European guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death 2022: cardiomyopathy. What’s new?

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In the new European recommendations for treating patients with ventricular arrhythmias (VAs), a large section is devoted to cardiomyopathies (CMPs). Cardiac arrhythmias are perhaps one of the key clinical symptoms of these relatively rare diseases, and sudden cardiac death (SCD) is the classic complication of most CMPs.

This section focuses on CMPs in the order they are presented in European recommendations.

Dilated cardiomyopathy (DCM)

DCM is characterized by dilatation and systolic dysfunction of the left ventricle or both ventricles and is not associated with ischemic heart disease (IHD) or abnormal hemodynamic loads (such as arterial hypertension and valvular disease) [1, 2]. SCD occurs in 12% of patients with DCM and accounts for 25%–35% of the overall cause of death in DCM [3–5].

According to the literature, DCM affects 1 per 2500–2700 populations [6, 7]. However, the true incidence is most likely higher.

The causes of the appearance of DCM in a patient can be genetic, acquired, or mixed when a genetic predisposition is formed in the presence of external factors, for example, the pre- and postpartum period, alcohol abuse, chemotherapy, and others [8]. Pathogenic mutations are detected in 25–55% of patients with DCM, with a predominant autosomal dominant type of inheritance [2]. More often than others, mutations are found in the titin (TTN) (31%) and lamin (LMNA) (14.3%) genes [9]. Mutations in genes such as LMNA, PLN (encodes the phospholamban protein), RBM20 (encodes the splicing transcription factor), and FLNC (encodes filamin C) are associated with a high risk of VAs and SCD [10–14]. Carriers of desmosomal and LMNA mutations have a high incidence of VAs and SCD, which does not depend on the LV ejection fraction (EF) [14]. The identification of pathogenic mutations plays an important role in SCD risk stratification.

The phenotype, particularly in a genetically determined disease, upon disease onset may not correspond to the standard criteria for the disease and may change over time. Thus, in the early disease stages, the patient may only have a decrease in EF without dilatation of the cardiac chambers. In this regard, a new category of DCM has been proposed, that is, hypokinetic nondilated cardiomyopathy (HNDCM) [8]. HNDCM is characterized by LV or biventricular global systolic dysfunction (LVEF <45%) without dilatation, and systolic dysfunction is not associated with abnormal myocardial stress or coronary artery disease [8]. The 2023 European guidelines for the management of patients with CMPs made a special attention to this syndrome. It has been proposed to initially replace the term “hypokinetic nondilated cardiomyopathy” with “nondilated left ventricular cardiomyopathy” (NDLVCMP) and then to identify NDLVCMP as a new independent phenotype of CMPs [15]. The term “NDLVCM” introduced in 2023 appears to be a broader concept than HNDCM. NDLVCMP is characterized by the presence of LV nonischemic scarring or fatty degeneration, regardless of the presence or absence of global or local impairment of wall mobility or isolated global hypokinesia of the LV walls without scarring. This disease is also characterized by ventricular rhythm disturbances.

An integrated approach to diagnosing DCM is essential. The role of echocardiography (EchoCG), particularly in the early disease stages, is undeniable. Magnetic resonance imaging (MRI) of the heart with contrast enhancement enables not only to determine LVEF but also to identify areas of fibrosis and, by their localization, clarify the etiology (ischemic, i.e., subendocardial, transmural fibrosis, corresponding in localization to the blood supply system of a certain coronary artery; nonischemic, i.e., diffuse interstitial intramural, subepicardial fibrosis, or subendocardial, but not corresponding to the blood supply system of a particular coronary artery) [16, 17]. In addition, MRI findings, along with genetic data, can contribute to SCD risk stratification [2]. According to a meta-analysis of 29 studies that pooled MRI findings from 2,948 patients with DCM, late gadolinium enhancement (LGE) is associated with an increased risk of arrhythmic endpoints (VA and SCD), major cardiovascular events, and all-cause death [18]. A recent study of 1020 patients with DCM revealed that both LGE and LVEF were risk markers for all-cause and cardiovascular deaths; however, only LGE was associated with the risk of SCD [19]. The recommendations emphasize the importance of performing cardiac MRI with contrast in patients with DCM/HNDCM.

The registration of electrocardiograms (ECG) is recommended not only for patients but also for their first-degree relatives. The presence of pathology of the sinus and atrioventricular (AV) nodes, most often in combination with bundle branch blocks, when the disease manifests at a young age should raise suspicion of LMNA-associated DCM with a poor prognosis [20].

The recommendations for genetic testing are presented in Table 1 [2].

 

Table 1. Recommendations for genetic testing for dilated/hypokinetic nondilated cardiomyopathy

Таблица 1. Рекомендации по генетическому тестированию при дилатационной / гипокинетической недилатационной кардиомиопатии

Note: DCM — dilated cardiomyopathy; HNDCM — hypokinetic nondilated cardiomyopathy; LMNA — nuclear lamin gene; PLN — phospholamban gene, RBM20 — gene encoding a splicing transcription factor; FLNC — filamin C gene.

Примечание: ДКМП — дилатационная кардиомиопатия; ГНДКМП — гипокинетическая недилатационная кардиомиопатия; LMNA — ген ядерных ламинов; PLN — ген фосфоламбана, RBM20 — ген, кодирующий транскрипционный фактор сплайсинга; FLNC — ген филамина С.

 

The recommendations for examining patients and their relatives are presented in Table 2 [2].

 

Table 2. Recommendations for the examination of patients suffering from dilated/hypokinetic non-dilated cardiomyopathy and their relatives

Таблица 2. Рекомендации по обследованию пациентов, страдающих дилатационной / гипокинетической недилатационной кардиомиопатией, и их родственников

Note: SCD — sudden cardiac death; DCM — dilated cardiomyopathy; HNDCM — hypokinetic nondilated cardiomyopathy; MRI — magnetic resonance imaging.

Примечание: ВСС — внезапная сердечная смерть; ДКМП — дилатационная кардиомиопатия; ГНДКМП — гипокинетическая недилатационная кардиомиопатия; МРТ — магнитно-резонансная томография.

 

The 2022 European guidelines provide an algorithm for risk stratification and primary prevention of sudden cardiac death in patients with DCM/HNDCM (Fig. 1) [2].

 

Fig. 1. Algorithm for risk stratification and primary prevention of sudden cardiac death in patients with dilated cardiomyopathy/hypokinetic non-dilated cardiomyopathy [2]

AV — atrioventricular; CMR — cardiac magnetic resonance; DCM — dilated cardiomyopathy; HNDCM — hypokinetic non-dilated cardiomyopathy; ICD — implantable cardioverter defibrillator; ILR — implantable loop recorder; LMNA — nuclear lamin gene; LVEF — left ventricular ejection fraction; N — no; NSVT — non-sustained ventricular tachycardia; PES, programmed electrical stimulation; SCD — sudden cardiac death; SMVT — sustained monomorphic ventricular tachycardia; VA — ventricular arrhythmias; Y — yes

^a Risk factors: unexplained syncope, pathogenic variants in PLN, FLNC, or RBM20, LGE on CMR, inducible SMVT at PES. ^b The 2018 ESC Guidelines for the diagnosis and management of syncope

Рис. 1. Алгоритм стратификации риска и первичной профилактики внезапной сердечной смерти у пациентов с дилатационной кардиомиопатией / гипокинетической недилатационной кардиомиопатией [2].

АВ — атриовентрикулярная; ВСС — внезапная сердечная смерть; ДКМП — дилатационная кардиомиопатия; ГНДКМП — гипокинетическая недилатационная кардиомиопатия; ЖА — желудочковые аритмии; ИПР — имплантируемые петлевые регистраторы; ИКД — имплантируемый кардиовертер-дефибриллятор; ЛЖ — левый желудочек; МРТ — магнитно-резонансная томография; НУЖТ — неустойчива желудочковая тахикардия; УМЖТ — устойчивая мономорфная желудочковая тахикардия; ФВ — фракция выброса; ЭФИ — электрофизиологическое исследование; LMNA — ген ядерных ламинов

^а Обмороки, фиброз при МРТ сердца, индуцируемые устойчивые мономорфные желудочковые тахикардии при эндоЭФИ, патогенные

 

Given the high risk of SCD, patients with DCM need not only secondary but also primary prevention of SCD. The 2022 European guidelines provide clear guidance on who is eligible for primary and secondary prevention of SCD. Because the main clinical manifestation of DCM/HNDCM is chronic heart failure (CHF), treatment of CHF, in accordance with current recommendations, is mandatory for at least 3 months before deciding on implantable cardioverter-defibrillator (ICD) implantation for the primary prevention of SCD [2]. The patient’s cardiac function and clinical status after 3 months of optimal medical therapy (OMT) must be re-evaluated before the initial prophylactic implantation of an ICD. LVEF with OMT can be significantly improved in DCM caused by myocarditis or TTN mutations [2].

The recommendations for the primary prevention of SCD are presented in Table 3 [2].

 

Таблица 3. Рекомендации по первичной профилактике внезапной сердечной смерти у пациентов, страдающих дилатационной / гипокинетической недилатационной кардиомиопатией

Table 3. Recommendations for the primary prevention of sudden cardiac death in patients suffering from dilated/hypokinetic nondilated cardiomyopathy

Note: AV — atrioventricular; CMR — cardiac magnetic resonance; DCM — dilated cardiomyopathy; HNDCM — hypokinetic non-dilated cardiomyopathy; EF — ejection fraction; ICD — implantable cardioverter defibrillator; LV, left ventricul; NYHA, New York Heart Association; LMNA — nuclear lamin gene; PES — programmed electrical stimulation; PLN — phospholamban gene; RBM20 — gene encoding a splicing transcription factor; FLNC — filamin C gene. ^а Based on the risk calculator LMNA-risk VTA calculator Risk Prediction Score for Life-Threatening Ventricular Tachyarrhythmias in Laminopathies (https://lmna-risk-vta.fr/).

Примечание: АВ — атриовентрикулярное; ДКМП — дилатационная кардиомиопатия; ГНДКМП — гипокинетическая недилатационная кардиомиопатия; ИКД — имплантируемый кардиовертер-дефибриллятор; ЛЖ — левый желудочек; МРТ — магнитно-резонансная томография; ОМТ — оптимальная медикаментозная терапия; ФВ — фракция выброса; ЭФИ — электрофизиологическое исследование; NYHA — New York Heart Association; LMNA — ген ядерных ламинов; PLN — ген фосфоламбана, RBM20 — ген, кодирующий транскрипционный фактор сплайсинга; FLNC — ген филамина С. ^а Риск рассчитывается с помощью калькулятора LMNA-risk VTA calculator Risk Prediction Score for Life-Threatening Ventricular Tachyarrhythmias in Laminopathies (https://lmna-risk-vta.fr/)

 

The recommendations for the secondary prevention of sudden cardiac death are presented in Table 4 [2].

 

Таблица 4. Рекомендации по вторичной профилактике внезапной сердечной смерти у пациентов, страдающих дилатационной / гипокинетической недилатационной кардиомиопатией

Table 4. Recommendations for secondary prevention of sudden cardiac death in patients suffering from dilated/hypokinetic nondilated cardiomyopathy

Note: DCM — dilated cardiomyopathy; HNDCM — hypokinetic nondilated cardiomyopathy; ICD — implantable cardioverter defibrillator.

Примечание: ДКМП — дилатационная кардиомиопатия; ГНДКМП — гипокинетическая недилатационная кардиомиопатия; ИКД — имплантируемый кардиовертер-дефибриллятор.

 

ICDs reduce the risk of not only arrhythmic death but also death from all causes [2]. Moreover, frequent, painful ICD shocks worsen the quality of life of the patients. The implantation of ICDs with antitachycardia pacing (ATP) functionality and optimization of ICD programing can reduce the number of ICD shocks delivered in response to ventricular tachycardia (VT); however, additional drug therapy is almost always required to reduce symptomatic episodes of VA [2]. The recommendations for antiarrhythmic drug selection are based on the results of the OPTIC trial, where 412 patients with ICD within 21 days after VT/ventricular fibrillation (VF) were randomized to three antiarrhythmic treatment groups: amiodarone plus beta-blocker, sotalol alone, or beta-blocker alone. The frequency of ICD shocks after 1 year was 10.3% in the amiodarone and beta-blocker group, 24.3% in the sotalol group, and 38.5% in the beta-blocker group [21]. Only limited data are available on the efficiency and safety of sodium channel blockers in reducing the number of ICD activations in DCM [2]. They may be useful for reducing VAs only in a few patients without severe heart failure and low LVEF. The recommendations emphasize the need to align the level of efficiency and drug-related side effects when choosing antiarrhythmic therapy.

In DCM, monomorphic VTs predominate (Fig. 2), which are based on the reentry mechanism.

 

Fig. 2. Genetic risk for VA/SCD, typical triggers for VA/SCD, age at presentation with VA/SCD, sex predominance, and typical VA in different diseases associated with VA/SCD

 

— presence of genetic risks; — trigger — physical and emotional stress;  — trigger — swimming, diving; — syncope during sleep; —trigger — a sharp sound; — trigger – physical stress

ACS — acute coronary syndrome; ARVC — arrhythmogenic right ventricular cardiomyopathy; BrS — Brugada syndrome; CAD — coronary artery disease; CPVT — catecholaminergic polymorphic ventricular tachycardia; DCM — dilated cardiomyopathy; HCM — hypertrophic cardiomyopathy; LQT — long QT syndrome; MVT — monomorphic ventricular tachycardia; PVT — polymorphic ventricular tachycardia; rTOF — repaired tetralogy of Fallot; SCD — sudden cardiac death; VA — ventricular arrhythmia

Рис. 2. Генетический риск желудочковой аритмии / внезапной сердечной смерти, типичные триггеры желудочковой аритмии / внезапной сердечной смерти, возраст при появлении желудочковой аритмии / внезапной сердечной смерти, преобладание пола и вариант типичной желудочковой аритмии при различных заболеваниях, связанных с желудочковой аритмией / внезапной сердечной смертью [2]

— наличие генетических рисков; — триггер — физическая и эмоциональная нагрузки; — триггер — плавание, ныряние; — синкопальные состояния во сне; — триггер — резкий звук; — триггер — физическая нагрузка ВСС — внезапная сердечная смерть; ЖА — желудочковые аритмии; МЖТ — мономорфная желудочковая тахикардия; ПЖТ — полиморфная желудочковая тахикардия

 

 

 

To reduce the number of monomorphic VTs, catheter ablation can be used in addition to drug therapy. However, the rate of recurrent VTs after catheterization procedures in patients with DCM is higher than that in patients with IHD, the VT-free survival 1 year after a catheter procedure in DCM is 40.5%, whereas in IHD, it is 57% [22]. Some patients require repeated procedures, after which the probability of the absence of recurrence of arrhythmia increases. When the arrhythmic focus is subepicardial, epicardial ablation is required in 27%–30% of the procedures [22, 23]. The outcome is particularly poor in patients with pathogenic LMNA mutations. Because of the deep transmural, anteroseptal location of the substrate, transcoronary ethanol ablation, bipolar ablation, and surgical ablation may be required [24–26].

The general recommendations for patients with LMNA mutations are presented in Table 5.

 

Table 5. General recommendations for patients with mutations in genes encoding lamin

Таблица 5. Общие рекомендации для пациентов с мутацией генов, кодирующих синтез ламинов

Note: DCM — dilated cardiomyopathy; HNDCM — hypokinetic nondilated cardiomyopathy; LMNA — nuclear lamin gene.

Примечание: ДКМП — дилатационная кардиомиопатия; ГНДКМП — гипокинетическая недилатационная кардиомиопатия; LMNA — ген ядерных ламинов.

 

Arrhythmogenic right ventricular cardiomyopathy (ACM)

ACM is characterized by the replacement of the myocardium with fibrous and fatty tissue [27]. Currently, it is more correct to talk about ACM of both ventricles [28]. The prevalence of ACM in the population ranges from 1:1000 to 1:5000 [29]. Most often, ACM is caused by pathogenic mutations in desmosomal genes (Dsc2, desmocollin-2; Dsg2, desmoglein-2; Dsp, desmoplakin; Рkg, plakoglobin; Pkp2, plakophilin-2) and less often in nondesmosomal genes. Similar to DCM, in ACM, some mutations are associated with a high risk of developing VA at a young age [30, 31]. The diagnosis of ACM is complex and requires searching and assessing certain criteria. Although the recommendations contain a reference in Guidelines 2022 to the publication of Corrado et al. (2020) [28], the criteria for diagnosing ACM are not the 2020 Padua criteria but the previous 2010 criteria [32]. As an advantage, the Padua criteria provide an algorithm for diagnosing not only the right ventricular but also the LV process. Figure 3 presents the ECG of our 16-year-old patient with arrhythmogenic cardiomyopathy. ECG was performed during sinus rhythm. At the beginning of the recording, the moment of the cessation of unstable polymorphic VT (three complexes) was recorded. In addition, frequent polymorphic single and paired premature ventricular complexes (PVC) of the bigeminy type were noted. The major Padua criterion for the diagnosis of right ventricular ACM was identified, namely, inverted T waves in right precordial leads V1, V2, and V3 in a patient with complete pubertal development, and the absence of complete right bundle branch block. In addition, minor Padua criteria were noted for the diagnosis of LV ACM, which are inverted T waves in left precordial leads V4–V6 in the absence of complete left bundle branch (LBB) block and low-amplitude QRS (< 0.5 mV peak-to-peak) in the limb leads to the absence of obesity, emphysema, and pericardial effusion.

 

Fig. 3. Electrocardiogram of a patient suffering from biventricular arrhythmogenic cardiomyopathy (explanation in the text)

Рис. 3. Электрокардиограмма пациента, страдающего бивентрикулярной аритмогенной кардиомиопатией (объяснение в тексте)

 

Figure 4 presents the ECG of one of the patients with right ventricular ACM during classical sustained VT, which is a major criteria for diagnosing right ventricular ACM —VT with QRS morphology similar to LBB block, causing the deviation of the electrical axis to the left upward (not from the right ventricle (RV) outflow tract, the focus is located in the area of the RV free wall).

 

Fig. 4. Electrocardiogram of a patient suffering from right ventricular arrhythmogenic cardiomyopathy, at the time of tipical ventricular tachycardia (explanation in text)

Рис. 4. Электрокардиограмма пациента, страдающего правожелудочковой аритмогенной кардиомиопатией, во время типичной желудочковой тахикардии (объяснение в тексте)

 

During the natural disease course in patients with ACM who have not been implanted with ICD, cardiac arrest occurs in 4.6%–6.1% of cases [33–36]. Because of the high incidence of VA and SCD in ACM, risk stratification of adverse arrhythmic events is required. In 16%–19% of cases, the indication for ICD is rapid VT (≥ 250 beats/min) or VF, which are considered surrogate markers of a potentially life-threatening event [37–40]. Recently, a risk model was developed to predict any persistent VA in ACM based on the analysis of the disease course of 528 patients with an established diagnosis of ACM and no history of VA. During model development, age, sex, arrhythmic syncope, nonsustained VT, number of ventricular PVC, number of leads with T-wave inversion, and RV EF (c-index 0.77) were collected [41]. Another model for predicting life-threatening VA was proposed based on the analysis of 864 patients with ACM, which included male sex, age, number of ventricular PVC within 24 h, and number of leads with T-wave inversion (c-index 0.74) as predictors [41]. However, validation studies are required before these risk models can be recommended for clinical use [2].

The recommendations for the diagnostics and management of patients with arrhythmogenic cardiomyopathy are presented in Table 6 [2].

 

Table 6. Recommendations for the diagnosis and management of patients suffering from arrhythmogenic cardiomyopathy

Таблица 6. Рекомендации по диагностике и ведению пациентов, страдающих аритмогенной кардиомиопатией

Note: ACM — arrhythmogenic cardiomyopathy; MRI — magnetic resonance imaging.

Примечание: АКМП — аритмогенная кардиомиопатия; МРТ — магнитно-резонансная томография.

 

The recommendations for the risk stratification and primary prevention of SCD are presented in Table 7 [2].

 

Table 7. Recommendations for risk stratification and primary prevention of sudden death in arrhythmogenic cardiomyopathy

Таблица 7. Рекомендации по стратификации риска и первичной профилактике внезапной смерт при аритмогенной кардиомиопатии

Note: ACM — arrhythmogenic cardiomyopathy; ICD — implantable cardioverter defibrillator; LV — left ventricle; RV — right ventricle. ^a Presyncope or palpitations indicating ventricular arrhythmias.

Примечание: АКМП — аритмогенная кардиомиопатия; ИКД — имплантируемый кардиовертер-дефибриллятор; ЛЖ — левый желудочек; ПЖ — правый желудочек. ^а Предобморочные состояния или учащенное сердцебиение, указывающее на желудочковые аритмии.

 

RV and LV dysfunctions are associated with high arrhythmic risk. The guidelines state that EF thresholds for indications for ICD implantation are difficult to define; however, even asymptomatic patients with severe RV dysfunction (right ventricular area fraction change ≤ 17% or RV EF ≤ 35%) should be advised to implant an ICD for the primary prevention of SCD. Similarly, patients with ACM with significant LV disease (LVEF ≤ 35%) are candidates for ICD implantation according to current ICD guidelines for DCM [2]. An ICD for the primary prevention of SCD should also be recommended in patients with symptomatic ACM (presyncope or palpitations suggestive of VA) and moderate RV dysfunction (EF of 40%–35%) and/or moderate LV dysfunction (EF of 45%–35%) [2].

The recommendations for the secondary prevention of sudden cardiac death and treatment of ventricular arrhythmias are presented in Table 8 [2].

 

Table 8. Recommendations for secondary prevention of sudden death and treatment of ventricular arrhythmias in arrhythmogenic cardiomyopathy

Таблица 8. Рекомендации по вторичной профилактике внезапной смерти и лечению желудочковых аритмий

Note: ACM — arrhythmogenic cardiomyopathy; ICD — implantable cardioverter defibrillator.

Примечание: АКМП — аритмогенная кардиомиопатия; ИКД — имплантируемый кардиовертер-дефибриллятор.

 

Beta-blockers are recommended as first-line therapy in both symptomatic and asymptomatic cases, although this is not supported by clinical trial data [2]. Sotalol is notably effective in preventing the reproducibility of VT during electrophysiological tests [43]; however, it does not suppress clinically significant arrhythmias in real life [43, 44]. Treatment with amiodarone or class 1 drugs is associated with a trend toward lower recurrent VT rates compared with sotalol [45]. The addition of flecainide to beta-blockers or sotalol was useful in a small group of patients [46]. Note that first-class drugs are contraindicated in patients with reduced EF. Catheter ablation may be an alternative to drug therapy. When choosing a therapeutic strategy, potential risks, drug side effects, and patient preferences must be considered [47].

The recommendations for managing relatives of patients with ACM are presented in Table 9 [2].

 

Table 9. Recommendations for the management of relatives of a patient with arrhythmogenic cardiomyopathy

Таблица 9. Рекомендация по ведению родственников больного аритмогенной кардиомиопатией

Note: ACM — arrhythmogenic cardiomyopathy.

Примечание: АКМП — аритмогенная кардиомиопатия.

 

Hypertrophic cardiomyopathy (HCM)

HCM is a disease characterized by an increase in LV wall thickness in the absence of pathological conditions associated with myocardial load, such as arterial hypertension or valvular diseases [1, 48].

Mutations in genes encoding the synthesis of sarcomeric proteins (myosin binding protein C [MYBPC3], myosin heavy chains [MYH7], cardiac troponin T [TNNT2], cardiac troponin I [TNNI3], and α-tropomyosin [TPM1], essential and regulatory light chains myosin [MYL3 and MYL2], and actin [ACTS]) are detected in 30%–60% of patients, most often in those with HCM diagnosed at a young age or with a family history of HCM [49, 50]. The recommendations emphasize the need for genetic testing of probands and screening of first-degree relatives.

In adults, the estimated prevalence of HCM is 1 per 500 populations [51]. Among children, the rate is much lower.

According to previous studies, annual mortality in HCM ranges from 0.5% to 2% [2, 48, 52]. Most HCM-associated deaths in patients aged up to 60 years occur suddenly, whereas older patients more often die from stroke, heart failure, obstruction, or supraventricular arrhythmias. The annual incidence of SCD or related ICD activation is approximately 0.8%; however, it largely depends on the age and risk profile of a patient [53–56]. SCD can also be triggered by exercise and participation in competitive sports [57].

Planning a management strategy for a patient with HCM begins with stratifying the risk of sudden cardiac death. A 5-year risk stratification scale for SCD has been developed based on seven factors, namely, age, LV wall thickness, left atrial (LA) dimension, LV outflow tract (LVOT) obstruction, nonsustained VT, unexplained syncope, and family history of SCD (HCM Risk-SCD: https://doc2do.com/hcm/webHCM.html) [2]. The calculator is not intended for evaluating professional athletes or persons with metabolic and infiltrative diseases, after myectomy or ethanol septal ablation. To stratify the risk of SCD in children (1–16 years), a special pediatric HCM risk-kids model was recently developed, including unexplained syncope, maximum LV wall thickness, LA diameter, LVOT gradient, and nonsustained VT (https://hcmriskkids.org) [2, 58].

The 2022 guidelines emphasize additional factors that are not reflected in the SCD risk model that should be considered in patients at intermediate or low estimated risk. Important additional factors include LV systolic dysfunction, aneurysm in the LV apex, extensive areas of late signal enhancement on contrast-enhanced cardiac MRI corresponding to fibrosis, and presence of single or multiple sarcomeric mutations [50, 59–64]. The identification of large areas of late MRI signal enhancement (≥15% of the LV mass) has been proposed as a good predictor of SCD. However, fibrosis thresholds are sometimes difficult to use because the quantification of late signal enhancement depends on the method by which the MR image was acquired and the type and amount of contrast used [2].

Because new risk factors may emerge in a patient’s life, periodic risk reassessment is an essential part of long-term patient follow-up.

The advisability of the electrophysiological test to induce VA in HCM, according to the recommendations, is controversial because according to the literature, rhythm disturbances obtained with the electrophysiological test are considered nonspecific, although there are other points of view [65, 66].

The recommendations for risk stratification, prevention of sudden cardiac death, and treatment of ventricular arrhythmias in hypertrophic cardiomyopathy are presented in Table 10 [2].

 

Table 10. Recommendations for risk stratification, prevention of sudden cardiac death, and treatment of ventricular arrhythmias in hypertrophic cardiomyopathy

Таблица 10. Рекомендации по стратификации риска, профилактике внезапной сердечной смерти и лечению желудочковых аритмий при гипертрофической кардиомиопатии

Note: SCD — sudden cardiac death; HCM — hypertrophic cardiomyopathy; VA — ventricular arrhythmias; VT — ventricular tachycardia; ICD — implantable cardioverter defirillator; LV — left ventricle; MRI — magnetic resonance imaging; EF — ejection fraction; VF — ventricular fibrillation.

Примечание: ВСС — внезапная сердечная смерть; ГКМП — гипертрофическая кардиомиопатия; ЖА — желудочковые аритмии; ЖТ — желудочковая тахикардия; ИКД — имплантируемый кардиовертер-дефириллятор; ЛЖ — левый желудочек; МРТ — магнитно-резонансная томография; ФВ — фракция выброса; ФЖ — фибрилляция желудочков.

 

Patients who experience cardiac arrest due to VT/VF or hemodynamically intolerable VT are at high risk of life-threatening VA and require an ICD for secondary prevention of SCD [2, 48, 67–69]. Following ICD implantation for primary or secondary prevention of SCD, the most common documented subtype of VA is sustained monomorphic VT, in which ATP is successful in 69%–76.5% of all episodes. In this regard, during implantation, preference should be given to ICDs with ATP functionality [70–72]. No randomized clinical or cohort studies have confirmed the important role of medications in preventing SCD in HCM [2, 48, 73]. Amiodarone can reduce the number of VA; however, data on its effectiveness in preventing SCD are inconsistent [73, 74]. Disopyramide and beta-blockers are effective in controlling symptoms and LVOT obstruction; however, no evidence shows that they reduce the risk of SCD [2, 48]. Similarly, surgical myectomy or ethanol ablation is not recommended to reduce the SCD risk in patients with LVOT obstruction [2, 48]. Despite the lack of clear data on the efficiency of antiarrhythmic drugs, beta-blockers, amiodarone, sotalol, and sodium channel blockers are prescribed to patients with HCM and symptomatic VAs [2]. Catheter ablation may also be used in carefully selected patients with HCM and sustained monomorphic VT for whom antiarrhythmic drugs are ineffective, contraindicated, or intolerable. The recommendations emphasize that the results after ablation for HCM are worse than those for other diseases of nonischemic etiology [75–77].

Left ventricular non-compaction (LVNC)

Since 1995, along with HCM, DCM, RCM, and ACM, a group of “unclassified” cardiomyopathies has been identified, including LVNC or noncompact cardiomyopathy (NCM) and Takotsubo syndrome. In the 2023 European Society of Cardiology guidelines on cardiomyopathies, the concept of “unclassified” cardiomyopathies was abolished and replaced by “syndromes associated with cardiomyopathic phenotypes” [15]. Taking into account the change in the approach to the classification of cardiomyopathies, the 2023 recommendations propose using the term “left ventricle hypertrabecularity” instead of LVNC.

In this article, we use the term LVNC because this is the term used in the 2022 European guidelines for the treatment of ventricular arrhythmias and the prevention of SCD. LVNC includes a heterogeneous group of phenotypically different diseases characterized by specific changes in the LV myocardium and sometimes RV myocardium [2, 78–80]. A structural pathology common to all phenotypes is abnormal trabeculae in the LV/RV or both ventricles, most often in the apical region [78–80]. Figure 5 presents an echocardiogram of one of our patients.

 

Fig. 5. Echocardiogram of a patient with left ventricular hypertrabeculation. Apical 4-chamber view. Noteworthy is the dilatation of the left ventricle and pronounced trabecularity in the area at the apex

Рис. 5. Эхокардиограмма пациента, имеющего гипертрабекулярность миокарда левого желудочка. Верхушечная 4-камерная позиция. Обращают на себя внимание дилатация левого желудочка и выраженная трабекулярность в области верхушки

 

LVNC may include LV dilatation, LV hypertrophy, systolic dysfunction, diastolic dysfunction, or both, and it may be associated with various congenital heart defects [78–80]. Clinically, the disease manifests as CHF, life-threatening VAs, complete AV block, and bundle branch blocks. Up to nine variants of the disease, hemodynamically and clinically occurring differently [79, 80]:

1) Isolated or benign form: LVNC with structural changes, absent hemodynamic disturbances, and clinical signs (registered in athletes and pregnant women);

2) Arrhythmogenic form: the main clinical manifestation is cardiac arrhythmia, primarily VA;

3) Dilated form: in addition to characteristic morphological changes, there is dilation and decreased contractility of the LV;

4) Hypertrophic form, with no pronounced dilatation, but with myocardial hypertrophy, primarily thickening of the myocardium, which is not involved in the noncompaction process;

5) “Mixed” form of non-compaction;

6) Restrictive form, in which severe diastolic dysfunction predominates;

7) Biventricular form of the non-compaction;

8) Excessive trabecularity of the RV with a normal structure of the LV;

9) Combination of non-compaction with congenital heart defects.

The association of the disease with genetic abnormalities is detected in 30%–50% of patients. Several genes encoding sarcomeric or cytoskeletal proteins have been identified; however, the identified genetic abnormalities occur not only in NCM but also in other cardiomyopathies, including Barth syndrome [79, 80].

Diagnostics of non-compaction are difficult; various proposed diagnostic criteria have not yet been validated, and none of them are given as diagnostic criteria in the recommendations. Cardiovascular mortality in patients with NCM is similar to that in patients with DCM [81]. The detection of focal fibrosis on contrast-enhanced MRI is associated with serious cardiovascular events, including arrhythmic events [82]. However, the risk stratification criteria for SCD in NCM have not yet been developed. Thus, in the future, combining MRI criteria with genetic testing data may overcome the current uncertainty regarding risk stratification for adverse events in NCM [2, 83]. In the meantime, when deciding on ICD implantation for diagnosed NCM, the criteria recommended for DCM/HNDCM should be used. The recommendations for ICD implantation for LVNC are presented in Table 11 [2].

 

Table 11. Recommendations for cardioverter defibrillator implantation in left ventricular non-compaction

Таблица 11. Рекомендации по имплантации кардиовертера-дефибриллятора при некомпактном миокарде левого желудочка

Note: SCD — sudden cardiac death; DCM — dilated cardiomyopathy; HNDCM — hypokinetic nondilated cardiomyopathy; ICD — implantable cardioverter defibrillator, MRI — magnetic resonance imaging.

Примечание: ВСС — внезапная сердечная смерть; ДКМП — дилатационная кардиомиопатия; ГНДКМП — гипокинетическая недилатационная кардиомиопатия; ИКД — имплантируемый кардиовертер-дефибриллятор: МРТ — магнитно-резонансная томография.

 

Restrictive cardiomyopathy (RCM)

The RCM phenotype is rare and can result from various causes, including genetically determined and acquired interstitial fibrosis, infiltrative disorders (e.g., amyloidosis), and storage diseases (e.g., Anderson–Fabry disease). Their identification is crucial for the choice of therapy because of certain diseases in which in the clinical course restrictive hemodynamics comes to the fore, and there is a specific disease-modifying therapy. Heart failure is a major symptom of any type of RCM. Depending on the phenotype, atrial or ventricular arrhythmias may predominate, including fatal ones. For example, in Fabry disease, the most reported cardiovascular deaths were classified as SCD [84]. Because RCM is the rarest among all CMPs, large randomized studies of this pathology are not yet available. The retrospective, observational nature of most minor, single-center studies and the low absolute number of deaths due to cardiovascular disease and SCD in these studies do not currently allow ICDs to be recommended for the primary prevention of SCD in RCM. The guidelines provide advice only ICD for cardiac amyloidosis (Table 12) [2]. Currently, an ICD should be recommended for patients with amyloid CMP and hemodynamically intolerable VT after careful consideration of the competing risks of nonarrhythmic and noncardiac death.

 

Table 12. Recommendations for implantation of a cardioverter-defibrillator in patients with cardiac amyloidosis

Таблица 12. Рекомендации по имплантации кардиовертера-дефибриллятора пациентам, страдающим амилоидозом сердца

Note: VT — ventricular tachycardia; ICD — implantable cardioverter defibrillator; CMP — cardiomyopathy.

Примечание: ЖТ — желудочковая тахикардия; ИКД — имплантируемый кардиовертер-дефибриллятор; КМП — кардиомиопатия.

 

Recommendations devoted to the urgent issues of determining CMP, diagnostics, risk stratification of SCD, and treatment of VA in CMPs are of great practical interest because fatal ventricular arrhythmias are a common complication of all CMPs.

ADDITIONAL INFORMATION

Competing interests. The authors declare that they have no competing interests.

Funding source. This study was not supported by any external sources of funding.

About the authors

Tatiana N. Novikova

North-Western State Medical University named after I.I. Mechnikov

Author for correspondence.
Email: novikova-tn@mail.ru
ORCID iD: 0000-0003-4655-0297
SPIN-code: 3401-0329

Cand. Sci. (Med.), associate professor of the Department of Hospital Therapy and Cardiology named after M.S. Kushakovskiy. North-Western State Medical University named after I.I. Mechnikov, Saint Petersburg

Russian Federation, Saint Petersburg

Fatima I. Bitakova

North-Western State Medical University named after I.I. Mechnikov

Email: Fatima.Bitakova@szgmu.ru
ORCID iD: 0000-0001-6637-8266
SPIN-code: 8624-7193

Cand. Sci. (Med.), associate professor

Russian Federation, Saint Petersburg

Valeria S. Ignateva

North-Western State Medical University named after I.I. Mechnikov

Email: valeria2311@bk.ru
ORCID iD: 0009-0008-9446-9374

6^th year student

Russian Federation, Saint Petersburg

Vladimir I. Novikov

North-Western State Medical University named after I.I. Mechnikov

Email: novikov-vi@mail.ru
ORCID iD: 0000-0002-2493-6300
SPIN-code: 6909-3377

Dr. Sci. (Med.), professor

Russian Federation, Saint Petersburg

Sergey A. Sayganov

North-Western State Medical University named after I.I. Mechnikov

Email: ssayganov@gmail.com
ORCID iD: 0000-0001-8325-1937
SPIN-code: 2174-6400

Dr. Sci. (Med.), professor, rector

Russian Federation, Saint Petersburg

Vladislava A. Shcherbakova

North-Western State Medical University named after I.I. Mechnikov

Email: shcher.vl@yandex.ru

6^th year student

Russian Federation, Saint Petersburg

References

Supplementary files