Apical hypertrophic cardiomyopathy (ApHCM) is a phenotypic variant of hypertrophic cardiomyopathy characterized by localized thickening of the left ventricular apex (1). While its clinical and imaging features—such as the characteristic “ace of spades” configuration on echocardiography and the potential for apical cavity obliteration—are well documented in guidelines and recent literature (2–5), uncommon presentations pose diagnostic challenges. Among these, the coexistence of MC and intense ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) uptake in ApHCM is particularly rare and diagnostically complex.

MC, categorized as dystrophic or metastatic, is unusual in hypertrophic cardiomyopathy and may result from endomyocardial ischemia and subsequent fibrosis (6, 7). Its detection and characterization rely on multimodality imaging, including echocardiography, cardiac computed tomography (CT), and cardiac magnetic resonance (CMR) (6–10). Notably, ¹⁸F-FDG positron emission tomography-CT (PET-CT), used to identify malignant or inflammatory processes, may show focally increased apical uptake in ApHCM (11–18), mimicking cardiac neoplasms or inflammatory disorders such as sarcoidosis (19, 20).

This overlap creates a diagnostic dilemma: distinguishing ApHCM with calcification and metabolic hyperactivity from malignant or other infiltrative cardiac diseases. To date, only sporadic cases of ApHCM with calcification have been reported, and the role of integrated imaging in resolving this diagnostic uncertainty has not been comprehensively addressed. Therefore, this article presents a detailed case of ApHCM complicated by EMF and calcification, with intense apical ¹⁸F-FDG uptake, and provides a systematic review of published cases to summarize the clinical and imaging characteristics of this rare entity (18, 21–28). We aim to highlight the diagnostic challenges and the essential role of a multimodal imaging approach.

A 54-year-old woman presented with exertional dyspnea and edema. Her symptoms began 30 years prior with dyspnea during brisk walking or uphill climbing, but she did not seek medical evaluation. Three years before admission, exercise tolerance markedly declined, accompanied by mild bilateral lower limb edema that alleviated with diuretics. Over the preceding 20 days, edema progressed and was associated with orthopnea. Her medical history included an 8-year history of diabetes mellitus managed with metformin.

Physical examination revealed an irregular heart rhythm with a rate of 104 beats per minute and blood pressure of 118/84 mmHg. Jugular venous distension was present. Bilateral basilar crackles were heard and severe pitting edema was noted in both lower limbs.

Laboratory tests revealed elevated troponin T (22.16 pg/mL, Normal value < 14 pg/mL) and CK-MB (72.7 U/L, Normal value < 24 U/L), and NT-proBNP (3,572 pg/mL, Normal value < 125 pg/mL). Liver function tests showed elevated ALT (75.1 U/L, Normal value 9–50 U/L) and AST (48.2 U/L, Normal value 15–40 U/L), with decreased albumin (33.5 g/L, Normal value 40–55 U/L). Complete blood count (including eosinophil count), serum calcium, phosphorus, parathyroid hormone, renal function, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), antinuclear antibody (ANA), and antineutrophil cytoplasmic antibody (ANCA) were normal.

Electrocardiography showed atrial fibrillation with a left bundle branch block (LBBB) and Q waves in leads I and aVL (Figure 1). Transthoracic echocardiography demonstrated left ventricular and biatrial enlargement, with measured dimensions of a left ventricular end-diastolic diameter (LVDEd) 63 mm, left atrial systolic diameter (LAS) 58 mm, and right atrial diameter (RA) 43 mm. Additional findings included apical hypertrophy, increased endocardial echogenicity, diffusely hypokinetic wall motion, and a left ventricular ejection fraction (LVEF) of 40% (Figure 2). No left ventricular outflow tract or mid-cavity blood flow acceleration was detected.

CMR cine imaging confirmed apical myocardial hypertrophy. A circumferential endocardial region showed low signal intensity without late gadolinium enhancement (LGE), suggestive of thrombus. Within the myocardium, an area of low signal intensity on T1- and T2-weighted images showed no LGE. The LGE pattern was biphasic: one component showed marked subendocardial enhancement, while the other presented as diffuse, patchy enhancement within the myocardial wall (Figure 3). To exclude a cardiac tumor, ¹⁸F-FDG PET-CT was performed after an 18-hour fast, identifying MC and intense ¹⁸F-FDG uptake at the cardiac apex (Figures 4A–C). Thoracoabdominal CT showed no mass lesions or lymphadenopathy. Endomyocardial biopsy of the apical lesion under ultrasound guidance revealed hypertrophic and focally atrophic cardiomyocytes with lipofuscin deposition, myofiber disarray, and focal fibrosis—findings consistent with hypertrophic cardiomyopathy (Figures 4D,E). Integrated imaging and histopathological analysis revealed that the apical structure comprised endomyocardial fibrosis, dystrophic calcification, and minimal inflammatory infiltrates. Whole-exome sequencing identified a likely pathogenic MYH7 variant (NM_000257.4: c.4145G>A, p.R1382Q). The final diagnosis was ApHCM with EMF and MC.

The patient received metoprolol (47.5 mg daily), torasemide (10 mg daily), tolvaptan (7.5 mg daily), and rivaroxaban (15 mg daily). To date, cardiac myosin inhibitors have not been established to provide clinical benefit in non-obstructive HCM. Accordingly, this patient did not receive myosin inhibitors. Her paroxysmal nocturnal dyspnea resolved, and edema improved at discharge. However, during the 4-month follow-up, she had persistent exertional dyspnea and edema, with a New York Heart Association (NYHA) functional class III. Four months after discharge, she was readmitted due to heart failure exacerbation from a respiratory tract infection, with aggravated edema and abdominal distention requiring intravenous diuretics. NT-proBNP was elevated (6,420 pg/mL). Echocardiography showed a left ventricular internal diameter of 57 mm and LVEF of 35%.

A systematic literature search was conducted in PubMed database using keywords “apical hypertrophic cardiomyopathy” AND “calcification”, “myocardial calcification” AND “hypertrophic cardiomyopathy", "endomyocardial fibrosis” AND “ hypertrophic cardiomyopathy” from the database's inception to 2025. The inclusion criteria were restricted to case reports or case series describing confirmed ApHCM with MC. Studies were excluded if they contained insufficient data, involved non-human subjects, or were duplicate publications. Relevant data on demographics, clinical manifestations, imaging features, diagnostic methods, treatment, and prognosis were extracted. Case reports quality was assessed using the CARE checklist.

Thirteen cases of ApHCM with MC have been reported (Table 1). Among these, six patients were female and seven male, with a median age of 60 years (range 29–88). Echocardiography, performed in all 13 patients, detected apical hypertrophy, hypokinesis of the apical segment, and mural thrombus. CMR, performed in 11/13 patients, was central for diagnosis and differential diagnosis, characterizing fibrosis, calcification, and the typical “double V” sign. CT, employed in 9/13 patients, best delineated calcification extent and nature. Radionuclide imaging (SPECT/PET) was used less frequently for perfusion and metabolism assessment. All patients (13/13) exhibited both apical hypertrophy and calcification; most (10/13) had concurrent endomyocardial fibrosis. Complications included thrombus formation (3 patients) and left ventricular dilation or aneurysm (3 patients). Genetic testing was performed in 7 patients, with mutations identified in 4 (involving MYH7, MYBPC3, TMPO, and GATA6). The remaining 3 were negative, underscoring the limited genetic detection rate and heterogeneity in this ApHCM phenotype (18, 21–28).

ApHCM with EMF and calcification is an extremely rare, with only 13 reported worldwide (18, 21–28).

In summary, ApHCM with MC is rare, its development is closely associated with the pathological cascade of endocardial ischemia, fibrosis, and calcification. Integrated multimodality imaging is essential not only for diagnosis rare calcification variants of ApHCM but also for preventing misdiagnosis in cases with atypical PET metabolic patterns.