Advanced Cardiovascular Imaging in Ventricular Arrhythmia

Eric Xie, MD, and Jonathan Chrispin, MD,,,,Division of Cardiology, Department of Medicine, Section of Cardiac Electrophysiology, Johns Hopkins University School of Medicine, Baltimore, Maryland

EP Review

Advanced Cardiovascular Imaging in Ventricular Arrhythmia

Eric Xie, MD, and Jonathan Chrispin, MD

Division of Cardiology, Department of Medicine, Section of Cardiac Electrophysiology, Johns Hopkins University School of Medicine, Baltimore, Maryland

August 2022

Ventricular arrhythmia (VA) is a significant cause of morbidity and mortality worldwide. It is a leading mechanism of sudden cardiac death (SCD), which accounts for 300,000-400,000 deaths per year.¹ In ischemic cardiomyopathy (ICM), functional and structural reentry occurs within ischemic and fibrotic myocardium precipitated by coronary artery disease (CAD).

Ventricular tachycardia (VT) or ventricular fibrillation precipitated by R-on-T phenomena can propagate through these reentrant circuits. On the other hand, nonischemic cardiomyopathy (NICM) describes a panoply of cardiac diseases, including genetic and infiltrative that can, via alternate mechanisms, lead to fibrosis and remodeling, also a substrate for VA. Clinically, primary prevention of VA is accomplished with an implantable cardioverter-defibrillator (ICD) and medical optimization, with different criteria in secondary prevention. These criteria include clinical signs of heart failure and imaging evidence of decreased ejection fraction (EF) <35%.² However, the value of imaging in the assessment and prediction of VA extends beyond solely measuring EF, as we seek to describe in this article.

Advanced cardiac imaging includes the modalities of computed tomography (CT), cardiac magnetic resonance imaging (CMR), positron emission tomography (PET), and single-photon emission computerized tomography (SPECT). These promise a noninvasive means of risk stratification by characterization of the myocardial substrate. Perhaps the most prominent example is late gadolinium enhancement (LGE) on CMR, which corresponds to myocardial fibrosis, and potentially, foci of reentry. Similarly, CT has been used to assess myocardial fat and wall thinning, which has also been linked with reentry. Finally, the utility of PET and SPECT has varied widely from the study of viability and innervation to inflammation. This article will focus predominantly on recent developments in CMR and CT.

Cardiac Magnetic Resonance

LGE in ICM

Chrispin Ventricular Arrhythmia Figure 1 — Figure 1. CMR examples. Arrows mark areas of the scar. (A) LGE showing aneurysmal basal inferior scar in a patient with ICM post-ICD implantation. (B) Thinned anteroapical infarct with transmural LGE in ICM. (C) Extensive patchy LGE in a patient with HCM. (D) Extensive septal LGE in a patient with NICM presenting with VT. (E) T1 mapping in NICM. (F) T2* mapping in NICM.

LGE assessment is well-established in clinical practice, particularly as a diagnostic tool, and its association with VA is widely described.^3,4 We include examples of LGE identified in patients with ICM (Figure 1A, 1B) and NICM (Figure 1C, 1D). Several studies among patients with ICM and ICDs have shown that characteristics of LGE based on regions of heterogeneous scar termed gray zone (GZ) predict VA after controlling for comorbidities and patient level factors.^5-7 Recently, it has been demonstrated that this association is not unique to low EF cohorts; among patients with an average EF of 46%, GZ mass was a better predictor of SCD than left ventricular (LV) EF.⁸ More complex assessments of scar and GZ have also been developed, such as LV entropy, a means of quantifying the distribution of pixel intensity of LGE.^9,10 Entropy may have a stronger association with outcomes than the presence or mass of LGE and is perhaps a quantitatively richer metric.^10,11 More directly regarding the outcome, LGE has also been used to identify conducting channels in CAD, mechanistically central to VA sustainability.¹² Notably, this was also applicable in a mixed ICM/NICM cohort, wherein the presence of these channels and their mass was associated with VA risk.¹³ An example of CMR with associated electroanatomic voltage mapping data is shown in Figure 2.

Chrispin Ventricular Arrhythmia Figure 2 — Figure 2. LGE CMR with associated mapping data. Arrow marks area of the scar. These images are from an anonymized patient with ICM presenting for a VT ablation. (A) The MRI shows LGE on the lateral wall. (B) These same findings can be appreciated on the electroanatomical map. (C) The 12-lead electrocardiogram of the VT shows a basal lateral LV exit corresponding to the imaging findings.

Of greater interest to general cardiologists may be that the absence of LGE has been used to identify subsets of patients with particularly low risk of VA.¹⁴ This has its parallel in the incorporation of the absence of coronary artery calcium (CAC) as a strong negative predictor of cardiovascular events.¹⁵ The utility of LGE for arrhythmic risk stratification is further supported by a random forest survival analysis in which scar and GZ mass by LGE were identified as top predictors of VA.¹⁶ In addition, serum biomarkers have been incorporated into such models, wherein a subgroup of patients with low high-sensitivity C-reactive protein and low GZ mass on LGE were identified to be at the lowest risk for VA.¹⁷

LGE in NICM

Chrispin Ventricular Arrhythmia Figure 3 — Figure 3. Comparison of PET and CMR. Arrows mark areas of the scar on CMR. (A) Fluorodeoxyglucose (FDG) PET myocardial perfusion images demonstrate a transmural perfusion defect of the apex, and apical-mid anterior, lateral, and inferior wall, consistent with infarcted tissue, in addition to nontransmural perfusion abnormality involving the mid-basal inferior and inferolateral wall. Viability images demonstrate a lack of significant activity in the apex and apical segments of the anterior, lateral, and inferior wall corresponding to transmural perfusion defect and consistent with the absence of hibernating myocardium. On the other hand, there is an area of increased FDG activity in the mid-basal inferolateral wall disproportionate to the mild-moderate intensity perfusion abnormality consistent with the presence of hibernating myocardium at that level. (B) and (C) CMR in the same patient shows LGE in the same distribution with a subendocardial pattern involving at least 50% of the myocardium consistent with an ischemic scar.

Because of the sheer breadth of cardiovascular diseases comprising NICM, many studies of LGE among these patients include a composite of phenotypes and etiologies.^18-20 Particular attention has been paid to patients with NICM who may not meet EF criteria for primary prevention ICD. In dilated cardiomyopathy (DCM), for example, the presence of mid-wall LGE among patients with EF >40% was associated with a higher risk for SCD or aborted SCD.²¹ Among patients with hypertrophic cardiomyopathy (HCM), LGE extent has, in some cases, exceeded the performance of traditional clinical risk models, including EF.^22-24 Along these lines, proposals have been made to define LGE thresholds as a means of risk stratification. LGE extent >10% identified HCM patients with an order of magnitude greater risk of VA and SCD than existing clinical risk scores suggest.²⁵ The value of LGE in prognostication has further been illustrated among cohorts where EF may not be significantly affected by disease progression. DCM patients with progression of fibrosis as detected by serial LGE imaging had, on average, minimal change in EF (<5%).²⁶ This subgroup was at considerably higher risk for all-cause mortality than those without fibrotic progression. It should be noted that while LGE has not yet been incorporated into clinical guidelines, there are several randomized control trials underway that will further elucidate the role of LGE in cardiologists’ daily practice.^4,18 We include an example of a patient imaged with both CMR and PET to illustrate how multimodality assessment may also play a role in the future (Figure 3).

Shortcomings of LGE and Other CMR

Though LGE is the most prominent feature of CMR for VA risk stratification, other sequences may be able to address some of its shortcomings. For example, LGE-CMR relies on the correct timing of contrast injection and appropriate selection of scanning parameters, which can confound the interpretation of resultant images when suboptimal. In addition, a well-known risk of gadolinium administration is its toxicity. While modern gadolinium agents have largely done away with nephrogenic systemic fibrosis, recent consensus documents recommend shared decision-making in gadolinium administration for patients with renal impairment.²⁷

Similar to how a moderately reduced or preserved EF does not fully encapsulate patients’ risk, there are also patients without LGE who nonetheless develop VA.²⁸ Other CMR measures, including extracellular volume (ECV) (Figure 1E) and native T1 mapping, may prove useful for these and cardiomyopathy patients at large. Compared to LGE identifying localized fibrosis, ECV and native T1 are measures of diffuse fibrosis.^29,30 In a study of DCM patients, of whom 73% had no LGE on CMR, native T1 was associated with all-cause mortality independent of LGE extent and EF.³¹ A smaller study specifically among HCM patients without LGE demonstrated a similar association of native T1 with SCD.³² Interestingly, in a mixed cohort of ICM and NICM, while native T1 was independently associated with VA, a measure based on GZ thresholds (ie, LGE) was more strongly associated with the outcome.³³ For completion, we mention T2^* mapping (Figure 1F), which has typically been used to identify pathologic iron accumulation in storage diseases but has recently been applied to fibrosis assessment.^34-36 Further research is warranted to determine the role of T2^* mapping for VA risk prediction.

Computed Tomography

Compared with CMR, CT is more widely available and typically lower cost for patients and payers, increasing its accessibility. Its spatial resolution is superior to CMR as a modality, though it is more limited in tissue characterization.³⁷ The role of CT for VA risk stratification has historically been via assessment of the coronaries, whether as a CAC score or definition of anatomy.³⁸ Beyond this, cardiac CT with delayed iodinated contrast enhancement has been used to detect fibrosis, which has been validated in specific phenotypes against LGE on CMR and even histology^.39,40 In HCM, fibrotic mass detected by CT was associated with VA after adjustment for clinical risk factors.⁴¹ Particularly pertinent to the electrophysiologist, myocardial wall thickness on CT has also been used to identify channels that could represent VT isthmuses in post-myocardial infarction patients, using the modality’s high resolution (eg, the MUSIC platform, Liryc, Université de Bordeaux, Bordeaux, France, and INRIA, Sophia Antipolis, France).⁴² Compared with the gold standard, EP mapping of isthmuses, CT channels were 100% sensitive, albeit with a 50% positive predictive value. Along similar lines, CT has been used to characterize myocardial fat deposition, which has been observed to signal regions of infarct in ICM and, ergo, potential VT circuit sites.⁴³ An example is shown in Figure 4. In arrhythmogenic right ventricular cardiomyopathy, characterized by fatty replacement of the myocardium, contrast-enhanced CT attenuation was closely associated with mapped conduction velocity and suggested a potential role of CT in guiding ablation.⁴⁴ This association was also observed in postinfarct patients, a considerably broader population.⁴⁵

Conclusion

We have described several advanced imaging modalities for risk stratification of VAs and examples of their applications, especially in CMR and CT. In coming years, these may become better established in clinical guidelines and make their way into routine practice. As a result, cardiologists and electrophysiologists in the future will likely have an expanded toolset for determining patients’ risks and appropriately intervening.

Disclosures: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Xie has no conflicts of interest to report regarding the content herein. Dr Chrispin reports consulting/honorarium from Biosense Webster and Abbott.

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