PDGFR is an important target for novel anticancer therapeutics because it is overexpressed in a wide variety of malignancies. Recently, however, several anticancer drugs that inhibit PDGFR signaling have been associated with clinical heart failure. Understanding this effect of PDGFR inhibitors has been difficult because the role of PDGFR signaling in the heart remains largely unexplored. As described herein, we have found that PDGFR-β expression and activation increase dramatically in the hearts of mice exposed to load-induced cardiac stress. In mice in which Pdgfrb was knocked out in the heart in development or in adulthood, exposure to loadinduced stress resulted in cardiac dysfunction and heart failure. Mechanistically, we showed that cardiomyocyte PDGFR-β signaling plays a vital role in stress-induced cardiac angiogenesis. Specifically, we demonstrated that cardiomyocyte PDGFR-β was an essential upstream regulator of the stress-induced paracrine angiogenic capacity (the angiogenic potential) of cardiomyocytes. These results demonstrate that cardiomyocyte PDGFR-β is a regulator of the compensatory cardiac response to pressure overload-induced stress. Furthermore, our findings may provide insights into the mechanism of cardiotoxicity due to anticancer PDGFR inhibitors.

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.

Background: 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. Hypothesis: Medical and revascularization therapy reduces mortality in cancer patients with MI. Methods: After approval by the institutional review board, we retrospectively reviewed all patients with a discharge diagnosis of acute MI who were admitted to the University of Texas MD Anderson Cancer Center between December 2000 and October 2006 and evaluated the association between cardiac treatments with survival outcomes.Results: A total of 456 patients with a discharge diagnosis of acute MI were identified and included in the study, of which 386 had non-ST-segment elevation MI (NSTEMI) and 70 had ST-segment elevation MI (STEMI). Compared with patients with NSTEMI, patients who had STEMI were more often prescribed aspirin (66% vs 43%; P = 0.004), β-blockers (61% vs 46%; P = 0.018), and thrombolytic therapy (9% vs 0.3%; P = 0.0001). In the multivariable analysis, aspirin use was associated with a 23% decreased risk of death (hazard ratio [HR]: 0.77, 95% confidence interval [CI]: 0.60-0.98, P = 0.033) and β-blocker use was associated with a 36% decreased risk of death (HR: 0.64, 95% CI: 0.51-0.81, P = 0.0002). Statins (HR: 0.82, P = 0.18) and catheterbased revascularization (HR: 0.57, P = 0.09) did not have an impact on the risk of death. Compared with patients with limited cancer, advanced cancer patients were twice as likely to die (HR: 2.12, 95 CI: 1.47-3.04, P < 0.0001). Previous chemotherapy (P = 0.005) and chest radiotherapy (P = 0.017) were associated with increased 1-year mortality, whereas hyperlipidemia (P = 0.018) was protective. Conclusions: In this study of cancer patients with MI, medical therapy with aspirin and β-blockers was associated with improved survival.

Cardiac tumors are a rare entity, comprised of tumors with diverse histology and natural history. We report the clinical characteristics, echocardiograhic findings, therapy and outcome of 59 patients with primary and metastatic cardiac tumors. Our institutional echocardiogram data base from 1993 through 2005 was reviewed to identify patients diagnosed with intra-cardiac tumor. A total of 59 patients with cardiac tumors were identified and included in the study. The patients' characteristics, presenting symptoms, diagnostic tests, location, histology of the tumor, treatment and the one year survival rate of this population was collected from the medical records. Of the 59 cardiac tumor cases, 16 (27%) were primary cardiac tumors and 43 (73%) were secondary cardiac tumors. The most common primary tumor was sarcoma affecting 13 (81%) of the 16 cases. Of these, 5 patients were angiosarcoma, 5 unclassified sarcoma, one myxoid sarcoma and 2 malignant fibrous histiocytoma. The mean age at presentation was 41.1 years, and the most common location was right atrium affecting 6 cases (37.5%). The most common symptom of dyspnea was present in 10 (62.5%) cases. Eleven (25.6%) of the 43 secondary cardiac tumors were metastasis from renal cell carcinoma. The mean age at presentation was 55.4 years. Right atrium was the most frequent location affecting 18 (42%) of the 43 patients. The most common presenting symptom was dyspnea in 15 (35%) cases. For both primary and secondary tumors, dyspnea was the most common symptom and right atrium was most frequently involved. Sarcoma was the most common primary cardiac tumor while metastasis from renal cell carcinoma was the most common secondary tumor.

Over the past decade, therapies for several previously untreatable types of cancer have emerged or have improved; thus, more focus has been given to long-term complications of cancer therapy. The most commonly known cardiac toxicities of cancer therapy are cardiac dysfunction or congestive heart failure. Vascular complications--such as ischemia, myocardial infarction, venous or arterial thrombosis, and newly developed or worsened hypertension--are also relatively common following cancer treatment, particularly in patients with advanced-stage cancer. Experimental studies have suggested a number of potential mechanisms that might account for vascular complications of cancer therapies, which include dysfunction or damage of endothelial cells, increased platelet aggregation, and modulation of nitric oxide levels. This Review describes the vascular complications of treatment with 5-fluorouracil, bevacizumab, and several new tyrosine kinase inhibitors, with special emphasis on thrombotic complications and hypertension.