ORAL ABSTRACT SESSION: RISK PREDICTORS BEYOND LVEF + ECG

570
Can serologic markers of fibrosis predict future shocks in icd recipients with dilated cardiomyopathy?

Abstract

Purpose: We investigated prospectively whether serum markers of collagen turnover could be used as predictors for the occurrence of malignant ventricular arrhythmias in patients with non-ischemic dilated cardiomyopathy (NIDC) implanted with an implantable cardioverter defibrillator (ICD) for primary prevention. Extracellular matrix (ECM) alterations in NIDC may provide electrical heterogeneity, thus potentially contributing to the occurrence of ventricular arrhythmia and subsequent SCD.

Methods: Serum C-terminal propeptide of collagen type-I (CICP), C-terminal telopeptide of collagen type-I (CITP), matrix metalloproteinase (MMP)-1, and tissue inhibitor of matrix metalloproteinases (TIMP)-1 were measured as markers of collagen synthesis and degradation in 70 patients with mildly to moderate symptomatic heart failure due to NIDC with LVEF <35%, who received an ICD for primary prevention of SCD. Patients were evaluated for any appropriate ICD delivered therapy, whether shock or antitachycardia pacing, during a 1-year follow-up period.

Results: Appropriate device therapies were delivered in 14 of the 70 patients during the follow-up period, with antitachycardia pacing in 2, antitachycardia pacing with shocks in 4, and shocks in 8. Preimplantation MMP-1 levels were significantly higher in patients who had appropriate ICD-delivered therapy than in those who did not have any therapy (27.7±1.6 ng/ml vs. 24.1±2.5 ng/ml, respectively, p<0.001). The same was true for baseline serum concentrations of TIMP-1 and CITP (89±14 ng/ml vs. 58±18 ng/ml, p=0.008 and 0.46±0.19 ng/ml vs. 0.19±0.07 ng/ml, p<0.001, respectively).

Conclusions: Undoubtedly, ECM alterations play a crucial role in the constitution of an arrhythmogenic substrate in NIDC and, given the availability of therapies to prevent fatal ventricular tachyarrhythmias, the quest for factors that have a very good correlation with appropriate ICD discharges in these patients is logical. Our results confirm the role of serum markers of collagen turnover as predictors of arrhythmic events in ICD recipients and could provide an auxiliary tool in this context.

571
Left atrial fibrosis quantification by late gadolinium enhancement MRI: can we find the optimal normalized thresholds

Abstract

Background: Late gadolinium enhancement MRI (LGE-MRI) is a promising technique to assess left atrial fibrosis. However, most studies have been carried out in AF patients and have failed in providing reproducible thresholds for atrial fibrosis.

Our aim was to set an atrial healthy tissue and dense scar threshold in a cohort of healthy volunteers and post-AF ablation patients.

Methods: ECG- and respiratory gated 3 Tesla LGE-MRI was performed in 10 healthy volunteers (20-25 years) and 10 patients with a previous pulmonary vein isolation procedure. Local Image Intensity Ratio (IIR) was calculated as absolute pixel intensity divided by mean blood pool intensity. IIR up to mean+2 standard deviations in healthy volunteers was considered normal. Scarring was defined as IIR > 60% of the maximum intensity pixel (MIP) in AF-ablated patients.

Results: Left atrial intensity histograms differed in both groups (Figure). Pixel intensity distribution in post-ablation patients showed a longer right tale (skewness 0.045±0.08 vs 1.052±0.08, volunteers vs post-ablation patients). Upper normality threshold was IIR=1.20 (mean+2SD in healthy volunteers). IIR values higher than 1.35 (60% of MIP in post-ablation patients) were considered as dense scar. IIR values between 1.2 and 1.35 identify interstitial fibrosis.

Conclusion: For the first time, we describe the healthy atrial tissue LGE-MRI threshold in healthy individuals (IIR<1.2). Higher values identify variable degrees of fibrosis. Our results provide a consistent, comparable and normalized tool to guide AF therapy

572
Identification of the arrhythmogenic substrate in acute phase of STEMI

Abstract

Introduction: A 3D reconstruction of the contrast enhanced-cardiac magnetic resonance (ce-CMR) allows visualization of scar and border zone (BZ) channels. BZ channels have been identified as critical isthmuses of ventricular tachycardia (VT). We hypothesized that this arrhythmogenic substrate could be identified in the acute phase of a ST elevation myocardial infarction (STEMI).

Methods: Consecutive patients with STEMI and primary percutaneous coronary intervention were included. A 3D high-resolution 3T ce-CMR was obtained within the first 6 days and at 6 month. LV volumes and left ventricular ejection fraction (LVEF) were measured. The LV wall was segmented and characterized using a pixel signal intensity algorithm at 10 myocardial layers. A 3D color-coded shell map was obtained for each layer to depict the scar core and BZ distribution. The presence/characteristics of BZ channels were registered for each layer in both studies. Myocardial scar was classified as arrhythmogenic if BZ channels were present.

Results: 63 patients (48 male, 58.08 ± 11.7 years) were included. LVEF and LV end diastolic volume increased significantly at 6 months. 38 BZ channels were present baseline and 31 of them (81.6%) were present in the same segment/orientation at 6 days and 6 months (Figure 1). 28 (44.4%) patients were classified as having arrhythmogenic scar at baseline and 24 (85.7%) persisted at 6 months. The only 2 patients with VA had BZ channels in the acute phase of STEMI.

Conclusions: Ce-CMR can identify BZ channels in acute phase of STEMI that persist visible in the healed infarction, suggesting its usefulness for sudden cardiac death risk stratification.

574
Noninvasive epi/endocardial mapping of ventricular arrhythmias

Abstract

Purpose: The aim of this study was to map the activation patterns of ventricular arrhythmias using noninvasive ECG imaging (ECGI).

Methods: We studied 15 patients undergoing an invasive electrophysiology study. Ventricular arrhythmias were induced in 8 patients (4 ischemic and 4 non-ischemic patients) by programmed ventricular stimulation. 224 electrodes and the defibrillation patches were applied to the patient's torso. Pre-procedural computed tomography imaging of the heart and torso was performed for each patient in order to determine cardiac anatomy and body surface electrode positions. This was followed by epi/endocardial surface rendering of both ventricles. During tachycardia the surface ECGs were recorded and approximately 5000 local unipolar electrograms on the ventricular epicardium and endocardium were reconstructed. The phase of the unipolar electrogram at each point was calculated using the Hilbert transform and a phase map was reconstructed using the AMYCARD 01C system (EP Solutions SA, Switzerland).

Results: VF/PMVT was induced in all non-ischemic patients, whereas only monomorphic ventricular tachycardia was inducible in ischemic patients. Epicardial activation patterns were observed in all non-ischemic patients, typically with a low number of phase singularities. In some cases, VF/PMVT was driven by a single reentrant wave spreading through the epicardium for several cycles; in other cases the dominant migrating rotor divided into several wavelets (Fig.).

Conclusions: Noninvasive ECGI in patients with VF/PMVT demonstrates that rotors and multiple wavelets can be observed simultaneously. Further studies are needed to investigate these findings and define targets for mechanism-based therapy of VF.

Spiral wave broken up to multiple waves

575
Focal hypermetabolic left ventricular cardiomyopathy: an underdiagnosed life-threatening arrhythmogenic disease

Abstract

Introduction: Cardiac sarcoidosis (CS) may be misinterpreted as an ARVC. The prevalence of isolated CS in pts referred for the ablation of ventricular arrhythmias (VAs) remains undetermined.

Method: Pts with VAs addressed for ablation underwent a comprehensive work-up starting with a coronary angiography (CA) and CMR. Those displaying normal CA but delayed enhancement (DE) within the left ventricle (LV) underwent a FDG-PET. Pts exhibiting focal hypermetabolic LV activity had a pulmonary and blood screening (autoantibodies, TB spot, sedimentation rate, CRP, plasmatic conversion enzyme activity).

Results: Over a 2-y period, 59 pts were addressed for symptomatic VAs ablation. Of these, 14 pts (24%, 56±13 yo, 10 males, LVEF 44±10%) displaying a focal hypermetabolic LV activity at FDG-PET underwent the comprehensive work-up. The immunologic, infectious and plasmatic screenings were within the normal limits, except for a positive TB-spot in 2 cases. LV biopsies (n=10) were abnormal in only 4 cases (29%); one showing lymphocytes and the others showing fibrosis, none with granuloma. The figure below shows an example of septal and lateral DE at CMR (A) and focal hypermetabolic LV activity at FDG-PET (B). Although unproven, isolated CS was suspected, which was treated in 9 pts (Prednisone, then Methotrexate sc). Focal hypermetabolic LV activity was erased in 5/9 (67%) and strongly reduced in 3/9 (33%) pts (C). Two pts required treatment of TB before immunosuppression.

Conclusion: In pts with symptomatic complex VAs, a comprehensive work-up based on CMR and FDG-PET identified a high proportion of focal hypermetabolic LV activity suggestive of isolated CS. There were no blood markers, but immunosuppressive therapy strongly reduced the hypermetabolic activity

576
‘islets’ of heterogenous myocardium within the scar predict ventricular tachycardia after myocardial infarction

Abstract

Purpose: High risk of sudden cardiac death(SCD) after prior MI has been identified mainly by the ejection fraction of left ventricle (LVEF) so far. The aim of this study was to find (an)other parameter(s) that could precisely evaluate the real SCD risk.

Methods: A group of 40 patients after prior MI were enrolled into the study and divided into 2 groups: with (A) (n=19) and without (B) (n=21) ventricular tachycardia (VT). In group A VT was confirmed in electrophysiological study, in group B there was no evidence of ventricular tachyarrhythmia in ECG monitoring. All of the patients had cardiac magnetic resonance (CMR) performed within 18±3 months after MI with evaluation of late gadolinium-enhancement within left ventricle (LV) muscle.

Results: Patients did not differ significantly in age (61,5±13,0y vs. 64,1±6,8y; p=0,86) and LVEF (33,9±11,7% vs. 37,2±9,6%; p=0,28) between groups. We found out that the only parameter that correlated with VT occurrence was the volume percentage of "islets" defined as small areas of heterogenous myocardium within or adjacent to the scar tissue that needed to have any connection to the rest of health myocardium (0,55±0,39% vs. 0,22±0,21%; p=0,02). We revealed no significant influence on the VT occurrence with all of the other parameters measured in CMR such as: scar volume, percentage of the scar in the heart muscle, number of LV segments with transmural and non-transmural scar, LV diameter, LV end-diastolic volume, LV mass, LV volume.

Conclusions: Among patients with prior MI “islets” of heterogenous myocardium within or adjacent to the scar tissue may form a substrate for ventricular tachycardia reentry loop. Finding and calculating the percentage of such “islets” may be probably a useful parameter to distinguish patients with preserved LVEF and risk of ventricular tachyarrhythmia, who would benefit from ICD.

577
Predictive role of circulating endothelial-derived apoptotic microparticles in chronic heart failure with atrial fibrillation

Abstract

Aim: To evaluate the prognostic value of circulating CD31+/annexin V+ microparticles (MPs) for cumulative survival in chronic heart failure (CHF) patients with atrial fibrillation.

Methods: A total of 154 patients with atrial fibrillation and moderate-to-severe CHF were enrolled in the study at discharge from the hospital. Observation period was up to 3 years. Blood samples for biomarkers measurements were collected. Flow cytometry analysis for quantifying the number of CD31+/annexin V+ MPs was used. CD31+/annexin V+ MPs number for cumulative survival cases due to CHF was tested. Additionally, all-cause mortality, and CHF-related death were examined.

Results: During a median follow-up of 2.18 years, 21 participants died and 106 subjects were hospitalized repetitively. Medians of circulating levels of CD31+/annexin V+ MPs in patients who survived and subjects who died were 0.286 n/mL (95% confidence interval [CI] = 0.271-0.309 n/mL) and 0.673 n/mL (95% CI = 0.65-0.74 n/mL) (P<0.001). Number of circulating MPs was distributed into Quartiles (Q): Q1 (< 0.341 n/mL), Q2 (0.342-0.514 n/mL), Q3 (0.521-0.848 n/mL), and Q4 (> 0.850 n/mL). ROC analysis has been shown that cut off point of CD31+/annexin V+ MPs number for cumulative survival function was 0.514 n/mL. Area under cure was 0.913 (Std. error = 0.025; 95% CI = 0.863-0.962), sensitivity and specificity were 89.6% and 69.7% respectively. It has been found a significantly divergence of Kaplan-Meier survival curves in patients with high quartile (MPs number >0.514 n/mL) of MPs numbers when compared with low quartiles. Using a stepwise model selection method for multivariable prediction model we investigated that CD31+/annexin V+ MPs number alone and combination of CD31+/annexin V+ MPs number with NT-pro-brain natriuretic peptide (NT-pro-BNP) remained statistically significant predictors for all-cause mortality, CHF-related death, and CHF-related re-hospitalisations, whereas combination of CD31+/annexin V+ MPs with both NT-pro-BNP and left ventricular ejection fraction did not.

Conclusion: Increased circulating CD31+/annexin V+ MPs in atrial fibrillation patients with CHF associates with increased 3-year CHF-related death, all-cause mortality, and risk for recurrent hospitalization due to CHF.

578
MRI based whole-heart inverse potential mapping of idiopathic ventricular ectopy

Abstract

Background: Inverse potential mapping (IPM) non-invasively reconstructs cardiac surface potentials (CSP) using body surface potentials (BSP). This requires a volume conductor model (VCM), usually constructed from computed tomography (CT).

However, CT exposes the patient to potentially harmful radiation and lacks detailed information about tissue structure. Magnetic resonance imaging (MRI), in contrast, is the gold standard for non-invasive tissue characterization including edema and fibrosis, and not associated with dangerous limitations.

This study investigated an MRI-based IPM approach.

Methods: Four patients with premature ventricular contractions (PVC) underwent 62 electrode body surface mapping. MRI was used to create the VCM. CSP were estimated from the BSP and used to determine the origin of electrical activation.

The PVC focus was invasively identified using electro-anatomical mapping (EAM), followed by targeted ablation. Subsequently the focus location was compared between IPM and EAM.

Results: The PVC focus was spatially (3-dimensional) located within 13±5 mm to the EAM defined PVC origin (Figure 1).

Conclusion: The MRI based whole-heart IPM method enabled accurate spatial localization of PVC.

IPM depicting ablation site (red dot)

579
Exploring mechanisms of Brugada syndrome using noninvasive electrocardiographic imaging

Abstract

Purpose: Noninvasive electrocardiographic imaging (ECGI) allows to reconstruct endocardial and epicardial local unipolar electrograms (EG) using body surface mapping based on CT or MRI data. The goal of this study was to investigate electrophysiological characteristics of Brugada syndrome (BrS) using ECGI.

Methods: 10 patients with a BrS (BrS group, 8 male, 37,7±11,4 years) had a spontaneous or ajmaline-induced BrS coved type ECG. For comparison, 5 patients without ECG abnormalities (control group, 2 male, 45,8±14 years) were also studied. All BrS patients were genotyped (6 SCN5A mutation carriers). ECGI procedure was performed in all patients using Amycard 01C System (EP Solutions SA, Switzerland).

Results: All patients with BrS had a zone of abnormal EGs in right ventriclar outflow tract (RVOT). EG changes included: fractionation of QRS (N=9; 90%), ST-segment elevation > 2 mV (N=7; 70%) and activation-recovery interval (ARI) prolongation due to the early repolarization (N=8; 80%). This changes significantly more expressed on the epicardium. Ajmaline challenge was strengthening existing and expanding the area of abnormal EGs (Fig.). The control patients had no abnormal EGs in RVOT. EG characteristics were not significantly different in patients with and without SCN5A mutations. In contrast, ST segment elevation, ARI prolongation and Epi-Endo voltage gradient were prevalent in symptomatic BrS patients (with spontaneous or induced VF; p≤0,05) (Tab.).

Conclusions: Results of this study have demonstrated that myocardial depolarization and repolarization abnormalities in BrS patients are located in the RVOT and prevailed in the epicardium cluster.

Reconstructed EG