Predicting cardiovascular events with fluoropyrimidine chemotherapy using a standard cardiovascular risk calculator.

AIMS: Fluoropyrimidine chemotherapy is important for treatment of many solid tumours but is associated with cardiotoxicity. The relationship of fluoropyrimidine-associated cardiotoxicity (FAC) with conventional cardiovascular (CV) risk factors is poorly understood, and standard cardiovascular risk scores are not validated in this context. METHODS AND RESULTS: Single-centre retrospective study of patients treated with fluoropyrimidine chemotherapy using electronic health records for cardiovascular risk factors (and calculation of QRISK3 score), cancer treatment, and clinical outcomes. FAC was defined by cardiovascular events during or within 3 months of fluoropyrimidine treatment, and Cox regression was used to assess associations of CV risk and cancer treatment with FAC. One thousand eight hundred ninety-eight patients were included (45% male; median age 64 years), with median follow up 24.5 (11.5-48.3 months); 52.7% of patients were at moderate or high baseline CV risk (QRISK3 score >10%) Cardiovascular events occurred in 3.1% (59/1898)-most commonly angina (64.4%, 38/59) and atrial fibrillation (13.6%, 8/59), with 39% events during cycle one of treatment. In univariable analysis, QRISK3 score >20% was significantly associated with incident FAC (HR 2.25, 95% CI 1.11-4.93, P = 0.03). On multivariable analysis, beta-blocker use (HR 1.04, 95% CI 1.00-1.08, P = 0.04) and higher BMI (HR 2.33, 95% CI 1.04-5.19, P = 0.04) were independently associated with incident CV events. Thirty-two of the 59 patients with FAC were subsequently rechallenged with fluoropyrimidine chemotherapy, with repeat CV events in 6% (2/32). Incident FAC did not affect overall survival (P = 0.50). CONCLUSIONS: High BMI and use of beta-blockers are associated with risk of CV events during fluoropyrimidine chemotherapy. QRISK3 score may also play a role in identifying patients at high risk of CV events during fluoropyrimidine chemotherapy. Re-challenge with further fluoropyrimidine chemotherapy can be considered in patients following CV events during prior treatment.

Clinical and echocardiographic predictors of decompensation in acute severe aortic regurgitation due to infective endocarditis.

BACKGROUND: Patients with acute severe aortic regurgitation (AR) due to infective endocarditis can progress rapidly from the hemodynamically stable patient to pulmonary edema and cardiogenic shock. We sought to identify patients at risk of decompensation where emergent surgery should be undertaken. METHODS: We identified 90 patients with acute severe AR from the echocardiography laboratory database. Baseline clinical, hemodynamic (heart rate (HR) and blood pressure (BP)), and echocardiographic data including mitral filling, premature mitral valve closure (PMVC), and diastolic mitral regurgitation (DMR) were identified. The primary endpoint was subsequent development of pulmonary edema or severe hemodynamic instability. RESULTS: Patients who met the primary endpoint had a higher HR (98.5 bpm vs 80.5 bpm), lower diastolic BP (54 mm Hg vs 61.5 mm Hg), higher mitral E-wave velocity (113 cm/s vs 83 cm/s), higher E/e' ratio (12.4 vs 8), higher proportion of DMR (27.8% vs 7.4%), and PMVC (25% vs 9.3%) than patients who did not meet the endpoint. The proportion of patients with the primary endpoint increased as HR increased ((≤81 bpm) 3/30 (10%), (81-94 bpm) 11/31 (35.5%), (≥94 bpm) 22/29 (75.9%), P < .0001) and as the diastolic BP reduced ((≤54 mm Hg) 19/31 (61.3%), (54-63 mm Hg) 12/31 (38.7%), (≥63 mm Hg) 5/28 (17.9%), P = .003). Independent predictors were a higher HR (OR 1.08 (95% CI 1.04-1.13) P = .0003) and DMR (OR 4.71 (95% CI 1.23-18.09), P = .02). CONCLUSION: Decompensation in acute severe AR is common. Independent predictors of decompensation are increasing HR(≥94 bpm) and the presence of DMR. Those with these adverse markers should be considered for emergent surgery.

Ablation guided by STAR-mapping in addition to pulmonary vein isolation is superior to pulmonary vein isolation alone or in combination with CFAE/linear ablation for persistent AF.

INTRODUCTION: The optimal ablation approach for persistent atrial fibrillation (AF) remains unclear. METHODS AND RESULTS: Objective was to compare the long-term rates of freedom from AF/AT in patients that underwent STAR mapping guided ablation against outcomes of patients undergoing conventional ablation procedures. Patients undergoing ablation for persistent AF as part of the Stochastic Trajectory Analysis of Ranked signals (STAR) mapping study were included. Outcomes following 'pulmonary vein isolation (PVI) plus STAR mapping guided ablation (STAR mapping cohort) were compared to patients undergoing PVI alone ablation during the same time period and also a propensity-matched cohort undergoing PVI plus the addition of complex fractionated electrogram (CFAE) and/or linear ablation ("conventional ablation"). Rates of procedural AF termination and freedom from AF/AT during follow-up were compared. Sixty-five patients were included in both the STAR cohort and propensity matched conventional ablation cohort. AF termination rates were significantly higher in the STAR cohort (51/65, 78.5%) than conventional ablation cohort (10/65, 15.4%) and PVI alone ablation cohort (13/50, 26.0%; STAR cohort vs. other 2 cohorts both p < .001). There was no significant difference in procedure time between the three cohorts. During ≥20 months follow-up a lower proportion of patients had AF/AT recurrence in the STAR cohort (20.0%) compared with the conventional ablation cohort (50.8%) or the PVI alone ablation cohort (50.0%; both p < .05 compared to STAR cohort). CONCLUSIONS: Outcomes of PVI plus STAR mapping guided ablation was superior to PVI alone or in combination with linear/CFAE ablation. A multicenter randomized controlled trial is planned to confirm these findings.

A meta-analysis of literacy and language in children with rolandic epilepsy.

AIM: Rolandic epilepsy is the most common childhood epilepsy, often presenting with neuropsychological impairments. The aim of the study was to formally assimilate the findings of existing studies varying widely in methodology, thereby confirming the nature and prevalence of impairments in literacy and language. METHODS: Using meta-analytical techniques, we evaluated 22 studies of literacy and/or language skills in children with rolandic epilepsy, published after 2000, among participants with IQs>70 and in which effect sizes could be acquired. Diagnosis required the presence of classical centrotemporal spikes arising from a normal background on electroencephalograms; a clinical history including at least one seizure; and no additional neurological condition. Overall effect size and heterogeneity were measured for single-word reading, phonological processing, and expressive and receptive language. RESULTS: Mean effect sizes (Cohen's d) ranged from 0.50 (95% confidence interval [CI] 0.23-0.78) for phonological processing, through 0.71 (95% CI 0.52-0.90) for word reading and 0.72 (95% CI 0.34-1.1) for receptive language, to 0.75 (95% CI 0.45-1.05) for expressive language. While group differences for reading measures were consistent, those for language were heterogeneous and varied across studies explained by age and IQ of samples. INTERPRETATION: The presence of reading and phonological processing deficits in children with rolandic epilepsy highlights the importance of early literacy and language assessment in this population.