Radiotherapy-Induced Cardiac Implantable Electronic Device Dysfunction in Patients With Cancer.

Radiotherapy can affect the electronic components of a cardiac implantable electronic device (CIED) resulting in malfunction and/or damage. We sought to assess the incidence, predictors, and clinical impact of CIED dysfunction (CIED-D) after radiotherapy for cancer treatment. Clinical characteristics, cancer, different types of CIEDs, and radiation dose were evaluated. The investigation identified 230 patients, mean age 78 ± 8 years and 70% were men. A total of 199 patients had pacemakers (59% dual chamber), 21 (9%) cardioverter-defibrillators, and 10 (4%) resynchronizators or defibrillators. The left pectoral (n = 192, 83%) was the most common CIED location. Sixteen patients (7%) experienced 18 events of CIED-D after radiotherapy. Reset to backup pacing mode was the most common encountered dysfunction, and only 1 (6%) patient of those with CIED-D experienced symptoms of atrioventricular dyssynchrony. Those who had CIED-D tended to have a shorter device age at the time of radiotherapy compared to those who did not (2.5 ± 1.5 vs 3.8 ± 3.4 years, p = 0.09). The total dose prescribed to the tumor was significantly greater among those who had CIED-D (66 ± 30 vs 42 ± 23 Gy, p <0.0001). Multivariate logistic regression analysis identified the total dose prescribed to the tumor as the only independent predictor for CIED-D (odds ratio 1.19 for each increase in 5 Gy, 95% confidence interval 1.08 to 1.31, p = 0.0005). In conclusion, in this large population of patients with CIEDs undergoing radiotherapy for cancer treatment, the occurrence of newly diagnosed CIED-D was 7%, and the reset to backup pacing mode was the most common encountered dysfunction. The total dose prescribed to the tumor was a predictor of CIED-D. Importantly, although the unpredictability of CIEDs under radiotherapy is still an issue, none of our patients experienced significant symptoms, life-threatening arrhythmias, or conduction disorders.

Objective criteria for septal fibrosis in non-ischemic dilated cardiomyopathy: validation for the prediction of future cardiovascular events.

BACKGROUND: Expert subjective reporting of mid-wall septal fibrosis on late gadolinium enhancement (LGE) images has been shown to predict major cardiovascular outcomes in patients with non-ischemic dilated cardiomyopathy (NIDCM). This study aims to establish objective criteria for non-experts to report clinically relevant septal fibrosis and compare its performance by such readers versus experts for the prediction of cardiovascular events. METHODS: LGE cardiovascular magnetic resonance (CMR) was performed in 118 consecutive patients with NIDCM (mean age 57 ± 14, 42 % female) and the presence of septal fibrosis scored by expert readers. CMR-naive readers performed signal threshold-based LGE quantification by referencing mean values of remote tissue and applying these to a pre-defined anatomic region to measure septal fibrosis. All patients were followed for the primary composite outcome of cardiac mortality or appropriate implantable cardioverter-defibrillator (ICD) therapy. RESULTS: The mean LVEF was 32 ± 12 %. At a median follow-up of 1.9 years, 20 patients (17 %) experienced a primary composite outcome. Expert visual scoring identified 55 patients with septal fibrosis. Non-expert septal fibrosis quantification was highly reproducible and identified mean septal fibrosis burden for three measured thresholds as follows; 5SD: 2.9 ± 3.6 %, 3SD: 6.9 ± 6.3 %, and 2SD: 11.1 ± 7.5 % of the left ventricular (LV) mass, respectively. By ROC analysis, optimal thresholds for prediction of the primary outcome were; 5SD: 2.74 % (HR 8.7, p < 0.001), 3SD: 6.63 % (HR 5.7, p = 0.001) and 2SD: 10.15 % (HR 6.1, p = 0.001). By comparison, expert visual scoring provided a HR of 5.3 (p = 0.001). In adjusted analysis, objective quantification by a novice reader (>5SD threshold) was the strongest independent predictor of the primary outcome (HR 8.7) and provided improved risk reclassification beyond LVEF alone (NRI 0.54, 95 % CI 0.16-0.92, p = 0.005). CONCLUSIONS: Novice readers were able to achieve superior risk prediction for future cardiovascular events versus experts using objective criteria for septal fibrosis in patients with NIDCM. Patients with a septal fibrosis burden >2.74 % of the LV mass (>5SD threshold) were at a 9-fold higher risk of cardiac death or appropriate ICD therapy versus those not meeting this criteria. As such, this study validates reproducible criteria applicable to all levels of expertise to identify NIDCM patients at high risk of future cardiovascular events.

Accuracy and reproducibility of semi-automated late gadolinium enhancement quantification techniques in patients with hypertrophic cardiomyopathy.

BACKGROUND: The presence and extent of late gadolinium enhancement (LGE) has been associated with adverse events in patients with hypertrophic cardiomyopathy (HCM). Signal intensity (SI) threshold techniques are routinely employed for quantification; Full-Width at Half-Maximum (FWHM) techniques are suggested to provide greater reproducibility than Signal Threshold versus Reference Mean (STRM) techniques, however the accuracy of these approaches versus the manual assignment of optimal SI thresholds has not been studied. In this study, we compared all known semi-automated LGE quantification techniques for accuracy and reproducibility among patients with HCM. METHODS: Seventy-six HCM patients (51 male, age 54 ± 13 years) were studied. Total LGE volume was quantified using 7 semi-automated techniques and compared to expert manual adjustment of the SI threshold to achieve optimal segmentation. Techniques tested included STRM based thresholds of >2, 3, 4, 5 and 6 SD above mean SI of reference myocardium, the FWHM technique, and the Otsu-auto-threshold (OAT) technique. The SI threshold chosen by each technique was recorded for all slices. Bland-Altman analysis and intra-class correlation coefficients (ICC) were reported for each semi-automated technique versus expert, manually adjusted LGE segmentation. Intra- and inter-observer reproducibility assessments were also performed. RESULTS: Fifty-two of 76 (68%) patients showed LGE on a total of 202 slices. For accuracy, the STRM >3SD technique showed the greatest agreement with manual segmentation (ICC = 0.97, mean difference and 95% limits of agreement = 1.6 ± 10.7 g) while STRM >6SD, >5SD, 4SD and FWHM techniques systematically underestimated total LGE volume. Slice based analysis of selected SI thresholds similarly showed the STRM >3SD threshold to most closely approximate manually adjusted SI thresholds (ICC = 0.88). For reproducibility, the intra- and inter-observer reproducibility of the >3SD threshold demonstrated an acceptable mean difference and 95% limits of agreement of -0.5 ± 6.8 g and -0.9 ± 5.6 g, respectively. CONCLUSIONS: FWHM segmentation provides superior reproducibility, however systematically underestimates total LGE volume compared to manual segmentation in patients with HCM. The STRM >3SD technique provides the greatest accuracy while retaining acceptable reproducibility and may therefore be a preferred approach for LGE quantification in this population.

Delayed efficient anticoagulation with heparin in patients with a weight of 110 kg and more treated for acute coronary syndrome.

OBJECTIVE: The use of a weight-based nomogram is considered as standard care for prescribing appropriate doses of unfractionated heparin (UFH). Because of the need for multiple other medications that may affect bleeding and that clinical data have relied on similar dosing algorithms, maximum initial bolus and infusion rates have been suggested (capped initial dose). Whether these weight-based heparin nomograms properly address therapeutic dosing in obese patients remains questionable. DESIGN AND METHODS: Thirty patients treated for acute coronary syndrome and weighing ≥110 kg were retrospectively compared with 90 controls (three groups of 30 patients, weighting 50-69.9, 70-89.9, or 90-109.9 kg), all treated with UFH, July 2008 to April 2009. The primary end point was the time required to obtain a threshold activated partial thromboplastin time (aPTT). RESULTS: Mean time to achieve threshold aPTT was longer for obese patients weighing ≥110 kg than for controls (31.47 vs. 12.89 hours; P < 0.0001). At 24 hours, 63% of obese patients weighing ≥110 kg had not reached threshold aPTT vs. 7% of controls (P < 0.0001). However, threshold infusion rate did not differ between weight categories (13.0 vs. 13.1 U/kg/h; P = NS) and approximated the initial infusion rate recommended by nomograms without applying the dose cap (12 U/kg/h). CONCLUSIONS: Adequate anticoagulation time doubled in patients weighing ≥110 kg, suggesting that these patients were not receiving appropriate heparin doses initially to achieve threshold aPTT rapidly. Using initial infusion rate recommended by a nomogram without capping for total body weight is suggested as acceptable in this study. This approach should be further evaluated in a prospective study.

Biorhythm theory does not predict admission for acute myocardial infarction.

OBJECTIVES: Temporal variations in the incidence of acute myocardial infarction (AMI) have been described. However, AMI occurrence and biorhythm theory, which proposes the existence of three endogenous independent infradian cycles and AMI occurrence, has not been well studied. The purpose of this study is to determine whether specific days in the biorhythm cycles are related to AMI incidence. MEASURES: Patients (40-85 years old) admitted for AMI at the Sherbrooke University Hospital Center, 1993-2008 were subjects of this study. Potential vulnerable days and performance days of the biorhythm cycles were calculated using birth and admission dates from the warehouse database. Observed AMI frequencies were compared to those expected using χ² tests. RESULTS: There were 11,395 admissions for AMI. No relation was noted between single, double, or triple critical or noncritical days and AMI (χ² = 3.78; p > 0.05). Observed and expected AMI frequencies for maximal and minimal performance days were similar (χ² = 15.06; p > 0.05). CONCLUSIONS: We found no evidence for a possible relationship between the date of AMI and critical maximum and minimum performance days of an individual's physical, emotional, or intellectual biorhythm cycles. We conclude that biorhythm theory does not predict admission for AMI.