Apical Hypertrophic Cardiomyopathy Patients Research Articles

THE DIAGNOSTIC VALUE OF CARDIAC MRI IN DETERMINING HYPERTROPHIC CARDIOMYOPATHY PHENOTYPES Using T1 and T2 mapping and late gadolinium enhancement to accurately diagnose hypertrophic cardiomyopathy

Objective: Hypertrophic cardiomyopathy (HCM) is a genetic disorder characterized by thickening of the heart muscle and may have serious consequences. Diversity in the distribution and degree of hypertrophy has led to the classification of HCM types. Cardiac MR (CMR) imaging is a non-invasive tool that maintains accurate and detailed data about cardiac functions and structure. The aim of the study was to observe and compare the CMR characteristics of the three HCM morphologic types (asymmetric, concentric, and apical). Materials and Methods: 56 patients (female/male: 29/58, mean age 46.31±15.12, body surface area (BSA) 1.88±0.19 m2) who were referred for HCM diagnosis or follow-up between January 2020- January 2023 were included in this single-center retrospective study. The imaging procedure was conducted using a 1.5 T device (Aera, Siemens Medical Systems, Erlangen, Germany). Cardiac volume and functions were determined quantitatively. The location and amount of late gadolinium enhancement (LGE) was evaluated qualitatively. The statistical analyses were performed using SPSS version 25.0. A P value under 0.05 was considered statistically significant. Results: LGE revealed myocardial fibrosis in apical HCM (ApHCM), a higher prevalence than in asymmetric and concentric HCM. ApHCM and asymmetric HCM patients widely presented midmyocardial fibrosis, where most concentric HCM patients had patchy involvement. The mean native myocardial T1 values for individuals with concentric HCM was found to be higher compared to those with asymmetric and ApHCM and the healthy participants. Conclusion: CMR imaging enables the multiparametric evaluation of HCM through the utilization of native T1 and T2 mapping techniques, as well as LGE. Both T1 and T2 values have the potential to be used in conjunction with LGE to identify regions of myocardial fibrosis.

Abstract 19218: Prognosis of Apical Hypertrophic Cardiomyopathy in Patients With Implantable Cardioverter Defibrillators

Aims: This Short Communication aims to identify the difference between the prognoses of apical and other types of hypertrophic cardiomyopathy (HCM) in patients with implantable cardioverter defibrillators (ICDs). Methods: We retrospectively analysed the database of our ICD clinic. All patients were implanted with ICDs from October 2006 to August 2017. We classified patients with HCM based on left ventricular (LV) outflow tract obstruction (LVOTO) and midventricular obstruction (MVO), in addition to apical HCM and other non-obstructive HCM types. Patient backgrounds, incidences of appropriate ICD therapies, hospitalizations for heart failure, electrical storms, and total deaths were examined. Results: A total of 64 consecutive Japanese patients with HCM and ICDs were enrolled in this study. The mean follow-up period was 86 ± 24 months, the mean age was 65 ± 14 years, and 83% of the patients were male. The LV ejection fraction was 56 ± 14%, the LV max wall-thickness was 19 ± 7 mm, 9.0% had LV apical aneurysms, and the HCM Risk-SCD was 4.4 ± 2.1. We classified the patients into two groups: 14 patients with apical HCM and 50 patients with other types of HCM. During the follow-up periods, there was no significant difference 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, respectively). Appropriate therapies occurred in 6 of 14 (43%) patients with apical HCM patients and 5 of 50 (10%) patients with other types of HCM (p=0.010). Conclusions: Compared with patients with other types of HCM, patients with apical HCM have a comparative prognosis, and treatment of ventricular arrhythmias should be strongly considered.

Improved Diagnostic Criteria for Apical Hypertrophic Cardiomyopathy

BackgroundThere is no acceptable maximum wall thickness (MWT) threshold for diagnosing apical hypertrophic cardiomyopathy (ApHCM), with guidelines referring to ≥15 mm MWT for all hypertrophic cardiomyopathy subtypes. A normal myocardium naturally tapers apically; a fixed diagnostic threshold fails to account for this. Using cardiac magnetic resonance, “relative” ApHCM has been described with typical electrocardiographic features, loss of apical tapering, and cavity obliteration but also with MWT <15 mm. ObjectivesThe authors aimed to define normal apical wall thickness thresholds in healthy subjects and use these to accurately identify ApHCM. MethodsThe following healthy subjects were recruited: healthy UK Biobank imaging substudy subjects (n = 4,112) and an independent healthy volunteer group (n = 489). A clinically defined disease population of 104 ApHCM subjects was enrolled, with 72 overt (MWT ≥15 mm) and 32 relative (MWT <15 mm but typical electrocardiographic/imaging findings) ApHCM subjects. Cardiac magnetic resonance–derived MWT was measured in 16 segments using a published clinically validated machine learning algorithm. Segmental normal reference ranges were created and indexed (for age, sex, and body surface area), and diagnostic performance was assessed. ResultsIn healthy cohorts, there was no clinically significant age-related difference for apical wall thickness. There were sex-related differences, but these were not clinically significant after indexing to body surface area. Therefore, segmental reference ranges for apical hypertrophy required indexing to body surface area only (not age or sex). The upper limit of normal (the largest of the 4 apical segments measured) corresponded to a maximum apical MWT in healthy subjects of 5.2 to 5.6 mm/m2 with an accuracy of 0.94 (the unindexed equivalent being 11 mm). This threshold was categorized as abnormal in 99% (71/72) of overt ApHCM patients, 78% (25/32) of relative ApHCM patients, 3% (122/4,112) of UK Biobank subjects, and 3% (13/489) of healthy volunteers. ConclusionsPer-segment indexed apical wall thickness thresholds are highly accurate for detecting apical hypertrophy, providing confidence to the reader to diagnose ApHCM in those not reaching current internationally recognized criteria.

Ethnic and sex-related differences at presentation in apical hypertrophic cardiomyopathy: An observational cross-sectional study

BackgroundWe investigated whether ethnicity and sex are associated with different clinical presentations and cardiovascular magnetic resonance (CMR) findings in individuals with apical hypertrophic cardiomyopathy (ApHCM). MethodsA retrospective observational cohort study of consecutive ApHCM patients from a large tertiary referral center in the United Kingdom (UK). Demographic, clinical, 12‑lead electrocardiogram (ECG) and CMR findings were collected. Participants presented in our clinics between 2010 and 2020. ‘Pure’ ApHCM was defined as isolated apical hypertrophy and ‘mixed’ with both apical and septal hypertrophy but with the apical segments of a greater wall thickness. Deep T-wave inversion was defined as ≥5 mm in any electrocardiogram lead. ResultsA total of 150 consecutive ApHCM patients (75% men, 25% women; 37% White, 25% Black, 24% Asian and 15% of Mixed/Other ethnicity) were included. Females were diagnosed at an older age compared to men, had less prominent ECG changes, had higher left atrial area index, and were more hypertensive. Black patients had higher left ventricular mass index, more hypertension, and more of the ‘mixed’ type of ApHCM. The majority of hypertensive male patients showed the ‘mixed’ phenotype. ConclusionsIndividuals of Black ethnicity and hypertensive male patients are more likely to present with mixed apical and basal hypertrophy, whereas White, Asian and non-hypertensive male patients tend to have hypertrophy limited to the apex. Females present at an older age and are less likely to have deep T wave inversion on ECG.

Myocardial deformation analysis using cardiac magnetic resonance in apical hypertrophic cardiomyopathy: is it an useful tool to predict adverse outcomes?

Apical hypertrophic cardiomyopathy (AHCM) has a broad phenotypic spectrum and still poses many diagnostic and prognostic challenges. Our team performed a retrospective study to examine the prognostic value of myocardial deformation obtained with cardiac magnetic resonance tissue tracking (CMR-TT) analysis in predicting adverse events in AHCM patients. We included patients with AHCM referred to CMR in our department from August 2009 to October 2021. CMR-TT analysis was performed to characterize the myocardial deformation pattern. Clinical, other complementary diagnostic exams characteristics and follow-up data were analysed. Primary endpoint was the composite of all-cause hospitalizations and mortality. During the 12-year period, 51 AHCM patients were evaluated by CMR, with a median age of 64 years-old and male predominance. 56,9% had an echocardiogram suggestive of AHCM. The most frequent phenotype was "the relative form" (43,1%). CMR evaluation revealed a median maximum left ventricle thickness of 15mm and the presence of late gadolinium enhancement in 78,4%. Applying CMR-TT analysis, median global longitudinal strain was - 14,4%, with a median global radial strain of 30,4% and global circumferential strain of -18,0%. During a median follow-up of 5,3 years, the primary endpoint occurred in 21,3% of patients, with a hospitalization rate of 17,8% and all-cause mortality rate of 6,4%. After multivariable analysis, longitudinal strain rate in apical segments was an independent predictor of the primary endpoint (p = 0,023), showing that CMR-TT analysis could be useful in predicting adverse events in AHCM patients.

Left ventricular strain and myocardial work in apical hypertrophic cardiomyopathy.

Apical hypertrophic cardiomyopathy (ApHCM) is recognized for its associated cardiovascular morbidity. Herein we describe left ventricular (LV) function and mechanics over long-term follow-up in ApHCM. A retrospective study of 98 consecutive ApHCM patients was performed (mean age: 64±15 years, 46% female) using 2D and speckle-tracking echocardiography. LV function and mechanics were characterized by global longitudinal strain (GLS), segmental strain, and myocardial work indices. Myocardial work was calculated by integrating longitudinal strain and blood pressure as estimated by the brachial artery cuff pressure, to generate an LV pressure-strain loop with adjusted ejection and isovolumetric periods. Composite complications were defined as all-cause mortality, sudden death, myocardial infarction, and/or stroke. Mean LV ejection fraction measured 67%±11% and GLS was -11.7%±3.9%. Global work index (GWI) was 1,073±349 mmHg%, constructive work was 1,379±449 mmHg%, wasted work was 233±164 mmHg%, and work efficiency was 82%±8%. In 72 patients with follow-up echocardiography, at a median of 3.9 years there was progressive impairment in GLS (-11.9% vs. -10.7%; P=0.006), GWI (1,105 vs. 989 mmHg%; P=0.02), and global constructive work (1,432 vs. 1,312 mmHg%; P=0.03), without change in wasted work or work efficiency. Atrial fibrillation (β=0.37; P<0.001), mitral annular e' velocity (β=-0.32; P=0.001), and glomerular filtration rate (β=-0.2; P=0.03) were independently associated with follow-up GLS; atrial fibrillation (β=-0.27; P=0.01) and glomerular filtration rate (β=0.23; P=0.04) were also associated with follow-up GWI. Global wasted work >186 mmHg% was predictive of composite complications (AUC =0.7, 95% CI: 0.53-0.82, sensitivity 93%, specificity 41%). ApHCM is associated with preserved LV ejection fraction but abnormal LV GLS and work indices, with progressive impairment. Important clinical and echocardiographic measures are independently predictive of long-term follow-up LV GLS, GWI and adverse events.

Right ventricular hypertrophy in apical hypertrophic cardiomyopathy.

Right ventricular hypertrophy (RVH+) in hypertrophic cardiomyopathy occurs in one third of patients, however, outcomes in apical hypertrophic cardiomyopathy (ApHCM) have not been described. We hypothesized that RVH+ in ApHCM is associated with more ventricular remodeling and dysfunction, and increased adverse events when compared with those without RVH (RVH-). Ninety-one ApHCM patients were retrospectively analyzed using 2D and speckle-tracking echocardiography (64±16 years old, 43% female). RVH+ was defined as wall thickness >5mm and was present in 23 (25%). Ventricular mechanics were characterized by global longitudinal strain (GLS), RV free wall strain, and myocardial work. New York Heart Association functional class>II, atrial fibrillation, and prior stroke were more prevalent in RVH+. Left ventricular (LV) size and ejection fraction were similar between groups, with greater septal (17vs. 14mm, p=.001) and apical (20vs. 18mm, p=.04) wall thickness in RVH+. When compared with RVH- patients, RVH+ had worse LV GLS (-8.6vs. -12.8%), global work index (820vs. 1172mmHg%) (both p<.001), and work efficiency (76vs. 83%, p=.001), as well as RV GLS (-14vs. -17.5%) and free wall strain (-17.3vs. -21.3%) (both p=.02). At 3-year follow-up RVH+ had greater incidence of heart failure hospitalization compared with RVH- (35vs. 7%, p=.003). RVH+ was associated with RV GLS (β =.2, p=.03), independent of clinical and echocardiographic variables. RVH+ patients with ApHCM have worse biventricular mechanics and myocardial work, and more heart failure hospitalization, as RVH- at mid-term follow-up.

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

Patients with hypertrophic cardiomyopathy (HCM) are at high risk of lethal arrhythmias, and implantable cardioverter defibrillators (ICDs) 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. 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. 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 cardiac death. 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) were enrolled in this study. We classified them into 14 apical HCM and 50 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 electrical storm, hospitalization for heart failure and cardiac 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). 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. Further studies are needed to clarify the manifestations and long-term outcome of apical HCM patients.

Left ventricular morphologic progression in apical hypertrophic cardiomyopathy

BackgroundLeft ventricular (LV) morphologic progression in apical hypertrophic cardiomyopathy (AHC) has not been well studied. We evaluated serial echocardiographic changes in LV morphology. MethodsSerial echocardiograms in AHC patients were assessed. LV morphology was categorized according to the presence of an apical pouch or aneurysm, and LV hypertrophic severity and extent; relative, pure, and apical-mid type defined as mild (<15 mm thickness) apical hypertrophy, significant (≥15 mm) apical hypertrophy, and both apical and midventricular hypertrophy, respectively. Adverse clinical events and late gadolinium enhancement (LGE) extent on cardiac magnetic resonance were evaluated for each morphologic type. ResultsIn 41 patients, 165 echocardiograms (maximal interval: 4.2 [IQR, 2.3–11.8] years) were evaluated. Morphologic changes were observed in 19 (46%) patients. Eleven (27%) patients displayed the progression of LV hypertrophy toward pure or apical-mid type. Five (12%) and 6 (15%) patients developed new pouches and aneurysms. Patients with progression tended to be younger (50 ± 15.6 vs 59 ± 14.4 years, P = 0.058) and had a longer period of follow-up (12 [5–14] vs 3 [2–4] years, P < 0.001). During a follow-up of 7.6 (IQR 3.0–12.1) years, 21 (51%) experienced clinical events. The relative, pure, and apical-mid types showed different LGE extents (2%, 6%, and 19%, P = 0.004). Patients with severe hypertrophic and apical involvement showed higher clinical event rates. ConclusionsAbout half of AHC patients had a progression of LV morphology to more hypertrophic involvement and/or an apical pouch or aneurysm formation. Advanced AHC morphologic types were associated with higher event rates and scar burdens.

Apical Ischemia Is a Universal Feature of Apical Hypertrophic Cardiomyopathy.

Apical hypertrophic cardiomyopathy (ApHCM) accounts for ≈10% of hypertrophic cardiomyopathy cases and is characterized by apical hypertrophy, apical cavity obliteration, and tall ECG R waves with ischemic-looking deep T-wave inversion. These may be present even with <15 mm apical hypertrophy (relative ApHCM). Microvascular dysfunction is well described in hypertrophic cardiomyopathy. We hypothesized that apical perfusion defects would be common in ApHCM. A 2-center study using cardiovascular magnetic resonance short- and long-axis quantitative adenosine vasodilator stress perfusion mapping. One hundred patients with ApHCM (68 overt hypertrophy [≥15 mm] and 32 relative ApHCM) were compared with 50 patients with asymmetrical septal hypertrophy hypertrophic cardiomyopathy and 40 healthy volunteer controls. Perfusion was assessed visually and quantitatively as myocardial blood flow and myocardial perfusion reserve. Apical perfusion defects were present in all overt ApHCM patients (100%), all relative ApHCM patients (100%), 36% of asymmetrical septal hypertrophy hypertrophic cardiomyopathy, and 0% of healthy volunteers (P<0.001). In 10% of patients with ApHCM, perfusion defects were sufficiently apical that conventional short-axis views missed them. In 29%, stress myocardial blood flow fell below rest values. Stress myocardial blood flow was most impaired subendocardially, with greater hypertrophy or scar, and with apical aneurysms. Impaired apical myocardial blood flow was most strongly predicted by thicker apical segments (β-coefficient, -0.031 mL/g per min [CI, -0.06 to -0.01]; P=0.013), higher ejection fraction (-0.025 mL/g per min [CI, -0.04 to -0.01]; P<0.005), and ECG maximum R-wave height (-0.023 mL/g per min [CI, -0.04 to -0.01]; P<0.005). Apical perfusion defects are universally present in ApHCM at all stages. Its ubiquitous presence along with characteristic ECG suggests ischemia may play a disease-defining role in ApHCM.

Clinical study on LVO-based evaluation of left ventricular wall thickness and volume of AHCM patients

ObjectiveThe aim of this study is to evaluate the clinical value of left ventricular opacification (LVO) in detecting left ventricular wall thickness (LVWT) and left ventricular (LV)volume in patients with apical hypertrophic cardiomyopathy (AHCM). MethodsConventional two-dimensional echocardiography (2DE) and LVO dynamic images of apical four-chamber (AP4C), apical two-chamber(AP2C), and short axis views of the basal, middle, and apical segments were collected from 27 AHCM patients and 33 normal subjects. LVWT（including 16 segments at 3 different levels）and LV volume were measured by both 2DE and LVO, compared between the two groups. Results(1) LVWT of the middle and the apical segments were higher in the AHCM than those in the control group measured by both LVO and 2DE (P < 0.001). (2) LVWT at the basal, middle and apical segments measured by LVO in the two groups were lower than those by 2DE, (P < 0.001). In the control group, the LVWT decreased from the basal to the apical segment, while in the AHCM group, the LVWT increased from the base to the apex,(P < 0.001).(3)LVEDV, LVESV, SV obtained by LVO were higher.than those by 2DE in the two groups (P < 0.001). LVEDV, LVESV and SV in the AHCM group were lower compared to the control group(P < 0.001).(4)The intra-observer repeatability of LVWT and LV volum in AHCM patients measured by LVO were higher than those by 2DE(P < 0.001). Conclusion(1)LVO can improve the delineation of the endocardial border, enabling more accurate diagnosis of AHCM than by 2DE. (2) LVO can improve display of the LV apical structure, leading to more accurate evaluation of LVWT, and LV volume, than by 2DE, in patients with AHCM; potentially providing more reliable information for clinical diagnosis and treatment and meriting wider clinical application.

Prognosis of hypertrophic cardiomyopathy in Japanese patients with an implantable cardioverter defibrillator -focus on apical hypertrophic cardiomyopathy

Abstract 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.

Improved diagnostic accuracy for apical hypertrophic cardiomyopathy

Abstract Introduction The diagnosis of apical hypertrophic cardiomyopathy (ApHCM) is contingent on demonstrating apical maximum wall thickness (MWT) of ≥15mm; the same threshold as other HCM subtypes. However, the myocardium naturally tapers towards the apex in healthy individuals, so ≥15mm MWT is proportionately higher in the apex than in naturally thicker basal segments. Using cardiac magnetic resonance (CMR), relative ApHCM has been described (typical ECG features, loss of apical tapering, cavity obliteration but hypertrophy &amp;lt;15mm). Wall thickness measurement using machine learning now exceeds human performance. Purpose We aimed to redefine the optimal diagnostic threshold for ApHCM using segment-specific criteria based on a large cohort of healthy control subjects. Methods Segmental wall thickness was measured using healthy subjects from the UK Biobank using a clinically validated machine learning algorithm1,2. A normative reference range was established for all 16 segments, conditioned to body surface area (BSA), sex and age. Derived segment-specific wall thickness thresholds were used to define optimal disease thresholds for patients clinically managed with overt (MWT ≥15mm) and relative ApHCM (MWT &amp;lt;15mm, but typical ECG and imaging findings). Results 4118 UK biobank subjects were used to define normal segmental thicknesses and reference ranges. These were applied to ApHCM (73 overt, 31 relative). There were no apical wall thickness age related differences. The upper limit of the 95% confidence interval corresponded to a combined maximum apical MWT for both males and females of 10.4mm using non-indexed measurement, or 5.6mm/m2 when indexed to BSA. Non-indexed segmental threshold identified 100% of ApHCM patients (true positives), 81% (25 of 31) relative ApHCM and 3% (115 of 4118) of healthy UK biobank subjects (false positives). Indexed segmental thresholds improved the diagnostic potential in relative ApHCM without an increase in false positives (100% of ApHCM patients, 84% (26 of 31) of relative ApHCM patients, and 3% healthy UK biobank (127 of 4118). Conclusion We propose new diagnostic criteria for ApHCM using segmental indexed apical wall thickness of &amp;gt;5.6 mm/m2 to better identify inappropriate apical hypertrophy in those whose wall thickness does not meet current criteria for diagnosis. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): British Heart Foundation

Improving the diagnostic accuracy of apical hypertrophic cardiomyopathy using machine learning

Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Dr Hughes is supported by the British Heart Foundation (grant number FS/17/82/33222). Introduction The imaging criteria for diagnosis of apical hypertrophic cardiomyopathy (ApHCM) is a maximum wall thickness (MWT) ≥15mm. CMR enables detection of subtle phenotypic features (e.g. loss of apical tapering, cavity obliteration) and coupled with characteristic electrocardiogram changes, ApHCM can be diagnosed without overt hypertrophy. However, these patients are not captured by current diagnostic criteria. Purpose We sought to use a machine learning tool to quantify wall thickness and identify patients with ‘relative’ ApHCM that do not reach current diagnostic thresholds. Methods CMR images from 4118 healthy participants from the UK Biobank were segmented automatically with a clinically validated machine learning algorithm and wall thickness measured at all point in the myocardium by solving a solution to Laplace’s equation. MWT were pooled into 16 AHA segments and indexed to body surface area (BSA). The non-indexed and indexed segmental upper limit of normal was calculated as the mean + 3 standard deviations (the equivalent of 95% confidence interval after correcting for multiple [16] comparisons using the Bonferroni method). Results 73 overt ApHCM subjects (MWT&amp;gt;15mm) and 31 relative ApHCM subjects underwent CMR scanning. In healthy controls, the non-indexed (and indexed) upper limits were calculated for the apical-anterior 10.2mm (5.2 mm/m2), apical-septal 11.1mm (5.6 mm/m2), apical-inferior 10.5mm (5.3 mm/m2) and apical-lateral 10.1mm (5.2 mm/m2) segments. With a non-indexed cut-off, all (73 of 73) overt ApHCM and 84% (26 of 31) relative ApHCM were classified as having an abnormally thick apex. 3% (127 of 4118) of the healthy UK Biobank cohort were classified as abnormal, as expected. Using an indexed cut-off, all overt ApHCM and 87% (27/31) relative ApHCM were classified as abnormal, and 3% (123 of 4118) of the healthy UK Biobank cohort were misclassified. Conclusion We can successfully classify 87% of relative ApHCM patients from a normative reference range derived from a large cohort of healthy patients – a significant improvement on existing methods. We show that the specificity and sensitivity is increased when MWT is indexed to BSA. For practical clinical application, we recommend a cut-off of 10mm or an indexed cut-off of 5mm/m2 in any apical segment to diagnose apical LVH. Overt and relative apical HCM examplesHealthy controls AHA maps (non-indexed)

Left Ventricular Apical Hypertrophic Cardiomyopathy After Heart Transplant: Case Report.

<h3>Background</h3> Apical hypertrophic cardiomyopathy (ApHCM) is a rare variant of HCM which predominantly involves the left ventricular apex, and therefore does not typically result in obstructive physiology. It has been infrequently reported in general, with a rarity in heart transplant patients, mostly due to a modest or delayed presentation with symptoms. We present a case of a heart transplant patient with a stable postoperative course who was incidentally found to have ApHCM during follow up non-invasive testing. <h3>Case presentation</h3> Patient is a 45-year-old gentleman with a history of cardiac transplantation in March 2013 for heart failure in the setting of arrhythmogenic right ventricular cardiomyopathy, on chronic dual immunosuppression therapy. He has maintained preserved allograft function with no treatable rejection. Mild donor-derived atherosclerotic disease was found on the first surveillance coronary angiogram with no progression over subsequent years. He has remained asymptomatic and extremely active. In September 2020, he underwent surveillance myocardial perfusion imaging, which showed a large area of moderately severe ischemia laterally extending from the mid ventricle to the apex, prompting coronary angiography which did not show significant epicardial coronary disease. A subsequent echocardiogram with contrast demonstrated normal biventricular function, with evidence of hypertrophy with classic spading of the apical myocardium, along with a corresponding reduction in longitudinal straining, consistent with ApHCM. Upon retrospective evaluation of prior echocardiograms, the finding was likely also present though less evident. Holter monitor detected no arrhythmia and treadmill exercise testing confirmed normal functional capacity, normal blood pressure response to exercise, and no arrhythmias.. Review of the details of the donor's death did not suggest cardiac etiology or arrhythmia. <h3>Conclusion</h3> In our literature search, we found only one similar presentation in a cardiac transplant patient with apical HCM. In general, familial ApHCM is known to follow an autosomal dominant inheritance, whereas sporadic forms are caused by acquired mutations of various sarcomeric and nonsarcomeric protein genes. Other associated factors include long-standing high-pressure states, as well as medications, with one case report suggesting a possible relation with tacrolimus. One literature review suggested a possible increase in mortality in ApHCM patients. Therefore, although it is usually a rare condition, pre and post transplant monitoring must take into account that this condition may clinically manifest post transplantation.

813 The added value of transthoracic three dimensional echocardiography in apical hypertrophic cardiomyopathy

Abstract We present the case of a 73-year-old patient with a recent diagnosis of hypertrophic cardiomyopathy (HCM). He was asymptomatic and has no family history of sudden cardiac death (SCD), syncope or ventricular arrhythmias. An echocardiogram performed at the moment of diagnosis (2020), showed left ventricular (LV) asymmetric apical hypertrophy with maximal wall thickness of 21 mm. Cardiac magnetic resonance (CMR) confirmed LV apical hypertrophy with mid-ventricular obliteration, and late gadolinium enhancement in the apical segments, without wall motion abnormalities present at rest. According to 2014 ESC guidelines, his calculated risk score for sudden cardiac death was low (1.23% at 5 years). On 2021, a comprehensive transthoracic echocardiographic examination including advanced techniques (three-dimensional echo-3DE-, and two-dimensional speckle-tracking-2DSTE) was done as part of his routine follow-up in our cardiomyopathy outpatient clinic. The echo study showed an asymmetric pattern of LV hypertrophy with a maximal wall thickness of 21 mm at the level of the anterolateral apical segment, normal LV volumes (end-diastolic volume 55 mL/m2) and ejection fraction (69%) by 3DE. LV longitudinal strain analysis by 2DSTE showed impaired LV myocardial deformation mainly at the apical LV segments (GLS = −13.6%). There was evidence of dynamic intracavitary obstruction (maximal gradient 32 mmHg at rest and raised to 52 mmHg during Valsalva manoeuvre). 3DE views of the LV (both multi-slice display and 3D rendered image) allowed to avoid foreshortening of the LV apical views, and to appreciate the actual wall motion at the real LV apex. They revealed a LV apical aneurysm which was not detected in the conventional LV-focused apical 2D views (Figure 1A and B). Apical hypertrophic cardiomyopathy (ApHCM) is a variant of HCM that is characteristic of focal thickening of the LV apical myocardium and was reported to have a more benign course than other non-apical forms. However, the presence of LV aneurysm in ApHCM patients is associated with an increased risk for ventricular arrhythmias, sudden cardiac death and thromboembolism. Accordingly, the detection of apical LV aneurysms has significant impact on patient management. Guidelines recommend the use of contrast echocardiography or CMR when the apical region of the LV is suboptimally visualized by conventional 2D echocardiography. However, contrast echocardiography may still be affected by apical foreshortening resulting in suboptimal accuracy, as it is a 2D technique. On the other end, CMR may be contraindicated or not widely available for routine yearly follow-up for all HCM patients requiring regular imaging follow-up. Our clinical case emphasizes the added value of 3DE to increase the sensitivity of transthoracic echocardiography in detecting apical LV aneurysms in patients with apical HCM with important clinical implications for the management of the patient. 813 Figure 1(A) 2D 4chamber-view showing maximal wall thickness in the apical segments (21 mm) with apical obliteration. At a first evaluation, apical aneurism is not easily detected. (B) 4D rendering of the apex showing the apical aneurism.

Clinical, echocardiographic and cardiac MRI predictors of outcomes in patients with apical hypertrophic cardiomyopathy.

Recent studies have found that some adverse cardiovascular events could also occur in patients with apical hypertrophic cardiomyopathy (ApHCM), which is different with previous studies suggesting benign nature of this condition. Therefore, the present study aimed to observe the clinical prognosis of ApHCM and to identify the predictors of poor prognosis in clinical, echocardiography and cardiac magnetic resonance (CMR). A total of 126 ApHCM patients with both echocardiography and CMR were identified retrospectively from January 2008 to December 2018. Adverse clinical events were defined as a composite of cardiac death, progressive heart failure, myocardial infarction, thromboembolic stroke, appropriate implantable cardioverter-defibrillator (ICD) interventions for ventricular tachycardia or ventricular fibrillation, and new-onset atrial fibrillation (AF). During a mean follow-up of 96.8 ± 36.0months, clinical events were observed in 34 (27.0%) patients. As compared with patients without clinical events, patients with clinical events were older and had a higher incidence of heart failure. Moreover, patients with clinical events had a higher incidence of non-sustained ventricular tachycardia (NSVT) and had larger left atrial volume index (LAVI), thicker apical thickness, lower peak systolic mitral annular velocity (S') than those without clinical events. In addition, late gadolinium enhancement (LGE) in CMR were more frequently observed in patients with clinical events. Five predictors of poor prognosis were identified: age ≥ 55years, LAVI ≥ 36.7ml/m2, S' ≤ 6.7cm/s, NSVT and LGE. ApHCM was not as benign as expected. Age ≥ 55years, LAVI ≥ 36.7ml/m2, S' ≤ 6.7cm/s along with NSVT and LGE were independent predictors for poor prognosis of ApHCM.

Prognosis of apical hypertrophic cardiomyopathy in patients with an implantable cardioverter defibrillator

Abstract 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.

B-type natriuretic peptide and outcome in patients with apical hypertrophic cardiomyopathy

BackgroundAlthough elevated B-type natriuretic peptide (BNP) levels predict outcome in patients with hypertrophic cardiomyopathy (HCM), the association between BNP levels and outcome in patients with the apical phenotype of HCM remains unclear. We evaluated the impact of elevated BNP levels on outcome in a cohort of apical HCM patients. MethodsAmong 432 HCM patients, 144 with an apical phenotype were examined. Plasma BNP levels were measured at the time of the initial evaluation. ResultsThe median (interquartile range) BNP level at initial evaluation in these patients was 188.5 (72.0–334.4) pg/mL. During a median follow-up period of 9.5 years, 34 patients experienced HCM-related adverse outcomes, including 2 patients with sudden death, 5 with appropriate implantable defibrillator shocks, 3 with stroke-related death, 8 with non-fatal stroke, and 16 with heart failure hospitalization. Receiver operating characteristic (ROC) curve analysis of the prognostic value of BNP for the combined endpoint gave an area under the ROC curve of 0.756, and optimal BNP cut-off point of 226.0pg/mL. Patients with high BNP levels (≥226.0pg/mL) were at significantly greater risk of the combined endpoint (log-rank p<0.001) than patients with low BNP levels. Multivariable analysis that included BNP levels and potential confounders showed that high BNP levels were an independent determinant of the combined endpoint (adjusted hazard ratio: 3.71; p=0.002). ConclusionsMeasuring BNP may help stratify the risk of HCM-related adverse outcome in apical HCM patients.

Echocardiographic Evaluation of Left Atrial Function to Discriminate Non-Valvular Atrial Fibrillation Development in Patients with Apical Hypertrophic Cardiomyopathy.

Data is limited on baseline left atrial (LA) myocardial mechanics between apical hypertrophic cardiomyopathy (ApHCM) patients who develop non-valvular atrial fibrillation (NVAF) during follow-up and those who do not. This retrospective study investigated the clinical outcomes of consecutive patients newly diagnosed with ApHCM between August 2011 and July 2014 who were followed-up for at least 3 years. The patients underwent 12-lead surface electrocardiography and/or 24-hour Holter electrocardiography at least once a year. The patients were divided into two groups, namely those who did or did not exhibit NVAF during follow-up, respectively. The baseline clinical and echocardiographic data of the two groups were compared. Twenty patients were studied, five of whom were lost to follow-up. Of the remaining 15 ApHCM patients, seven developed NVAF. No differences were observed in the clinical characteristics of the two groups. However, for the echocardiographic data, the NVAF development group exhibited a larger LA volume and impaired LA reservoir, conduit and booster functions. The NVAF development group also showed lower peak LA strain and stiffer left atrium. The LA volume, function, global strain and stiffness were all statistically associated with NVAF development. Among these parameters, a LA conduit function of ≤ 24.9% was found to be the best parameter to discriminate NVAF development. The baseline LA function was impaired in the ApHCM patients who subsequently developed NVAF during follow-up. A LA conduit function of ≤ 24.9% was strongly associated with NVAF development.