Area-weighted unipolar voltage to predict heart failure outcomes in patients with ischaemic cardiomyopathy and ventricular tachycardia.

AIMS: Patients with ischaemic cardiomyopathy (ICM) referred for catheter ablation of ventricular tachycardia (VT) are at risk for end-stage heart failure (HF) due to adverse remodelling. Local unipolar voltages (UV) decrease with loss of viable myocardium. A UV parameter reflecting global viable myocardium may predict prognosis. We evaluate if a newly proposed parameter, area-weighted unipolar voltage (awUV), can predict HF-related outcomes [HFO; HF death/left ventricular (LV) assist device/heart transplant] in ICM. METHODS AND RESULTS: From endocardial voltage maps of consecutive patients with ICM referred for VT ablation, awUV was calculated by weighted interpolation of local UV. Associations between clinical and mapping parameters and HFO were evaluated and validated in a second cohort. The derivation cohort consisted of 90 patients [age 68 ±8 years; LV ejection fraction (LVEF) 35% interquartile range (IQR) (24-40)] and validation cohort of 60 patients [age 67 ± 9, LVEF 39% IQR (29-45)]. In the derivation cohort, during a median follow-up of 45 months [IQR (34-83)], 36 (43%) patients died and 23 (26%) had HFO. Patients with HFO had lower awUV [4.51 IQR (3.69-5.31) vs. 7.03 IQR (6.08-9.2), P < 0.001]. A reduction in awUV [optimal awUV (5.58) cut-off determined by receiver operating characteristics analysis] was a strong predictor of HFO (3-year HFO survival 97% vs. 57%). The cut-off value was confirmed in the validation cohort (2-year HFO-free survival 96% vs. 60%). CONCLUSION: The newly proposed parameter awUV, easily available from routine voltage mapping, may be useful at identifying ICM patients at high risk for HFO.

Unipolar voltage mapping in right ventricular cardiomyopathy: pitfalls, solutions and advantages.

AIMS: Endocardial unipolar and bipolar voltage mapping (UVM/BVM) of the right ventricle (RV) are used for transmural substrate delineation. However, far-field electrograms (EGMs) and EGM changes due to injury current may influence automatically generated UVM. Epicardial BVM is considered less accurate due to the impact of fat thickness (FT). Data on epicardial UVM are sparse. The aim of the study is two-fold: to assess the influence of the manually corrected window-of-interest on UVM and the potential role of epicardial UVM in RV cardiomyopathies. METHODS AND RESULTS: Consecutive patients who underwent endo-epicardial RV mapping with computed-tomography (CT) integration were included. Mapping points were superimposed on short-axis CT slices and correlated with local FT. All points were manually re-analysed and the window-of-interest was adjusted to correct for false high unipolar voltage (UV). For opposite endo-epicardial point-pairs, endo-epicardial bipolar voltage (BV) and UV were correlated for different FT categories. A total of 3791 point-pairs of 33 patients were analysed. In 69% of endocardial points and 63% of epicardial points, the window-of-interest needed to be adjusted due to the inclusion of far-field EGMs, injury current components, or RV-pacing artifacts. The Pearson correlation between corrected endo-epicardial BV and UV was lower for point-pairs with greater FT; however, this correlation was much stronger and less influenced by fat for UV. CONCLUSION: At the majority of mapping sites, the window-of-interest needs to be manually adjusted for correct UVM. Unadjusted UVM underestimates low UV regions. Unipolar voltage seems to be less influenced by epicardial fat, suggesting a promising role for UVM in epicardial substrate delineation.

The transmural activation interval: a new mapping tool to identify ventricular tachycardia substrates in right ventricular cardiomyopathy.

AIMS: In right ventricular cardiomyopathy (RVCM), intramural scar may prevent rapid transmural activation, which may facilitate subepicardial ventricular tachycardia (VT) circuits. A critical transmural activation delay determined during sinus rhythm (SR) may identify VT substrates in RVCM. METHODS AND RESULTS: Consecutive patients with RVCM who underwent detailed endocardial-epicardial mapping and ablation for scar-related VT were enrolled. The transmural activation interval (TAI, first endocardial to first epicardial activation) and maximal activation interval (MAI, first endocardial to last epicardial activation) were determined in endocardial-epicardial point pairs located <10 mm apart. VT-related sites were determined by conventional substrate mapping and limited activation mapping when possible. Nineteen patients (46 ± 16 years, 84% male, 63% arrhythmogenic right ventricular cardiomyopathy, 37% exercise-induced arrhythmogenic remodelling) were inducible for 44 VT [CL 283 (interquartile range, IQR 240-325)ms]. A total of 2569 endocardial-epicardial coupled point pairs were analysed, including 98 (4%) epicardial VT-related sites.The TAI and MAI were significantly longer at VT-related sites compared with other electroanatomical scar sites [TAI median 31 (IQR 11-50) vs. 2 (-7-11)ms, P < 0.001; MAI median 65 (IQR 45-87) vs. 23 (13-39)ms, P < 0.001]. TAI and MAI allowed highly accurate identification of epicardial VT-related sites (optimal cut-off TAI 17 ms and MAI 45 ms, both AUC 0.81). Both TAI and MAI had a better predictive accuracy for VT-related sites than endocardial and epicardial voltage and electrogram (EGM) duration (AUC 0.51-0.73). CONCLUSION: The transmural activation delay in SR can be used to identify VT substrates in patients with RVCM and predominantly hemodynamically non-tolerated VT, and may be an important new mapping tool for substrate-based ablation.

The arrhythmogenic cardiomyopathy phenotype associated with PKP2 c.1211dup variant.

BACKGROUND: The arrhythmogenic cardiomyopathy (ACM) phenotype, with life-threatening ventricular arrhythmias and heart failure, varies according to genetic aetiology. We aimed to characterise the phenotype associated with the variant c.1211dup (p.Val406Serfs*4) in the plakophilin­2 gene (PKP2) and compare it with previously reported Dutch PKP2 founder variants. METHODS: Clinical data were collected retrospectively from medical records of 106 PKP2 c.1211dup heterozygous carriers. Using data from the Netherlands ACM Registry, c.1211dup was compared with 3 other truncating PKP2 variants (c.235C > T (p.Arg79*), c.397C > T (p.Gln133*) and c.2489+1G > A (p.?)). RESULTS: Of the 106 carriers, 47 (44%) were diagnosed with ACM, at a mean age of 41 years. By the end of follow-up, 29 (27%) had experienced sustained ventricular arrhythmias and 12 (11%) had developed heart failure, with male carriers showing significantly higher risks than females on these endpoints (p < 0.05). Based on available cardiac magnetic resonance imaging and echocardiographic data, 46% of the carriers showed either right ventricular dilatation and/or dysfunction, whereas a substantial minority (37%) had some form of left ventricular involvement. Both geographical distribution of carriers and haplotype analysis suggested PKP2 c.1211dup to be a founder variant originating from the South-Western coast of the Netherlands. Finally, a Cox proportional hazards model suggested significant differences in ventricular arrhythmia-free survival between 4 PKP2 founder variants, including c.1211dup. CONCLUSIONS: The PKP2 c.1211dup variant is a Dutch founder variant associated with a typical right-dominant ACM phenotype, but also left ventricular involvement, and a possibly more severe phenotype than other Dutch PKP2 founder variants.

The harm of delayed diagnosis of arrhythmogenic cardiac sarcoidosis: a case series.

AIMS: Cardiac sarcoidosis (CS) is a known cause of ventricular tachycardia (VT). However, an arrhythmogenic presentation may not prompt immediate comprehensive evaluation. We aimed to assess the diagnostic and disease course of patients with arrhythmogenic cardiac sarcoidosis (ACS). METHODS AND RESULTS: From the Leiden VT-ablation-registry, consecutive patients with CS as underlying aetiology were retrospectively included. Data on clinical presentation, time-to-diagnosis, cardiac function, and clinical outcomes were collected. Patients were divided in early (<6 months from first cardiac presentation) and late diagnosis. After exclusion of patients with known causes of non-ischaemic cardiomyopathy (NICM), 15 (12%) out of 129 patients with idiopathic NICM were ultimately diagnosed with CS and included. Five patients were diagnosed early; all had early presentation with VTs. Ten patients had a late diagnosis with a median delay of 24 (IQR 15-44) months, despite presentation with VT (n = 5) and atrioventricular block (n = 4). In 6 of 10 patients, reason for suspicion of ACS was the electroanatomical scar pattern. In patients with early diagnosis, immunosuppressive therapy was immediately initiated with stable cardiac function during follow-up. Adversely, in 7 of 10 patients with late diagnosis, cardiac function deteriorated before diagnosis, and in only one cardiac function recovered with immunosuppressive therapy. Six (40%) patients died (five of six with late diagnosis). CONCLUSION: Arrhythmogenic cardiac sarcoidosis is an important differential diagnosis in NICM patients referred for VT ablation. Importantly, the diagnosis is frequently delayed, which leads to a severe disease course, including irreversible cardiac dysfunction and death. Early recognition, which can be facilitated by electroanatomical mapping, is crucial.

Whole human heart histology to validate electroanatomical voltage mapping in patients with non-ischaemic cardiomyopathy and ventricular tachycardia.

Aims: Electroanatomical voltage mapping (EAVM) is an important diagnostic tool for fibrosis identification and risk stratification in non-ischaemic cardiomyopathy (NICM); currently, distinct cut-offs are applied. We aimed to evaluate the performance of EAVM to detect fibrosis by integration with whole heart histology and to identify the fibrosis pattern in NICM patients with ventricular tachycardias (VTs). Methods and results: Eight patients with NICM and VT underwent EAVM prior to death or heart transplantation. EAVM data was projected onto slices of the entire heart. Pattern, architecture, and amount of fibrosis were assessed in transmural biopsies corresponding to EAVM sites. Fibrosis pattern in NICM biopsies (n = 507) was highly variable and not limited to mid-wall/sub-epicardium. Fibrosis architecture was rarely compact, but typically patchy and/or diffuse. In NICM, biopsies without abnormal fibrosis unipolar voltage (UV) and bipolar voltage (BV) showed a linear association with wall thickness (WT). The amount of viable myocardium showed a linear association with both UV and BV. Accordingly, any cut-off to delineate fibrosis performed poorly. An equation was generated calculating the amount of fibrosis at any location, given WT and UV or BV. Conclusion: Considering the linear relationships between WT, amount of fibrosis and both UV and BV, the search for any distinct voltage cut-off to identify fibrosis in NICM is futile. The amount of fibrosis can be calculated, if WT and voltages are known. Fibrosis pattern and architecture are different from ischaemic cardiomyopathy and findings on ischaemic substrates may not be applicable to NICM.

Automated left ventricle segmentation in late gadolinium-enhanced MRI for objective myocardial scar assessment.

PURPOSE: To develop and validate an objective and reproducible left ventricle (LV) segmentation method for late gadolinium enhanced (LGE) magnetic resonance imaging (MRI), which can facilitate accurate myocardial scar assessment. MATERIALS AND METHODS: A cohort of 25 ischemic patients and 25 nonischemic patients were included. A four-step algorithm was proposed: first, the Cine-MRI and LGE-MRI volume were globally registered; second, the registered Cine-MRI contours were fitted to each LGE-MRI slice via the constructed contour image; third, the fitting was optimized in full LGE-MRI stack; finally, the contours were refined by taking into account patient-specific scar patterns. The automated LV segmentation results were compared with that of manual segmentation from two experienced observers. RESULTS: The accuracy of automated segmentation, expressed as the average contour distances to manual segmentation, was 0.82 ± 0.19 pixels, in the same order as interobserver difference between manual results (0.90 ± 0.26 pixels), but with lower variability (0.60 ± 0.37 pixels, P < 0.05). The myocardial scar identification based on automated LV segmentation further demonstrated higher consistency than that of manual segmentation (Pearson correlation 0.97 vs. 0.84). CONCLUSION: An automated LV segmentation method for LGE-MRI was developed, providing high segmentation accuracy and lower interobserver variability compared to fully manual image analysis. The method facilitates objective assessment of myocardial scar.

Epicardial substrate mapping for ventricular tachycardia ablation in patients with non-ischaemic cardiomyopathy: a new algorithm to differentiate between scar and viable myocardium developed by simultaneous integration of computed tomography and contrast-enhanced magnetic resonance imaging.

AIMS: During epicardial electroanatomical mapping (EAM), it is difficult to differentiate between fibrosis and fat, as both exhibit attenuated bipolar voltage (BV). The purpose of this study was to assess whether unipolar voltage (UV), BV, and electrogram characteristics (EC) can distinguish fibrosis from viable myocardium and fat during epicardial EAM for ventricular tachycardia (VT) ablation in non-ischaemic cardiomyopathy (NICM). METHODS AND RESULTS: Ten NICM patients (7 males, 56 ± 13 years) with VT underwent epicardial EAM with real-time integration of computed tomography-derived epicardial fat and contrast-enhanced MRI-derived scar. Bipolar voltage (filtered 30-400 Hz), UV (filtered 1-240 Hz), and EC (duration and morphology) were correlated with the presence of fat and scar. At sites devoid of fat, the optimal cutoff values to differentiate between scar and myocardium were 1.81 mV for BV and 7.95 mV for UV. Bipolar voltage, UV, and electrogram duration >50 ms distinguished scar from myocardium in areas covered with <2.8 mm fat (all P < 0.001), but not ≥ 2.8 mm fat. In contrast, electrogram morphology-characteristics could also detect scar covered with ≥ 2.8 mm fat (P = 0.001). A newly developed three-step algorithm combining electrogram morphology, duration, and UV could correctly identify scar with a sensitivity of 75%. Unipolar voltage but not BV could detect intramural scar in the absence of fat. CONCLUSIONS: Both BV ≤ 1.81 mV and UV ≤ 7.95 mV are useful for detection of scar during epicardial EAM, in the absence of ≥ 2.8 mm fat. However, EC can be used to detect scar covered with fat. A newly developed algorithm combining UV and EC can differentiate between scar and viable myocardium. Unipolar voltage but not BV could detect intramural scar.

Excellent Outcomes After First-Line Ablation in Post-MI Patients With Tolerated VT and LVEF >35.

BACKGROUND: Post-myocardial infarction (MI) patients with ventricular tachycardia (VT) are considered at risk for VT recurrence and sudden cardiac death (SCD). Recent guidelines indicate that in selected patients catheter ablation should be considered instead of an implantable cardioverter-defibrillator (ICD). OBJECTIVES: This study aimed to analyze outcomes of patients referred for VT ablation according to left ventricular ejection fraction (LVEF), tolerance of VT, and acute ablation outcome. METHODS: Post-MI patients without prior ICD undergoing VT ablation at a single center between 2009 and 2022 were included. Patients who presented with tolerated VT and who had an LVEF >35% were offered catheter ablation as first-line therapy. ICD implantation was offered to all patients but was subject to shared decision according to clinical presentation, LVEF, and ablation outcome. RESULTS: Eighty-six patients (mean age 69 ± 9 years, 84% male, mean LVEF 41 ± 9%) underwent VT ablation. In 66 patients, LVEF was >35%, of whom 51 had tolerated VT. Of these 51 patients, 37 (73%) were rendered noninducible. In 5 of 37 noninducible and in 11 of 14 inducible patients, an ICD was implanted. During a median follow-up of 40 months (Q1-Q3: 24-70 months), 10 of 86 patients had VT recurrence. The overall mortality was 27%, and 1 patient with ICD died suddenly. Among the 37 patients (none on antiarrhythmic drugs) with LVEF >35%, tolerated VT, and noninducibility, no SCD or VT recurrence occurred. Among the 14 patients with LVEF >35%, tolerated VT, and inducibility after ablation, no SCD occurred, but VT recurred in 29%. CONCLUSIONS: Post-MI patients with LVEF >35%, tolerated VT, and noninducibility after ablation have an excellent prognosis. Deferring ICD implantation seems to be safe in these patients.

Validation of a prediction model for early reconnection after cryoballoon ablation.

BACKGROUND: We previously developed an early reconnection/dormant conduction (ERC) prediction model for cryoballoon ablation to avoid a 30-min waiting period with adenosine infusion. We now aimed to validate this model based on time to isolation, number of unsuccessful cryo-applications, and nadir balloon temperature. METHODS: Consecutive atrial fibrillation patients who underwent their first cryoballoon ablation in 2018-2019 at the Leiden University Medical Center were included. Model performance at the previous and at a new optimal cutoff value was determined. RESULTS: A total of 201 patients were included (85.57% paroxysmal AF, 139 male, median age 61 years (IQR 53-69)). ERC was found in 35 of 201 included patients (17.41%) and in 41 of 774 veins (5.30%). In the present study population, the previous cutoff value of - 6.7 provided a sensitivity of 37.84% (previously 70%) and a specificity of 89.07% (previously 86%). Shifting the cutoff value to - 7.2 in both study populations resulted in a sensitivity of 72.50% and 72.97% and a specificity of 78.22% and 78.63% in data from the previous and present study respectively. Negative predictive values were 96.55% and 98.11%. Applying the model on the 101 patients of the present study with all necessary data for all veins resulted in 43 out of 101 patients (43%) not requiring a 30-min waiting period with adenosine testing. Two patients (2%) with ERC would have been missed when applying the model. CONCLUSIONS: The previously established ERC prediction model performs well, recommending its use for centers routinely using adenosine testing following PVI.

Pleomorphic Ventricular Tachycardia in Dilated Cardiomyopathy Predicts Ventricular Tachycardia Recurrence After Ablation Independent From Cardiac Function: Comparison With Patients With Ischemic Heart Disease.

BACKGROUND: In dilated cardiomyopathy (DCM), outcome after catheter ablation of ventricular tachycardia (VT) is modest, compared with ischemic heart disease (IHD). Pleomorphic VT (PL-VT) has been associated with fibrotic remodeling and end-stage heart failure in IHD. The prognostic role of PL-VT in DCM is unknown. METHODS: Consecutive IHD (2009-2016) or DCM (2008-2018) patients undergoing ablation for monomorphic VT were included. PL-VT was defined as ≥1 spontaneous change of the 12-lead VT-morphology during the same induced VT episode. Patients were followed for VT recurrence and mortality. RESULTS: A total of 247 patients (86% men; 63±13 years; IHD n=152; DCM n=95) underwent ablation for monomorphic VT. PL-VT was observed in 22 and 29 patients with IHD and DCM, respectively (14% versus 31%, P=0.003). In IHD, PL-VT was associated with lower LVEF (28±9% versus 34±12%, P=0.02) and only observed in those with LVEF<40%. In contrast, in DCM, PL-VT was not related to LVEF and induced in 27% of patients with LVEF>40%. During a median follow-up of 30 months, 79 (32%) patients died (IHD 48; DCM 31; P=0.88) and 120 (49%) had VT recurrence (IHD 59; DCM 61; P<0.001). PL-VT was associated with mortality in IHD but not in DCM. In IHD, VT recurrence was independently associated with LVEF, number of induced VTs, and procedural noncomplete success. Of note, in DCM, PL-VT (HR, 2.62 [95% CI, 1.47-4.69]), pathogenic mutation (HR, 2.13 [95% CI, 1.16-3.91]), and anteroseptal VT substrate (HR, 1.75 [95% CI, 1.00-3.07]) independently predicted VT recurrence. CONCLUSIONS: In IHD, PL-VT was associated with low LVEF and mortality. In DCM, PL-VT was not associated with mortality but a predictor of VT recurrence independent from LVEF. PL-VT in DCM may indicate a specific arrhythmic substrate difficult to control by current ablation techniques.

Volume-Weighted Unipolar Voltage Predicts Heart Failure Mortality in Patients With Dilated Cardiomyopathy and Ventricular Arrhythmias.

BACKGROUND: Patients with dilated cardiomyopathy (DCM) who are undergoing catheter ablation of ventricular arrhythmias (VAs) are at risk of rapidly progressive heart failure (HF). Endocardial voltages decrease with loss of viable myocardium. Global left ventricular (LV) voltage as a surrogate for the amount of remaining viable myocardium may predict prognosis. OBJECTIVES: This study evaluated whether the newly proposed parameter volume-weighted (vw) unipolar voltage (UV) can predict HF-related adverse outcomes (HFOs), including death, heart transplantation, or ventricular assist device implantation, in DCM. METHODS: In consecutive patients with DCM referred for VA ablation, vwUV was calculated by mathematically integrating UV over the left ventricle, divided by the endocardial LV surface area and wall thickness. Patients were followed for HFOs. RESULTS: A total of 103 patients (57 ± 14 years of age; left ventricular ejection fraction [LVEF], 39% ± 13%) were included. Median vwUV was 9.75 (IQR: 7.27-12.29). During a median follow-up of 24 months (IQR: 8-47 months), 25 patients (24%) died, and 16 had HFOs 7 months (IQR: 1-18 months) after ablation. Patients with HFOs had significantly lower LVEF (29% ± 10% vs 41% ± 12%), vw bipolar voltage (BV) (3.00 [IQR: 2.47-3.53] vs 5.00 [IQR: 4.12-5.73]), and vwUV (5.94 [IQR: 5.28-6.55] vs 10.37 [IQR: 8.82-12.81]; all P < 0.001), than patients without HFOs. In Cox regression analysis and goodness-of-fit tests, vwUV was the strongest and independent predictor for HFOs (HR: 3.68; CI: 2.09-6.45; likelihood ratio chi-square, 33.05; P < 0.001). CONCLUSIONS: The novel parameter vwUV, as a surrogate for the amount of viable myocardium, identifies patients with DCM with VA who are at high risk for HF progression and mortality.

Nonsustained Ventricular Tachycardia Is Independently Associated With Sustained Ventricular Arrhythmias in Nonischemic Dilated Cardiomyopathy.

BACKGROUND: Spontaneous nonsustained ventricular tachycardia (NSVT) on Holter, VT inducibility during electrophysiology study, and late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) have been associated with sustained ventricular arrhythmias (SVAs) in nonischemic dilated cardiomyopathy (DCM). This study aimed to analyze whether these parameters carry independent prognostic value for spontaneous SVA in DCM. METHODS: Between 2011 and 2018, patients with the DCM clinical spectrum and documented SVA, suspected SVA, or considered to be at intermediate or high risk for SVA were enrolled in the prospective Leiden Nonischemic Cardiomyopathy Study. Patients underwent a comprehensive evaluation including 24-hour Holter, LGE-CMR, and electrophysiology study. Holters were assessed for the presence of NSVT (≥3 beats; rate, ≥120 bpm; lasting <30 s) and NSVT characteristics (coupling interval, duration, cycle length, morphology, regularity). Patients were followed at 6 to 12 monthly intervals. RESULTS: Of all 115 patients (age, 59±12 years; 77% men; left ventricular ejection fraction, 33±13%; history of SVA, 36%; LGE in 63%; median LGE mass, 13 g; interquartile range, 8-23 g), 62 (54%) had NSVT on Holter, and sustained monomorphic VT was inducible in 34 of 114 patients (30%). NSVT was not associated with LGE on CMR or VT inducibility during electrophysiology study nor were its features (all P>0.05). During 4.0±1.8 years of follow-up, SVA occurred in 39 patients (34%). NSVT (HR, 4.47 [95% CI, 1.87-10.72]; P=0.001) and VT inducibility (HR, 3.08 [95% CI, 1.08-8.81]; P=0.036) were independently associated with SVA during follow-up. A bivariable model including only noninvasively acquired parameters also allowed identification of a high-risk subgroup (ie, those with both NSVT and LGE on CMR). The findings remained similar when only patients without prior SVA were included. CONCLUSIONS: In patients with DCM, NSVT on Holter and VT inducibility during electrophysiology study predict SVA during follow-up independent of LGE on CMR. NSVTs may serve as an initiator, and sustained VT inducibility indicates the presence of the substrate for SVA in DCM. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01940081.

Ventricular Arrhythmia Substrate Distribution and Its Relation to Sympathetic Innervation in Nonischemic Cardiomyopathy Patients.

BACKGROUND: Nonischemic cardiomyopathy patients referred for catheter ablation of ventricular arrhythmias (VAs) typically have either inferolateral (ILS) or anteroseptal (ASS) VA substrate locations, with poorer outcomes for ASS. Sympathetic denervation is an important determinant of arrhythmogenicity. Its relation to nonischemic fibrosis in general and to the different VA substrates is unknown. OBJECTIVES: This study sought to evaluate the association between VA substrates, myocardial fibrosis, and sympathetic denervation. METHODS: Thirty-five patients from the Leiden Nonischemic Cardiomyopathy Study, who underwent electroanatomic voltage mapping and iodine-123 metaiodobenzylguanidine imaging between 2011 and 2018 were included. Late gadolinium-enhanced cardiac magnetic resonance data were collected when available. The relation between global cardiac sympathetic innervation and area-weighted unipolar voltage (UV) as a surrogate for diffuse fibrosis was evaluated. For regional analysis, patients were categorized as ASS or ILS. The distribution of low UV, sympathetic denervation, and late gadolinium enhancement (LGE) scar were compared using the 17-segment model. RESULTS: Median area-weighted UV was 12.3 mV in patients with normal sympathetic innervation and 8.7 mV in patients with sympathetic denervation. Global sympathetic denervation correlated with diffuse myocardial fibrosis (R = 0.53; P = 0.02). ILS (n = 13) matched with low UV, sympathetic denervation, and LGE scar in all patients, whereas ASS (n = 11) matched with low UV in all patients, with LGE scar in 63% (P = 0.20), but with sympathetic denervation in only 27% of patients (P = 0.0002). CONCLUSIONS: Global cardiac sympathetic denervation is related to fibrosis in nonischemic cardiomyopathy patients with VA. The mismatch between regional fibrosis and preserved innervation for ASS may contribute to a VA substrate difficult to control by catheter ablation.

Composition of carotid atherosclerotic plaque is associated with cardiovascular outcome: a prognostic study.

BACKGROUND: Identification of patients at risk for primary and secondary manifestations of atherosclerotic disease progression is based mainly on established risk factors. The atherosclerotic plaque composition is thought to be an important determinant of acute cardiovascular events, but no prospective studies have been performed. The objective of the present study was to investigate whether atherosclerotic plaque composition is associated with the occurrence of future vascular events. METHODS AND RESULTS: Atherosclerotic carotid lesions were collected from patients who underwent carotid endarterectomy and were subjected to histological examination. Patients underwent clinical follow-up yearly, up to 3 years after carotid endarterectomy. The primary outcome was defined as the composite of a vascular event (vascular death, nonfatal stroke, nonfatal myocardial infarction) and vascular intervention. The cumulative event rate at 1-, 2-, and 3-year follow-up was expressed by Kaplan-Meier estimates, and Cox proportional hazards regression analyses were performed to assess the independence of histological characteristics from general cardiovascular risk factors. During a mean follow-up of 2.3 years, 196 of 818 patients (24%) reached the primary outcome. Patients whose excised carotid plaque revealed plaque hemorrhage or marked intraplaque vessel formation demonstrated an increased risk of primary outcome (risk difference=30.6% versus 17.2%; hazard ratio [HR] with [95% confidence interval]=1.7 [1.2 to 2.5]; and risk difference=30.0% versus 23.8%; HR=1.4 [1.1 to 1.9], respectively). Macrophage infiltration (HR=1.1 [0.8 to 1.5]), large lipid core (HR=1.1 [0.7 to 1.6]), calcifications (HR=1.1 [0.8 to 1.5]), collagen (HR=0.9 [0.7 to 1.3]), and smooth muscle cell infiltration (HR=1.3 [0.9 to 1.8]) were not associated with clinical outcome. Local plaque hemorrhage and increased intraplaque vessel formation were independently related to clinical outcome and were independent of clinical risk factors and medication use. CONCLUSIONS: The local atherosclerotic plaque composition in patients undergoing carotid endarterectomy is an independent predictor of future cardiovascular events.

RV Tissue Heterogeneity on CT: A Novel Tool to Identify the VT Substrate in ARVC.

OBJECTIVES: This study sought to evaluate whether right ventricular (RV) tissue heterogeneity on computed tomography (CT): 1) is associated with conduction delay in arrhythmogenic right ventricular cardiomyopathy (ARVC); and 2) distinguishes patients with ARVC from those with exercise-induced arrhythmogenic remodeling (EIAR) and control individuals. BACKGROUND: ARVC is characterized by fibrofatty replacement, related to conduction delay and ventricular tachycardias. Distinguishing ARVC from acquired, EIAR is challenging. METHODS: Patients with ARVC or EIAR and combined endocardial-epicardial electroanatomic voltage mapping for VT ablation with CT integration were enrolled. Patients without structural heart disease served as control individuals. Tissue heterogeneity on CT (CT heterogeneity) was automatically quantified within the 2-mm subepicardium of the entire RV free wall at normal sites and low voltage sites harboring late potentials (LP+) in ARVC/EIAR. RESULTS: Seventeen patients with ARVC (15 males; age: 50 ± 17 years), 9 patients with EIAR (7 males; age: 45 ± 14 years) and 17 control individuals (14 males; age: 50 ± 15 years) were enrolled. Of 5,215 ARVC mapping points, 560 (11%) showed LP+. CT heterogeneity was higher at sites with LP+ compared to normal sites (median: 31 HU/mm; IQR: 23 to 46 HU/mm vs. median: 16 HU/mm; IQR: 13 to 21 HU/mm; p < 0.001). The optimal CT heterogeneity cutoff for detection of LP+ was 25 HU/mm (area under the curve [AUC]: 0.80; sensitivity: 72%; specificity: 78%). Overall CT heterogeneity allowed highly accurate differentiation between patients with ARVC and control individuals (AUC: 0.97; sensitivity: 100%; specificity: 82%) and between ARVC and EIAR (AUC: 0.78; sensitivity: 65%; specificity: 89%). CONCLUSIONS: In patients with ARVC, tissue heterogeneity on CT can be used to identify LP+ as a surrogate for ventricular tachycardia substrate. The overall tissue heterogeneity on CT allows the distinguishing of patients with ARVC from those with EIAR and control individuals.

Electroanatomical Voltage Mapping to Distinguish Right-Sided Cardiac Sarcoidosis From Arrhythmogenic Right Ventricular Cardiomyopathy.

OBJECTIVES: This study sought to investigate the value of electroanatomical voltage mapping (EAVM) to distinguish cardiac sarcoidosis (CS) from arrhythmogenic right ventricular cardiomyopathy (ARVC) in patients with ventricular tachycardia from the right ventricle (RV). BACKGROUND: CS can mimic ARVC. Because scar in ARVC is predominantly subepicardial, this study hypothesized that the relative sizes of endocardial low bipolar voltage (BV) to low unipolar voltage (UV) areas may distinguish CS from ARVC. METHODS: Patients with CS affecting the RV (n = 14), patients with gene-positive ARVC (n = 13), and a reference group of patients without structural heart disease (n = 9) who underwent RV endocardial EAVM were included. RV region-specific BV and UV cutoffs were derived from control subjects. In CS and ARVC, segmental involvement was determined and low-voltage areas were measured, using <1.5 mV for BV and <3.9 mV, <4.4 mV, and <5.5 mV for UV. The ratio between low BV and low UV area was calculated generating 3 parameters: Ratio3.9, Ratio4.4 and Ratio5.5, respectively. RESULTS: In control subjects, BV and UV varied significantly among RV regions. The basal septum was involved in 71% of CS patients and in none of ARVC patients. Ratio5.5 discriminated CS from ARVC the best. An algorithm including Ratio5.5 ≥0.45 and basal septal involvement identified CS with 93% sensitivity and 85% specificity. This was validated in a separate population (CS [n = 6], ARVC [n = 10]) with 100% sensitivity and 100% specificity. CONCLUSIONS: EAVM provides detailed information about scar characteristics and scar distribution in the RV. An algorithm combining Ratio5.5 (area BV <1.5 mV/area UV <5.5 mV) and bipolar basal septal involvement allows accurate diagnosis of (isolated) CS in patients presenting with monomorphic ventricular tachycardia from the RV.

Entropy as a Novel Measure of Myocardial Tissue Heterogeneity for Prediction of Ventricular Arrhythmias and Mortality in Post-Infarct Patients.

OBJECTIVES: This study proposed entropy as a new late gadolinium enhanced cardiac magnetic resonance-derived parameter to evaluate tissue inhomogeneity, independent of signal intensity thresholds. This study hypothesized that entropy within the scar is associated with ventricular arrhythmias (VAs), whereas entropy of the entire left ventricular (LV) myocardium is associated with mortality. BACKGROUND: In patients after myocardial infarction, the heterogeneity of fibrosis determines the substrate for VA. Fibrosis in remote areas has been associated with heart failure and mortality. Late gadolinium-enhanced cardiac magnetic resonance has been used to delineate fibrosis, but available methods depend on signal intensity thresholds and results have been inconsistent. METHODS: Consecutive post-myocardial infarction patients undergoing late gadolinium enhanced cardiac magnetic resonance prior to implantable cardioverter-defibrillator implantation were included. From cardiac magnetic resonance imaging, total scar size, scar gray zone, scar transmurality, and tissue entropy were derived. Patients were followed for appropriate implantable cardioverter-defibrillator therapy and mortality. RESULTS: A total of 154 patients (age 64 ± 10 years, 84% male, LV ejection fraction 29 ± 10%, 47% acute revascularization) were included. During a median follow-up of 56 (interquartile range: 40 to 73) months, appropriate implantable cardioverter-defibrillator therapy occurred in 46 patients (30%), and 41 patients (27%) died. From multivariable analysis, higher entropy of the scar (hazard ratio [HR]: 1.9; 95% confidence interval [CI]: 1.0 to 3.5; p = 0.042) was independently associated with VA, after adjusting for multivessel disease, acute revascularization, LV ejection fraction, scar gray zone, and transmurality. Entropy of the entire LV was independently associated with mortality (HR: 3.2; 95% CI: 1.1 to 9.9; p = 0.038). CONCLUSIONS: High entropy within the scar was associated with VA and may indicate an arrhythmogenic scar. High entropy of the entire LV was associated with mortality and may reflect a fibrosis pattern associated with adverse remodeling.

Fast nonclinical ventricular tachycardia inducible after ablation in patients with structural heart disease: Definition and clinical implications.

BACKGROUND: Noninducibility of ventricular tachycardia (VT) with an equal or longer cycle length (CL) than that of the clinical VT is considered the minimum ablation endpoint in patients with structural heart disease. Because their clinical relevance remains unclear, fast nonclinical VTs are often not targeted. However, an accepted definition for fast VT is lacking. The shortest possible CL of a monomorphic reentrant VT is determined by the ventricular refractory period (VRP). OBJECTIVE: The purpose of this study was to propose a patient-specific definition for fast VT based on the individual VRP (fVTVRP) and assess the prognostic significance of persistent inducibility after ablation of fVTVRP for VT recurrence. METHODS: Of 191 patients with previous myocardial infarction or with nonischemic cardiomyopathy undergoing VT ablation, 70 (age 63 ± 13 years; 64% ischemic) remained inducible for a nonclinical VT and composed the study population. FVTVRP was defined as any VT with CL ≤VRP400 + 30 ms. Patients were followed for VT recurrence. RESULTS: After ablation, 30 patients (43%) remained inducible exclusively for fVTVRP and 40 (57%) for any slower VT. Patients with only fVTVRP had 3-year VT-free survival of 64% (95% confidence interval [CI] 46%-82%) compared to 27% (95% CI 14%-48%) for patients with any slower remaining VT (P = .013). Inducibility of only fVTVRP was independently associated with lower VT recurrence (hazard ratio 0.38; 95% CI 0.19-0.86; P = .019). Among 36 patients inducible for any fVTVRP, only 1 had recurrence with fVTVRP. CONCLUSION: In patients with structural heart disease, inducibility of exclusively fVTVRP after ablation is associated with low VT recurrence.