Syed Wamique Yusuf

Thrombolytics for PE and right ventricular dysfunction.

www.thelancet.com Vol 372 August 9, 2008 447 Departments of Psychiatry, Epidemiology and Public Health and Obstetrics and Gynecology and Reproductive Science, Yale School of Medicine, 142 Temple Street, Suite 301, New Haven, CT 06510, USA (KY); Department of Pharmacology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, Goteborg University, Sweden (EE); and Keele University Medical School, University Hospital of North Staff ordshire, Stoke on Trent, UK (SO’B)

Radiation-Induced Heart Disease: A Clinical Update

Cardiovascular diseases and cancer are the two leading causes of morbidity and mortality worldwide. Improvement in cancer therapy has led to increasing number of cancer survivors, some of whom may suffer from adverse cardiovascular effects of radiation therapy. Longterm followup is essential, as the cardiac complication may manifest years after completion of radiation therapy. In this paper, we have discussed the cardiovascular effects of radiation therapy.

Vascular Inflammation Imaging with 18F-FDG PET/CT: When to Image?

We prospectively investigated the ideal imaging time to measure vascular uptake after injection of 18F-FDG. Methods: A total of 17 patients with atherosclerotic abdominal aortic aneurysm underwent dynamic abdominal PET/CT using 2-min frames between 45 and 53, 57 and 65, 115 and 123, and 175 and 183 min after injection of 18F-FDG. For each period of dynamic imaging, vessel wall and lumen uptake were measured using the maximum standardized uptake value (SUVmax) and target-to-background ratio (TBR). Results: No significant difference in TBR across all time points (repeated measures ANOVA, P = 0.206) was observed, despite a significant difference in aortic wall and lumen uptake with time (repeated measures ANOVA, P = 0.02 and P < 0.001, respectively). There was no significant difference between aortic wall uptake at 60 min (SUVmax, 2.15 ± 0.11 SE) and 180 min (SUVmax, 1.99 ± 0.18 SE) (paired t test, P = 0.367). There was a significant difference in lumen uptake at 60 min (SUVmax, 2.4 ± 0.11 SE) and 180 min (SUVmax, 1.7 ± 0.1 SE) (paired t test, P = 0.001). There was no significant difference in TBR between 60 min (0.91 ± 0.03) and 180 min (1.01 ± 0.06 SE) (paired t test, P = 0.131). With increasing delayed imaging, there was increasing variability (SE) in the SUVmax for the aortic wall and TBRs. Conclusion: There was no significant advantage in imaging at 3 h over 1 h after 18F-FDG injection.

The Association Between Autonomic Dysfunction and Survival in Male Patients with Advanced Cancer: A Preliminary Report

CONTEXT Autonomic nervous system dysfunction (AD) is a common syndrome in patients with advanced cancer. It is associated with decreased survival in several patient populations, including diabetes mellitus, heart failure, and neurological diseases. Based on this evidence, we hypothesized that autonomic dysfunction is associated with decreased survival in patients with advanced cancer. OBJECTIVES The objective of this preliminary study was to test the association between AD, as measured by the standardized Ewing test and heart rate variability (HRV) measures, and survival in this patient population. METHODS We examined the relationship between survival and parameters of AD in subjects who participated in a prospective study of autonomic dysfunction and hypogonadism in male patients with advanced cancer. Eligibility criteria were defined based on the prospective study protocol. We collected demographic information, date of death (obtained from the online Social Security Death Index database), date of study entry, and Ewing and HRV scores. We defined survival as the interval between study entry and date of death. A survival analysis was used to test the association between survival (in days) and Ewing test (0-5) and measures of HRV, including time domain (standard deviation of normal to normal beat interval [SDNN]) and frequency domain (ultra low, very low, low, and high). Four patients were still alive at the time of this study and included in the survival analysis as being censored. RESULTS Forty-seven male patients were included in this study. Median age was 59 years (range: 20-79), and 30 out of 47 (63%) were Caucasians. AD, defined as Ewing score greater than 2, was present in 38 out of 47 (80%) of the patients. Median Ewing score was 3 (1-5), indicating moderate to severe AD. Spearman correlation for Ewing score and SDNN was 0.44 (P = 0.002). There was a significant association between abnormal Ewing score and survival (P < 0.0001) and abnormal SDNN HRV and survival (P = 0.056). CONCLUSION AD is associated with shorter survival in male patients with advanced cancer. Further longitudinal research in a large cohort is justified based on.

Investigating vulnerable atheroma using combined (18)F-FDG PET/CT angiography of carotid plaque with immunohistochemical validation.

Inflammation and angiogenesis are hypothesized to be important factors contributing to plaque vulnerability, whereas calcification is suggested to confer stability. To investigate this in vivo, we combined CT angiography and PET and compared the findings with immunohistochemistry for patients undergoing carotid endarterectomy. Methods: Twenty-one consecutive patients (18 men, 3 women; mean age ± SD, 68.3 ± 7.3) undergoing carotid endarterectomy were recruited for combined carotid 18F-FDG PET/CT angiography. Plaque 18F-FDG uptake was quantified with maximum standardized uptake value, and CT angiography quantified percentage plaque composition (calcium and lipid). Surgical specimens underwent ex vivo CT aiding image registration, followed by immunohistochemical staining for CD68 (macrophage density) and vascular endothelial growth factor (angiogenesis). Relationships between imaging and immunohistochemistry were assessed with Spearman rank correlation and multivariable regression. Results: The mean (±SD) surgically excised carotid plaque 18F-FDG metabolism was 2.4 (±0.5) versus 2.2 (±0.3) contralaterally (P = 0.027). There were positive correlations between plaque 18F-FDG metabolism and immunohistochemistry with CD68 (ρ = 0.55; P = 0.011) and vascular endothelial growth factor (ρ = 0.47; P = 0.031). There was an inverse relationship between plaque 18F-FDG metabolism and plaque percentage calcium composition on CT (ρ = −0.51; P = 0.018) and between calcium composition and immunohistochemistry with CD68 (ρ = −0.57; P = 0.007). Regression showed that maximum standardized uptake value and calcium composition were independently significant predictors of angiogenesis, and calcium composition was a predictor of macrophage density. Conclusion: We provide in vivo evidence that increased plaque metabolism is associated with increased biomarkers of angiogenesis and inflammation, whereas plaque calcification is inversely related to PET and histologic biomarkers of inflammation.

Treatment and Outcomes of Acute Coronary Syndrome in the Cancer Population

Randomized trials have established the benefit of medical therapy and revascularization in the treatment of acute myocardial infarction (MI). Cancer and cardiovascular disease are the 2 most common diseases worldwide. In clinical practice, cancer patients are frequently afflicted with MI. The benefit of medical and/or revascularization therapy in the cancer population with MI is less well known.

Outcomes of Cancer Patients Undergoing Percutaneous Pericardiocentesis for Pericardial Effusion

BACKGROUND Pericardial effusion (PE) is common in cancer patients, but the optimal therapeutic approach is not well defined. Percutaneous pericardiocentesis is less invasive than surgery, but its long-term effectiveness and safety have not been well documented. OBJECTIVES The goal of this study was to evaluate outcomes of cancer patients undergoing percutaneous pericardiocentesis for PE and assess the procedures safety in patients with thrombocytopenia. METHODS Cancer patients who underwent percutaneous pericardiocentesis for PE between November 2009 and October 2014 at the MD Anderson Cancer Center were included. Procedure-related complications, effusion recurrence rate, and overall survival were analyzed. RESULTS Of 1,645 cancer patients referred for PE, 212 (13%) underwent percutaneous pericardiocentesis. The procedure was successful in 99% of the cases, and there were no procedure-related deaths. Four patients had major procedure-related bleeding that did not vary by platelet count <50,000/μl or ≥50,000/μl (p = 0.1281). Patients with catheter drainage for 3 to 5 days had the lowest recurrence rate (10%). Median overall survival was 143 days; older age (i.e., >65 years), lung cancer, platelet count <20,000/μl, and malignant pericardial fluid were independently associated with poor prognosis. Lung cancer patients with proven malignant effusions had a significantly shorter median 1-year survival compared with those with nonmalignant effusions (16.2% vs. 49.0%, respectively; log-rank test p = 0.0101). A similar difference in 1-year survival was not observed in patients with breast cancer (40.2% vs. 40.0%; log-rank test p = 0.4170). CONCLUSIONS Percutaneous pericardiocentesis with extended catheter drainage was safe and effective as the primary treatment for PE in cancer patients, including in those with thrombocytopenia. Malignant PE significantly shortened the survival outcome of patients with lung cancer but not those with breast cancer.

Prospective exploratory analysis of cardiac biomarkers and electrocardiogram abnormalities in patients receiving thoracic radiation therapy with high-dose heart exposure.

Introduction: Acute effects of incidental cardiac irradiation in patients treated for thoracic cancer are not well characterized. We evaluated longitudinal changes in cardiac biomarkers for patients undergoing conformal radiation therapy (RT) with thoracic malignancies with high-dose cardiac exposure. Methods: Twenty-five patients enrolled in a prospective trial (February 2009–December 2012) received more than or equal to 45 Gy to the thorax, with pretreatment estimates of more than or equal to 20 Gy to the heart. Chemotherapy was allowed except for doxorubicin or fluorouracil. Electrocardiographic (ECG), troponin-I (TnI), and brain natriuretic peptide (BNP) measurements were obtained before RT, within 24 hours of the first fraction, at the end of RT, and at first follow-up (1–2 months). These biomarkers were quantified at specific times and changes from baseline were evaluated with paired t tests. Results: The median heart dose was 25.9 Gy (range 10.1–35.1 Gy). After the first RT fraction, no changes were noted in ECG or median TnI or BNP levels; at the end of RT, two patients had elevated TnI and BNP, but neither difference was statistically significant. At first follow-up, TnI had returned to normal but the median BNP remained elevated (p = 0.042). BNP did not increase over time in the 18 patients who received only RT. Twelve patients experienced acute ECG changes during RT, which resolved in seven patients by the next measurement. No patients experienced clinically significant RT-related events. Conclusion: Increases in BNP and ECG changes were observed during high doses of radiation to the heart. The findings of this pilot study warrant further investigation and validation.

Management and outcomes of severe aortic stenosis in cancer patients

BACKGROUND Aortic stenosis (AS) is the commonest native valve lesion, affecting 43% of all patients with valvular heart disease. The optimal treatment of severe AS in cancer patients is unknown. The purpose of this study was to assess the impact of aortic valve replacement (AVR) on survival of cancer patients with severe AS. METHODS Cancer patients with severe AS seen at our center between January 2001 and April 2007 were identified. Baseline demographics, symptoms, cancer diagnosis, laboratory data, treatment, and outcome were collected. Patient who had AVR were matched with controls who did not have AS. RESULTS Out of 39,071 echocardiograms performed over the study period, 1,299 had AS (3.3%), of which 50 patients (0.13%) were identified as having severe AS. Thirteen patients (27%) underwent AVR, and 35 were managed medically. Two patients underwent valvuloplasty and were excluded. Survival was significantly longer in patients with severe AS who underwent AVR and was independent of cancer status or presence of metastases. No difference in survival was found between patients who underwent AVR and matched cancer controls. In a multivariable Cox proportional hazard regression analysis, AVR was the only significant predictor of longer survival (adjusted hazard ratio = 0.22, P = .028). CONCLUSIONS Cancer patients with severe AS who underwent AVR had an improved survival, regardless of cancer status.

5-Fluorouracil-induced coronary vasospasm.

Cardiotoxicity due to 5-fluorouracil involves rare and life-threatening cardiotoxic events occurring in less than 1% of the patients. We describe a case of coronary vasospasm due to parenteral 5-fluorouracil, which did not recur with oral capecitabine. We also give a brief review of the cardiotoxicity of 5-fluorouracil, its treatment and prevention.