Timm Dickfeld

Background: Cardiac magnetic resonance (CMR) characteristics of ventricular radiofrequency ablation (RFA) lesions have only been incompletely defined.Aim: To determine the detectability and imaging characteristics of ventricular RFA lesions in an unselected patient cohort undergoing ventricular arrhythmia ablation.Methods and results: A retrospective chart review (n = 249) identified 36 patients with either pre‐/postablation CMR (n = 14) or only postablation CMR (n = 22). Ablation lesions could be identified in 50% (n = 18) of patients. Nonvisualized lesions had more preexisting transmural late gadolinium enhancement (LGE) >75% at the ablation sites (21% vs 0.0%, P = .042), more prevalent ICD artifact (50% vs 0%, P = .001), and lower ejection fraction (35.8 ± 14.2% vs 45.3 ± 13.4%, P = .048). Early CMR imaging demonstrated a central “black” signal void (microvascular obstruction [MVO], n = 12, 67%) up to 32 days post‐RFA, whereas late imaging showed a homogenously “white” gadolinium enhancement pattern (n = 6, 33%). MVO was only observed in nonfibrotic myocardium without preexisting LGE (n = 12) but was not observed in the scar with preexisting LGE (n = 3, P = .002) suggesting different wash‐in/wash‐out kinetics in scar/nonscar myocardium. Signal intensity (1909 vs 2534, P = .009) and contrast‐to‐noise ratio (−7.8 vs 16.3, P = .009) were significantly different between MVO and LGE lesions, respectively.Conclusion: Ventricular ablation lesions visualization is negatively affected by preexisting transmural scar, ICD artifact, and low ejection fraction. The transition of “black” MVO appearance to “white” LGE appearance on CMR occurs around 1 month following ablation, suggesting a change in histological characteristics of ablation lesions. This may affect the utility of CMR in the evaluation of the ventricular lesions, when undergoing real‐time or repeat VT ablations.

Hibernating myocardium (HM) is associated with sudden cardiac death (SCD). Little is known about the electrophysiological properties of HM and the basis of its association with SCD. We aimed to electrophysiologically characterize HM in patients with ventricular tachycardia (VT). Endocardial voltage mapping, metabolic ¹⁸FDG-positron emission tomography (PET) and perfusion ⁸²Rb, ²⁰¹Tl, or ^99mTc scans were performed in 61 ischemic heart disease patients with VT. Hibernating areas were identified which was followed by three-dimensional PET reconstructions and integration with voltage maps to allow hybrid metabolic-electro-anatomic assessment of the arrhythmogenic substrate. Of 61 patients with ischemic heart disease and refractory VT, 7 were found to have hibernating myocardium (13%). A total of 303 voltage points were obtained within hibernating myocardium (8.2 points per 10 cm²) and displayed abnormal voltage in 48.5 and 78.3% of bipolar and unipolar recordings, respectively, with significant heterogeneity of bipolar (p < 0.0001) and unipolar voltage measurements (p = 0.0004). Hibernating areas in 6 of 7 patients contained all three categories of bipolar voltage-defined scar (1.5 mV). The characteristics of local electrograms were also assessed and found abnormal in most recordings (76.6, 10.2% fractionated, 5.3% isolated potentials). Exit sites of clinical VTs were determined in 6 patients, of which 3 were located within hibernating myocardium. Hibernating myocardium displays abnormal and heterogeneous electrical properties and seems to contribute to the substrate of VT. These observations may underlie the vulnerability to reentry and SCD in patients with hypoperfused yet viable myocardium.

Due to an increase in the number of patients with heart failure and ventricular arrhythmias, ventricular tachycardia ablation has a growing clinical role. Long-term success rates remain suboptimal and require creating a detailed electroanatomic map during the procedure to identify fibrotic areas responsible for arrhythmias. Nuclear imaging can identify areas of abnormal myocardial perfusion, metabolism, and innervation, which all may enhance our ability to identify ablation targets, thus decreasing procedure time and improving success rates. Myocardial scar, as assessed by single-photon emission computed tomography (SPECT) perfusion imaging, has been shown to correlate with abnormal areas found during electroanatomic mapping. Abnormal metabolism as identified by ¹⁸fluorodeoxyglucose-positron-emission tomography (PET) imaging has been shown to predict successful ablation sites and help correct errors made in the creation of the electroanatomic map. Abnormal cardiac sympathetic innervation can be identified using the purpose ¹²³I-meta-iodobenzylguanidine SPECT imaging, which may help in identifying triggers that initiate ventricular tachycardia and also predict successful ablation sites within an otherwise normal myocardium. In conclusion, these imaging modalities can not only offer new insights into the pathophysiology of ventricular arrhythmias but also have the potential to improve outcomes from ventricular tachycardia ablation procedures.

Cardiac innervation is a critical component of ventricular arrhythmogenesis that can be noninvasively assessed with ¹²³I-MIBG. However, the effect of ventricular tachycardia (VT) ablation on global and regional left ventricular sympathetic innervation and clinical outcomes has not been previously assessed. Methods: In this prospective, single-center feasibility study, 13 patients with cardiomyopathy (n = 9 ischemic, n = 4 nonischemic) who were scheduled to undergo ablation of drug-refractory VT underwent 15-min and 4-h ¹²³I-MIBG scans before and 6 mo after the ablation procedure. Planar and arrhythmia-specific 757-segment analysis of short-axis SPECT images was performed in all datasets. Results: Global innervation assessed with heart-to-mediastinal ratio and washout rates was preserved in all patients at baseline (1.8 [continuous variables are expressed as median and quartile: Q1–Q3, 1.7–2.4] and 54% [Q1–Q3, 47%–67%]) and did not change significantly at the 6-mo follow-up (1.9 [Q1–Q3, 1.6–2.2], P = 0.9; and 56% [Q1–Q3, 41%–62%], P = 0.6). However, segmental analysis demonstrated that ischemic patients had larger areas of abnormal innervation at baseline (52.1% vs. 19.6%, P = 0.011) and at the 6-mo follow-up (56.7% vs. 27.5%, P = 0.011) than the nonischemic patients. Innervation defects affected 40% of the inferior segments in all ischemic cardiomyopathy patients, whereas they affected only 10% of inferior segments in 75% of nonischemic patients. When segmental data were further analyzed in denervated (DZ), transition (TZ), and normal (NZ) zones, there were changes in these designated innervation categories from baseline to the 6-mo follow-up for ischemic (19% DZ, 59% TZ, 22% NZ) and nonischemic (6% DZ, 45% TZ, 15% NZ) patients. In ischemic patients, relative changes were significantly greater in the TZ segments than in the DZ, which demonstrated the second highest proportional changes (P = 0.028). Receiver operating characteristic curves defined best cutoffs of DZ, TZ, and NZ as less than 30.5%, 30.6%–47.1%, and more than 47.1%, respectively. Conclusion: Patients with ischemic cardiomyopathy have larger areas of abnormal innervation than those with nonischemic cardiomyopathy. Although VT ablation did not change global innervation, a novel arrhythmia-specific segmental analysis demonstrated significant dynamic changes in innervation categories and allowed quantitative definitions of DZ, TZ, and NZ. These findings provide novel insights into the mechanics of sympathetic innervation in patients undergoing VT ablation and may have diagnostic and therapeutic implications.

Background—: Innervation is a critical component of arrhythmogenesis and may present an important trigger/substrate modifier not used in current ventricular tachycardia (VT) ablation strategies. Methods and Results—: Fifteen patients referred for ischemic VT ablation underwent preprocedural cardiac ¹²³ I- meta -iodobenzylguanidine ( ¹²³ I- m IBG) imaging, which was used to create 3-dimensional (3D) innervation models and registered to high-density voltage maps. 3D ¹²³ I- m IBG innervation maps demonstrated areas of complete denervation and ¹²³ I- m IBG transition zone in all patients, which corresponded to 0% to 31% and 32% to 52% uptake. ¹²³ I- m IBG denervated areas were ≈2.5-fold larger than bipolar voltage–defined scar (median, 24.6% [Q1–Q3, 18.3%–34.4%] versus 10.6% [Q1–Q3, 3.9%–16.4%]; P P =0.07). Bipolar/unipolar voltages varied widely within areas of denervation (0.8 mV [Q1–Q3, 0.3–1.7 mV] and 4.0 mV [Q1–Q3, 2.9–5.6 mV]) and ¹²³ I- m IBG transition zones (0.8 mV [Q1–Q3, 0.4–1.8 mV] and 4.6 mV [Q1–Q3, 3.2–6.3 mV]). Bipolar voltages in denervated areas and ¹²³ I- m IBG transition zones were 1.5 mV in 35%, 36%, and 29%, as well as 35%, 35%, and 30%, respectively ( P >0.05). Successful ablation sites were within bipolar voltage–defined scar (7%), border zone (57%), and areas of normal voltage (36%), but all ablation sites were abnormally innervated (denervation/ ¹²³ I- m IBG transition zone in 50% each). Conclusions—: ¹²³ I- m IBG innervation defects are larger than bipolar voltage–defined scar and cannot be detected with standard voltage criteria. Thirty-six percent of successful VT ablation sites demonstrated normal voltages (>1.5 mV), but all ablation sites were within the areas of abnormal innervation. ¹²³ I- m IBG innervation maps may provide critical information about triggers/substrate modifiers and could improve understanding of VT substrate and facilitate VT ablation. Clinical Trial Registration—: URL: http://www.clinicaltrials.gov . Unique Identifier: NCT01250912.

Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) imaging is the gold standard for myocardial scar evaluation. Heterogeneous areas of scar (‘gray zone’), may serve as arrhythmogenic substrate. Various gray zone protocols have been correlated to clinical outcomes and ventricular tachycardia channels. This study assessed the quantitative differences in gray zone and scar core sizes as defined by previously validated signal intensity (SI) threshold algorithms. High quality LGE-CMR images performed in 41 cardiomyopathy patients [ischemic (33) or non-ischemic (8)] were analyzed using previously validated SI threshold methods [Full Width at Half Maximum (FWHM), n-standard deviation (NSD) and modified-FWHM]. Myocardial scar was defined as scar core and gray zone using SI thresholds based on these methods. Scar core, gray zone and total scar sizes were then computed and compared among these models. The median gray zone mass was 2–3 times larger with FWHM (15 g, IQR: 8–26 g) compared to NSD or modified-FWHM (5 g, IQR: 3–9 g; and 8 g. IQR: 6–12 g respectively, p < 0.001). Conversely, infarct core mass was 2.3 times larger with NSD (30 g, IQR: 17–53 g) versus FWHM and modified-FWHM (13 g, IQR: 7–23 g, p < 0.001). The gray zone extent (percentage of total scar that was gray zone) also varied significantly among the three methods, 51 % (IQR: 42–61 %), 17 % (IQR: 11–21 %) versus 38 % (IQR: 33–43 %) for FWHM, NSD and modified-FWHM respectively (p < 0.001). Considerable variability exists among the current methods for MRI defined gray zone and scar core. Infarct core and total myocardial scar mass also differ using these methods. Further evaluation of the most accurate quantification method is needed.