Joseph Swafford

Cardiovascular Complications of Cancer Therapy Diagnosis, Pathogenesis, and Management

The cardiotoxicity of anticancer agents can lead to significant complications that can affect patients being treated for various malignancies. The severity of such toxicity depends on many factors such as the molecular site of action, the immediate and cumulative dose, the method of administration, the presence of any underlying cardiac condition, and the demographics of the patient. Moreover, toxicity can be affected by current or previous treatment with other antineoplastic agents. Cardiotoxic effects can occur immediately during administration of the drug, or they may not manifest themselves until months or years after the patient has been treated. In this article we review commonly used chemotherapy agents, including several recently approved medications, for their propensity to cause cardiotoxicity. Further research will be required to more accurately predict which patients are at risk for developing cardiotoxicity. In addition, management plans, as well as strategies to reduce cardiotoxicity, need to be developed.

Impact of aspirin therapy in cancer patients with thrombocytopenia and acute coronary syndromes

Patients with cancer who have thrombocytopenia may experience acute coronary syndromes (ACS), and the use of aspirin (ASA) poses an increased risk of bleeding. The purpose of this study was to test the hypothesis that the benefit of ASA therapy in the treatment of ACS would extend to cancer patients with thrombocytopenia and outweigh the risks of severe bleeding.

Cardiovascular Complications of Cancer Therapy

Cancer treatment today employs a combination of chemotherapy, radiotherapy, and surgery to prolong life and provide cure. However, many of these treatments can cause cardiovascular complications such as heart failure, myocardial ischemia/infarction, hypertension, thromboembolism, and arrhythmias. In this article we review the incidence of cardiotoxicity caused by commonly used chemotherapeutic agents as well as discuss the pathogenesis, diagnosis, management, and prevention of these cardiovascular side effects. Cardiotoxicity related to anticancer treatment is important to recognize as it may have a significant impact on the overall prognosis and survival of cancer patients, and it is likely to remain a significant challenge for both cardiologists and oncologists in the future due to an increasing aging population of patients with cancer and the introduction of many new cancer therapies.

Late doxorubicin-associated cardiotoxicity in children

Background. The most frequently encountered doxorubicin related cardiac toxicity is a dose‐related myocardial dysfunction occurring 1‐6 months after chemotherapy. Recently, late cardiotoxicity has been the focus of interest. This paper explores the possibility that acute intercurrent viral illness may trigger late cardiotoxicity.

CARDIAC DIASTOLIC FUNCTION IN PEDIATRIC PATIENTS RECEIVING DOXORUBICIN

The purpose of the study was to compare systolic and diastolic function in pediatric patients treated with doxorubicin. Left ventricular function was evaluated in 61 children prior to and following chemotherapy. None had clinical evidence of cardiac decompensation prior to treatment. All received relatively low cumulative doses of doxorubicin; the majority received the drug by continuous infusion. Systolic function was estimated using fractional shortening; diastolic function was estimated using A wave velocity, E wave velocity, E to A ratio, and deceleration time. There was a small but significant decline in systolic cardiac function as estimated from changes in fractional shortening that could not be appreciated in any of the measured parameters of diastolic function. A variety of reasons that could be responsible for the absence of significant changes in diastolic function are discussed. For the present, estimations of systolic function are preferred over the studied parameters of diastolic function in the evaluation of cardiac status in pediatric patients receiving doxorubicin containing regimens.

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.

Quantitative Coronary Arteriography and Its Assessment of Atherosclerosis: Part I. Examining the Independent Variables

Background. Previous work has demonstrated that quantitative coronary arteriography (QCA) can accurately measure phantom images to within ±0.1 mm and has been accepted as a reliable and reproducible method of measuring human coronary artery disease (CAD). Assessment of CAD by QCA involves the measurement of numerous variables, which are currently required to calculate stenosis flow reserve (SFR). Methods and Results. In this study 1040 stenotic lesions were analyzed by two well- accepted methods with demonstrated accuracy and reproducibility. These methods measure percent diameter stenosis (%DS), absolute diameter, percent area stenosis, length, as well as entry and exit angles to and from a stenotic coronary artery lesion respectively Based upon these results, the mean ± standard deviations and range seen in CAD were determined for each of these independent variables. This study demonstrated that atherosclerotic coronary artery lesions do not appear to exceed an entry angle of -39°, an exit angle of +35°, or an absolute length of 4.84 cm when accurately measured by QCA. It was also noted that, once percent diameter stenosis exceeded 89% (regardless (continued on next page) of the visual estimate) or percent area stenosis exceeds 99%, coronary arteries become completely occluded as measured by QCA. Conclusions. While previously suspected that once certain critical limits are exceeded in the deposit of cholesterol and calcium within the coronary artery, the artery will close, this study demonstrated by QCA what the limitations in human coronary arteries appear to be. These limits may be in part due to turbulent factors resulting in platelet activation or local mediators from endothelium of the coronary artery. ABSTRACT Contemporary quantitative coronary arteriography (QCA) was used to measure the different variables present in atherosclerotic coronary arteries. While the interaction of each of the independent variables undoubtedly plays a role in the determination of coronary artery blood flow and closure, the limitations of each of these variables have not yet been defined in humans. This study, based on the results of human coronary arteri ograms as analyzed by QCA, demonstrates the limitations of each of these variables, after which coronary arteries close and blood flow equals zero.

Computerized tomographic finding of saddle pulmonary embolism is associated with high mortality in cancer patients

Background: Large pulmonary embolism (PE) is associated with high mortality in cancer patients. Several risk stratification methods have been used in PE setting. While computer‐assisted tomography (CT) is now the preferred diagnostic modality for PE, its prognostic value is not well established.

Culture-positive and culture-negative endocarditis in patients with cancer: A retrospective observational study, 1994-2004

Abstract: Endocarditis is uncommon in patients with cancer. The characteristics of culture-positive (CPE) and culture-negative endocarditis (CNE) in high-risk cancer patients are not known; therefore we sought to evaluate the disease characteristics in patients with endocarditis at a comprehensive cancer center. We retrospectively reviewed the transthoracic (TTE) and transesophageal (TEE) echocardiograms obtained from 654 consecutive cancer patients in whom endocarditis was suspected between 1994 and 2004. Endocarditis was confirmed in 45 (7%) of 654 patients using modified Duke University criteria based on information obtained from hospital records and computerized data systems. In 21 (95%) of 22 cases, TEE examinations were diagnostic, and 16 (42%) of 38 patients with initially nondiagnostic TTE studies had the diagnosis confirmed by TEE study; this difference between diagnostic TEE and initial nondiagnostic TTE was significant (p < 0.0001). Among the 26 (58%) patients with CPE, Staphylococcus aureus (35%) was the most common organism isolated, followed by coagulase-negative Staphylococcus species (23%). Eighteen (78%) of 23 patients with a central venous catheter had CPE, whereas only 8 (36%) of 22 patients without a central venous catheter had CPE (odds ratio [OR], 6.3; 95% confidence interval [CI], 1.69-23.53; p < 0.006). Vegetations were larger in patients with CPE than in patients with CNE (median ± standard deviation, 10 ± 8.8 vs. 8.7 ± 3.9 mm). Fifteen patients (58%) with CPE and 10 (53%) with CNE had embolic complications. We note that cutaneous and septic pulmonary emboli were more common in patients with CPE than in patients with CNE (31% vs. 11% and 15% vs. 0%, respectively), whereas embolic cerebrovascular and fatal embolic coronary events were more common in patients with CNE than in those with CPE (37% vs. 12% and 21% vs. 0%, respectively; p = 0.026). The 4-week endocarditis-attributable death rate did not differ significantly between the groups (CPE, 15% vs. CNE, 32%; p = 0.28). On stepwise multivariate regression analysis, patients with neutropenia (OR, 22.52; 95% CI, 2.25-225.48; p < 0.008) and those with embolic cerebrovascular events (OR, 17.07; 95% CI, 1.63-178.45; p < 0.01) had an increased probability of death due to endocarditis. The clinical spectrums of CPE and CNE differed in these patients with cancer. In patients with CNE, embolic cerebrovascular and fatal myocardial infarction were relatively common. Abbreviations: CI = confidence interval, CNE = culture-negative endocarditis, CoNS = coagulase-negative Staphylococcus species, CPE = culture-positive endocarditis, NBTE = nonbacterial thrombotic endocarditis, OR = odds ratio, TEE = transesophageal echocardiogram, TTE = transthoracic echocardiogram.

Use of deep intravenous sedation with propofol and the laryngeal mask airway during transesophageal echocardiography

OBJECTIVE To describe the use of either deep intravenous sedation with propofol or light sedation with midazolam and topical anesthesia during transesophageal echocardiography (TEE) and to report the incidence of respiratory complications and their management. DESIGN Retrospective study from March 2000 through August 2002. SETTING Single institution, specialized cancer center. PARTICIPANTS All patients undergoing TEE examination in the specified time period (n = 42). MAIN RESULTS Eight patients received light sedation and 34 patients received deep intravenous sedation with propofol. An airway event occurred in one patient in the light sedation group and in six patients in the deep sedation group. The patient in the light sedation group was managed with the use of a face-mask and a manual resuscitation bag. All airway events in the deep sedation group were managed successfully using the laryngeal mask airway (LMA). CONCLUSION Deep sedation with intravenous propofol can provide both excellent patient comfort and optimal conditions for TEE examination, particularly in patients who may require more lengthy procedures or in whom other techniques have failed. Although the incidence of respiratory depression was higher in patients receiving deep sedation with propofol than in patients who were lightly sedated (17.6% versus 12.5%, respectively), all six patients who had respiratory depression while under deep sedation with propofol were successfully ventilated using the LMA trade mark, without the need to remove the TEE probe and without terminating the examination prematurely. In contrast, in the one patient in the light sedation group who had respiratory depression, the TEE probe had to be removed to ventilate the patient via a face mask, and the procedure was cancelled.