The relationship between apical hypertrophic cardiomyopathy and sudden cardiac death: benign indeed?

Background Hypertrophic cardiomyopathy (HCM) is a genetic heart disease that poses a risk for sudden cardiac death. It has not been studied systematically in Southeast Asian countries. The purpose of this study was to investigate the characteristics and patterns of fibrosis in HCM, as well as to determine the risk of sudden cardiac death in relation to age, sex, and myocardial fibrosis in Brunei Darussalam. Methods All patients diagnosed with HCM from 2011 to 2017 were studied in Brunei Darussalam. Data was acquired from clinical notes of these patients and studied for the demographic profile of the disease, clinical manifestations, and risks for sudden cardiac death. Results A total of 39 patients with HCM were identified, with a mean age at diagnosis of 47.46±12.27 years. Roughly half of HCM patients (51.3%) were found to be asymptomatic. A total of 30 patients underwent cardiac magnetic resonance (CMR). Myocardial fibrosis was found in 53.8%. This was more prevalent and significant in apical HCM compared to asymmetrical septal HCM, in 10 (83.3%) and nine (60%) patients (p=0.032), respectively. Apical and asymmetrical septal HCM were the most common types of HCM in the population, 15 (38.5%) and 16 (41%), respectively. Asymmetrical septal HCM presented with more murmurs than apical HCM patients, nine (56.3%) and one (6.7%) patients(p=0.001), respectively. Asymmetrical septal HCM has a higher median risk score compared to apical HCM, with medians of 2.05 (IRQ: 1.78) and 1.44 (IRQ: 0.85; p=0.025), respectively. There was no statistical difference in terms of clinical and imaging characteristics between male and female HCM patients. Conclusion Demographics and clinical presentation of the disease are comparable to those of other studies. However, the risk for sudden cardiac death was higher in asymmetrical septal HCM compared to apical HCM. We also found that myocardial fibrosis on CMR is more significant in apical HCM.

Calculated Risk for Sudden Cardiac Death in Patients with Apical Versus Nonobstructive Nonapical Hypertrophic Cardiomyopathy

The Case Files

Apical Hypertrophic Cardiomyopathy: Prevalence and Correlates of Apical Outpouching

Key role of the molecular autopsy in sudden unexpected death

PO-03-087 PROGNOSIS OF HYPERTROPHIC CARDIOMYOPATHY IN JAPANESE PATIENTS WITH AN IMPLANTABLE CARDIOVERTER DEFIBRILLATOR -FOCUS ON APICAL HYPERTROPHIC CARDIOMYOPATHY

Apical hypertrophic cardiomyopathy (AHCM) is a subtype of HCM, and few studies on the prognosis in AHCM are available. This study aimed to explore the clinical prognosis for AHCM and non-AHCM patients through clinical data based on propensity score matching (PSM) in a large cohort of Chinese HCM patients. The cohort study included 2268 HCM patients, 226 AHCM and 2042 non-AHCM patients from 13 tertiary hospitals, who were treated between 1996 and 2021. Fifteen demographic and clinical variables of 226 AHCM patients and 2042 non-AHCM patients were matched using 1:2 PSM. A Cox proportional hazard regression model was constructed to assess the effect of AHCM on mortality. During a median follow-up of 5.1 (2.4-8.4) years, 353 (15.6%) of the 2268 HCM patients died, of whom 205 died due to cardiovascular mortality/cardiac transplantation and 94 experienced sudden cardiac death (SCD). In the matched cohort, the ACHM patients had lower rates of all-cause mortality (P = 0.003), cardiovascular mortality/cardiac transplantation (P = 0.03), and SCD (P = 0.02) than the non-AHCM patients. Furthermore, the Cox proportional hazard regression model showed that AHCM was an independent prognostic predictor of all-cause HCM mortality (P = 0.004) and a univariable prognostic predictor of cardiovascular mortality/cardiac transplantation (P = 0.03) and for SCD (P = 0.03). However, AHCM was not significant in multivariable Cox regression models in relation to cardiovascular mortality/cardiac transplantation and SCD. AHCM had a favorable prognosis both before and after matching, with lower all-cause mortality, cardiovascular mortality/cardiac transplantation, and SCD than non-AHCM.

Funding Acknowledgements Type of funding sources: None. Background Apical hypertrophic cardiomyopathy (HCM) is considered to have a benign prognosis in terms of cardiovascular mortality. Sudden cardiac arrest and ventricular fibrillation (VF) in patients with apical HCM is rarely reported. Methods Between July 2001 and May 2021, 96 HCM patients who had undergone implantable cardioverter-defibrillator (ICD) implantation from three tertiary hospitals were reviewed. We evaluated the prevalence of aborted sudden cardiac death and/or documented VF in apical HCM and known risk markers for sudden cardiac death in those populations. Result Fifteen patients (15.6%) were apical HCM in total population. Among apical HCM, seven patients (40.0%) presented with aborted sudden cardiac death or documented VF, therefore received ICD implantation for the secondary prevention. All seven patients had at least one risk marker suggested either 2020 ACC/AHA guideline or 2014 ESC guideline. One patient had three risk factors and two patients had two risk factors and four patients had one risk factor. Late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR), personal history of unexplained syncope and non-sustained ventricular tachycardia (VT) were the common risk factors. Conclusions Clinical outcomes in patients with apical HCM are not always as benign as previously thought. ICD implantation should be considered in high-risk patients with apical HCM as the same manner with the septal type of HCM according to the current guideline recommendations.

Although apical hypertrophic cardiomyopathy (HCM) has been considered to be more benign than asymmetric HCM, few studies have directly compared their clinical features. We compared the electrocardiographic data and longterm outcomes between patients with apical HCM versus asymmetric HCM. This retrospective study enrolled 796 patients (243 apical HCM and 553 asymmetric HCM). We assessed long-term all-cause and cardiac mortalities using an inverse probability of treatment weighted (IPTW) method and propensity score matched (PSM) analysis. In patients with asymmetric HCM, QT prolongation, QRS widening, PR prolongation, and pathologic Q wave were significantly more frequent. The incidences of early repolarization were similar (11% in apical and 12% in asymmetric HCM, P = 0.19). The median follow-up duration was 6.5 years. There was a borderline significant difference in overall survival rates between the apical and asymmetric HCM groups (73% versus 69%, log rank P = 0.38, IPTW: P = 0.05, PSM: P = 0.05). Regarding cardiac death, asymmetric HCM was more hazardous than apical HCM (89% versus 77%, log rank P = 0.04, IPTW: P = 0.03, PSM: P = 0.03). There was no electrocardiographic predictor for the long-term outcomes, although beta-blocker use was significantly associated with lower overall death (HR = 0.58, 95% CI = 0.41-0.81) and slightly lower cardiac death (HR = 0.86, 95% CI = 0.55-1.33). The overall survival rate of apical HCM was as high as that of asymmetric HCM, but the cardiac survival rate was significantly lower in patients with asymmetric HCM. Beta-blocker use was associated with better long-term outcomes.

Background Prophylactic use of implantable cardioverter-defibrillators (ICDs) to prevent sudden cardiac death (SCD) is widely spread all over the world in patients with hypertrophic cardiomyopathy (HCM). Apical HCM is a phenotype variant of HCM, with hypertrophy predominantly affecting apex, that was initially described 30 years ago. Apical HCM patients may have different clinical prognosis compared with other subsets of HCM. In previous studies, apical HCM patients seem to have a more benign prognosis than other types of HCM. However, little is known about the long-term outcomes of apical HCM and there are many unclear points. Moreover, there are few reports about the clinical prognosis in apical HCM patients with an ICD. Objective The aim of this study is to identify the difference between the prognosis of apical and the other HCM patients with an ICD. Methods We retrospectively analyzed the database of our ICD clinic. All subjects had been implanted with an ICD from October 2006 to August 2017. We classified HCM patients into LV outflow tract obstruction (LVOTO) and midventricular obstruction (MVO), apical HCM and other non-obstructive types. We divided all the patients into apical and other types of HCM, and examined their background, incidence of appropriate ICD therapies, hospitalization for heart failure, electrical storm and death. Results A total of consecutive 62 Japanese HCM patients with an ICD (follow-up period, 86±25 months; age, 67±14 years; male sex, 85%; left ventricular ejection fraction, 57±12%; LV max wall-thickness, 19±5mm; LV apical aneurysm, 9.7%; HCM Risk-SCD, 4.4±3.0) were enrolled in this study. We classified them into 14 apical HCM and 48 other types of HCM patients. The clinical characteristics and major events of these patients are shown in the Figure. During the follow-up periods, there were no significant differences in the incidence of hospitalization for heart failure, electrical storm and death between the 2 groups (p=0.40; p=0.22; p=0.23). Appropriate therapies occurred in 5 of 14 (36%) patients with apical HCM and 4 of 48 (8.3%) patients with other types of HCM (p=0.022). Conclusions Appropriate ICD therapy was more prevalent in patients with apical HCM, compared to patients with other types of HCM. However, the incidences of hospitalization for heart failure, electrical storm and death were not significantly different between two groups. Funding Acknowledgement Type of funding sources: None.

Ventricular Tachycardia in Hypertrophic Cardiomyopathy With Apical Aneurysm

Background Patients with hypertrophic cardiomyopathy (HCM) are at high risk of lethal arrhythmias, and implantable cardioverter defibrillators (ICD) are widely used for prevention of sudden cardiac death (SCD). Apical HCM is a phenotype variant of HCM, with hypertrophy predominantly affecting apex, that was initially described 30 years ago. Apical HCM patients may have different clinical prognosis compared with other subsets of HCM. In previous studies, apical HCM patients seem to have a more benign prognosis than other types of HCM. However, little is known about the long-term outcomes of apical HCM patients and there are many unclear points. Moreover, there are few reports about the clinical prognosis in apical HCM patients with an ICD. Objective The aim of this study is to identify the difference between the prognosis of apical and the other types of HCM patients with an ICD. Methods We retrospectively analyzed the database of our ICD clinic. All subjects underwent ICD implantation between October 2006 and September 2018. We classified HCM patients into LV outflow tract obstruction (LVOTO) and midventricular obstruction (MVO), apical HCM and other non-obstructive types. We divided all the patients into apical and other types of HCM, and examined their background, incidence of appropriate ICD therapies, hospitalization for heart failure, electrical storm and death. Results A total of consecutive 64 Japanese HCM patients with an ICD (follow-up period, 86±24 months; age, 65±14 years; male sex, 83%; left ventricular ejection fraction, 56±14%; LV max wall-thickness, 19±7mm; LV apical aneurysm, 9.4%; 5-year risk of SCD, 4.4±2.1) were enrolled in this study. We classified them into 14 apical HCM and 50 other types of HCM patients. The clinical characteristics and major clinical events of these patients are shown in the Table 1. During the follow-up periods, there were no significant differences in the incidence of electrical storm, hospitalization for heart failure and death between the 2 groups (p=0.11; p=0.60; p=0.39). Appropriate ICD therapies occurred in 6 of 14 (43%) patients with apical HCM and 5 of 50 (10%) patients with other types of HCM (p=0.010). The risk factors of patients with apical HCM patients are shown in Table 2. Conclusions Appropriate ICD therapy was more prevalent in patients with apical HCM, compared to patients with other types of HCM. Aggressive intervention such as catheter ablation for ventricular tachycardia and ventricular fibrillation may be considered in patients with apical HCM and higher score of 5-year risk of SCD. Further studies are needed to clarify the manifestations and long-term outcome of apical HCM patients. Funding Acknowledgement Type of funding sources: None.

Objectives: As reported, diagnostic age, gender and presence of outflow tract obstruction have an impact on prognosis in patients with hypertrophic cardiomyopathy. The aim of this study was to compare the long-term outcome between apical hypertrophic cardiomyopathy (ApHCM) and asymmetric septal hypertrophic cardiomyopathy (ASHCM) after the exclusion of these factors. Methods: A total of 540 patients (270 with ApHCM and 270 with ASHCM) identified in a consecutive single-center cohort were retrospectively studied. The two groups were matched by diagnostic age, gender and the presence of outflow tract obstruction. Clinical characteristics and long-term outcomes were compared. Results: The mean follow-up duration in ASHCM and ApHCM were 6.6 ± 5.5 and 7.6 ± 4.1 years, respectively. During follow-up, 16 patients experienced cardiovascular death in the ASHCM group, while 2 patients experienced cardiovascular death in the ApHCM group (6.3 vs. 0.7%, p < 0.01). Cardiovascular morbidity in the ASHCM and ApHCM groups were 39.9 and 18.5% (p < 0.01). In the multivariate Cox regression analysis late gadolinium enhancement (LGE; HR 4.81, 95% CI 1.28-78.0, p = 0.03) and unexplained syncope (HR 9.68, 95% CI 1.9-17.2, p < 0.01) were independent predictors for cardiovascular mortality. Unexplained syncope was independently associated with a higher risk for sudden cardiac death (HR 4.3, 95% CI 1.2-15.3, p = 0.02). Conclusions: After eliminating the interference of diagnostic age, gender and outflow tract obstruction, ASHCM represented a worse prognosis with a higher incidence of cardiovascular mortality and morbidity than ApHCM. LGE was a strong predictor for cardiovascular death.

A previously healthy 32-year-old female undergoes evaluation after a syncopal episode. Physical examination reveals a systolic ejection murmur. Echocardiography demonstrates a vigorous LV with marked asymmetric septal hypertrophy, systolic anterior motion of the mitral valve, and a 50–mm Hg outflow tract gradient. Family history is notable for unexpected death in 4 paternal family members. She has 2 children (Figure 1A). Figure 1. A, HCM is a genetic cardiovascular disease. This family shows autosomal dominant inheritance with &50% of the family affected and equal numbers of affected male (▪) and female (•) family members. The case patient is indicated by an arrow. Deceased individuals are indicated by a diagonal slash (all died suddenly). B, DNA sequence analysis can identify sarcomere mutations that cause HCM. Top, The normal sequence of a portion of the cardiac troponin T gene is displayed with a triplet codon, TCC, encoding serine present. Bottom, DNA sequence obtained from a patient with HCM. The normal sequence is present on the allele inherited from the unaffected parent; the other allele shows a single base-pair substitution of a thymidine residue for the normal cytosine residue. This triplet codon, TTC, encodes phenylalanine and results in the substitution of a phenylalanine residue for the normal serine residue at amino acid position 179. The prevalence of unexplained left ventricular hypertrophy (LVH) in the general population is estimated to be 1 in 500.1,2 Hypertrophic cardiomyopathy (HCM) caused by sarcomere mutations may account for up to 60% of unexplained LVH, making HCM the most common genetic cardiovascular disorder.3–5 Accurate diagnosis of HCM is important for appropriate management of major HCM comorbidities, including atrial fibrillation, stroke, heart failure, and sudden cardiac death (SCD).6,7 HCM typically is diagnosed by unexplained LVH on echocardiography. Age of onset of LVH ranges from early childhood to …

A 20-year-old asymptomatic man was diagnosed with hypertrophic cardiomyopathy (HCM) after routine physical examination during which a systolic heart murmur was detected.Echocardiography showed massive left ventricular (LV) hypertrophy with ventricular septal thickness of 36 mm extending into the anterolateral wall (30 mm); outflow obstruction was absent.Ambulatory (Holter) ECG showed 3 isolated premature ventricular contractions, and blood pressure response to exercise was normal.Echocardiographic examinations in parents and siblings were negative for HCM.Although 2 centers advised against an implantable cardioverter-defibrillator (ICD) based on the presence of only 1 risk factor for sudden death (ie, extreme hypertrophy), a prophylactic device was recommended by a third cardiac consultant.After an uneventful 16-month period during which the ICD neither detected nor treated arrhythmias, an unprovoked episode of ventricular fibrillation triggered a defibrillation shock that immediately restored sinus rhythm (Figure 1).