Raltitrexed as a substitute for capecitabine in metastatic gastric cancer: a case report and literature review.

Background: 5-Fluorouracil and its oral prodrug, capecitabine, are frequently used in the treatment of gastrointestinal cancers-including gastric cancer-but carry a cardiotoxicity risk. Raltitrexed (brand name Tomudex), a direct inhibitor of thymidylate synthase, has been successfully used as an alternative to fluoropyrimidines in patients with 5-fluorouracil-induced cardiac events. We report the first case, to our knowledge, of raltitrexed used with trastuzumab and platinum-based chemotherapy as a substitute for fluoropyrimidines following cardiotoxicity in a 78-year-old male patient with metastatic gastric cancer. Case Description: The patient experienced a myocardial infarction 3 days after beginning treatment with capecitabine, carboplatin, and trastuzumab for metastatic HER2+ gastric adenocarcinoma. Capecitabine was replaced with raltitrexed, and the patient ultimately received seven cycles of chemotherapy, five of which included raltitrexed. There were no cardiotoxic events attributable to raltitrexed, although the patient did experience hypotensive episodes, premature ventricular contractions, myelosuppression, and anemia. Progression-free survival was 4.5 months, within the expected range achieved with the ToGA regimen (trastuzumab, cisplatin, 5-fluorouracil chemotherapy). At time of writing, the patient has been alive for 48 weeks since diagnosis. Conclusions: In summary, raltitrexed appears to be a safe alternative to fluoropyrimidines when combined with trastuzumab and platinum, although more data is needed to determine its relative effectiveness.

Association of Left Ventricular Ejection Fraction with Mortality and Hospitalizations.

BACKGROUND: Although echocardiography is widely used to measure left ventricular ejection fraction (LVEF), its prognostic value has not been demonstrated in a broad range of patients including those acutely hospitalized for cardiac or noncardiac causes. We determined whether greater degrees of left ventricular systolic dysfunction were associated with progressively increasing risks of death or cardiovascular hospitalizations among patients in hospital or outpatient settings. METHODS: A total of 27,323 patients with LVEF measured and 19,445 matched controls were followed for 223,034 person-years. Outcomes of total mortality, cardiovascular death, cardiovascular hospitalizations, and heart failure hospitalizations were examined using cause-specific hazard competing-risks analysis. RESULTS: In the study cohort (median age, 68 [interquartile range, 58-77], 14,828 women [31.7%]), the hazard ratios (95% CI) for all-cause death were 1.67 (1.57-1.77), 1.30 (1.24-1.36), and 1.17 (1.11-1.23) when LVEF was <25%, 25%-35%, or 36%-45% compared with LVEF 46%-55% (all P < .001). Rates of cardiovascular death were similarly higher with lower LVEF. The hazard ratios for cardiovascular hospitalization were 1.35 (1.27-1.42), 1.21 (1.16-1.27), and 1.13 (1.07-1.18) for LVEFs <25%, 25%-35%, and 36%-45%, respectively (all P < .001). The rate of heart failure hospitalizations was amplified, with hazard ratios of 1.71 (1.59-1.85), 1.39 (1.31-1.48), and 1.21 (1.13-1.29) for LVEFs <25%, 25%-35%, or 36%-45% (all P < .001). The rate of mortality and hospitalizations increased comparably with greater reductions in LVEF during both inpatient cardiac or noncardiac admissions (P < .001). CONCLUSIONS: Quantitative echocardiographic LVEF stratified the risk of death and hospitalization in a wide range of clinical settings, including during noncardiac admissions.

Cryptogenic stroke and patent foramen ovale: clinical clues to paradoxical embolism.

BACKGROUND: Patent foramen ovale (PFO) is an independent risk factor for cerebral infarction. Since ~25% of the population have a PFO, the simple association of PFO with stroke is not enough to establish the diagnosis of paradoxical embolism. We evaluated possible clinical clues to the diagnosis of paradoxical embolism. METHODS: Among patients with cryptogenic ischemic stroke (CS) who were investigated for a right-to-left shunt (RLS), we compared clinical, coagulation and biochemical parameters in patients with PFO versus without PFO. RESULTS: Among 1689 new patients referred for TIA/non-disabling stroke between 2001 and 2007, 175 with cryptogenic stroke (CS) were investigated for RLS by transcranial Doppler (TCD) bubble studies; 89 (5.5%) with positive TCD had a PFO confirmed by TEE. In multivariate logistic regression, a history of DVT or pulmonary embolism (OR, 4.39; 95% CI, 1.23-15.69; p=0.023), prolonged travel (OR, 8.77; 95% CI, 1.775-43.3; p=0.008) , migraine (OR, 2.30: 95% CI, 1.07-4.92; p=0.031), a Valsalva maneuver preceding the onset of focal neurological symptoms (OR, 3.33; 95% CI, 1.15-9.64; p=0.026) and waking up with stroke/TIA (OR, 4.53, 95% CI, 1.26-16.2; p=0.018) were independently associated with PFO-associated cerebrovascular events. Patients with PFO had higher plasma total homocysteine levels than patients without PFO (8.9+/-3 versus 7.9+/-2.6 micromol/L respectively; p=0.021). CONCLUSIONS: A history of DVT or pulmonary embolism, migraine, recent prolonged travel, sleep apnea, waking up with TIA or stroke or a Valsalva maneuver preceding the event are clinical clues to the diagnosis of paradoxical embolism among patients with CS.

Determination of left ventricular ejection fraction using intravenous contrast and a semiautomated border detection algorithm.

Manual endocardial tracing using Simpson's method (MANUAL SIMP) provides an accurate assessment of left-ventricular ejection fraction (LVEF). We have previously demonstrated in patients who are difficult to image: (1) the incremental accuracy of contrast-enhanced power harmonic imaging and MANUAL SIMP in the calculation of LVEF; and (2) the use of intravenous contrast-combined MANUAL SIMP was the most accurate method of LVEF determination. However, MANUAL SIMP is time-consuming, requires accurate planimetry of the endocardial borders, and is difficult to apply routinely in the clinical situation. The current study prospectively studied the accuracy of intravenous contrast and a semiautomated endocardial border detection algorithm in the determination of LVEF in 51 patients with suboptimal images. LVEF was also calculated using contrast-enhanced power harmonic imaging and MANUAL SIMP. We demonstrated that there was good agreement between LVEF determined using both MANUAL SIMP and semiautomated endocardial border detection, and radionuclide angiography (standard of comparison).

Intracardiac echocardiography guided device closure of atrial septal defects.

OBJECTIVES: This study was designed to determine the feasibility and accuracy of intracardiac echocardiography (ICE) in guiding percutaneous closure of atrial septal defects (ASD). BACKGROUND: Intracardiac echocardiography is a novel imaging technique that might be used to guide interventional procedures. The sensitivity and specificity of ICE, compared to standard imaging techniques, in detecting potentially adverse procedural events and guiding remedial action will be an important consideration in its use. METHODS: In a prospective study, 24 patients underwent device closure of ASD using ICE as the primary echocardiographic imaging modality. Feasibility was expressed as proportion of cases in which complete diagnostic ICE imaging was achieved. Accuracy was expressed as the percent agreement between ICE and simultaneously performed transesophageal echocardiography (TEE). RESULTS: High-quality ICE images were acquired in all patients, though images were limited in two patients with aneurysmal septa. Intracardiac echocardiography successfully guided closure of 24 out of 25 ASDs (96%) in 23 patients. There was close agreement between ICE and TEE in their assessment of device position and the adequacy of septal capture before device release (98%) and in identifying the presence of significant residual shunts. Intracardiac echocardiography detected all potentially adverse events, including four malpositions, and guided appropriate remedial action. CONCLUSIONS: Intracardiac echocardiography guided device closure of secundum ASDs is feasible in the majority of patients and provides diagnostic data comparable to TEE. These data indicate that ICE may be used to guide routine closure of ASDs in adults without the need for TEE and general anesthesia.