Serum levels of Growth Arrest-Specific 6 protein and soluble AXL in patients with ST-segment elevation myocardial infarction.

BACKGROUND: Serum soluble AXL (sAXL) and its ligand, Growth Arrest-Specific 6 protein (GAS6), intervene in tissue repair processes. AXL is increased in end-stage heart failure, but the role of GAS6 and sAXL in ST-segment elevation myocardial infarction (STEMI) is unknown. OBJECTIVES: To study the association of sAXL and GAS6 acutely and six months following STEMI with heart failure and left ventricular remodelling. METHODS: GAS6 and sAXL were measured by enzyme-linked immunosorbent assay at one day, seven days and six months in 227 STEMI patients and 20 controls. Contrast-enhanced magnetic resonance was performed during admission and at six months to measure infarct size and left ventricular function. RESULTS: GAS6, but not sAXL, levels during admission were significantly lower in STEMI than in controls. AXL increased progressively over time (p<0.01), while GAS6 increased only from day 7. GAS6 or sAXL did not correlate with brain natriuretic peptide or infarct size. However, patients with heart failure (Killip >1) had higher values of sAXL at day 1 (48.9±11.9 vs. 44.0±10.7 ng/ml; p<0.05) and at six months (63.3±15.4 vs. 55.9±13.7 ng/ml; p<0.05). GAS6 levels were not different among subjects with heart failure or left ventricular remodelling. By multivariate analysis including infarct size, Killip class and sAXL at seven days, only the last two were independent predictors of left ventricular remodelling (odds ratio 2.24 (95% confidence interval: 1.08-4.63) and odds ratio 1.04 (95% confidence interval: 1.00-1.08) respectively). CONCLUSION: sAXL levels increased following STEMI. Patients with heart failure and left ventricular remodelling have higher sAXL levels acutely and at six month follow-up. These findings suggest a potential role of the GAS6-AXL system in the pathophysiology of left ventricular remodelling following STEMI.

Coronary computed tomographic angiography findings and their therapeutic implications in asymptomatic patients with familial hypercholesterolemia. Lessons from the SAFEHEART study.

BACKGROUND: Familial hypercholesterolemia (FH) confers an increased risk of premature atherosclerotic disease. Coronary computed tomographic angiography (CTA) can assess preclinical coronary atherosclerosis. OBJECTIVES: To describe coronary CTA findings in asymptomatic molecularly defined FH individuals, to identify those factors related to its presence and extension, and to assess the impact of these results in patients' care and estimated risk. METHODS: Four hundred and forty individuals with FH, without clinical cardiovascular disease, were consecutively enrolled and underwent a coronary CTA that was used to analyze coronary atherosclerosis based on coronary calcium score (CCS), sum of stenosis severity, and plaque composition sum (PCS). For FH patients, cardiovascular risk was estimated using the specific SAFEHEART risk equation. Follow-up was performed using a standardized protocol. RESULTS: Mean age was 46.4 years (231 women, 52%). Coronary calcium was present in 55%, mean CCS was 130.9, 46% had a plaque with lumen involvement, and mean PCS was 1.1. During follow-up, there were 17 (4%) nonfatal events and 2 (1%) fatal events. CCS was independently associated to the estimated risk and low-density lipoprotein-cholesterol life-years, sum of stenosis severity to the estimated risk, and PCS to the estimated risk and low-density lipoprotein-cholesterol life-years. CTA findings induced a positive change in patients' care and in their estimated risk. CONCLUSION: Coronary artery atherosclerosis is highly prevalent in asymptomatic patients with FH and it is independently associated to cardiovascular risk. More advanced disease on CTA was associated with subsequent intensification of therapy and reduction of estimated risk. Further longitudinal studies are required to know if these findings might improve the risk stratification in patients with FH.

Scar Characterization to Predict Life-Threatening Arrhythmic Events and Sudden Cardiac Death in Patients With Cardiac Resynchronization Therapy: The GAUDI-CRT Study.

OBJECTIVES: The aim of this study was to analyze whether scar characterization could improve the risk stratification for life-threatening ventricular arrhythmias and sudden cardiac death (SCD). BACKGROUND: Among patients with a cardiac resynchronization therapy (CRT) indication, appropriate defibrillator (CRT-D) therapy rates are low. METHODS: Primary prevention patients with a class I indication for CRT were prospectively enrolled and assigned to CRT-D or CRT pacemaker according to physician's criteria. Pre-procedure contrast-enhanced cardiac magnetic resonance was obtained and analyzed to identify scar presence or absence, quantify the amount of core and border zone (BZ), and depict BZ distribution. The presence, mass, and characteristics of BZ channels in the scar were recorded. The primary endpoint was appropriate defibrillator therapy or SCD. RESULTS: 217 patients (39.6% ischemic) were included. During a median follow-up of 35.5 months (12 to 62 months), the primary endpoint occurred in 25 patients (11.5%) and did not occur in patients without myocardial scar. Among patients with scar (n = 125, 57.6%), those with implantable cardioverter-defibrillator (ICD) therapies or SCD exhibited greater scar mass (38.7 ± 34.2 g vs. 17.9 ± 17.2 g; p < 0.001), scar heterogeneity (BZ mass/scar mass ratio) (49.5 ± 13.0 vs. 40.1 ± 21.7; p = 0.044), and BZ channel mass (3.6 ± 3.0 g vs. 1.8 ± 3.4 g; p = 0.018). BZ mass (hazard ratio: 1.06 [95% confidence interval: 1.04 to 1.08]; p < 0.001) and BZ channel mass (hazard ratio: 1.21 [95% confidence interval: 1.10 to 1.32]; p < 0.001) were the strongest predictors of the primary endpoint. An algorithm based on scar mass and the absence of BZ channels identified 148 patients (68.2%) without ICD therapy/SCD during follow-up with a 100% negative predictive value. CONCLUSIONS: The presence, extension, heterogeneity, and qualitative distribution of BZ tissue of myocardial scar independently predict appropriate ICD therapies and SCD in CRT patients.

Cardiac magnetic resonance-aided scar dechanneling: Influence on acute and long-term outcomes.

BACKGROUND: Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) provides tissue characterization of ventricular myocardium and scar that can be depicted as pixel signal intensity (PSI) maps. OBJECTIVE: To assess the possible benefit of guiding the ventricular tachycardia (VT) substrate mapping by integrating these PSI maps into the navigation system. METHODS: In total, 159 consecutive patients (66 ± 11 years old, 151 men [95%]) with scar-related left ventricular (LV) VT were included. VT substrate ablation used the scar dechanneling technique. A CMR-aided ablation using the PSI maps was performed in 54 patients (34%). Procedural data as well as acute and long-term outcomes were compared with those of the remaining 105 patients (66%). RESULTS: Mean procedure duration and fluoroscopy time were 229 ± 67 minutes and 20 ± 9 minutes, respectively, without significant differences between groups. Both the number of radiofrequency (RF) applications and RF delivery time were lower in the CMR-aided group (28 ± 18 applications vs 36 ± 18 applications, P = .037, and 19 ± 12 minutes vs 27 ± 16 minutes, P = .009, respectively). After substrate ablation, monomorphic VT inducibility was lower in the CMR-aided than in the control group (17 [32%] vs 53 [51%] patients, P = .022). After a mean follow-up period of 20 ± 19 months, patients from the CMR-aided group had a lower recurrence rate than those in the control group (10 patients [18.5%] vs 46 patients [43.8%], respectively, P = .002; log-rank P = .017). Multivariate analysis found that CMR-aided ablation (hazard ratio, 0.48 [95% Confirdence Interval (CI) 0.24-0.96], P = .037) was an independent predictor of recurrences. CONCLUSION: CMR-aided scar dechanneling is associated with a lower need for RF delivery, higher noninducibility rates after substrate ablation, and a higher VT-recurrence-free survival.

Central airway pathology: clinic features, CT findings with pathologic and virtual endoscopy correlation.

OBJECTIVES: To describe the imaging features of the central airway pathology, correlating the findings with those in pathology and virtual endoscopy. To propose a schematic and practical approach to reach diagnoses, placing strong emphasis on multidetector computed tomography (MDCT) findings. METHODS: We reviewed our thoracic pathology database and the central airway pathology-related literature. Best cases were selected to illustrate the main features of each disease. MDCT was performed in all cases. Multiplanar and volume-rendering reconstructions were obtained when necessary. Virtual endoscopy was obtained from the CT with dedicated software. RESULTS: Pathological conditions affecting the central airways are a heterogeneous group of diseases. Focal alterations include benign neoplasms, malignant neoplasms, and non-neoplastic conditions. Diffuse abnormalities are divided into those that produce dilation and those that produce stenosis and tracheobronchomalacia. Direct bronchoscopy (DB) visualises the mucosal layer and is an important diagnostic and therapeutic weapon. However, assessing the deep layers or the adjacent tissue is not possible. MDCT and post-processing techniques such as virtual bronchoscopy (VB) provide an excellent evaluation of the airway wall. CONCLUSION: This review presents the complete spectrum of the central airway pathology with its clinical, pathological and radiological features. TEACHING POINTS: • Dividing diseases into diffuse and focal lesions helps narrow the differential diagnosis. • Focal lesions with nodularity are more likely to correspond to tumours. • Focal lesions with stenosis are more likely to correspond to inflammatory disease. • Posterior wall involvement is the main feature in diffuse lesions with stenosis.

Identification of the potentially arrhythmogenic substrate in the acute phase of ST-segment elevation myocardial infarction.

BACKGROUND: Predicting sudden cardiac death risk in the first months after ST-segment elevation myocardial infarction (STEMI) remains challenging. OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Utility of galectin-3 in predicting post-infarct remodeling after acute myocardial infarction based on extracellular volume fraction mapping.

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 180days. 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 180days 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 6months (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 10.15ng/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.

Infarct transmurality as a criterion for first-line endo-epicardial substrate-guided ventricular tachycardia ablation in ischemic cardiomyopathy.

BACKGROUND: There is no consensus on the appropriate indications for the epicardial approach in substrate ablation of post-myocardial infarction (MI) ventricular tachycardia (VT). OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

3D delayed-enhanced magnetic resonance sequences improve conducting channel delineation prior to ventricular tachycardia ablation.

AIMS: Non-invasive depiction of conducting channels (CCs) is gaining interest for its usefulness in ventricular tachycardia (VT) ablation. The best imaging approach has not been determined. We compared characterization of myocardial scar with late-gadolinium enhancement cardiac magnetic resonance using a navigator-gated 3D sequence (3D-GRE) and conventional 2D imaging using either a single shot inversion recovery steady-state-free-precession (2D-SSFP) or inversion-recovery gradient echo (2D-GRE) sequence. METHODS AND RESULTS: We included 30 consecutive patients with structural heart disease referred for VT ablation. Preprocedural myocardial characterization was conducted in a 3 T-scanner using 2D-GRE, 2D-SSFP and 3D-GRE sequences, yielding a spatial resolution of 1.4 × 1.4 × 5 mm, 2 × 2 × 5 mm, and 1.4 × 1.4 × 1.4 mm, respectively. The core and border zone (BZ) scar components were quantified using the 60% and 40% threshold of maximum pixel intensity, respectively. A 3D scar reconstruction was obtained for each sequence. An electrophysiologist identified potential CC and compared them with results obtained with the electroanatomic map (EAM). We found no significant differences in the scar core mass between the 2D-GRE, 2D-SSFP, and 3D-GRE sequences (mean 7.48 ± 6.68 vs. 8.26 ± 5.69 and 6.26 ± 4.37 g, respectively, P = 0.084). However, the BZ mass was smaller in the 2D-GRE and 2D-SSFP than in the 3D-GRE sequence (9.22 ± 5.97 and 9.39 ± 6.33 vs. 10.92 ± 5.98 g, respectively; P = 0.042). The matching between the CC observed in the EAM and in 3D-GRE was 79.2%; when comparing the EAM and the 2D-GRE and the 2D-SSFP sequence, the matching decreased to 61.8% and 37.7%, respectively. CONCLUSION: 3D scar reconstruction using images from 3D-GRE sequence improves the overall delineation of CC prior to VT ablation.

T1 mapping: characterisation of myocardial interstitial space.

UNLABELLED: Myocardial fibrosis is always present in end-stage heart failure and is a major independent predictor of adverse cardiac outcome. Cardiac magnetic resonance (CMR) is an imaging method that permits a non-invasive assessment of the heart and has been established as the "gold standard" for the evaluation of cardiac anatomy and function, as well as for quantifying focal myocardial fibrosis in both ischaemic and non-ischaemic heart disease. However, cardiac pathologies characterised by diffuse myocardial fibrosis cannot be evaluated by late gadolinium enhancement (LGE) imaging, as there are no reference regions of normal myocardium. Recent improvements in CMR imaging techniques have enabled parametric mapping of relaxation properties (T1, T2 and T2*) clinically feasible within a single breath-hold. T1 mapping techniques performed both with and without contrast enable the quantification of diffuse myocardial fibrosis and myocardial infiltration. This article reviews current imaging techniques, emerging applications and the future potential and limitations of CMR for T1 mapping. TEACHING POINTS: • Myocardial fibrosis is a common endpoint in a variety of cardiac diseases. • Myocardial fibrosis results in myocardial stiffness, heart failure, arrhythmia and sudden death. • T1-mapping CMR techniques enable the quantification of diffuse myocardial fibrosis. • Native T1 reflects myocardial disease involving the myocyte and interstitium. • The use of gadolinium allows measurement of the extracellular volume fraction, reflecting interstitial space.

Exercise echocardiography and multidetector computed tomography for the evaluation of acute chest pain.

INTRODUCTION AND OBJECTIVES: Up to 4% of patients with acute chest pain, normal electrocardiogram, and negative troponins present major adverse cardiac events as a result of undiagnosed acute coronary syndrome. Our aim was to compare the diagnostic performance of multidetector computed tomography and exercise echocardiography in patients with a low-to-intermediate probability of coronary artery disease. METHODS: We prospectively included 69 patients with acute chest pain, normal electrocardiogram, and negative troponins who underwent coronary tomography angiography and exercise echocardiography. Patients with coronary stenosis ≥ 50% or Agatston calcium score ≥ 400 on coronary tomography angiography or positive exercise echocardiography, or with inconclusive results, were admitted to rule out acute coronary syndrome. RESULTS: An acute coronary syndrome was confirmed in 17 patients (24.6%). This was lower than the suspected 42% based on coronary tomography angiography (P<.05) and not significantly different than the suspected 29% based on the results of exercise echocardiography (P=.56). Exercise echocardiography was normal in up to 37% of patients with pathological findings on coronary tomography angiography. The latter technique provided a higher sensitivity (100% vs 82.3%; P=.21) but lower specificity (76.9% vs 88.4%; P=.12) than exercise echocardiography for the diagnosis of acute coronary syndrome, although without reaching statistical significance. Increasing the stenosis cutoff point to 70% increased the specificity of coronary tomography angiography to 88.4%, while maintaining high sensitivity. CONCLUSIONS: Coronary tomography angiography offers a valid alternative to exercise echocardiography for the diagnosis of acute coronary syndrome among patients with low-to-intermediate probability of coronary artery disease. A combination of both techniques could improve the diagnosis of acute coronary syndrome.

CMR-guided approach to localize and ablate gaps in repeat AF ablation procedure.

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.

Usefulness of contrast-enhanced cardiac magnetic resonance in identifying the ventricular arrhythmia substrate and the approach needed for ablation.

AIMS: The endocardial vs. epicardial origin of ventricular arrhythmia (VA) can be inferred from detailed electrocardiogram (ECG) analysis. However, despite its clinical usefulness, ECG has limitations. Alternatively, scarred tissue sustaining VAs can be identified by contrast-enhanced cardiac magnetic resonance (ce-CMR). The objective of this study was to determine the clinical value of analysing the presence and distribution pattern of scarred tissue in the ventricles to identify the VA site of origin and the ablation approach required. METHODS AND RESULTS: A ce-CMR study was carried out before the index ablation procedure in a cohort of 80 patients with non-idiopathic VA. Hyper-enhancement (HE) in each ventricular segment was coded as absent, subendocardial, transmural, mid-myocardial, or epicardial. The endocardial or epicardial VA site of origin was also assigned according to the approach needed for ablation. The clinical VA was successfully ablated in 77 (96.3%) patients, all of them showing HE on ce-CMR. In segments with successful ablation of the clinical ventricular tachycardia, HE was absent in 3 (3.9%) patients, subendocardial in 19 (24.7%), transmural in 36 (46.7%), mid-myocardial in 8 (10.4%), and subepicardial in 11 (14.3%) patients. Epicardial ablation of the index VA was necessary in 3 (6.1%) ischaemic and 12 (42.9%) non-ischaemic patients. The presence of subepicardial HE in the successful ablation segment had 84.6% sensitivity and 100% specificity in predicting an epicardial origin of the VA. CONCLUSION: Contrast-enhanced cardiac magnetic resonance is helpful to localize the target ablation substrate of non-idiopathic VA and also to plan the approach needed, especially in non-ischaemic patients.

Transthoracic epicardial ablation of mitral isthmus for treatment of recurrent perimitral flutter.

BACKGROUND: Perimitral flutter (PMF) is a common form of left atrial tachycardia after atrial fibrillation (AF) ablation. The mitral isthmus (MI) is the standard ablation target. However, in some cases bidirectional block cannot be achieved. OBJECTIVE: The purpose of this study was to describe the first experience using a transthoracic epicardial (TTE) approach to treat recurrent PMF after prior unsuccessful ablation. METHODS: This is a case series of four patients with recurrence of highly symptomatic drug-refractory PMF (all male, median age 55 years, 3/4 hypertensive, 2/4 persistent AF, median AF period 24 months). Three patients presented with PMF-related tachymyocardiopathy. TTE ablation of MI was performed after a median of two prior endocardial MI and coronary sinus ablation attempts, using an open-tip 3.5-mm irrigated catheter (40 W, 45ºC). Persistent bidirectional block was assessed by activation mapping and differential pacing and was achieved in all patients. RESULTS: No PMF recurrence was observed after median follow-up of 18 months (range 15-22 months; two patients without antiarrhythmic drugs and two with previously ineffective amiodarone). Left ventricular function normalized in all three patients with tachycardiomyopathy. There were no complications related to TTE approach. CONCLUSION: The present study is the first to report the feasibility of a TTE approach for highly symptomatic PMF refractory to endocardial and coronary sinus MI ablation.

Role of circulating angiotensin converting enzyme 2 in left ventricular remodeling following myocardial infarction: a prospective controlled study.

Angiotensin-converting enzyme 2 (ACE2) cleaves Angiotensin-II to Angiotensin-(1-7), a cardioprotective peptide. Serum soluble ACE2 (sACE2) activity is raised in chronic heart failure, suggesting a compensatory role in left ventricular dysfunction. Our aim was to study the relationship between sACE2 activity, infarct size, left ventricular systolic function and remodeling following ST-elevation myocardial infarction (STEMI). A contrast-enhanced cardiac magnetic resonance study was performed acutely in 95 patients with first STEMI and repeated at 6 months to measure LV end-diastolic volume index, ejection fraction and infarct size. Baseline sACE2 activities, measured by fluorescent enzymatic assay 24 to 48 hours and at 7 days from admission, were compared to that obtained in 22 matched controls. Patients showed higher sACE2 at baseline than controls (104.4 [87.4-134.8] vs 74.9 [62.8-87.5] RFU/µl/hr, p<0.001). At seven days, sACE2 activity significantly increased from baseline (115.5 [92.9-168.6] RFU/µl/hr, p<0.01). An inverse correlation between sACE2 activity with acute and follow-up ejection fraction was observed (r = -0.519, p<0.001; r = -0.453, p = 0.001, respectively). Additionally, sACE2 directly correlated with infarct size (r = 0.373, p<0.001). Both, infarct size (ß = -0.470 [95%CI:-0.691:-0.248], p<0.001) and sACE2 at 7 days (ß = -0.025 [95%CI:-0.048:-0.002], p = 0.030) were independent predictors of follow-up ejection fraction. Patients with sACE2 in the upper tertile had a 4.4 fold increase in the incidence of adverse left ventricular remodeling (95% confidence interval: 1.3 to 15.2, p = 0.027). In conclusion, serum sACE2 activity rises in relation to infarct size, left ventricular systolic dysfunction and is associated with the occurrence of left ventricular remodeling.

Enalapril and carvedilol for preventing chemotherapy-induced left ventricular systolic dysfunction in patients with malignant hemopathies: the OVERCOME trial (preventiOn of left Ventricular dysfunction with Enalapril and caRvedilol in patients submitted to intensive ChemOtherapy for the treatment of Malignant hEmopathies).

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).

Use of myocardial scar characterization to predict ventricular arrhythmia in cardiac resynchronization therapy.

AIMS: There is insufficient evidence to implant a combined cardiac resynchronization therapy (CRT) device with defibrillation capabilities (CRT-D) in all CRT candidates. The aim of the study was to assess myocardial scar size and its heterogeneity as predictors of sudden cardiac death (SCD) in CRT candidates. METHODS AND RESULTS: A cohort of 78 consecutive patients with dilated cardiomyopathy and class I indication for CRT-D were prospectively enrolled. Before CRT-D implantation, a contrast-enhanced cardiac magnetic resonance (ce-CMR) was performed. The core and border zone (BZ) of the myocardial scar were characterized and quantified with a customized post-processing software. The first appropriate implantable cardioverter defibrillator (ICD) therapy was considered as a surrogate of SCD. During a mean follow-up of 25 months (25-75th percentiles, 15-34), appropriate ICD therapy occurred in 11.5% of patients. In a multivariate Cox proportional hazards regression model for clinical and ce-CMR variables, the scar mass percentage [hazards ratio (HR) per 1% increase 1.1 (1.06-1.15), P < 0.01], the BZ mass [HR per 1 g increase 1.06 (1.04-1.09), P < 0.01], and the BZ percentage of the scar [HR per 1% increase 1.06 (1.02-1.11), P < 0.01], were the only independent predictors of appropriate ICD therapy. Receiver-operating characteristic curve analysis showed that a scar mass <16% and a BZ < 9.5 g had a negative predictive value of 100%. CONCLUSIONS: The presence, size, and heterogeneity of myocardial scar independently predict appropriate ICD therapies in CRT candidates. The ce-CMR-based scar analysis might help identify a subgroup of patients at relatively low risk of SCD.

Ischaemic postconditioning revisited: lack of effects on infarct size following primary percutaneous coronary intervention.

AIMS: To assess the short- and long-term effects of postconditioning (p-cond) on infarct size, extent of myocardial salvage, and left ventricular ejection fraction (LVEF) in a series of patients presenting with evolving ST-elevation myocardial infarction (STEMI). Previous studies have shown that p-cond during primary percutaneous coronary intervention (PCI) confers protection against ischaemia-reperfusion injury and thus might reduce myocardial infarct size. METHODS AND RESULTS: Seventy-nine patients undergoing PCI for a first STEMI with TIMI grade flow 0-1 and no collaterals were randomized to p-cond (n= 39) or controls (n= 40). Postconditioning was performed by applying four consecutive cycles of 1 min balloon inflation, each followed by 1 min deflation. Infarct size, myocardial salvage, and LVEF were assessed by cardiac-MRI 1 week and 6 months after MI. Postconditioning was associated with lower myocardial salvage (4.1 ± 7.2 vs. 9.1 ± 5.8% in controls; P= 0.004) and lower myocardial salvage index (18.9 ± 27.4 vs. 30.9 ± 20.5% in controls; P= 0.038). No significant differences in infarct size and LVEF were found between the groups at 1 week and 6 months after MI. CONCLUSION: This randomized study suggests that p-cond during primary PCI does not reduce infarct size or improve myocardial function recovery at both short- and long-term follow-up and might have a potential harmful effect.

Prevention of chemotherapy-induced left ventricular dysfunction with enalapril and carvedilol: rationale and design of the OVERCOME trial.

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.

Pulmonary sarcoidosis: typical and atypical manifestations at high-resolution CT with pathologic correlation.

Sarcoidosis is a multisystem disorder that is characterized by noncaseous epithelioid cell granulomas, which may affect almost any organ. Thoracic involvement is common and accounts for most of the morbidity and mortality associated with the disease. Thoracic radiologic abnormalities are seen at some stage in approximately 90% of patients with sarcoidosis, and an estimated 20% develop chronic lung disease leading to pulmonary fibrosis. Although chest radiography is often the first diagnostic imaging study in patients with pulmonary involvement, computed tomography (CT) is more sensitive for the detection of adenopathy and subtle parenchymal disease. Pulmonary sarcoidosis may manifest with various radiologic patterns: Bilateral hilar lymph node enlargement is the most common finding, followed by interstitial lung disease. At high-resolution CT, the most typical findings of pulmonary involvement are micronodules with a perilymphatic distribution, fibrotic changes, and bilateral perihilar opacities. Atypical manifestations, such as masslike or alveolar opacities, honeycomb-like cysts, miliary opacities, mosaic attenuation, tracheobronchial involvement, and pleural disease, and complications such as aspergillomas, also may be seen. To achieve a timely diagnosis and help reduce associated morbidity and mortality, it is essential to recognize both the typical and the atypical radiologic manifestations of the disease, take note of features that may be suggestive of diseases other than sarcoidosis, and correlate imaging features with pathologic findings to help narrow the differential diagnosis.