Cardiac magnetic resonance imaging contributing to primary prevention and secondary prevention of sudden cardiac death: Contemporary usefulness and limitations

Abstract

Sudden cardiac death (SCD) is one of the most devastating sequelae of myocardial diseases and can be the initial symptom in younger athletes or middle-aged businesspeople. An implantable cardioverter defibrillator (ICD) prevents SCD and dramatically reduces the arrhythmic events in these patients; hence, the risk stratification for the SCD is important. In survivors of out-of-hospital cardiac arrest, identification of its etiologies is required to select the appropriate treatments following ICD installation. Cardiac magnetic resonance imaging (MRI) is useful for evaluating the morphology and function of the heart and for tissue characterization, MRI can therefore be used to stratify the risk of SCD associated with various myocardial diseases and leads to primary prevention using ICD. MRI can predict arrhythmic events, which suggest the progression of myocardial damage, following secondary prevention. In this review, we provide a clinical and MRI focused update and MRI protocol for the primary and secondary prevention of SCD. We summarize the contribution and limitations of cardiac MRI for prevention SCD using ICD implantation.

Key Words: Sudden cardiac death; Cardiac magnetic resonance; Late gadolinium enhancement; Implantable cardioverter defibrillator; Prevention

Core Tip: Sudden cardiac death can be prevented by implantable cardioverter defibrillator installation based on appropriate risk stratification. Cardiac magnetic resonance imaging may contribute to the primary and secondary prevention of sudden cardiac death because it can be used to evaluate the tissue characterization and predict arrhythmic events after implantable cardioverter defibrillator installation.

INTRODUCTION

The annual incidence of sudden cardiac death (SCD) is approximately 0.05%-0.1% of the general population[1], and approximate 25% of cardiovascular deaths involve SCD[2]. In adolescents, the causes of SCD are hypertrophic cardiomyopathy (HCM), viral myocarditis, and channelopathy, whereas in older adults, the leading causes are coronary artery diseases and heart failure (HF)[1,3-6]. Male patients often experience out-of-hospital cardiac arrest (OHCA) during sports or under emotional stress, and their lifestyle must be modified to avoid SCD[1,3,4]. Electrocardiogram reveals ventricular fibrillation (VF) or sustained ventricular tachycardia (SVT) in 90% of SCD victims[1,2].

Because SCD can be the initial symptom associated with some myocardial diseases, especially in younger athletes or middle-aged businesspeople, the risk of SCD should be stratified[3,7]. Maron et al[8] showed that an implantable cardioverter defibrillator (ICD) prevents SCD and dramatically reduces the mortality rate in patients with HCM. ICD therapy is also effective for preventing SCD in survivors of OHCA induced by myocardial infarction (MI) and coronary vasospasm (CVS)[6,9,10].

Cardiac magnetic resonance imaging (MRI) is used as a tool for risk stratification of SCD in HCM patients according to the American guidelines[4,7,8]. Late gadolinium enhancement (LGE) imaging is particularly useful for identifying myocardial scars related to critical ventricular tachyarrhythmias and systolic dysfunction associated with HCM[4,8,11]. Because cardiac MRI is useful for evaluating the morphology and function of the heart as well as myocardial scarring, it can also be applied to risk stratification for SCD in other myocardial diseases, including MI, dilated cardiomyopathy (DCM), and cardiac sarcoidosis[6,12-15]. By contrast, the limited ability of LGE imaging to identify myocardial substrates related to VF has been reported[16-18].

In this review, we demonstrate the contribution and limitations of cardiac MRI to the primary and secondary prevention of SCD using ICD implantation. By retrospectively investigating cardiac MRI in patients presenting with ventricular tachyarrhythmias after ICD installation and in those with SCD, we elucidate the usefulness of cardiac MRI in identifying OHCA etiologies and predicting arrhythmic events after secondary prevention.

PRIMARY AND SECONDARY PREVENTION OF SCD

The primary prevention of SCD is defined as the prophylactic installation of an ICD in “high-risk” patients with known myocardial diseases, who have not yet experienced OHCA[2,6,8,9,19]. A detailed interview regarding the clinical symptoms and family history of SCD is essential for identifying high-risk patients[8,10,19]. Holter electrocardiography is used to identify ventricular tachyarrhythmias, including repeated nonsustained ventricular tachycardia and SVT[4,15]. Measurement of the left ventricular ejection fraction (LVEF) by echocardiography or cardiac MRI is required in stratifying the risk of SCD[19]. Nonetheless, the current method for stratifying the risk is suboptimal for the primary prevention of SCD because of its failure to reduce all-cause mortality, lack of appropriate ICD discharge, and inappropriate discharge of the ICD[6,13,14,20,21]. Cardiac MRI, especially LGE imaging, is expected to provide incremental value for risk stratification of SCD[4,5,7,8,13-15]. The secondary prevention of SCD is defined as the installation of an ICD to eliminate recurrent fatal arrhythmic events and reduce mortality in survivors of OHCA[2,8-10]. Episodes of OHCA are the absolute indication for ICD installation. Nonetheless, myocardial damage can progress and induce arrhythmic events repeatedly in some patients even after ICD installation[6,22]. If the progression of myocardial damage can be predicted before ICD installation, appropriate medication, coronary intervention, or ablation therapy can be performed following ICD therapy. Cardiac MRI is expected to identify the myocardial substrate leading to ventricular tachyarrhythmias after ICD installation[22].

CARDIAC MRI SEQUENCES USED FOR RISK STRATIFICATION OF SCD AND PREDICTION OF ARRHYTHMIC EVENTS

Cine MRI has been established as the gold standard for measuring LVEF. Cine imaging provides feature tracking data retrospectively. In addition, it visualizes significant changes in cardiac morphology, including apical aneurysm and dilatation of the cardiac chambers. Thus, cine MRI is essential for stratifying the risk of SCD and determining primary prevention. T2-weighted imaging is sensitive to myocardial edema and inflammation, which can be acute and temporary myocardial substrate inducing fatal ventricular tachyarrhythmias[21]. T1 and T2 mapping quantitatively confirm the presence of myocardial edema or fibrosis[5]. The extracellular volume fraction derived from pre- and postcontrast T1 mapping has been reported to predict malignant ventricular arrhythmias and SCD associated with nonischemic cardiomyopathy[23]. Among cardiac MRI sequences, LGE MRI is the most powerful sequence for differentiating myocardial diseases showing ventricular tachyarrhythmias or OHCA and for stratifying the risk of SCD because of its excellent ability to visualize myocardial scars. The presence of LGE, its extent, location, or heterogeneity have been shown to be related to malignant ventricular tachyarrhythmias and the risk for SCD[6,8,11,15,17,24,25]. Although an ICD prevents arrhythmic events and death from VF in many patients, it cannot prevent the progression of myocardial ischemia or cardiomyopathy[6,22]. LGE can reflect myocardial damage that leads to ventricular tachyarrhythmias even after ICD installation[22,24]. Therefore, LGE is useful for differentiating myocardial diseases requiring primary or secondary prevention using an ICD. It is also useful for risk stratification in candidates of primary prevention, while it may predict recurrent arrhythmic events in patients receiving secondary prevention. Table 1 summarizes the relationship between cardiac MRI findings and myocardial damage related to the risk for SCD or OHCA that should be treated using ICD.

Table 1 Relationship between cardiac magnetic resonance imaging findings and myocardial damages related to risk for sudden cardiac death or out-of-hospital cardiac arrest.

	Primary prevention	Secondary prevention
Myocardial diseases	Chronic MI, sarcoidosis, HCM, DCM	Acute MI, CVS, acute myo-carditis, HCM
Cardiac MRI
Cine imaging	Systolic dysfunction, aneurysm, marked hypertrophy edema related to preceding syncope or chest pain scar related to reentry or slowing of active potential	Systolic dysfunction, marked thinning, marked hypertrophy, acute and transient arrhythmic, substrates such as edema and inflammation progressive myocardial damage
T2-weighed imaging
T1T2 mapping
LGE, ECV

Cardiac magnetic resonance imaging identifies myocardial damages related to the risk for sudden cardiac death or out-of-hospital cardiac arrest, which should be treated using implantable cardioverter defibrillator. MI: Myocardial infarction; HCM: Hypertrophic cardiomyopathy; DCM: Dilated cardiomyopathy; CVS: Coronary vasospasm; MRI: Magnetic resonance imaging; LGE: Late gadolinium enhancement; ECV: Extracellular volume fraction.

CONTRIBUTION OF CARDIAC MRI TO PRIMARY PREVENTION AND RELATED MYOCARDIAL DISEASES

Contribution of cardiac MRI to primary prevention of SCD

Critical ventricular tachyarrhythmias and associated symptoms indicate the use of ICD for the primary prevention of SCD[3,5,8]. Younger ages, family history of SCD or primary cardiomyopathy are also important contributors to the selection of ICD therapies[8]. ICD is effective for preventing arrhythmic events in patients younger than 70 years[2]. Cardiac MRI contributes to determining primary prevention of SCD, because cine imaging provides LVEF with high reproducibility. In HCM, a reduced LVEF indicates end-stage HCM, which is often associated with malignant ventricular arrhythmias, HF, and SCD[11]. Cine MRI reveals regional thinning of the myocardium, which may be related to myocardial scars and arrhythmic substrates[8,26]. The dilated right ventricle and its reduced function are diagnostic criteria for arrhythmogenic right ventricular cardiomyopathy[27]. By contrast, marked myocardial hypertrophy ≥ 30 mm is an important risk factor for SCD in HCM[4,8]. LGE imaging is the most powerful imaging tool for identifying the myocardial substrate related to ventricular tachyarrhythmia and SCD. Midwall LGE, especially in the interventricular septum, is significantly related to the risk of SCD in DCM and viral myocarditis, and a cardiac resynchronization therapy defibrillator is often implanted to both improve cardiac function and defibrillate ventricular tachyarrhythmias[5,20]. Piers et al[16] have reported that transmural, extensive or basal LGE may predict monomorphic SVT but not VF. Cardiac MRI has a significant advantage in visualizing the myocardial scar in the apical region and right ventricle owing to its unrestricted view and high spatial and contrast resolution. This myocardial scarring is related to ventricular tachyarrhythmias associated with arrhythmogenic right ventricular cardiomyopathy, cardiac sarcoidosis, and HCM[8,15,27-29]. Heterogeneous LGE may reflect the mixture of viable myocytes and scarred tissues that induce reentry circuits or regional slowing of active potentials[6,12]. Extensive LGE may interrupt electrophysiological conduction and induce ventricular tachyarrhythmias and systolic dysfunction[5,11,24] (Table 1).

Chronic MI

Chronic MI, particularly involving the basal to midventricular anterior wall, can lead to a reduction in LVEF and ventricular arrhythmias[6]. Chronic MI affecting the basal to midventricular inferior wall is also related to SVT[26]. Heterogeneous LGE on MRI reflects a mixture of viable myocytes and scarred tissues, which induce electric instabilities (Figure 1A)[6,12]. The heterogeneity of the infarct tissue is assessed using visual inspection, quantitative analyses of LGE, and postcontrast T1 mapping (Figure 1B)[6,12,25].

Figure 1 Chronic myocardial infarction presenting with ventricular fibrillation. A: Heterogeneous late gadolinium enhancement is observed at the midventricular inferior wall (arrows); B: Postcontrast T1 mapping confirms the heterogeneous distribution of gadolinium in the inferior myocardium (circle).

HCM

HCM is the most common primary cardiomyopathy, with disease-related gene mutations observed in one out of every 200 people[30]. HCM is the leading cause of SCD in the younger population[1,3,4]. Cardiac MRI is useful for diagnosing HCM (Figure 2A)[4]. Cardiac MRI features of HCM are incorporated into the contemporary risk stratification for SCD in HCM, including extensive LGE and apical aneurysm (Figure 2B)[4,8].

Figure 2 Hypertrophic cardiomyopathy associated with nonsustained ventricular tachycardia. A: Late gadolinium enhancement (LGE) at the insertion points, a characteristic magnetic resonance imaging feature of hypertrophic cardiomyopathy, is observed (arrows); B: In addition to the typical LGE (arrow), apical aneurysm with LGE is identified, which is related to serious ventricular arrhythmias (arrowhead).

DCM

DCM is the second common primary cardiomyopathy, characterized by reduced LVEF, a dilated left ventricular cavity, and normal coronary arteries. The primary symptom of DCM is HF, while ventricular arrhythmias can also occur[13,14]. Myocardial LGE, which is observed in one-third of DCM patients, is significantly associated with ventricular arrhythmias and mortality (Figures 3 and 4)[13,14,23]. Feng et al[14] demonstrated that septal midwall LGE is predictive of arrhythmic events beyond LVEF (Figure 3). Di Marco et al[23] reported that extracellular volume fraction ≥ 30% can identify DCM patients with arrhythmic risk within DCM patients with LGE.

Figure 3 Dilated cardiomyopathy with nonsustained ventricular tachycardia and systolic dysfunction. A and B: Septal midwall late gadolinium enhancement is observed (arrow). A cardiac resynchronization therapy defibrillator was implanted immediately after magnetic resonance imaging.

Figure 4 Dilated cardiomyopathy with sustained ventricular tachycardia. A: Late gadolinium enhancement is observed in both the septal and lateral walls (arrows); B: Endomyocardial biopsy reveals myocardial fibrosis; C: An implantable cardioverter defibrillator was installed.

Cardiac sarcoidosis

Sarcoidosis is a multisystemic granulomatous disease that affects the lungs, lymph nodes, eyes, and skin. Cardiac involvement is not uncommon and can lead to HF, conduction disturbances, and ventricular tachyarrhythmias[28]. LGE MRI should be the primary imaging modality for diagnosing cardiac sarcoidosis, followed by ¹⁸F-fluorodeoxyglucose positron emission tomography (Figure 5)[28]. Yodogawa et al[15] showed that the right ventricular LGE is significantly associated with SVT in cardiac sarcoidosis (Figure 5).

Figure 5 Cardiac sarcoidosis with nonsustained ventricular tachycardia. A: Late gadolinium enhancement is observed in the anterior wall of both the left (arrow) and right ventricles (arrowhead); B: ¹⁸F-fluorodeoxyglucose positron emission tomography shows increased uptake in the anterior and septal wall (arrows).

Limitations of cardiac MRI

Although the relationship between LGE and ventricular arrhythmias requiring ICD therapies is strongly suggested, it is not a binary determinant for ICD installation. Indeed, we have encountered several cases of SVT or VF that do not exhibit LGE but have a family history of SCD or cardiomyopathies. It remains unclear whether T1 mapping and diffusion-weighted imaging, which reportedly detect early myocardial alterations, can identify the arrhythmogenic substrate of the myocardium in patients with VF who lack LGE[16,31,32].

CONTRIBUTION OF CARDIAC MRI TO SECOND PREVENTION AND RELATED MYOCARDIAL DISEASES

Contribution of cardiac MRI to secondary prevention of SCD

Survivors of OHCA often have clinical backgrounds similar to those of candidates for primary prevention[1,2,6]. Cardiac MRI findings are also shared between candidates for the primary and secondary prevention of SCD[6,8,11,12,18,24,29]. Septal LGE has been investigated in survivors of OHCA with viral myocarditis[5]. Some patients with CVS and OHCA exhibit ischemic or nonischemic LGE[33], whereas others, a nonnegligible proportion of patients with CVS or VF, do not show LGE[16,18]. Although cardiac MRI findings of Brugada syndrome have been reported, they are not specific and have not yet been fully established[34]. Therefore, cardiac MRI should be evaluated with caution when assessing myocardial substrates that induce OHCA (Table 1).

Acute MI

Acute coronary syndrome, including acute MI, is a major cause of OHCA and SCD[1,3]. Immediate treatment is required upon onset, whereas cardiac MRI may be performed in patients with undetermined coronary angiograms or in those where acute MI is difficult to identify because of a history of chronic MI. T2-weighted imaging is useful for detecting acute MI because of its sensitivity to myocardial edema (Figure 6A)[21]. Myocardial edema may be an acute and transient substrate of ventricular tachyarrhythmias, and LGE can visualize both acute and chronic MI (Figures 1A and 6B)[17,21,24]. Cardiac MRI can help determine the need for percutaneous coronary intervention as well as ICD implantation in cases of acute MI and OHCA.

Figure 6 Recurrent acute myocardial infarction presenting with ventricular fibrillation and cardiac arrest. A: T2-weighted imaging exhibits myocardial edema as high signal intensity (arrows); B: It is difficult to identify acute infarction on late gadolinium enhancement images (arrows).

CVS

CVS cannot be diagnosed by coronary angiography alone; instead, its diagnosis requires coronary angiography with acetylcholine administration. CVS is one of the important causes of OHCA in younger athletes[35]. Cardiac MRI exhibits ischemic or nonischemic midwall LGE at the basal septum in patients with CVS (Figure 7)[33]. Neilan et al[17] reported that LGE with normal coronary artery indicates CVS that can induce OHCA.

Figure 7 Coronary vasospasm in a patient with a history of cardiac arrest. A and B: Septal midwall late gadolinium enhancement is observed on cardiac magnetic resonance imaging before implantable cardioverter defibrillator installation (arrow). Ventricular fibrillation occurred even after implantable cardioverter defibrillator installation in this patient.

Acute myocarditis

Acute myocarditis is one of the major causes of OHCA and SCD, especially in younger adults[1,5,17]. The Lake Louise Criteria recommend the use of cardiac MRI for diagnosing myocarditis[36]. Interventricular septal LGE and lateral LGE are observed in acute myocarditis (Figure 8A)[5]. T1 mapping and T2-weighted imaging are sensitive to myocardial edema or fibrosis associated with acute myocarditis (Figure 8B)[5,21,36]. Myocarditis can progress to HF or DCM-like diseases even though the patients recover from OHCA.

Figure 8 Acute myocarditis associated with cardiac arrest after running. A: Late gadolinium enhancement is identified in the interventricular septum (arrow); B: T1 mapping reveals elevated T1 values (> 1100 ms, the upper limit of normal in our institution, circle) in the septum, where late gadolinium enhancement is present.

HCM

HCM is recognized as the leading cause of SCD in the younger population[1,3,4]. Cardiac MRI is useful for diagnosing HCM in patients with OHCA[4,29]. Specific HCM subtypes associated with OHCA include reverse-curve HCM with marked myocardial hypertrophy, HCM with midventricular obstruction and apical aneurysm, and that with extensive HCM (Figure 9)[4].

Figure 9 Hypertrophic cardiomyopathy in a patient with out-of-hospital cardiac arrest. A: Cine magnetic resonance imaging shows a reverse-curve, markedly hypertrophic septum and a thin apex; B: Late gadolinium enhancement is observed in the septal wall (arrows).

Limitations of cardiac MRI

Some patients with CVS and OHCA exhibit ischemic or nonischemic LGE[33], while a nonnegligible proportion of patients with CVS or VF do not show LGE (Figure 10)[16,18]. Although cardiac MRI findings of Brugada syndrome have been reported, they are not yet fully established[34]. Therefore, cardiac MRI is not necessarily useful for identifying myocardial substrates that induce OHCA, especially in cases of CVS and channelopathy (Figure 10).

Figure 10  Coronary vasospasm with cardiac arrest during a marathon. A: No myocardial late gadolinium enhancement is observed; B: An implantable cardioverter defibrillator was implanted.

USE OF CARDIAC MRI TO PREDICT VENTRICULAR TACHYARRHYTHMIA AFTER ICD INSTALLATION

Although ICD prevents arrhythmic events and death from VF in many patients, it cannot prevent the progression of myocardial ischemia or cardiomyopathy[6,22]. This may be related to the fact that patients with HF and ICD discharge have a greater risk of progressive HF and mortality than patients with HF without discharge after primary prevention[20,37]. Therefore, predicting the recurrence of ventricular tachyarrhythmias after ICD installation is important in survivors of OHCA[37]. Because LGE can be consistent with a myocardial substrate that induces malignant ventricular tachyarrhythmia and progresses continuously in some myocardial diseases, LGE MRI may be useful for identifying patients with ventricular arrhythmia that occurs after ICD installation (Figure 7)[13,22,24,38]. However, the absence of LGE cannot predict the lack of VF[16-18]. Nevertheless, in practical situations, antiarrhythmic medication, coronary intervention, or ablation therapy can be given to patients who survive OHCA and present myocardial LGE before ICD installation[22].

RETROSPECTIVE INVESTIGATION OF CARDIAC MRI IN INDIVIDUALS AFFECTED BY SCD

We reviewed antemortem cardiac MRI data from three individuals affected by SCD retrospectively. One patient had end-stage HCM with a reduced LVEF, a mixture of thick and thin myocardium and extensive LGE (Figure 11). Another SCD patient with HCM presented focal LGE, a hypertrophied myocardium with a maximum thickness of 28 mm, and a family history of HCM. Both patients were aged below 60 years and declined to have an ICD. A maximum thickness of 30 mm is a well-known risk factor for SCD in HCM; this criterion is determined by echocardiography but not necessarily by cardiac MRI[39]. Much more attention should be paid to patients with HCM with LGE, younger ages, or a family history of HCM. The third patient with long QT syndrome experienced OHCA twice and died during the second event. This patient showed no particularly abnormal findings on MRI.

Figure 11  End-stage hypertrophic cardiomyopathy who died suddenly 6 months after the magnetic resonance imaging study. A and B: Extensive late gadolinium enhancement is observed at antemortem cardiac magnetic resonance imaging (arrows); C: Endomyocardial biopsy reveals myocytes enlargement, myocardial disarray and collagen fiber infiltration.

CONCLUSION

Cardiac MRI is useful for determining the primary prevention of SCD using an ICD in various myocardial diseases because of its wide range of views, high reproducibility, and excellent tissue characterization. In some survivors of OHCA, cardiac MRI findings are common across the candidates for primary prevention. LGE imaging may be useful for identifying survivors of OHCA who will exhibit ventricular tachyarrhythmia after the secondary prevention using an ICD. However, cardiac MRI fails to demonstrate abnormal findings in patients with CVS, channelopathy or VF occasionally. Therefore, the combination of cardiac MRI with detailed interviews of the patients’ ages, family history of SCD or cardiomyopathy, and clinical symptoms is essential for prevention of SCD using an ICD.