Background In primary angioplasty (primary percutaneous coronary intervention PPCI) for acute myocardial infarction, institutional logistical delays can increase door-to-balloon times, resulting in ...increased mortality. Methods We moved from a thrombolysis (TL) service to 24/7 PPCI for direct access and interhospital transfer in April 2004. Using autonomous ambulance diagnosis with open access to the myocardial infarction center catheter laboratory, we compared reperfusion times and clinical outcomes for the final 2 years of TL with the first 3 years of PPCI. Results Comparison was made between TL (2002-2004, n = 185) and PPCI (2004-2007, n = 704); all times are medians in minutes (interquartile range): for TL, symptom to needle 153 (85-225), call to needle 58 (49-73), first professional contact (FPC) to needle 47 (39-63), door to needle 18 (12-30) (mortality: 7.6% at 30 days, 9.2% at 1 year); for interhospital transfer PPCI (n = 227), symptom to balloon 226 (175-350), call to balloon 135 (117-188), FPC to balloon 121 (102-166), first door-to-balloon 100 (80-142) (mortality: 7.0% at 30 days, 12.3% at 1 year); for direct-access PPCI (n = 477), symptom to balloon 142 (101-238), call to balloon 79 (70-93), FPC to balloon 69 (59-82), door to balloon 20 (16-29) (mortality: 4.6% at 30 days, 8.6% at 1 year). There was no difference between direct-access PPCI and TL times for symptom to needle/balloon. Direct-access PPCI was significantly quicker for the group than in-hospital thrombolysis for door to needle/balloon times due to the lack of any long wait patients ( P < .001). Conclusions Interhospital transfer remains slow even with rapid institutional door-to-balloon times. With autonomous ambulance diagnosis and open access direct to the catheter laboratory, a median door-to-balloon time of <30 minutes day and night was achieved, and >95% of patients were reperfused within 1 hour.
We tested the hypothesis that intravenous iron improves exercise tolerance in anemic and nonanemic patients with symptomatic chronic heart failure (CHF) and iron deficiency.
Anemia is common in heart ...failure. Iron metabolism is disturbed, and administration of iron might improve both symptoms and exercise tolerance.
We randomized 35 patients with CHF (age 64 +/- 13 years, peak oxygen consumption pVO2 14.0 +/- 2.7 ml/kg/min) to 16 weeks of intravenous iron (200 mg weekly until ferritin >500 ng/ml, 200 mg monthly thereafter) or no treatment in a 2:1 ratio. Ferritin was required to be <100 ng/ml or ferritin 100 to 300 ng/ml with transferrin saturation <20%. Patients were stratified according to hemoglobin levels (<12.5 g/dl anemic group vs. 12.5 to 14.5 g/dl nonanemic group). The observer-blinded primary end point was the change in absolute pVO2.
The difference (95% confidence interval CI) in the mean changes from baseline to end of study between the iron and control groups was 273 (151 to 396) ng/ml for ferritin (p < 0.0001), 0.1 (-0.8 to 0.9) g/dl for hemoglobin (p = 0.9), 96 (-12 to 205) ml/min for absolute pVO2 (p = 0.08), 2.2 (0.5 to 4.0) ml/kg/min for pVO2/kg (p = 0.01), 60 (-6 to 126) s for treadmill exercise duration (p = 0.08), -0.6 (-0.9 to -0.2) for New York Heart Association (NYHA) functional class (p = 0.007), and 1.7 (0.7 to 2.6) for patient global assessment (p = 0.002). In anemic patients (n = 18), the difference (95% CI) was 204 (31 to 378) ml/min for absolute pVO2 (p = 0.02), and 3.9 (1.1 to 6.8) ml/kg/min for pVO2/kg (p = 0.01). In nonanemic patients, NYHA functional class improved (p = 0.06). Adverse events were similar.
Intravenous iron loading improved exercise capacity and symptoms in patients with CHF and evidence of abnormal iron metabolism. Benefits were more evident in anemic patients. (Effect of Intravenous Ferrous Sucrose on Exercise Capacity in Chronic Heart Failure; http://www.clinicaltrials.gov/ct/show/NCT00125996; NCT00125996).
Abstract Background Mechanical surrogates are used to assess fetal cardiac electrical activity. Aims To compare electrical PR interval measured using non-invasive fetal electrocardiography (fECG) ...with mechanical atrioventricular (AV) interval using Doppler. Study design and subjects Prospective study of 55 recordings made in 50 human fetuses. Those with structural heart defects, second degree or complete heart block were excluded. Outcome measures Mechanical AV interval was measured from the onset of mitral A wave to onset of aortic ejection. Electrical PR interval was measured from a coherent averaged signal obtained using non-invasive fECG recorded from the maternal abdomen. Wilcoxon signed rank test was used to compare both methods. Agreement between AV and PR intervals was assessed using linear regression and by Bland–Altman plots. Bland–Altman analysis assessed inter-observer and intra-observer variability. Results There was no significant difference in the heart rates of the 55 paired traces measured consecutively using both methods ( p < 0.35). AV interval was longer than PR (median range 116 96–169 vs. 102 75–143 ms; p < 0.001), with mean difference − 16.47 ms (95% Confidence Interval − 43.43, 10.44), reflecting the increased proportion of the cardiac cycle measured. Using fECG, PR inter-observer and intra-observer mean differences were 0.4 ms (CI − 7.29, 8.09) and 0.7 ms (CI − 3.22, 4.62) respectively. R values for inter and intra-observer studies were 0.95 and 0.99 respectively. Using Doppler methods, AV inter-observer and intra-observer mean differences were − 2.69 ms, (CI − 15.33, 9.95) and 0.92 ms, (CI − 9.41, 11.26) respectively. R values for AV measurements were 0.93 for inter-observer and 0.96 for intra-observer variation. Conclusions Non-invasive fECG is a robust tool to measure the PR interval with narrow limits of agreement.
There is a need to standardise non-invasive measurements of liver iron concentrations (LIC) so clear inferences can be drawn about body iron levels that are associated with hepatic and extra-hepatic ...complications of iron overload. Since the first demonstration of an inverse relationship between biopsy LIC and liver magnetic resonance (MR) using a proof-of-concept T2* sequence, MR technology has advanced dramatically with a shorter minimum echo-time, closer inter-echo spacing and constant repetition time. These important advances allow more accurate calculation of liver T2* especially in patients with high LIC.
Here, we used an optimised liver T2* sequence calibrated against 50 liver biopsy samples on 25 patients with transfusional haemosiderosis using ordinary least squares linear regression, and assessed the method reproducibility in 96 scans over an LIC range up to 42 mg/g dry weight (dw) using Bland-Altman plots. Using mixed model linear regression we compared the new T2*-LIC with R2-LIC (Ferriscan) on 92 scans in 54 patients with transfusional haemosiderosis and examined method agreement using Bland-Altman approach.
Strong linear correlation between ln(T2*) and ln(LIC) led to the calibration equation LIC = 31.94(T2*)-1.014. This yielded LIC values approximately 2.2 times higher than the proof-of-concept T2* method. Comparing this new T2*-LIC with the R2-LIC (Ferriscan) technique in 92 scans, we observed a close relationship between the two methods for values up to 10 mg/g dw, however the method agreement was poor.
New calibration of T2* against liver biopsy estimates LIC in a reproducible way, correcting the proof-of-concept calibration by 2.2 times. Due to poor agreement, both methods should be used separately to diagnose or rule out liver iron overload in patients with increased ferritin.
late mortality after repair of total anomalous pulmonary venous connection is frequently associated with pulmonary venous obstruction (PVO). We aimed to describe the morphological spectrum of total ...anomalous pulmonary venous connection and identify risk factors for death and postoperative PVO.
we conducted a retrospective, international, collaborative, population-based study involving all 19 pediatric cardiac centers in the United Kingdom, Ireland, and Sweden. All infants with total anomalous pulmonary venous connection born between 1998 and 2004 were identified. Cases with functionally univentricular circulations or atrial isomerism were excluded. All available data and imaging were reviewed. Of 422 live-born cases, 205 (48.6%) had supracardiac, 110 (26.1%) had infracardiac, 67 (15.9%) had cardiac, and 37 (8.8%) had mixed connections. There were 2 cases (0.5%) of common pulmonary vein atresia. Some patients had extremely hypoplastic veins or, rarely, discrete stenosis of the individual veins. Sixty (14.2%) had associated cardiac anomalies. Sixteen died before intervention. Three-year survival for surgically treated patients was 85.2% (95% confidence interval 81.3% to 88.4%). Risk factors for death in multivariable analysis comprised earlier age at surgery, hypoplastic/stenotic pulmonary veins, associated complex cardiac lesions, postoperative pulmonary hypertension, and postoperative PVO. Sixty (14.8%) of the 406 patients undergoing total anomalous pulmonary venous connection repair had postoperative PVO that required reintervention. Three-year survival after initial surgery for patients with postoperative PVO was 58.7% (95% confidence interval 46.2% to 69.2%). Risk factors for postoperative PVO comprised preoperative hypoplastic/stenotic pulmonary veins and absence of a common confluence.
preoperative clinical and morphological features are important risk factors for postoperative PVO and survival.
Objectives In this pre-specified subanalysis of the SENIORS (Study of Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors With Heart Failure) trial, which examined the ...effects of nebivolol in elderly heart failure (HF) patients, we explored the effects of left ventricular ejection fraction (EF) on outcomes, including the subgroups impaired EF (≤35%) and preserved EF (>35%). Background Beta-blockers are established drugs in patients with HF and impaired EF, but their value in preserved EF is unclear. Methods We studied 2,111 patients; 1,359 (64%) had impaired (≤35%) EF (mean 28.7%) and 752 (36%) had preserved (>35%) EF (mean 49.2%). The effect of nebivolol was investigated in these 2 groups, and it was compared to explore the interaction of EF with outcome. Follow-up was 21 months; the primary end point was all-cause mortality or cardiovascular hospitalizations. Results Patients with preserved EF were more often women (49.9% vs. 29.8%) and had less advanced HF, more hypertension, and fewer prior myocardial infarctions (all p < 0.001). During follow-up, the primary end point occurred in 465 patients (34.2%) with impaired EF and in 235 patients (31.2%) with preserved EF. The effect of nebivolol on the primary end point (hazard ratio HR of nebivolol vs. placebo) was 0.86 (95% confidence interval: 0.72 to 1.04) in patients with impaired EF and 0.81 (95% confidence interval: 0.63 to 1.04) in preserved EF (p = 0.720 for subgroup interaction). Effects on all secondary end points were similar between groups (HR for all-cause mortality 0.84 and 0.91, respectively), and no p value for interaction was <0.48. Conclusions The effect of beta-blockade with nebivolol in elderly patients with HF in this study was similar in those with preserved and impaired EF.
We hypothesized that fibrosis detected by late gadolinium enhancement (LGE) cardiovascular magnetic resonance predicts outcomes in patients with transposition of the great arteries post atrial ...redirection surgery. These patients have a systemic right ventricle (RV) and are at risk of arrhythmia, premature RV failure, and sudden death.
Fifty-five patients (aged 27±7 years) underwent LGE cardiovascular magnetic resonance and were followed for a median 7.8 (interquartile range, 3.8-9.6) years in a prospective single-center cohort study. RV LGE was present in 31 (56%) patients. The prespecified composite clinical end point comprised new-onset sustained tachyarrhythmia (atrial/ventricular) or decompensated heart failure admission/transplantation/death. Univariate predictors of the composite end point (n=22 patients; 19 atrial/2 ventricular tachyarrhythmia, 1 death) included RV LGE presence and extent, RV volumes/mass/ejection fraction, right atrial area, peak Vo(2), and age at repair. In bivariate analysis, RV LGE presence was independently associated with the composite end point (hazard ratio, 4.95 95% confidence interval, 1.60-15.28; P=0.005), and only percent predicted peak Vo(2) remained significantly associated with cardiac events after controlling for RV LGE (hazard ratio, 0.80 95% confidence interval, 0.68-0.95; P=0.009/5%). In 8 of 9 patients with >1 event, atrial tachyarrhythmia, itself a known risk factor for mortality, occurred first. There was agreement between location and extent of RV LGE at in vivo cardiovascular magnetic resonance and histologically documented focal RV fibrosis in an explanted heart. There was RV LGE progression in a different case restudied for clinical indications.
Systemic RV LGE is strongly associated with adverse clinical outcome especially arrhythmia in transposition of the great arteries, thus LGE cardiovascular magnetic resonance should be incorporated in risk stratification of these patients.
•Dabrafenib monotherapy or combination with trametinib showed preliminary evidence of clinical efficacy in BRAF V600–mutant pediatric LCH.•The safety profile in pediatric BRAF V600–mutant LCH was ...similar to that observed in solid tumors in adults.
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Langerhans cell histiocytosis (LCH) is a rare, heterogenous, neoplastic disorder primarily affecting children. BRAF mutations have been reported in >50% of patients with LCH. The selective BRAF inhibitor, dabrafenib, in combination with the MEK1/2 inhibitor, trametinib, has been approved in select BRAF V600–mutant solid tumors. Two open-label phase 1/2 studies were conducted in pediatric patients with BRAF V600–mutant, recurrent/refractory malignancies treated with dabrafenib monotherapy (CDRB436A2102; NCT01677741) or dabrafenib plus trametinib (CTMT212X2101; NCT02124772). The primary objectives of both studies were to determine safe and tolerable doses that achieve similar exposure to the approved doses for adults. Secondary objectives included safety, tolerability, and preliminary antitumor activity. Thirteen and 12 patients with BRAF V600–mutant LCH received dabrafenib monotherapy and in combination with trametinib, respectively. Investigator-assessed objective response rates per Histiocyte Society criteria were 76.9% (95% confidence interval CI, 46.2-95.0) and 58.3% (95% CI, 27.7-84.8) in the monotherapy and combination studies, respectively. More than 90% of responses were ongoing at study completion. The most common treatment-related adverse events (AEs) were vomiting and increased blood creatinine with monotherapy and pyrexia, diarrhea, dry skin, decreased neutrophil count, and vomiting with combination therapy. Two patients each discontinued treatment with monotherapy and combination therapy because of AEs. Overall, dabrafenib monotherapy or in combination with trametinib demonstrated clinical efficacy and manageable toxicity in relapsed/refractory BRAF V600–mutant pediatric LCH, with most responses ongoing. Safety was consistent with that reported in other pediatric and adult conditions treated with dabrafenib plus trametinib.
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