Hypertrophic cardiomyopathy (HCM) is a genetic heart disorder defined by the presence of a maximal wall thickness of at least 15 mm with two main forms: obstructive (oHCM) and nonobstructive (nHCM). While oHCM is characterized by left ventricular (LV) outflow tract obstruction (LVOTO), nHCM lacks this feature and shows significant variability in its hemodynamic and anatomical traits. In nHCM, LV hypertrophy (LVH) presents diverse morphologies, including apical hypertrophy and reverse septal curvature, the latter potentially causing mid-ventricular obstruction and near-complete LV emptying. Apical hypertrophy is associated with the risk of LV aneurysms, potentially leading to arrhythmias and thromboembolism. These findings challenge the belief that nHCM is a more benign phenotype than oHCM and highlight the necessity for improved diagnostic and therapeutic strategies. Symptoms in nHCM, such as fatigue and dyspnea, are often attributed to diastolic dysfunction, whereas symptoms like angina are attributed to microvascular dysfunction. However, current treatment options remain limited, as traditional heart failure therapies frequently fail to provide substantial benefits. Given its heterogeneity, a more personalized treatment approach is warranted, including optimizing comorbidities, assessing coronary microvascular dysfunction, and considering alternative pharmacologic strategies. Emerging therapies, such as myosin inhibitors mavacamten and aficamten, target sarcomeric hypercontractility and show promise in early trials, but their clinical impact on nHCM is still under investigation. Gene therapies also hold potential, though their applicability to nHCM is limited by the high rate of mutation-negative cases and the potential irreversibility of advanced disease states. This review critically analyzes the pathophysiological mechanisms of nHCM, evaluates current and emerging therapeutic strategies, and provides guidance on contemporary management approaches for this complex and often underrecognized condition.

Apical hypertrophic cardiomyopathy (ApHCM) is a distinct variant of hypertrophic cardiomyopathy (HCM). Few studies have focused on the genetic determinants of this subtype. We aimed to investigate the genetic basis of apical hypertrophy in a Swedish cohort.

Longitudinal data on 58 unrelated index patients with ApHCM from the Southeast healthcare region in Sweden from 2010 to 2024 were assessed retrospectively. Additionally, the original raw data from genetic testing were re-evaluated using AI-based Emedgene software. Patients were 47 ± 14 years old, and 60% males. A total of 72.4% had the pure apical type and the remaining had the mixed phenotype, dominant distal. In the cohort, 50/58 (86.2%) underwent genetic testing, of whom 7/50 (14%) were considered genotype positive for a pathogenic/likely pathogenic variant, mainly in MYH7 (43%) and in the non-sarcomeric ALPK3 gene (28.6%). A re-evaluation of the original data from genetic testing identified a previously unreported variant in the skeletal muscle α-actin (ACTA1) gene. Overall, 21 of 58 patients (36.2%) had HCM-related events during their disease course: 10% had a stroke, and 12% had heart failure. Atrial fibrillation was present in 41.4% and non-sustained ventricular tachycardia occurred in 29.3% of the patients. Apical aneurysm was observed in 17.2% of cases. Patients with a positive genotype were more likely to have a positive family history of HCM compared to those with a negative genotype (p = 0.020).

In ApHCM, a positive genotype was found less frequently compared to classic HCM. Only 14% of patients with ApHCM were found to be genotype positive, indicating that apical hypertrophy represents a genetically unique population with low risk of mortality. Nevertheless, patients with ApHCM faced higher rates of atrial fibrillation, ventricular arrhythmias, and apical aneurysms.

Apical hypertrophic cardiomyopathy (HCM) is a rare variant of HCM, often considered to have a benign prognosis. This study aimed to compare the clinical characteristics and genetic predisposition of apical HCM with non-apical HCM.

We included 195 patients with HCM who underwent next-generation sequencing at two tertiary centres in South Korea (2017-2024). The primary outcome was a composite of lethal arrhythmic events (LAE), including death, ventricular arrhythmia, implantable cardioverter defibrillator (ICD) implantation and appropriate ICD shock. Secondary outcomes included major adverse cardiovascular events (MACE), such as new-onset atrial fibrillation, ischaemic stroke, heart failure hospitalisation, septal reduction therapy or heart transplant.

Of the 195 patients, 67 (34.4%) had apical HCM. Patients with apical HCM were older at diagnosis and had lower maximal left ventricular wall thickness compared with non-apical HCM. Disease-causing variants were less frequent in apical HCM (20.9% vs 46.9%, p<0.001). MYBPC3 and MYH7 variants were less common in apical HCM (50.0%) than in non-apical HCM (75.0%). MACE occurred less frequently in apical HCM (HR 0.38, 95% CI 0.19 to 0.75), but no difference was observed in LAE (HR 0.62, 95% CI 0.36 to 1.08). The presence of disease-causing variants was independently associated with LAE (adjusted HR 2.50, 95% CI 1.44 to 4.35).

Although apical HCM is associated with less hypertrophy and lower genetic yield, it is not entirely benign. The presence of disease-causing variants is an important predictor of arrhythmic risk, underscoring the value of genetic testing in all HCM patients, regardless of phenotype.

Hypertrophic cardiomyopathy (HCM) is the common cause of sudden cardiac death in young people and is characterized by cardiac hypertrophy. Non-HCM caused left ventricular hypertrophy (LVH) is more common in the population, especially in people with hypertension, obesity, and diabetes. In order to identify high-risk populations, a screening technique that can rapidly differentiate between HCM and LVH patients should be developed. Plasma metabolomics may help develop useful biomarkers for the disease diagnosis. We performed a comprehensive plasma metabolomic analysis on a total of 720 individuals, included 441 HCM patients, 160 LVH patients, and 119 normal controls (NC) (derivation cohort = 368, validation cohort = 352). Orthogonal partial least squares discriminant analysis (OPLS-DA) was used to construct discriminant models based on metabolomics, and the result showed significant changes in plasma metabolic profiling among the HCM, LVH, and NC. The prospective diagnostic biomarkers for HCM patients have been examined using variable importance in projection, fold change, and FDR. Acylcarnitines efficiently distinguished HCM and LVH patients, with a C14:0-carnitine AUC of 0.937 shown by the reiver operator characteristic (ROC) curve analysis. The biomarkers for the diagnosis of HCM patients was verified in another independent validation cohort. This study is the largest plasma metabolomics analysis of Chinese Han patients with HCM, finding biomarkers that can be used to distinguish between HCM from LVH patients. These results highlight the great potential value of plasma metabolic profiling analysis on HCM diagnoses.

This study aimed to evaluate the prognostic value of left atrial (LA) strain in patients with apical hypertrophic cardiomyopathy (ApHCM), as assessed by cardiac magnetic resonance (CMR) imaging.

Four hundred and five consecutive patients with ApHCM who underwent CMR examination were retrospectively included. The study endpoint included all-cause death, heart transplant, aborted sudden cardiac death, hospitalization for heart failure, stroke, and new-onset atrial fibrillation (AF).

After a median follow-up of 97 months, 75 patients (18.5%) reached the endpoint. Patients were divided into two groups based on the median LA reservoir strain of 29.4%. The group with lower LA reservoir strain had thicker maximum wall thickness, greater late gadolinium enhancement extent, and smaller end-diastolic volume index, stroke volume index, and cardiac index (all p < 0.02). For LA parameters, this subgroup showed greater diameter and volume index and worse ejection fraction, reservoir, conduit, and booster strain (all p < 0.001). In the multivariable model, age (HR 1.88, 95% CI: 1.06-3.31, p = 0.030), baseline AF (HR 2.95, 95% CI: 1.64-5.28, p < 0.001), LA volume index (LAVi) (HR 2.07, 95% CI: 1.21-3.55, p = 0.008) and LA reservoir strain (HR 2.82, 95% CI: 1.51-5.26, p = 0.001) were all associated with the outcome. Adding LAVi and LA reservoir strain in turn to the multivariable model (age and baseline AF) resulted in significant improvements in model performance (p < 0.001).

In ApHCM patients, LA reservoir strain is independently associated with cardiovascular risk events and has an incremental prognostic value.

Left atrial reservoir strain measured by cardiac magnetic resonance is highly correlated with the prognosis of apical hypertrophic cardiomyopathy and has potential incremental value in the prognosis of major adverse cardiac events.

Left atrial (LA) strain parameters may be useful for risk stratification and treatment of apical hypertrophic cardiomyopathy (ApHCM). Apical hypertrophic cardiomyopathy (ApHCM) is independently associated with LA morphology and function. Cardiac MR examination, especially its feature-tracking technology, provides the possibility to prognosticate ApHCM at an early stage.

Original apical hypertrophic cardiomyopathy was characterized by left ventricular hypertrophy confined to the apex below the papillary muscle level. In contrast, apical hypertrophic cardiomyopathy in Western countries often includes hypertrophy extending to the midventricular septum. Recognizing these phenotypic differences is essential as they may influence the clinical prognosis. The aim of this study was to delineate the clinical and genetic disparities between the pure-apical form, according to the original definition, and the distal-dominant form, in which hypertrophy extends to the ventricular septum without basal septal hypertrophy.

A retrospective analysis was conducted for 111 consecutive patients with apical hypertrophic cardiomyopathy with assessment of hypertrophic cardiomyopathy-related adverse events including hypertrophic cardiomyopathy-related death, heart failure admission, embolic stroke admission, and sustained ventricular tachycardia with hemodynamic instability or appropriate implantable cardioverter-defibrillator discharge. Genetic testing for hypertrophic cardiomyopathy-associated genes was performed in 72 patients.

Among the patients, 60 were classified as pure-apical form, and 51 were classified as distal-dominant form. The median age at diagnosis was 63 years, with a predominance of men in both groups. Over a follow-up period of 11.0 years, the incidence of hypertrophic cardiomyopathy-related adverse events was significantly higher in the distal-dominant group than in the pure-apical group (log-rank, P<0.001). The detection rate of pathogenic or likely pathogenic variants was also significantly higher in the distal-dominant group than in the pure-apical group (26% versus 3%; P=0.005).

Distinct clinical and genetic profiles of the 2 apical hypertrophic cardiomyopathy phenotypes warrant their recognition and differentiation in clinical practice due to distinct prognoses and genetic backgrounds.

Yamaguchi syndrome, also known as apical hypertrophic cardiomyopathy (AHCM), is a genetic disorder predominantly affecting the apex of the left ventricle and often presenting similarly to acute coronary syndrome, making precise imaging crucial for diagnosis. This condition, first identified in Japanese populations, is more common in Asian communities but varies in frequency across different populations. We are presenting the case of a 30-year-old African-American male patient with a history of hyper-lipidemia, asthma and obesity, who reported palpitations, dizziness and chest pain radiating to the left arm and jaw, particularly under stress. Echocardiography and cardiovascular magnetic resonance (CMR) revealed severe left ventricular hypertrophy, mild valvular regurgitation and marked apical obliteration, confirming the diagnosis of apical hypertrophic cardiomyopathy. This case highlights the need to consider apical hypertrophic cardiomyopathy in the differential diagnosis of patients with hypertrophic features, especially when conventional imaging findings are unclear.

Hypertrophic cardiomyopathy (HCM) is a hereditary disease of the myocardium characterized by asymmetric hypertrophy (mainly the left ventricle) not caused by pressure or volume load. Most cases of HCM are caused by genetic mutations, particularly in the gene encoding cardiac myosin, such as MYH7, TNNT2, and MYBPC3. These mutations are usually inherited autosomal dominantly. Approximately 30-60% of HCM patients have a family history of similar cases among their immediate relatives. This underscores the significance of genetic factors in the development of HCM. Therefore, we summarized the gene mutation mechanisms associated with the onset of HCM and potential treatment directions. We aim to improve patient outcomes by increasing doctors' awareness of genetic counseling, early diagnosis, and identification of asymptomatic patients. Additionally, we offer valuable insights for future research directions, as well as for early diagnosis and intervention.

There are no approved therapies for patients with symptomatic nonobstructive hypertrophic cardiomyopathy (nHCM). The authors describe the baseline characteristics of ODYSSEY-HCM (A Study of Mavacamten in Non-Obstructive Hypertrophic Cardiomyopathy), a phase 3, randomized, double-blind, placebo-controlled trial conducted worldwide at 201 sites evaluating mavacamten in symptomatic adult patients with nHCM. The 2 primary endpoints are the changes from baseline to week 48 in: 1) Kansas City Cardiomyopathy Questionnaire 23-item Clinical Summary Score; and 2) peak oxygen consumption (pVO2) on cardiopulmonary exercise testing. Dose titrations are made on blinded core laboratory assessments. Of 1,088 patients screened, 580 are randomized (mean age 56 ± 15 years, 46% women, 43% with family histories). All patients are nonobstructive and symptomatic (70% in NYHA functional class II and 30% class III), with a mean Kansas City Cardiomyopathy Questionnaire 23-item Clinical Summary Score of 58 ± 20, and 77% are on beta-blockers. The mean left ventricular ejection fraction and pVO2 are 66% ± 4% and 18 ± 6 mL/kg/min, respectively. ODYSSEY-HCM will report if mavacamten improves patient-reported health status and exercise capacity in patients with symptomatic nHCM. (A Study of Mavacamten in Non-Obstructive Hypertrophic Cardiomyopathy (ODYSSEY-HCM); NCT05582395).

Apical hypertrophic cardiomyopathy (AHCM) is a subtype of hypertrophic cardiomyopathy (HCM). The expression level of high-sensitive cardiac troponin T (hs-cTNT) and N-terminal pro-BNP (NT-proBNP) in AHCM patients, and these relationships between echocardiography parameters were still unclear.

We retrospectively screened AHCM patients between January 2019 and December 2021 in Zhongshan Hospital Fudan University. The relationship between the level of hs-cTNT, NT-proBNP and echocardiography parameters were analyzed. The risk factors for elevated hs-cTNT and NT-proBNP level were investigated with linear regression analysis.

A total of 267 AHCM patients were enrolled. They were divided into hs-cTNT normal (129, 48.3%) and abnormal (138, 51.7%) group. Compared with hs-cTNT normal group, hs-cTNT abnormal group were elder (68.3 ± 11.6 vs. 63.8 ± 10.6, P = 0.001); with higher rate of atrial fibrillation (AF) (41.3% vs. 17.8%, P < 0.001) and higher level of NT-proBNP concentration (752.0 [343.8-1345.5] vs. 249.0 [104.0-541.0], P < 0.001). For echocardiography parameters, hs-cTNT abnormal patients have thicker interventricular septum (IVS) (11.6 ± 2.0 vs. 11.0 ± 1.7, P = 0.02), thicker left ventricular apical (LVA) (16.9 ± 3.0 vs. 14.9 ± 2.3, P < 0.001) and larger left atrium diameter (LAD) (45.9 ± 6.6 vs. 42.4 ± 5.1, P < 0.001). LVA was independently correlated with both the level of hs-cTNT and NT-proBNP (hs-cTNT r = 0.224, P = 0.143; NT-proBNP r = 0.370, P < 0.001). Linear regression analysis revealed that LVA was independent risk factor of both the elevated hs-cTNT and NT-proBNP level.

More than half of AHCM patients had abnormal hs-cTNT level. LVA was positively and independently correlated with the level of hs-cTNT and NT-proBNP.

Apical hypertrophic cardiomyopathy (ApHCM) is a unique disease with pathologic hypertrophy mainly at the left ventricular (LV) apex. Although previous studies have indicated apical dysfunction in ApHCM, how apical mechanics change during disease progression has not been thoroughly examined. The aims of this study were to characterize the mechanics of the LV apex in patients with ApHCM at different disease stages and to explore the clinical significance of these alterations.

One hundred four patients with ApHCM were divided into three subtypes on the basis of LV apical maximum wall thickness (AMWT) and extent of hypertrophy: relative type (isolated apical hypertrophy with AMWT < 15 mm), pure type (isolated apical hypertrophy with AMWT ≥ 15 mm), and mixed type (both apical and midventricular hypertrophy with AMWT ≥ 15 mm). Two-dimensional speckle-tracking echocardiography was used to analyze LV segmental strain, global strain, and twist. Comparisons of these parameters were performed among ApHCM subtypes and 30 healthy control subjects. Logistic regression and Cox proportional-hazards regression analyses were used to explore associations between myocardial mechanics and clinical indicators. A composite outcome of new-onset atrial fibrillation, heart failure hospitalization, myectomy, and all-cause mortality was assessed.

Even in relative ApHCM patients, apical longitudinal strain (LS), circumferential strain, and radial strain (RS) were significantly impaired compared with control subjects (LS: -14.6 ± 4.1% vs -20.0 ± 1.7% [P = .001]; circumferential strain: -19.6 ± 2.5% vs -25.6 ± 3.7% [P = .002]; RS: 26.6 ±7.4% vs 35.6 ± 11.1% [P = .026]), while apical rotation and LV twist remained unchanged. In patients with greater apical hypertrophy (mixed and pure patients), apical LS and RS were more abnormal. Moreover, apical rotation showed significant reductions compared with relative-type patients. After adjusting for clinical and myocardial mechanical parameters, apical rotation was independently associated with New York Heart Association functional class ≥ II (odds ratio, 0.81; 95% CI, 0.66-0.99; P = .036) and the composite outcome (hazard ratio, 0.82; 95% CI, 0.73-0.91; P = .001).

Relative ApHCM demonstrates apical dysfunction but sparing of apical rotation, which was abnormal in more extensive phenotypes. LV apex mechanics were closely related to clinical patterns, with apical rotation correlated with both New York Heart Association functional class ≥ II and clinical events.

Approximately 10% of hypertrophic cardiomyopathy (HCM) patients have left ventricular systolic dysfunction (end-stage HCM) leading to severe heart-failure; however, risk stratification to identify patients at risk of progressing to end-stage HCM remains insufficient.

In this study, the authors sought to elucidate whether the coexistence of other cardiovascular disease (CVD)-related variants is associated with progression to end-stage HCM in patients with HCM harboring pathogenic or likely pathogenic (P/LP) sarcomeric variants.

The authors performed genetic analysis of 83 CVD-related genes in HCM patients from a Japanese multicenter cohort. P/LP variants in 8 major sarcomeric genes (MYBPC3, MYH7, TNNT2, TNNI3, TPM1, MYL2, MYL3, and ACTC1) definitive for HCM were defined as "sarcomeric variants." In addition, P/LP variants associated with other CVDs, such as dilated cardiomyopathy and arrhythmogenic cardiomyopathy, were referred to as "other CVD-related variants."

Among 394 HCM patients, 139 carried P/LP sarcomeric variants: 11 (7.9%) carried other CVD-related variants, 6 (4.3%) multiple sarcomeric variants, and 122 (87.8%) single sarcomeric variants. In a multivariable Cox regression analysis, presence of multiple sarcomeric variants (adjusted HR [aHR]: 3.35 [95% CI: 1.25-8.95]; P = 0.016) and coexistence of other CVD-related variants (aHR: 2.80 [95% CI: 1.16-6.78]; P = 0.022) were independently associated with progression to end-stage HCM. Coexisting other CVD-related variants were also associated with heart failure events (aHR: 2.75 [95% CI: 1.27-5.94]; P = 0.010).

Approximately 8% of sarcomeric HCM patients carried other CVD-related variants, which were associated with progression to end-stage HCM and heart failure events. Comprehensive surveillance of CVD-related variants within sarcomeric HCM patients contributes to risk stratification and understanding of mechanisms underlying end-stage HCM.

In patients with apical hypertrophic cardiomyopathy (HCM), progressive electrocardiographic changes are observed during long-term follow-up. However, it is difficult to correspond these changes to the specific myocardial changes. Cardiac magnetic resonance (CMR) imaging can elucidate myocardial changes by late gadolinium enhancement. Here, we present the long-term follow-up (>18 years) on a patient with apical HCM, whereupon, precise and continuous changes in the myocardium, causing ST segment and T wave changes on electrocardiography, were observed on CMR images. The combination of electrocardiography and CMR facilitates management of patients with apical HCM because it helps explain and understand the nature of electrocardiography changes over time.

Apical hypertrophic cardiomyopathy (aHCM) is a distinct variant characterized by predominant hypertrophy of the left ventricle apex.

This study sought to describe aHCM patients' characteristics and develop a risk score for aHCM patients.

A total of 462 patients (age 58 ± 15 years, 68% male) diagnosed with aHCM were included. The primary endpoint was death, appropriate defibrillator discharge, or need for cardiac transplantation. Variables showing potential association with the composite endpoint were considered to develop an aHCM-specific risk score.

At baseline, 67% patients were asymptomatic and 69% had no risk factors for sudden death. On echocardiography, the mean left ventricle ejection fraction, left atrial volume index, and right ventricular systolic pressure were 64% ± 8%, 36 ± 15 ml/m2, and 32 ± 10 mm Hg, respectively, with 51(11%) demonstrating an apical aneurysm. Baseline cardiac magnetic resonance, performed in 246 (53%) patients, demonstrated delayed gadolinium enhancement in 170 (71%) patients (mean percentage of 4.9% ± 6.6%). At age 6.3 ± 4.8 years, the composite events occurred in 80 (17%, death in 62 [13%]) patients. The aHCM-specific risk score, incorporating age, apical aneurysm, left atrial volume index, serum creatinine, and right ventricular systolic pressure, demonstrated good discrimination (C-statistic = 0.75) with an expected to observed ratio of 1.02 and a calibration slope of 0.91. The risk score ranged between 0 and 8 points, with a higher score associated with higher composite events.

aHCM constituted 6.8% of our overall HCM cohort with a composite event rate of 2.8%/year. The aHCM risk score provided good discrimination in predicting the composite primary endpoint, with a higher score associated with a higher rate of events.

Apical hypertrophic cardiomyopathy (ApHCM) is a variant of hypertrophic cardiomyopathy, with distinct clinical characteristics and outcomes. We aimed to clarify the natural history of patients with ApHCM and identify the risk of end-stage heart failure incidence.

This retrospective study was conducted on patients with hypertrophic cardiomyopathy in China between January 2009 and February 2024. Patients were stratified into ApHCM and non-ApHCM groups. The primary outcome was a composite of major adverse cardiovascular events, including all-cause deaths, heart failure hospitalization, sudden cardiac death, and ventricular tachycardia. The secondary outcome was the incidence of end-stage heart failure, defined as left ventricular ejection fraction <50%. Kaplan-Meier and univariable and multivariable Cox proportional analyses were applied. Adjustment variables were included for important baseline characteristics, comorbidities, and medication use. Of 5653 patients enrolled with hypertrophic cardiomyopathy, 584 (10.3%) had ApHCM and 5069 (89.7%) had non-ApHCM. During the median follow-up period of 4.6 years (1.6-8.0 years), major adverse cardiovascular events occurred in 32.2% (n=1808), with a lower incidence in patients with ApHCM than non-ApHCM (20.4% versus 33.3%, P<0.001). Non-ApHCM was an independent predictor of major adverse cardiovascular events (hazard ratio [HR], 1.65 [95% CI, 1.36-1.99]; P<0.001). In the serial cohort, patients with ApHCM exhibited a lower incidence of end-stage heart failure than those with non-ApHCM (12.4% versus 2.7%, P<0.001). Non-ApHCM was associated with a higher risk of end-stage heart failure development (HR, 2.31 [95% CI, 1.28-4.15]; P<0.001). In subgroup and sensitivity analysis, the results were consistent for our main and secondary outcomes.

ApHCM is relatively common in hypertrophic cardiomyopathy and shows lower rates of all-cause mortality and heart failure hospitalizations than non-ApHCM.

Non-obstructive hypertrophic cardiomyopathy, or apical hypertrophic cardiomyopathy (ApHCM), also referred to as Yamaguchi syndrome, is a type of hypertrophic cardiomyopathy (HCM) characterized by significant thickening of the left ventricular apex without blockage in the left ventricular outflow tract. It is a very rare variant of HCM. Patients with non-obstructive HCM often experience symptoms such as chest pain, palpitations, shortness of breath, and syncope, which may resemble those seen in various cardiovascular and non-cardiac conditions. Yamaguchi syndrome presents as a challenging yet manageable condition in the ED. Early recognition, accurate diagnosis, and appropriate management are crucial for better outcomes. We report a case of a young female who presented to the ED with breathlessness and chest pain. The ECG findings suggested acute coronary syndrome (ACS), but echocardiography and cardiac biomarkers indicated otherwise, leading to the diagnosis of Yamaguchi Syndrome.

The electrocardiogram (ECG) is a valuable tool for interpreting ventricular repolarization. This article aims to broaden the diagnostic scope beyond the conventional ischemia-centric approach, integrating an understanding of pathophisiological influences on ST-T wave changes.

A review was conducted on the physiological underpinnings of ventricular repolarization and the pathophisiological processes that can change ECG patterns. The research encompassed primary repolarization abnormalities due to uniform variations in ventricular action potential, secondary changes from electrical or mechanical alterations, and non-ischemic conditions influencing ST-T segments.

Primary T waves are characterized by symmetrical waves with broad bases and variable QT intervals, indicative of direct myocardial action potential modifications due to ischemia, electrolyte imbalances, and channelopathies. Secondary T waves are asymmetric and often unassociated with significant QT interval changes, suggesting depolarization alterations or changes in cardiac geometry and contractility.

We advocate for a unified ECG analysis, recognizing primary and secondary ST-T changes, and their clinical implications. Our proposed analytical framework enhances the clinician's ability to discern a wide array of cardiac conditions, extending diagnostic accuracy beyond myocardial ischemia.

Hypertrophic cardiomyopathy with left ventricular apical aneurysm is a phenotype associated with a 4-fold increase in the risk for sudden cardiac death. In this study, we describe the surgical outcome of concomitant apical aneurysm repair in patients undergoing transapical myectomy for hypertrophic cardiomyopathy.

We identified 67 patients with left ventricular apical aneurysms who underwent transapical myectomy and apical aneurysm repair between July 2000 and August 2020. Long-term survival was compared with that of 2746 consecutive patients undergoing transaortic septal myectomy for obstructive hypertrophic cardiomyopathy with subaortic obstruction.

Transapical myectomy was indicated for midventricular obstruction (n = 44) or left ventricular remodeling for diastolic heart failure (n = 29). Preoperatively, 74.6% (n = 50) of patients were in New York Heart Association class III/IV heart failure, and 34.3% (n = 23) of patients had experienced syncope or presyncope. Atrial fibrillation was documented in 22 patients (32.8%), and episodes of ventricular arrhythmias were recorded in 30 patients (44.8%). Thrombus was present in the apical aneurysm in 6 patients. During a median (interquartile range) follow-up of 4.9 (1.8-7.6) years, the estimated 1- and 5-year survivals were 98.5% and 94.5%, respectively, which were not significantly different from that of patients undergoing transaortic septal myectomy for obstructive hypertrophic cardiomyopathy (P = .52) or an age- and sex-matched US general population (P = .40).

Apical aneurysm repair in conjunction with septal myectomy is a safe procedure, and the good long-term survival of patients suggests that the procedure may reduce cardiac-related death in this high-risk hypertrophic cardiomyopathy population.

Hypertrophic cardiomyopathy (HCM) is a primary myocardial disease that is genetically transmitted as an autosomal dominant trait. Even apical HCM (ApHCM) induces atrial fibrillation (AF) based on underlying left ventricle (LV) diastolic dysfunction, where anticoagulation therapy is recommended. However, anticoagulation for AF in patients at high risk of bleeding is a double-edged sword. A 98-year-old woman living in a nursing home presented to our hospital with sudden-onset dyspnea and palpitation persisting for two hours. The patient had a history of apical HCM and bronchiectasis. An electrocardiogram showed a regular tachycardia with a heart rate of 130 bpm, suggesting atrial flutter with 2:1 atrioventricular conduction. Intravenous verapamil (5 mg) resulted in the conversion into AF, and subsequent cibenzoline (70 mg) failed to restore sinus rhythm. Given the impossibility of continuous anticoagulation, electrical cardioversion was planned. Electrical cardioversion was successful in converting AF into sinus rhythm. Given the very high risk of hemoptysis, anticoagulation was avoided. This case gives an insight into how to manage a practical therapeutic problem, which is the coexistence of AF and bronchiectasis. A variety of individual factors should be considered for clinical decision-making and management of patients with concomitant HCM and AF.

Symptomatic limitations in apical hypertrophic cardiomyopathy may occur because of diastolic dysfunction with resultant elevated left ventricular filling pressures, cardiac output limitation to exercise, pulmonary hypertension (PH), valvular abnormalities, and/or arrhythmias. In this study, the authors aimed to describe invasive cardiac hemodynamics in a cohort of patients with apical hypertrophic cardiomyopathy.

Patients presenting to a comprehensive hypertrophic cardiomyopathy center with apical hypertrophic cardiomyopathy were identified (n=542) and those who underwent invasive hemodynamic catheterization (n=47) were included in the study. Of these, 10 were excluded due to postmyectomy status or incomplete hemodynamic data. The mean age was 56±18 years, 16 (43%) were women, and ejection fraction was preserved (≥50%) in 32 (91%) patients. The most common indication for catheterization was dyspnea (48%) followed by suspected PH (13%), and preheart transplant evaluation (10%). Elevated left ventricular filling pressures at rest or exercise were present in 32 (86%) patients. PH was present in 30 (81%) patients, with 6 (20%) also having right-sided heart failure. Cardiac index was available in 25 (86%) patients with elevated resting filling pressures. Of these, 19 (76%) had reduced cardiac index and all 6 with right-sided heart failure had reduced cardiac index. Resting hemodynamics were normal in 8 of 37 (22%) patients, with 5 during exercise; 3 of 5 (60%) patients had exercise-induced elevation in left ventricular filling pressures.

In patients with apical hypertrophic cardiomyopathy undergoing invasive hemodynamic cardiac catheterization, 86% had elevated left ventricular filling pressures at rest or with exercise, 81% had PH, and 20% of those with PH had concomitant right-sided heart failure.

To evaluate the left atrial (LA) function in participants with apical hypertrophic cardiomyopathy (AHCM) by cardiovascular magnetic resonance feature tracking (CMR-FT).

Thirty typical AHCM (TAHCM) patients, 23 subclinical AHCM (SAHCM) patients and 32 normal healthy volunteers who underwent CMR exam were retrospectively analyzed. LA reservoir, conduit, and contractile function were quantified by volumetric and CMR-FT derived strain and strain rate (SR) parameters from 2-chamber and 4-chamber cine imaging.

Compared with healthy participants, both TAHCM and SAHCM patients had impaired LA reservoir function (total strain [%]: TAHCM 31.3±12.2, SAHCM 31.8±12.3, controls 40.4±10.7, P <0.01; total SR [/s]: TAHCM 1.1±0.4, SAHCM 1.1±0.5, controls 1.4 ± 0.4, P <0.01) and conduit function (passive strain [%]: TAHCM 14.4±7.6, SAHCM 16.4±8.8, controls 23.3±8.1, P <0.01; passive SR [/s]: TAHCM -0.5±0.3, SAHCM -0.6±0.3, controls -1.0±0.4, P <0.01). Regarding contraction function, although TAHCM and SAHCM patients had preserved active emptying fraction and strain (all P >0.05), patients with TAHCM had the lowest active SR value among the 3 groups ( P= 0.03). LA reservoir and conduit strain were both significantly associated with left ventricular mass index and maximal wall thickness (all P <0.05). A moderate correlation between LA passive SR and left ventricular cardiac index ( P <0.01).

The LA reservoir and conduit function are predominately impaired and appeared in both SAHCM and TAHCM patients.

Since the first description of apical hypertrophic cardiomyopathy (ApHCM) in 1976, contrasting information from all over the world has emerged regarding the natural history of the disease. However, the recommended guidelines on hypertrophic cardiomyopathy (HCM) pay a cursory reference to ApHCM, without ApHCM-specific recommendations to guide the diagnosis and management. In addition, cardiologists may not be aware of certain aspects that are specific to this disease subtype, and a robust understanding of specific disease features can facilitate recognition and timely diagnosis. Therefore, the review covers the incidence, pathogenesis, and characteristics of ApHCM and imaging methods. Echocardiography and cardiovascular magnetic resonance imaging (CMR) are the most commonly used imaging methods. Moreover, this review presents the management strategies of this heterogeneous clinical entity. In this review, we introduce a novel transapical beating-heart septal myectomy procedure for ApHCM patients with a promising short-time result.

Impaired left ventricular global longitudinal strain (GLS) and coronary artery disease (CAD) each confer adverse prognosis in hypertrophic cardiomyopathy (HCM). Despite their prevalence, data on GLS in co-existent HCM and CAD is lacking. Ninety-six patients with HCM and CAD were retrospectively identified between 2005 and 2021, and analyzed using 2D speckle-tracking echocardiography. Obstructive and non-obstructive CAD patients were compared, multivariate linear regression tested associations between clinical and echocardiographic variables with GLS, and Receiver Operating Characteristic Curve assessed the utility of GLS to predict all-cause mortality at follow-up. Mean age was 71 ± 12.2 years, 41% had obstructive HCM, 78% had obstructive CAD, and 75% had prior acute coronary syndrome. At 4.8-year follow-up, GLS decreased compared with baseline (- 12.5 ± 4.5 vs. - 14 ± 4.2%, p = 0.007), with basal segments experiencing the greatest impairment. GLS was lower in obstructive versus non-obstructive CAD patients at follow-up, although the magnitude was attenuated (baseline: - 13.2 vs. - 17.1%, p < 0.001; follow-up: - 12 vs. - 14.1%, p = 0.05). Interventricular septal thickness (β = 0.54), apical HCM (β = 0.48), and right ventricular systolic pressure (β = 0.39) were associated with more impaired GLS (all p < 0.001), independent of obstructive CAD (β = 0.09, p = 0.44). There were 9 follow-up deaths, with baseline GLS > - 13.5% being a good predictor of all-cause mortality (AUC 0.78, 95% CI 0.64-0.92, sensitivity 88%, specificity 57%, p = 0.01). Patients with HCM and CAD experience progressive GLS impairment over long-term follow-up, with GLS > - 13.5% appearing to be a threshold for predicting all-cause mortality. Apical HCM phenotype is independently associated with worse GLS.

A 63-year-old symptomatic female with apical hypertrophic cardiomyopathy and diastolic disfunction was admitted to the hospital. What is the best way to manage this patient? This study is a literature review that was performed to answer this question. The following PubMed search strategy was used: 'Hypertrophic obstructive cardiomyopathy' [All Fields] OR 'apical myectomy' [All Fields], NOT 'animal [mh]' NOT 'human [mh]' NOT 'comment [All Fields]' OR 'editorial [All Fields]' OR 'meta-analysis [All Fields]' OR 'practice-guideline [All Fields]' OR 'review [All Fields]' OR 'pediatrics [mh]'. The natural history of the disease has a benign prognosis; however, a watchful strategy was associated with the risk of adverse cardiovacular events. Contrastingly, transapical myectomy was associated with low surgical risk and acceptable outcomes. In our case, the patient underwent transapical myectomy with an unconventional post-operative period. Control echocardiography showed marked left ventricular (LV) cavity enlargement: LV end-diastolic volume, 74 mL; LV ejection fraction, 65%; and LV stroke volume index increased to 27 mL/m2. The patient was discharged 7 days after myectomy. At 6 months post-operation, the patient was NYHA Class I, with a 6 min walk test score of 420 m. Therefore, transapical myectomy may be considered as a feasible procedure in patients with apical hypertrophic cardiomyopathy and progressive heart failure.

Apical hypertrophic cardiomyopathy, also called Yamaguchi syndrome, is a rare variant of hypertrophic cardiomyopathy. Yamaguchi syndrome is characterized by hypertrophy almost confined to the apical region of the left ventricle rather than the left ventricular septum. A case of 65-year-old Saudi man presented to the ER with angina, and the ECG, echocardiogram, and nuclear study confirmed the diagnosis with Yamaguchi. Reporting this case serves to help physicians broaden their vision in approaching patients with symptoms mimicking acute coronary syndrome.

Hypertrophic cardiomyopathy (HCM) is a group of diseases affecting the left ventricle heart muscle that share a common feature of left ventricular hypertrophy without associated cardiac or systemic disorder. It was found to have a genetic basis with autosomal dominant mutations in the sarcomeric protein genes. Apical HCM is a rare subtype and underappreciated variant of HCM that primarily affects the apex of the heart. Apical HCM is dissimilar to classic HCM, with more challenges in diagnosis and inconsistent clinical course than other types. We report a case of a 91-year-old female who presented with a syncopal episode. Workup revealed atypical nonclassic features. Her transthoracic echocardiogram revealed a "spade-like" configuration of the left ventricular cavity at end-diastole consistent with apical hypertrophic cardiomyopathy. The remaining of her workup was consistent with the apical hypertrophic cardiomyopathy as a reason for the syncopal episode on presentation. Apical HCM is a distinct form of HCM that requires more attention among clinicians. In our case, the patient ended up having an implantable cardioverter defibrillator (ICD) for secondary prevention and a prescription of a beta blocker with a good outcome in her case.

Hypertrophic cardiomyopathy (HCM) is a complicated, heterogeneous genetic condition that causes left ventricular hypertrophy, fibrosis, hypercontractility, and decreased compliance. Despite the advances made over the past 3 decades in understanding the molecular and cellular mechanisms aggravating HCM, the relationship between pathophysiological stress stimuli and distinctive myocyte growth profiles is still imprecise. Currently, mavacamten, a selective and reversible inhibitor of cardiac myosin ATPase, is the only drug approved by the US FDA for the treatment of HCM. Thus, there is an unmet need for developing novel disease-specific therapeutic approaches. This article provides an overview of emerging therapeutic targets for the treatment of HCM based on various molecular pathways and novel developments that are hopefully soon to enter the clinical study. These newly discovered targets include the dual specificity tyrosine-phosphorylation-regulated kinase 1B, the absence of the melanoma 1 inflammasome, the leucine-rich repeat kinase 2 enzyme, and the cluster of differentiation 147.

Hypertrophic cardiomyopathy (HCM) is a hereditary cardiac disorder characterized by abnormal thickening of the left ventricular myocardium. This can lead to various clinical manifestations, including sudden death.

To investigate the cardiac remodeling and functional changes in patients with HCM over a specific time period and explore the impact of different treatment regimens on disease progression.

We conducted a prospective longitudinal observational study involving 100 patients diagnosed with HCM. Baseline clinical data, including demographics, medical history, and echocardiographic measurements, were collected. Follow-up assessments were performed at regular intervals over 24 months to track changes in cardiac structure, function, and clinical status. Statistical analysis, including paired t-tests and subgroup analysis, was conducted to identify significant associations and differences between treatment groups.

A total of 100 patients (mean age = 55 years, 50% male) were enrolled in the study. At baseline, echocardiography revealed increased left ventricular wall thickness (mean = 18.5 mm), left atrial dimensions (mean = 39 mm), and ventricular mass (mean = 230 g). During the follow-up period, there was a progressive increase in left ventricular wall thickness (mean change = 1.0 mm/year, p < 0.001), left atrial dimensions (mean change = 3.0 mm/year, p < 0.001), and ventricular mass (mean change = 8 g/year, p = 0.003). Additionally, alterations in diastolic and systolic function parameters were noted, with a decline in E/A ratio (mean change = -0.1 units/year, p = 0.008) and a reduction in ejection fraction (mean change = -2.0% per year, p = 0.001).

Our longitudinal observational study provides important insights into the cardiac remodeling and functional changes in patients with HCM over time. The progressive increase in cardiac parameters indicates ongoing disease progression. Additionally, beta-blocker therapy was associated with a slower rate of left ventricular wall thickening. These findings contribute to a better understanding of HCM's natural history and may guide targeted therapeutic approaches to improve patient outcomes.

Accelerated stenotic flow (AsF) in the entire left anterior descending coronary artery (LAD), assessed by transthoracic enhanced color Doppler (E-Doppler TTE), can reveal coronary stenosis (CS) and its severity, enabling a distinction between the microcirculatory and epicardial causes of coronary flow reserve (CFR) impairment.

Eighty-four consecutive patients with a CFR <2.0 (1.5 ± 0.4), as assessed by E-Doppler TTE, scheduled for coronary angiography (CA) and eventually intracoronary ultrasounds (IVUS), were studied. CFR was calculated by the ratio of peak diastolic flow velocities: during i.v. adenosine (140 mcg/Kg/m) over resting; AsF was calculated as the percentage increase of localized maximal velocity in relation to a reference velocity.

CA showed ≥50% lumen diameter narrowing of the LAD (critical CS) in 68% of patients (57/84) vs. non-critical CS in 32% (27/84). Based on the established CA/IVUS criteria, the non-critical CS subgroup was further subdivided into 2 groups: subcritical/diffuse [16/27 pts (57%)] and no atherosclerosis [11/27 pts (43%)]. CFR was similar in the three groups: 1.4 ± 0.3 in critical CS, 1.5 ± 0.4 in subcritical/diffuse CS, and 1.6 ± 0.4 in no atherosclerosis (p = ns). Overall, at least one segment of accelerated stenotic flow in the LAD was found in 73 patients (87%), while in 11 (13%) it was not. The AsF was very predictive of coronary segmental narrowing in both angio subgroups of atherosclerosis but as expected with the usage of different cutoffs. On the basis of the ROC curve, the optimal cutoff was 109% and 16% AsF % increment to successfully distinguish critical from non-critical CS (area under the curve [AUC] = 0.99, p < 0.001) and diffuse/subcritical from no CS (AUC = 0.91%, p < 0.001). Sensitivity and specificity were 96% and 100% and 82% and 100%, respectively.

E-Doppler TTE is highly feasible and reliable in detecting the CS of any grade of severity, distinguishing epicardial athero from microvascular causes of a severe CFR reduction.

Apical hypertrophic cardiomyopathy (ApHCM) is a variant of hypertrophic cardiomyopathy (HCM) with distinct imaging and clinical characteristics. Data on the prognosis of this HCM subgroup appear conflicting. Our study aims to clarify the natural history of ApHCM and identify predictors of outcomes.

A total of 856 patients with HCM were retrospectively examined. ApHCM was defined as asymmetric left ventricular hypertrophy confined predominantly at the apex, either isolated (pure ApHCM type) or with co-existent hypertrophy of the interventricular septum (mixed ApHCM). Echocardiographic, clinical, and survival data were compared between individuals with ApHCM and non-ApHCM.

A total of 143 (16.7%) patients were diagnosed with ApHCM. Compared with non-ApHCM, subjects with apical HCM were diagnosed at an older age and had better echocardiographic indices and more comorbidities at baseline. Apical aneurysms were more prevalent among the ApHCM phenotype (6.3% vs. 1.7%, p = 0.003). During a mean follow-up of 6 ± 3 years, ApHCM was characterized by lower all-cause, cardiovascular, heart failure-related mortality, and ventricular arrhythmic events compared with non-ApHCM. Multivariate analysis identified atrial fibrillation and HCM risk-sudden cardiac death (SCD) as independent predictors of the composite outcome of overall mortality and hospitalizations for cardiovascular reasons (hazard ratio [HR] 4.3, 95% confidence interval [CI] 1.9-9.5 for atrial fibrillation and HR 1.2, 95% CI 1.02-1.3 for HCM risk-SCD) in ApHCM.

ApHCM exhibited a lower rate of all-cause mortality and arrhythmic events in the middle-aged population of patients with HCM. Atrial fibrillation and HCM risk-sudden cardiac death were independent predictors of a composite of overall mortality and cardiovascular hospitalizations among those with ApHCM.

Apical hypertrophic cardiomyopathy (AHCM) is a relatively rare phenotype of hypertrophic cardiomyopathy, which is characterized by focal thickening of the left ventricular (LV) apical myocardium, showing a spade-shaped shadow on the left ventricle. We present the case of a 59-year-old man who was found to have AHCM, is an asymptomatic orthotopic heart transplantation (HTx) patient. This rare and progressive case of LV apical hypertrophy emerged from the fourth year post surgery. We analyzed the etiology of this case and summarized the clinical manifestations and prognosis of AHCM following HTx by reviewing our case and the literature.

In this case study, we present the evaluation of an orthotopic heart transplant (OHT) patient who presented with persistent shortness of breath and dizziness upon standing. The investigation uncovered the presence of progressive hypertrophic cardiomyopathy (HCM) in the transplanted heart, a condition first detected 11 years after the transplantation. Utilizing echocardiography with global longitudinal strain (GLS), we determined that the HCM likely originated from genetic predominance inherited from the heart donor rather than hypertensive disease. This finding highlights the significance of genetic factors in post-transplant complications and warrants further investigation into the long-term effects of heart transplantation on recipient health.

Previous studies have revealed that patients with hypertrophic cardiomyopathy (HCM) exhibit differences in symptom severity and prognosis, indicating potential HCM subtypes among these patients. Here, 793 patients with HCM were recruited at an average follow-up of 32.78 ± 27.58 months to identify potential HCM subtypes by performing consensus clustering on the basis of their echocardiography features. Furthermore, we proposed a systematic method for illustrating the relationship between the phenotype and genotype of each HCM subtype by using machine learning modeling and interactome network detection techniques based on whole-exome sequencing data. Another independent cohort that consisted of 414 patients with HCM was recruited to replicate the findings. Consequently, two subtypes characterized by different clinical outcomes were identified in HCM. Patients with subtype 2 presented asymmetric septal hypertrophy associated with a stable course, while those with subtype 1 displayed left ventricular systolic dysfunction and aggressive progression. Machine learning modeling based on personal whole-exome data identified 46 genes with mutation burden that could accurately predict subtype propensities. Furthermore, the patients in another cohort predicted as subtype 1 by the 46-gene model presented increased left ventricular end-diastolic diameter and reduced left ventricular ejection fraction. By employing echocardiography and genetic screening for the 46 genes, HCM can be classified into two subtypes with distinct clinical outcomes.

Apical hypertrophic cardiomyopathy is a rare variant of hypertrophic cardiomyopathy characterized by abnormal heart muscle thickening, specifically affecting the left ventricle's apex. Classically revealing both giant T-wave inversions in the precordial leads of an electrocardiogram and a spade-like configuration of the left ventricular cavity on ventriculograms, the diagnosis of the apical variant has evolved with cardiac magnetic resonance imaging. Despite being well known among East Asian populations, the diagnosis of apical hypertrophic cardiomyopathy is often underestimated and overlooked among American patients due to the non-specific nature of echocardiography. In this case report, we present the diagnosis of apical hypertrophic cardiomyopathy in a middle-aged African American male with chronic palpitations. The diagnosis was confirmed using cardiac magnetic resonance imaging, which revealed extensive myocardial fibrosis. Ultimately, the patient was treated with an implantable cardioverter-defibrillator. Our case aims to enhance the understanding and facilitate the recognition and management of apical hypertrophic cardiomyopathy, particularly among non-Asian individuals. Current challenges revolve around robust risk stratification strategies for patients at high risk for sudden cardiac death that require device therapy.

Apical hypertrophic cardiomyopathy (ApHCM) is thought to be an uncommon variant of hypertrophic cardiomyopathy (HCM). This article is a literature review focusing on the characteristic electrocardiogram (EKG) and 2D echocardiogram findings as currently there are no specific ACC/AHA/ESC guidelines set as diagnostic criteria for ApHCM.

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.