Left Ventricular Noncompaction Cardiomyopathy in an Elderly Patient: A Case Report and Literature Review

Isolated left ventricular noncompaction cardiomyopathy (LVNC), also known as spongy myocardium, is an extremely rare congenital disorder belonging to unclassified cardiomyopathies by the World Health Organization and classified as a genetic cardiomyopathy by the American Heart Association. Adult prevalence is 0.017-0.26% in observational echocardiographic studies. The disease occurs due to the intrauterine arrest of normal myocardial compaction, leading to left ventricular dysfunction. Reported mortality is high, ranging from 35 to 47% over a 42- to 72-month follow-up period. Knowledge regarding proper diagnosis, morbidity, and prognosis is limited; thus, this disease is subdiagnosed. Our aim is to highlight a diagnostic approach to LVNC in an elderly patient and to stress specific diagnostic signs that make the disease more recognizable. We are reporting a case of noncompaction cardiomyopathy in a 62-year-old male without any significant past medical history who was referred to our clinic for arrhythmia evaluation. The patient had several brief episodes of palpitations over the past two months. On physical examination, he presented a blowing systolic murmur at the apex and an irregularly irregular rhythm. The 12-lead electrocardiogram (ECG) demonstrated atrial fibrillation and ST-T segment depression in the V4-V6 leads. A transthoracic echocardiogram (TTE) showed signs of dilated cardiomyopathy, severe eccentric left ventricular hypertrophy, decreased contractility with an ejection fraction (EF) <30%, moderate mitral and tricuspid regurgitations, and moderate pulmonary hypertension. Multiple prominent trabeculations were noticed in the middle and apical segments of the left ventricle. The noncompacted to compacted myocardium ratio was >2.5:1. Cardiac catheterization excluded ischemic heart disease. Cardiac magnetic resonance (CMR) imaging confirmed the diagnosis of LVNC. The patient started treatment with carvedilol, ramipril, verospiron, torasemide, and rivaroxaban. An implantable cardioverter-defibrillator (ICD) was recommended. In conclusion, the diagnosis of LVNC in the adult population is often delayed because of similarities with more frequently diagnosed diseases. TTE is the initial diagnostic test of choice. Additional imaging modalities (contrast echocardiography, CMR) can help confirm the diagnosis. Early diagnosis is crucial because of the high incidence of life-threatening complications related to heart failure, thromboembolic events, and ventricular arrhythmias. Additional prospective studies are needed to improve the management and outcomes of this rare cardiomyopathy.


Introduction
Isolated left ventricular noncompaction cardiomyopathy (LVNC), also known as spongy myocardium, is an extremely rare congenital disorder belonging to unclassified cardiomyopathies by the World Health Organization [1] and classified as a genetic cardiomyopathy by the American Heart Association [2]. Adult prevalence is 0.017-0.26% in observational echocardiographic studies (with a 3:1 male:female ratio) [3]. The disease occurs due to intrauterine arrest of normal myocardial compaction at the fifth to eighth week of embryogenesis resulting in prominent trabeculae, deep intertrabecular recesses, and thickening of the myocardium in two distinct layers: compacted and noncompacted [4].
Transthoracic echocardiogram (TTE) demonstrated signs of dilated cardiomyopathy with enlarged left cardiac chambers: left ventricle (LV), 73 mm; left atrium (LA), 55 mm; severely abnormal LA volume index, 82 mL/m 2 ; severely increased myocardial mass index, 164 g/m 2 ; and severe eccentric left ventricular hypertrophy. Moderate mitral regurgitation due to leaflet restriction and mild tricuspid regurgitation were revealed. LV contractility was significantly decreased (ejection fraction (EF) <30%). Multiple prominent trabeculations were noticed in the middle and apical segments of the lateral and posterior walls of the left ventricle. The noncompacted to compacted myocardium ratio (NC/C) in the midventricular segments was >2.5:1 in both parasternal short axis and apical four-chamber views ( Figure 2). During color Doppler flow imaging, there was direct blood flow from the ventricular cavity into deep intertrabecular recesses. Mild pericardial layer separation (4 mm) was noticed. There were signs suggestive of mild pulmonary hypertension present (tricuspid regurgitation gradient: 33 mmHg). Taking into consideration the patient's complaints and his age, ischemic heart disease was included in the differential diagnosis. Troponin I levels were negative. Cardiac catheterization was performed, and ischemic heart disease was excluded. A 24-hour Holter monitor showed couplets of premature ventricular contractions, one triplet with a wide QRS complex ( Figure 3).   The patient was prescribed heart failure therapy, including beta-blocker carvedilol, angiotensinconverting enzyme inhibitor (ACEi) ramipril, diuretics verospiron and torasemide, as well as anticoagulant rivaroxaban. In several months, ACEi was switched to sacubitril/valsartan, which was gradually adjusted to the maximum tolerated dosage. The patient had improved clinically, and left ventricular ejection fraction (LVEF) increased to 35%. The patient's two sons underwent cardiological family screening with electrocardiography and echocardiography, which did not reveal any pathology. The patient was followed up every six months for five years with periodic worsening of heart failure, which was corrected with pharmacological adjustments.

Discussion
The diagnosis of LVNC in an adult population is often delayed or missed because of similarities with more frequently diagnosed diseases, such as ischemic and nonischemic dilated cardiomyopathy, hypertensive heart disease, myocarditis, apical thrombi, and apical hypertrophic and restrictive cardiomyopathy. Physiological trabeculations, false tendons, and aberrant chords may also imitate LVNC. Other diseases mimicking LVNC must be considered as a differential diagnosis, including eosinophilic heart disease, endomyocardial fibroelastosis, cardiac fibroma, cardiac metastases, and intramyocardial abscesses [7].
Clinical presentation of the disease is highly variable. There are nine clinical types of LVNC, including (1) the isolated or benign form with normal systolic function, (2) the arrhythmogenic form, (3) the dilated form, (4) the hypertrophic form, (5) the mixed form, (6) the restrictive form, (7) the biventricular form, (8) the right ventricular hypertrabeculation with normal left ventricle form, and (9) the congenital heart disease form of LVNC [8]. As we know from previously published case reports, the patients may present with acute coronary syndrome, transient ischemic attack (TIA) or stroke, newly diagnosed HF, syncope or presyncope, arrhythmias, including recent-onset paroxysmal atrial fibrillation or newly diagnosed left bundle branch block. Some patients remain asymptomatic at the time of diagnosis but may have a murmur on physical examination [3][4][5][6][7][8].
Two-dimensional echocardiography is the standard diagnostic test of choice. It can detect a two-layer myocardium in the mid-ventricular and apical levels with a thin compacted layer and a thick noncompacted layer, which consists of trabeculations with deep intertrabecular recesses [9]. There are three sets of echocardiographic criteria for LVNC diagnosis. The Jenni criteria, also known as Zurich criteria, are the most widely accepted validated echocardiographic criteria for LVNC. They are assessed in the parasternal shortaxis view at the base, mid, and apical levels [9]. The Jenni criteria include (1) bilayered myocardium with thin compacted and thick noncompacted layers; (2) end-systolic noncompacted to compacted ratio more than 2 (in parasternal short-axis view at mid-ventricular level); (3) communication with the intertrabecular space demonstrated with color Doppler; and (4) absence of coexisting heart disease [9]. The presence of all four criteria is required for the diagnosis of LVNC. In addition, hypokinesis of noncompacted segments may also be present [9].
Alternatively, some clinicians use the Chin or Stöllberger criteria, which have also been validated. The Chin, or California, criterion defines LVNC as the ratio X-to-Y less than or equal to 0.5, where X is the distance from the epicardium to the trough of a trabeculation and Y is the distance from the epicardium to the peak of a trabeculation [10]. This criterion is applied to trabeculae at the LV apex on subxiphoid or apical fourchamber views at end diastole [10]. The Stöllberger criteria, also known as Vienna criteria, emphasize hypertrabeculation. They include (1) more than three prominent trabeculations protruding into the LV cavity, visible in one imaging plane; (2) intertrabecular spaces perfused from the ventricular cavity, visualized on color Doppler imaging [11]. A role for three-dimensional echocardiography has not been established. A role for contrast echocardiography has been incompletely evaluated in LVNC.
CMR imaging helps identify LVNC more precisely. CMR criteria by Peterson with sensitivity of 86% and specificity of 99% include assessment of the noncompacted to compacted ratio, which has to be more than 2.3 during the diastole in any long-axis LV image to make a diagnosis of LVNC [12]. Jacquier et al. proposed to use a highly sensitive and specific criterion: a trabeculated left ventricular mass should be more than 20% of the total LV mass [13]. Cardiac magnetic resonance also identifies the extent of cardiac fibrosis using late gadolinium enhancement, which is related to adverse clinical events [12].
Cardiac catheterization is needed to rule out coronary artery disease in an adult population. Cardiological family screening with electrocardiography and echocardiography is important to identify LVNC in family members. Genetic testing may provide unique information to research the genetic heterogeneity of the disease and the genotype-phenotype correlation.
The incidence of life-threatening complications is high. They are related to HF, ventricular arrhythmias, and thromboembolic events. According to the German LV noncompaction (LVNC) registry, 61% of the patients experience HF symptoms at the time of initial diagnosis [14]. The severity of the symptoms varies from mild to severe, leading to the necessity of LV assist device implantation and heart transplantation. Systolic dysfunction in combination with fibrosis often causes cardiac arrhythmias; 26% of the patients present with arrhythmias as an initial symptom [14]. The range of arrhythmias varies, including both supraventricular and ventricular. The most frequent arrhythmia is atrial fibrillation, which accounts for 18% and often occurs in patients with severely reduced LV function [8,14]. So, Holter monitoring is indicated in patients with LVNC. Thromboembolic complications are related to LV systolic dysfunction and stasis of blood in the intertrabecular recesses and are associated with atrial fibrillation. The incidence of thromboembolic complications ranges from 5% to 38% [15], of which 10-15% lead to neurologic complications [16].
Decreased LV contractility <50%, in particular in patients with midbasal extent of noncompaction, is a statistically significant predictor of overall mortality [17]. HF, graded New York Heart Association, Functional Class III-IV (NYHA III-IV), LVEF <35%, sustained ventricular arrhythmias, and dilated left atrium (left atrial volume index (LAVI) >34 cm 2 /m 2 ) are associated with cardiovascular death [16]. It is crucial to diagnose LVNC early, so life expectancy can be extended through early treatment of HF, use of oral anticoagulants (in patients with EF <40% and thromboembolic episodes of atrial fibrillation), use of antiarrhythmic medications, cardiac resynchronization therapy (in patients with low EF and a prolonged QRS duration), automatic ICD implantation (in patients with sustained ventricular tachycardia (VT) or ventricular fibrillation for sudden cardiac death prevention), and heart transplantation when other treatment options are ineffective [2,5,14].
Twenty-three previously published cases of noncompaction cardiomyopathy reported for the past 10 years (2012-2022) in the patient population aged 60 years and older are presented in Table 1. We summarized data to present a comprehensive review, including information about the first authors of the studies, year of publication, patient's age and sex, initial presentation, imaging studies, and patient follow-up. Additional prospective studies are needed to improve the management and outcomes of this rare cardiomyopathy.

Conclusions
The diagnosis of LVNC in the adult population is often delayed because of similarities with more frequently diagnosed diseases, such as ischemic and nonischemic dilated cardiomyopathy, apical hypertrophic cardiomyopathy, and hypertensive heart disease. Two-dimensional echocardiography is the standard diagnostic test of choice. Using strict Jenni, Chin, and Stöllberger echocardiographic criteria, we can increase recognition of this disease. Additional imaging modalities (contrast echocardiography, CMR) can help confirm the diagnosis. Early detection and treatment of the disease are crucial to prevent lifethreatening complications. Life expectancy can be extended through early treatment of heart failure, use of oral anticoagulants, and automatic ICD implantation. Heart transplantation is the last resort treatment for such patients. Definitive screening for family members should be established. Additional prospective studies are needed to improve the management and outcomes of this rare cardiomyopathy.

Additional Information Disclosures
Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.