Apical Hypertrophic Cardiomyopathy: Diagnostic Challenges in a Patient with Hypertension and Obstructive Sleep Apnea

Introduction

Apical hypertrophic cardiomyopathy (ApHCM) is a relatively rare variant of hypertrophic cardiomyopathy (HCM) characterized by myocardial hypertrophy predominantly involving the left ventricular (LV) apex, typically without dynamic left ventricular outflow tract (LVOT) obstruction [1]. Initially described in Japan and subsequently reported across diverse populations, ApHCM exhibits variable regional prevalence and clinical expression, reflecting differences in referral patterns and ascertainment [1,2]. Pathophysiologically, localized apical thickening increases chamber stiffness and impairs diastolic relaxation, predisposing to elevated filling pressures, left atrial remodeling, and arrhythmias, with symptoms ranging from exertional dyspnea and chest discomfort to palpitations [1–3]. Clinically, its presentation is heterogeneous, with some patients remaining asymptomatic, while others develop exertional dyspnea, chest discomfort, or arrhythmias. ApHCM is often under-recognized or initially misattributed to more common causes of left ventricular hypertrophy (LVH), such as long-standing hypertensive heart disease [1,2]. Obstructive sleep apnea (OSA) is prevalent among patients with HCM and is associated with intermittent hypoxemia, sympathetic surges, afterload spikes, diastolic dysfunction, and increased atrial fibrillation risk, which can confound attribution of LVH and symptoms in ApHCM [3]. In patients with chronic hypertension and OSA, attribution of LVH and diastolic dysfunction can be particularly challenging due to overlapping mechanisms and shared remodeling pathways.

First described in Japan over 4 decades ago, ApHCM has been subject to evolving perspectives on its natural history. Early reports suggested a relatively benign course with low risk of sudden cardiac death [1], but more recent studies have identified considerable long-term morbidity and a non-negligible mortality risk associated with this phenotype [2,3]. Contemporary cohorts indicate that approximately 25% to 30% of patients with ApHCM experience major cardiovascular complications, such as atrial fibrillation, progressive heart failure, or even myocardial infarction, over time, and cumulative mortality rates range from approximately 4% in some series to nearly 30% in others, depending on the length of follow-up and population studied [2,3]. The defining diagnostic features include apical wall thickness typically greater than or equal to 15 mm or an apical-to-basal wall-thickness ratio greater than 1.3 to 1.5, characteristic “ace-of-spades” end-diastolic cavity configuration on imaging, giant negative T-wave inversions in precordial leads on electrocardiogram (ECG), and the absence of significant LVOT obstruction [4]. Against this background, the present case underscores the diagnostic attribution problem posed by coexisting hypertension and OSA and frames 3 practical questions: (1) which clinical and electrocardiographic features should prompt consideration of ApHCM when long-standing hypertension is present; (2) how diastolic dysfunction and left atrial remodeling inform risk appraisal in this phenotype; and (3) what implications this differentiation holds for longitudinal surveillance and family evaluation [1–3]. By articulating these questions at the outset, we aim to situate the case within contemporary evidence and to highlight potential implications for clinical practice and future inquiry, including refinement of risk stratification in ApHCM with common comorbidities. Finally, the aim of this report is to describe a 53-year-old man with chronic hypertension and OSA diagnosed with ApHCM based on ECG, echocardiography, and MRI, and to highlight the diagnostic and management implications.

Case Report

A 53-year-old male patient presented to the outpatient clinic reporting difficulty breathing and pulsatile holocranial headaches occurring over several months. Dyspnea was consistent with New York Heart Association (NYHA) class II, with gradual progression over several months and trigger by minimal exertion, such as walking several blocks. His headaches were graded as 6 out of 10 in intensity, were intermittent over the same period, and were not accompanied by nausea, vomiting, chest pain, or syncope. His past medical history was significant for long-standing hypertension, managed with atenolol 25 mg twice daily and enalapril 20 mg daily, and aspirin 100 mg daily. Additionally, the patient reported chronic untreated snoring and OSA of undetermined duration, with no prior polysomnography or continuous positive airway pressure (CPAP) therapy. Family history was notable for cardiovascular events: his father died of acute myocardial infarction at 72 years, his mother experienced a fatal cerebrovascular event at 82 years, and his brother was diagnosed with hypertension as an adult 5 years prior. He denied tobacco use, alcohol consumption, and illicit drug use, maintaining regular moderate physical activity.

At presentation, vital signs were stable with a heart rate of 80 beats per minute, respiratory rate of 18 breaths per minute, blood pressure of 140/80 mmHg, and oxygen saturation of 91% on ambient air. He was alert, oriented, hydrated, afebrile, and exhibited no lymphadenopathy, jugular venous distension, or thyroid abnormalities. Chest examination revealed preserved expansibility and clear bilateral lung sounds. Cardiac auscultation revealed regular rhythm and normal heart sounds; a murmur was noted but was not further characterized. There was no hepatomegaly or peripheral edema, and distal pulses were palpable bilaterally.

Laboratory analysis revealed elevated hemoglobin and hematocrit levels at 17.1 g/dL (reference 13.5–17.5 g/dL) and 48.6% (reference 41–53%), respectively, potentially related to chronic OSA. Lipid profile values were within normal limits (per institutional reference intervals), while the N-terminal pro–B-type natriuretic peptide (NT-proBNP) level of 461.1 pg/mL (reference <125 pg/mL for age <75 years) correlated with cardiac remodeling and diastolic dysfunction. All reported reference ranges corresponded to our institution’s clinical laboratory. ECG exhibited sinus rhythm with a normal QRS axis at 60°, extensive subepicardial anterolateral ischemic changes, and giant deep T-wave inversions in precordial leads, consistent with ApHCM (Figure 1).

Transthoracic echocardiography demonstrated severe appearing concentric LVH with preserved left ventricular ejection fraction, moderate diastolic dysfunction (grade III), and moderate left atrial remodeling. Recognizing that apical thickness can be underestimated by echocardiography due to the distal location, subsequent cardiac MRI with gadolinium enhancement confirmed myocardial hypertrophy predominantly in the infero-septal medial segments and throughout the apical portion, measuring up to 19 mm in thickness, with preserved biventricular systolic function, left atrial dilation, and absence of LVOT obstruction (Figures 2–4). MRI additionally demonstrated a characteristic ace-of-spades configuration of the left ventricular cavity in diastole and late gadolinium enhancement (LGE) in hypertrophied apical myocardium, establishing the diagnosis of ApHCM.

Differential diagnoses considered included other variants of HCM, hypertensive heart disease, and ischemic heart disease. Multiple features favored ApHCM over isolated hypertensive heart disease: apical-predominant distribution with apical thickness 19 mm and ace-of-spades cavity configuration on MRI; giant precordial T-wave inversions disproportionate to the patient’s blood pressure levels; absence of basal septal predominance or concentric remodeling typical of pressure-overload cardiomyopathy; preserved systolic function without LV cavity dilation; and no history of severely uncontrolled, long-standing hypertension. The localization of hypertrophy to the apex with an ace-of-spades cavity configuration, absence of LVOT obstruction, and presence of apical LGE favored ApHCM over hypertensive heart disease; the clinical and imaging profile did not support ischemic cardiomyopathy. These features supported the final diagnosis.

Given the diagnosis and symptomatic presentation, management with atenolol was maintained as first-line therapy, aimed at reducing myocardial oxygen consumption and controlling symptoms related to ventricular arrhythmias and dyspnea. Because OSA had not been previously evaluated or treated, we referred the patient for formal polysomnography and CPAP initiation. If symptoms proved refractory to beta-blockade, our contingency plan included a trial of a non-dihydropyridine calcium channel blocker and ambulatory rhythm monitoring; septal reduction therapy was not indicated in the absence of LVOT obstruction. The patient was counseled on lifestyle modifications, ongoing monitoring, and symptom management. The clinical evolution was favorable, with symptomatic improvement under beta-blockade. Additionally, due to the familial nature of the disease, formal genetic testing was discussed but deferred; we proceeded with guideline-concordant genetic counseling and phenotype-based screening of first-degree relatives (baseline ECG and transthoracic echocardiography with re-screening every 3–5 years, or earlier if symptoms develop), with a plan for cascade testing if a pathogenic variant is subsequently identified.

At follow-up, the patient remained stable and asymptomatic, reinforcing the effectiveness of the medical management strategy in addressing clinical manifestations related to ApHCM and associated diastolic dysfunction.

Discussion

This case highlights three practical lessons: first, giant precordial T-wave inversions on ECG and apical-predominant hypertrophy with an ace-of-spades cavity on MRI reliably distinguish ApHCM when hypertension and OSA confound attribution of LVH; second, left atrial remodeling and diastolic dysfunction inform risk appraisal and follow-up intensity; and third, management emphasizes medical therapy (rather than septal reduction) plus aggressive treatment of comorbid OSA and hypertension, ambulatory rhythm surveillance, and family screening. ApHCM is a rare and often under-recognized variant of HCM that poses diagnostic challenges, especially in patients with coexisting conditions causing LVH such as longstanding hypertension. In our patient, the presence of hypertension and OSA initially obscured the diagnosis by providing alternative explanations for LVH and diastolic dysfunction. ApHCM was first described in Japan over 40 years ago, and it remains more prevalent in East Asian populations (approximately 15–25% of HCM cases) than in Western populations (around 1–10% of HCM cases) [4]. This case underscores that ApHCM should be considered in patients with otherwise unexplained LVH and characteristic electrocardiographic features despite competing etiologies. The profound, “giant” T-wave inversions on his ECG were a critical clue pointing toward ApHCM, as diffuse deep T-wave inversions in precordial leads are an electrocardiographic hallmark of this condition [4].

Historically, ApHCM was regarded as a relatively benign HCM subtype. Early North American series reported low rates of sudden cardiac death and suggested a favorable prognosis, contributing to a misconception that ApHCM confers minimal risk compared to septal (obstructive) HCM [4]. However, more recent evidence has challenged this notion. Contemporary cohort studies have demonstrated that ApHCM can be associated with considerable long-term morbidity and mortality, dispelling the earlier benign interpretation [5,6]. For example, a large recent study of 462 patients with ApHCM (predominantly from a Western cohort) reported a composite rate of major adverse events (including death, appropriate implantable cardioverter-defibrillator shocks, or heart transplant) of about 17% over an average 6-year follow-up, with all-cause mortality of 13% (approximately 2.1% per year) [5]. These event rates approach those observed in more common HCM phenotypes, indicating that ApHCM is not innocuous. Similarly, a Chinese cohort of patients with ApHCM followed over several years found that adverse cardiac events, though variable, did occur in a substantial subset, reinforcing that ApHCM can have a progressive clinical course rather than remaining quiescent [6]. Taken together, the accumulating data now suggest that roughly one-quarter to one-third of patients with ApHCM may experience serious cardiovascular complications (such as atrial fibrillation, heart failure progression, ventricular arrhythmias, or stroke) over long-term follow-up [5,6]. Reported annual mortality rates in ApHCM range from approximately 0.5% up to 4% to 5% in different series, overlapping with the risk range for non-apical HCM [4,5]. Therefore, current understanding holds that ApHCM, while sometimes latent for years, cannot be considered truly benign. Therefore, vigilant follow-up and risk stratification are warranted, as exemplified by our patient’s need for ongoing surveillance despite initial symptom improvement.

The clinical presentation of ApHCM is heterogeneous, ranging from asymptomatic individuals to those with severe symptoms of chest pain, dyspnea, or syncope. About half of patients with ApHCM ultimately develop some symptoms related to their condition [4]. In our patient’s case, exertional dyspnea (NYHA class II) was the chief complaint, attributable to the impaired diastolic filling and elevated LV end-diastolic pressure caused by apical hypertrophy. His significantly elevated NT-proBNP level (461 pg/mL) corroborated the presence of increased intracardiac pressures and myocardial strain. Importantly, he did not report anginal chest pain or syncope. Chest pain in ApHCM, when present, is often due to demand-supply mismatch and microvascular ischemia in the hypertrophied myocardium rather than epicardial coronary artery disease. The apex, when markedly thickened, can develop narrowed intramyocardial arterioles and increased oxygen demand, leading to ischemic chest discomfort even in the absence of coronary stenoses [4]. This mechanism may explain why some patients with ApHCM experience angina-like pain, particularly during exertion. Our patient’s lack of chest pain might be related to his relatively preserved coronary flow or perhaps limited activity level; however, the diffuse repolarization abnormalities on his ECG, namely giant T-wave inversions, signified underlying myocardial changes that often correlate with such ischemic potential. He also experienced frequent headaches in conjunction with OSA-related nocturnal hypoxemia; while not a direct symptom of ApHCM, these headaches and his elevated hemoglobin and hematocrit levels can be viewed as peripheral effects of long-standing OSA, which in turn can compound cardiac workload and blood pressure control.

Multimodality cardiac imaging was pivotal in our case for confirming the apical phenotype of HCM and excluding other differential diagnoses. Transthoracic echocardiography showed severe LV hypertrophy that appeared concentric, a finding that could be attributed to hypertension; however, the discrepancy between the degree of hypertrophy and the patient’s moderate blood pressure levels, along with the peculiar ECG findings, raised suspicion for ApHCM. Echocardiography in ApHCM can sometimes underestimate apical hypertrophy due to the distal location; therefore, cardiac MRI was used for more definitive assessment. The cardiac MRI with gadolinium enhancement clearly demonstrated hypertrophy localized to the apical and inferoseptal segments (maximal thickness 19 mm) and a characteristic ace-of-spades configuration of the LV cavity on end-diastolic images, which is pathognomonic for ApHCM [4]. Equally important, MRI confirmed the absence of any systolic anterior motion of the mitral valve or subaortic gradient, differentiating ApHCM from hypertrophic obstructive cardiomyopathy. It also allowed for evaluation of myocardial fibrosis using LGE, which guides risk assessment, as mentioned above. These imaging findings directly informed management by confirming no role for septal reduction therapy, prioritizing surveillance for apical aneurysm formation, and emphasizing ambulatory rhythm monitoring and rigorous control of blood pressure and OSA.

Risk stratification after diagnostic clarification focused on features associated with adverse outcomes in ApHCM. Similar to classic HCM, the presence of certain clinical and imaging features portends a worse prognosis in ApHCM. Notably, left atrial enlargement is a marker of chronically elevated filling pressures and has been associated with an elevated risk of atrial fibrillation and heart failure in patients with ApHCM [6]. Our patient’s moderate left atrial dilation, as found on echocardiography, is consistent with significant diastolic dysfunction and places him in a category that literature suggests requires closer monitoring. Apical aneurysm is another critical prognostic feature unique to a subset of patients with ApHCM. Approximately 10% of patients with ApHCM develop a thin-walled LV apical aneurysm, often in the context of mid-ventricular obstruction or very localized disease in the apex [5]. The presence of an apical aneurysm markedly increases the risk of adverse outcomes, as demonstrated by a recent meta-analysis that found ApHCM patients with apical aneurysms have over 4-fold higher odds of sudden cardiac death and a similarly elevated risk of thromboembolic events as those without aneurysm [7]. This reflects the arrhythmogenic potential of scarred aneurysmal tissue and the propensity for mural thrombus formation in akinetic apical segments. Although our patient fortunately did not exhibit an apical aneurysm on MRI, this finding would have escalated his management to include considerations for placement of an implantable cardioverter-defibrillator for primary prevention and anticoagulation to mitigate sudden cardiac death and stroke risk [7]. Other predictors of poor outcome identified in ApHCM include advanced age at presentation, female sex, and the presence of diffuse myocardial fibrosis. In particular, LGE on cardiac MRI, an indicator of myocardial fibrosis, is common in ApHCM, with studies reporting LGE in the majority of patients imaged, and LGE has been linked to higher rates of ventricular arrhythmias and heart failure events [6]. Our patient’s MRI did not explicitly report LGE, and if fibrosis was minimal, this bodes favorably; nonetheless, the absence of LGE does not eliminate risk, and regular re-evaluation is prudent. In summary, while our patient lacked several high-risk features (no aneurysm, no documented arrhythmia, no family history of sudden cardiac death), he did have significant diastolic dysfunction with left atrium enlargement and exertional symptoms, which aligns with intermediate risk. Accordingly, we instituted periodic rhythm surveillance and imaging to detect progression that might alter management.

Management of ApHCM focuses on alleviating symptoms, mitigating risk of sudden death, and addressing any contributing comorbidities. There are no randomized controlled trials specific to ApHCM; therefore, management is generally extrapolated from guidelines for HCM and tailored to the absence of outflow obstruction in the apical variant. Beta-blockers are the cornerstone of therapy for symptomatic ApHCM patients, as they are for other forms of HCM. By reducing heart rate and myocardial contractility, beta-blockers prolong diastole and improve ventricular filling, while also diminishing myocardial oxygen demand and the propensity for exercise-induced arrhythmias. Our patient was already receiving a beta1-selective blocker (atenolol) for hypertension, which likely contributed to his relatively preserved exercise tolerance. We continued beta-blockade as the first-line treatment, and over follow-up he reported improvement in dyspnea, consistent with the known benefits of this therapy in HCM [4]. We selected a beta-blocker rather than an initial non–dihydropyridine calcium-channel blocker because it simultaneously addressed exertional dyspnea and blood pressure while maximizing diastolic filling; if intolerance or inadequate control occurred, verapamil or diltiazem would be considered as alternatives [4,8]. In ApHCM, there is typically no role for septal reduction therapy (surgical myectomy or alcohol ablation), since there is no subaortic obstruction to relieve. Instead, emphasis is placed on medical management and control of exacerbating factors. In our patient, aggressive control of blood pressure was reinforced, and his ACE inhibitor (enalapril) was continued alongside beta-blockade. Although data are limited, some studies in HCM suggest that renin–angiotensin system inhibitors may help attenuate hypertrophy and fibrosis over time, especially in patients with hypertension, making their use appropriate in patients like ours who have coexistent hypertension [4]. Equally important, we addressed the patient’s untreated OSA. OSA can worsen diastolic dysfunction and increase the risk of atrial fibrillation through recurrent nocturnal hypoxemia and sympathetic activation [9]; therefore, formal sleep evaluation and initiation of CPAP were incorporated into the treatment plan. In our patient, the elevation in hemoglobin and hematocrit levels was another indirect consequence of chronic hypoxemia from OSA, and this polycythemia could increase thrombotic risk. We counseled the patient on weight loss and referred him for formal sleep study and treatment (eg, CPAP therapy), expecting that effective OSA management would not only improve his headaches and oxygenation but also alleviate cardiovascular stress. Practical follow-up included annual clinical review, echocardiography every 12 to 24 months with attention to apical thickness and aneurysm surveillance, ambulatory rhythm monitoring to detect atrial fibrillation or ventricular tachycardia, optimization of blood pressure (<130/80 mmHg), and adherence to CPAP therapy. By addressing hypertension and OSA – 2 significant “mechanical stressors” on the heart – we aim to prevent further pathological hypertrophy and arrhythmias in this patient with ApHCM, as recommended in the literature for comprehensive HCM care [4].

Given the non-negligible risks associated with ApHCM, long-term follow-up and preventive strategies are crucial. Our patient’s prognosis is guardedly optimistic: at the time of this report, he was asymptomatic with preserved systolic function, and he had not exhibited any arrhythmic events to date. With continued medical therapy and risk factor modification, many patients with ApHCM can remain stable for extended periods. Nonetheless, we have arranged periodic evaluations to monitor for any emerging signs of disease progression. This includes regular clinical assessments, surveillance echocardiograms to check for changes such as apical aneurysm formation or worsening diastolic function, and periodic Holter monitoring to screen for occult atrial fibrillation or ventricular tachycardia. Current consensus guidelines for HCM recommend that risk stratification in ApHCM be approached similarly to that of traditional HCM, since the potential for sudden death exists if certain high-risk features develop [8]. Indications for primary-prevention implantable cardioverter-defibrillators, such as history of ventricular fibrillation or sustained ventricular tachycardia, unexplained syncope, massive LV hypertrophy ≥30 mm, extensive LGE, or family history of premature sudden cardiac death, are applied to patients with ApHCM in the same manner [8]. In our patient, none of these implantable cardioverter-defibrillator triggers were present at his last follow-up, but this could change with new clinical findings; therefore, reassessment of sudden cardiac death risk factors will be a routine part of his follow-up. We also pursued genetic counseling and cascade screening for his family. Although ApHCM can occur sporadically, it often has an autosomal dominant genetic basis, similar to other HCM variants. In line with guidelines, genetic testing was offered but deferred by the patient; first-degree relatives were advised to undergo baseline ECG and echocardiography with periodic re-screening every 3 to 5 years, and cascade genetic testing will be considered if a pathogenic variant is identified in the proband [8]. Furthermore, even if no mutation is identified or if relatives decline genetic testing, we recommended that his immediate family members undergo baseline cardiac evaluation with ECG and echocardiography. Those relatives with normal initial findings should still have periodic re-screening every few years given the possibility of late-onset phenotypic expression of HCM despite negative genotype or in the absence of genetic testing [8]. We also clarified the implications of genetic counseling for the family: education regarding inheritance, individualized screening intervals, and shared decision-making about genetic testing based on clinical yield and preferences [8].

This case emphasizes the importance of recognizing ApHCM as a distinct cause of unexplained LVH and diastolic heart failure symptoms, especially when the ECG shows characteristic deep T-wave inversions. Coexisting conditions such as hypertension and OSA, as seen in our patient, can delay the diagnosis by mimicking or exacerbating the cardiac findings, but they should be managed aggressively once ApHCM is diagnosed, as part of a comprehensive treatment plan. ApHCM, once thought to confer a benign prognosis, is now understood to carry meaningful risks of arrhythmias, heart failure, and even sudden cardiac death, thereby necessitating careful long-term management. Through the use of guideline-directed medical therapy (such as beta-blockade) and risk factor modification, our patient achieved symptomatic improvement and stable cardiac function. Ongoing surveillance and familial screening were implemented to address the variable and lifelong nature of this cardiomyopathy. Future research should refine risk prediction models in ApHCM by integrating comorbidities such as OSA and hypertension with imaging markers (eg, apical geometry and LGE) to better inform surveillance and primary prevention strategies [5–8].

Conclusions

ApHCM carries meaningful risks of arrhythmia, heart failure progression, and mortality, comparable to that of other HCM phenotypes, and should be considered in patients with otherwise unexplained LVH and characteristic electrocardiographic findings, such as giant precordial T-wave inversions. In this case, MRI confirmed apical and inferoseptal hypertrophy (maximum 19 mm) with an ace-of-spades cavity configuration and no LVOT obstruction, findings that directed medical rather than septal reduction therapy and informed longitudinal surveillance. Clinically, coexisting chronic hypertension and OSA complicated attribution of diastolic dysfunction, underscoring the need to evaluate and treat modifiable comorbidities, alongside disease-specific management. Practical implications include beta-blocker-based therapy for symptom control, rigorous blood pressure optimization, formal sleep evaluation with CPAP when indicated, ambulatory rhythm monitoring, and structured follow-up, consisting of clinical review, echocardiography every 12 to 24 months with attention to apical thickness and aneurysm surveillance, and family screening with ECG and echocardiography at baseline, with periodic re-evaluation. Future work should refine risk prediction in ApHCM by integrating comorbidities such as OSA and hypertension with imaging markers, such as apical geometry, LGE, and left atrial remodeling, in prospective, multicenter cohorts to better guide surveillance and primary prevention strategies.