Objectives This study sought to evaluate the efficacy of enalapril and carvedilol to prevent chemotherapy-induced left ventricular systolic dysfunction (LVSD) in patients with hematological ...malignancies. Background Current chemotherapy may induce LVSD. Angiotensin-converting enzyme inhibitors and beta-blockers prevent LVSD in animal models of anthracycline-induced cardiomyopathy. Methods In this randomized, controlled study, 90 patients with recently diagnosed acute leukemia (n = 36) or patients with malignant hemopathies undergoing autologous hematopoietic stem cell transplantation (HSCT) (n = 54) and without LVSD were randomly assigned to a group receiving enalapril and carvedilol (n = 45) or to a control group (n = 45). Echocardiographic and cardiac magnetic resonance (CMR) imaging studies were performed before and at 6 months after randomization. The primary efficacy endpoint was the absolute change from baseline in LV ejection fraction (LVEF). Results The mean age of patients was 50 ± 13 years old, and 43% were women. At 6 months, LVEF did not change in the intervention group but significantly decreased in controls, resulting in a −3.1% absolute difference by echocardiography (p = 0.035) and −3.4% (p = 0.09) in the 59 patients who underwent CMR. The corresponding absolute difference (95% confidence interval CI) in LVEF was −6.38% (95% CI: −11.9 to −0.9) in patients with acute leukemia and −1.0% (95% CI: −4.5 to 2.5) in patients undergoing autologous HSCT (p = 0.08 for interaction between treatment effect and disease category). Compared to controls, patients in the intervention group had a lower incidence of the combined event of death or heart failure (6.7% vs. 22%, p = 0.036) and of death, heart failure, or a final LVEF <45% (6.7% vs. 24.4%, p = 0.02). Conclusions Combined treatment with enalapril and carvedilol may prevent LVSD in patients with malignant hemopathies treated with intensive chemotherapy. The clinical relevance of this strategy should be confirmed in larger studies. (Prevention of Left Ventricular Dysfunction During Chemotherapy OVERCOME; NCT01110824 )
Predicting sudden cardiac death risk in the first months after ST-segment elevation myocardial infarction (STEMI) remains challenging.
The purpose of this study was to investigate the ability of late ...gadolinium enhancement cardiac magnetic resonance (LGE-CMR) to identify the potentially arrhythmogenic substrate and its temporal evolution after STEMI.
One hundred consecutive patients with a first STEMI were included. Three-dimensional high-resolution LGE-CMR was obtained at 3 T on days 7 and 180. Left ventricular wall was segmented and characterized by pixel signal intensity algorithm in 5 layers from endocardium to epicardium. A 3-dimensional color-coded shell map was obtained for each layer, depicting scar core and border zone (BZ) distribution. Presence and characteristics of BZ channels were registered for each layer.
At 180 days, left ventricular ejection fraction had improved significantly (from 46.7% ± 10% to 51.5% ± 10%; P <.001) and scar mass was reduced (from 22.6 ± 20 g to 13.8 ± 12 g; P <.001). Most BZ channels (89%) were identified in the same myocardial layer and American Heart Association (AHA) segment, with the same orientation and morphology in both studies. Early LGE-CMR had 96% sensitivity and 90% specificity for predicting presence of BZ channels at 180 days. Greater presence was observed in patients with no-reflow phenomenon at baseline (P = .01).
Most BZ channels can be identified by LGE-CMR at day 7 post-STEMI and, despite scar mass reduction, remain unaltered at 6 months, suggesting that the potentially arrhythmogenic substrate is established within the first week post-STEMI.
Abstract Objectives The aim of this study was to test the feasibility and usefulness of a new delayed-enhancement cardiac magnetic resonance (DE-CMR)–guided approach to ablate gaps in redo ...procedures. Background Recurrences of atrial fibrillation (AF) after pulmonary vein isolation (PVI) may be related to gaps at the ablation lines. DE-CMR allows identification of radiofrequency lesions and gaps (CMR gaps). Methods Fifteen patients undergoing repeated AF ablations were included (prior procedure was PVI in all patients and roof-line ablation in 8 patients). Pre-procedure 3-dimensional (3D) DE-CMR was performed with a respiratory-navigated (free-breathing) and electrocardiographically gated inversion-recovery gradient-echo sequence (voxel size 1.25 × 1.25 × 2.5 mm). Endocardium and epicardium were manually segmented to create a 3D reconstruction (DE-CMR model). A pixel signal intensity map was projected on the DE-CMR model and color-coded (thresholds 40 ± 5% and 60 ± 5% of maximum intensity). The DE-CMR model was imported into the navigation system to guide the ablation of CMR gaps, with the operator blinded to electrical data. Fifteen conventional procedures were used as controls to compare procedural duration, radiofrequency, and fluoroscopy times. Results Fifteen patients (56 pulmonary veins PVs; 57 ± 8 years of age; 9 with paroxysmal AF) were analyzed. In total, 67 CMR gaps were identified around PVs (mean 4.47 gaps/patient; median length 13.33 mm/gap) and 9 at roof line. All of the electrically reconnected PVs (87.5%) had CMR gaps. The site of electrical PV reconnection (assessed by circular mapping catheter) matched with a CMR gap in 79% of PVs. CMR-guided ablation led to reisolation of 95.6% of reconnected PVs (median radiofrequency time of 13.3 interquartile range: 7.5 to 21.7 min/patient) and conduction block through the roof line in all patients (1.4 interquartile range: 0.7 to 3.1 min/patient). Compared with controls, the CMR-guided approach shortened radiofrequency time (1,441 ± 915 s vs. 930 ± 662 s; p = 0.026) but not the procedural duration or fluoroscopy time. Conclusions DE-CMR can successfully guide repeated PVI procedures by accurately identifying and localizing gaps and may reduce procedural duration and radiofrequency application time.
There is no consensus on the appropriate indications for the epicardial approach in substrate ablation of post-myocardial infarction (MI) ventricular tachycardia (VT).
The purpose of this study was ...to investigate whether infarct transmurality (IT) could identify patients who would benefit from a combined first-line endo-epicardial approach.
Before ablation, IT was assessed by contrast-enhanced cardiac magnetic resonance imaging (hyperenhancement ≥75% of the wall thickness in ≥1 segment), echocardiography (dyskinesia/akinesia + hyperrefringency + wall thinning), computed tomography (wall thinning), or scintigraphy (transmural necrosis). Prospectively from January 2011, an endocardial approach was used in patients with subendocardial MI (group 1) and a combined endo-epicardial approach in patients with transmural MI (group 2). Outcomes in both groups were compared with those in patients with transmural MI and only endocardial approach due to previous cardiac surgery or procedure performed before January 2011 (group 3). The primary end point was VT/ventricular fibrillation recurrence-free survival.
Ninety patients (92.2% men; mean age 67.4 ± 9.8 years) undergoing VT substrate ablation were included: group 1, n = 34; group 2, n = 24; group 3, n = 32. During a mean follow-up duration of 22.5 ± 13.7 months, 5 patients in group 1 (14.7%), 3 patients in group 2 (12.5%), and 13 patients in group 3 (40.6%) had VT recurrences (P = .011). Time to recurrence was the shortest in group 3 (log-rank, P = .018). The endocardial approach in patients with transmural MI was associated with an increased risk of recurrence (hazard ratio 4.01; 95% confidence interval 1.41-11.3; P = .009).
The endocardial approach in patients with transmural MI undergoing VT substrate ablation is associated with an increased risk of recurrence. IT may be a useful criterion for the selection of a first-line combined endo-epicardial approach.
Abstract Aims ST-segment elevation myocardial infarction (STEMI) triggers remote extracellular matrix expansion. Myocardial extracellular volume fraction (ECV), determined by cardiovascular magnetic ...resonance, permits quantification of interstitial space expansion. Our aim was to determine the relationship between early serum fibrosis biomarkers and 180-day post-infarct remote myocardium remodeling using ECV. Methods and results In 26 patients with STEMI, functional imaging, T1-mapping, and late-gadolinium-enhancement were performed on a 3-T CMR scanner at baseline (days 3 to 5) and 180 days. Biomarkers were measured at days 1, 3, and 7 after STEMI. The mean initial and follow-up left ventricular ejection fraction (LVEF) were 48.3 ± 18.1% and 52.6 ± 12.3%, respectively. Initial infarct size was 11.6 ± 16.8% of LV mass. ECV in the remote myocardium at 180 days correlated with indexed end-systolic volume (r = 0.4, p = 0.045). A significant correlation was observed between galectin-3 at day 7 and ECV at 6 months (r = 0.428, p = 0.037). A trend towards a direct correlation was found for BNP (r = 0.380, p = 0.059). Multivariate analysis revealed that BNP and galectin-3 were independent predictors of long-term changes in ECV and explained nearly 30% of the variance in this parameter (r2 = 0.34; p = 0.01). A galectin-3 cutoff value of 10.15 ng/mL was the most powerful predictor of high ECV values (≥ 28.5%) at follow-up. Galectin-3 at day 7 was an independent predictor of high ECV values at follow-up (OR = 22.51; CI
95%: 2.1–240.72; p = 0.01) with 0.76 AUC (CI: 0.574–0.964; p = 0.03). Conclusions Galectin-3 measured acutely after STEMI is an independent predictor of increased ECV at 6-month follow-up that might be useful for long-term risk stratification.
Catheter contact force (CF) has a strong correlation with lesion formation during radiofrequency ablation. Delayed-enhancement cardiac magnetic resonance (DE-CMR) provides lesion information in ...patients with prior atrial fibrillation (AF) ablation.
The aim of this study was to determine the CF threshold to create permanent lesions detected by DE-CMR.
A total of 36 patients referred for AF ablation were included. A CF catheter was used during the ablation procedure, and DE-CMR was performed 3 months after the ablation procedure. Eighteen pulmonary vein (PV) segments were defined, and 3-dimensional (3D) reconstructions of the left atrium (LA) derived from the DE-CMR images were obtained. One observer evaluated the presence of any discontinuity of previous ablation lesions (gap) in the 3D reconstructions of the LA, and another observer (blinded to the gap findings) determined the minimum CF value in each PV segment.
The PV segments where a gap was observed had a lower maximal CF value than did the segments without gap in the 3D LA reconstructions (6.7 ± 4.4 g vs 12.2 ± 4.7 g; P < .001). In receiver operating characteristic analysis, a CF threshold of >8 g provided 73% sensitivity and 81% specificity in the prediction of a complete PV lesion (positive predictive value PPV 84%). A CF threshold of >12 g had a specificity of 94% and increased the PPV to 91% in creating a complete lesion in the LA wall (area under the curve 0.834).
A CF threshold of >12 g H5H20 predicts a complete lesion with high specificity and PPV when a dragging ablation strategy is used in AF ablation.
Abstract Background The current treatment of hematologic malignancies includes diverse potentially cardiotoxic chemotherapy agents, including high-dose myeloablative regimens used in autologous ...hematopoietic stem cell transplantation (HSCT). Many of these treatments could induce left ventricular dysfunction (LVD), and limit their efficacy. Angiotensin-converting enzime inhibitors and beta-blockers prevent LVD and prolong survival after infarction, and recent animal and pilot clinical studies suggest that they can prevent the development of chemotherapy-induced cardiac toxicity. Methods This is a prevention, parallel-assignment, randomized, controlled, clinical efficacy study. Ninety patients recently diagnosed of acute leukemia or undergoing autologous HSCT and with normal LV ejection fraction will be randomized to enalapril and carvedilol or to the control group. Echocardiogram and a cardiac magnetic resonance imaging studies will be performed at baseline and 6–9 months after randomization. The primary efficacy endpoint is the change from baseline in LV ejection fraction. Secondary endpoints include the assessment of LV volumes and diastolic function, and the incidence of death, heart failure, or LVD. Conclusions The OVERCOME study will be the first clinical trial to test the preventive efficacy on LVD of combined treatment with enalapril and carvedilol administered to patients with hematologic malignancies submitted to current treatment with intensive chemotherapy.
Shortening symptom-to-reperfusion time improves prognosis in patients with ST-segment elevation myocardial infarction. Accordingly, current guidelines target a door-to-balloon time <90 minutes, ...irrespective of symptom-to-door time; nevertheless, the relation between door-to-balloon and symptom-to-door time and its potential impact on myocardial salvage remains largely unknown. We investigated the influence of door-to-balloon guideline fulfillment on myocardial salvage in patients presenting with different symptom-to-door times. Contrast-enhanced magnetic resonance study was performed acutely to measure infarct size in 172 patients admitted for primary percutaneous coronary intervention of their first ST-segment elevation myocardial infarction to 2 tertiary hospitals. The Bari score was adapted to quantify the angiographic area at risk, and the myocardial salvage index (MSI) was computed as percent area at risk that spared necrosis. Increased symptom-to-balloon time was associated with a significant decrease in MSI only within the first 5 hours (p <0.001). Accomplishment of a target door-to-balloon <90 minutes was associated with a significant increase in MSI only in patients presenting within the first hour of symptom onset (48.5 ± 30.9 vs 29.6 ± 22.3%, p <0.05). Achieving a door-to-balloon time <60 minutes further increased MSI in patients presenting within the second hour of symptoms (43.5 ± 8.6 vs 26.3 ± 20.5%, p <0.01). In conclusion, myocardial salvage progressively decreases up to 5 hours after symptom onset. However, the benefit of the recommended door-to-balloon time appears to be confined to patients presenting within 1 hour of symptom onset.
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