype-guided vs clinical dosing. CONCLUSIONS AND RELEVANCE In this meta-analysis of randomized clinical trials, a genotype-guided dosing strategy did not result in a greater percentage of time that the INR was within the therapeutic range, fewer patients with an INR greater than 4, or a reduction in major bleeding or thromboembolic events compared with clinical dosing algorithms.

Anabolic steroids, acute myocardial infarction and polycythemia: A case report and review of the literature

The association between testosterone-replacement therapy and cardiovascular risk remains unclear with most reports suggesting a neutral or possibly beneficial effect of the hormone in men and women. However, several cardiovascular complications including hypertension, cardiomyopathy, stroke, pulmonary embolism, fatal and nonfatal arrhythmias, and myocardial infarction have been reported with supraphysiologic doses of anabolic steroids. We report a case of an acute ST-segment elevation myocardial infarction in a patient with traditional cardiac risk factors using supraphysiologic doses of supplemental, intramuscular testosterone. In addition, this patient also had polycythemia, likely secondary to high-dose testosterone. The patient underwent successful percutaneous intervention of the right coronary artery. Phlebotomy was used to treat the polycythemia acutely. We suggest that the chronic and recent “stacked” use of intramuscular testosterone as well as the resultant polycythemia and likely increased plasma viscosity may have been contributing factors to this cardiovascular event, in addition to traditional coronary risk factors. Physicians and patients should be aware of the clinical consequences of anabolic steroid abuse.

Early Afterdepolarization Formation in Cardiac Myocyte

Early Afterdepolarization Formation, introduction: Early afterdepolarizations (EADs) are among the mechanisms proposed to underlie ventricular arrhythmias. Sea anemone toxin, ATXII, known to delay Na inactivation and to induce plateau level voltage oscillations, was used to study the formation of EADs.

Pregnancy in patients with pre-existing cardiomyopathies.

To varying extents, women with pre-existing cardiomyopathies have a limited cardiovascular reserve. The hemodynamic challenges of pregnancy, labor, and delivery pose unique risks to this group of patients, which can result in clinical decompensation with overt heart failure, arrhythmias, and rarely, maternal death. A multidisciplinary team approach and a controlled delivery are crucial to adequate management of patients with underlying heart disease. Pre-conception planning and risk assessment are essential, and proper counseling should be offered to expectant mothers with regard to both the risks that pregnancy poses and the implications for future offspring. In this article, we will review the hemodynamic stressors that pregnancy places upon women with pre-existing cardiomyopathies and risk assessment and discuss what evidence exists with regard to the management of 2 forms of cardiomyopathy during pregnancy, labor, and delivery: dilated and hypertrophic cardiomyopathy.

Pregnancy Complicated by Valvular Heart Disease: An Update

Cardiovascular disease complicates ≈1% to 3% of all pregnancies and is responsible for 10% to 15% of maternal mortality. Although its prevalence is considered relatively low in pregnant women, heart disease is the most common cause of maternal mortality. Because more women with congenital or

Takotsubo cardiomyopathy: A review

Abstract Takotsubo cardiomyopathy can occur after acute mental or physical stress, subarachnoid hemorrhage, ischemic stroke, major head trauma, acute medical illness or acute pheochromocytoma crisis. It is characterized by transient systolic dysfunction of the apical and/or midventricular segments in patients without epicardial coronary artery disease. The condition occurs most commonly in postmenopausal women, and is characterized by transient left ventricular dysfunction. The pathophysiology of the disorder remains to be elucidated but may involve catecholamine excess and vasospasm. Future studies, perhaps in the form of an international registry, may clarify the incidence, pathophysiology, clinical course, and prognosis of this disorder.

Right ventricular strain rate predicts clinical outcomes in patients with acute pulmonary embolism

Background: Echocardiographic quantification of global and regional right ventricular (RV) function is critical in patients with acute pulmonary embolism (PE), but remains a challenge particularly in acute RV dilatation. Methods: Apical two-dimensional images of patients with acute PE were analyzed using both conventional and speckle tracking imaging compared with controls; patients with PE were divided into those who received thrombolysis and those who did not. The basal, mid and apical segments of the RV free wall and septum were analyzed. Correlations between speckle tracking measurements and in-hospital mortality were made. Results: 53 patients with PE were compared with 15 controls. Of the PE patients, 98.1% were treated with systemic anticoagulation, 15.1% with thrombolysis; 38% required ICU admission and 5.6% died. Strain rate of the mid interventricular septum and strain of the basal and mid interventricular septal segments were significantly lower in patients with PE than control. However, strain rate of the basal RV free wall was higher than controls. In thrombolysed patients, basal RV free wall strain rate was lower than in non-thrombolysed patients. RV strain rate significantly correlated with in-hospital mortality. Conclusions: Speckle tracking may be a sensitive tool for assessing RV dysfunction and predicting mortality in patients with PE in this pilot study.