Left ventricular noncompaction (LVNC) is a poorly understood and much debated morphological abnormality of the LV myocardium. This cardiac abnormality also is known as spongy myocardium (10) or LV hypertrabeculation (14). The term “left ventricular hypertrabeculation” was introduced by Finsterer et al. (15) in 2001 because the term “noncompaction” implies the unproven etiology of an arrest in the physiological compaction process during embryogenesis. This pathological entity was classified as a primary cardiomyopathy of genetic origin by the American Heart Association in 2006 and is included in the World Health Organization classification of cardiomyopathies (29). LVNC is characterized anatomically by an increase in the number of trabeculations beyond three, typically involving the apex, distal, and/or middle segments of the lateral walls of the LV (11). In this disease, there is a thickened myocardium with a compacted and noncompacted wall and deep intratrabecular recesses that do not connect to coronary circulation (16,37). Before 1984, LVNC had been described only in association with other congenital anomalies, but over the last 30 years, isolated noncompaction of the LV myocardium has been described well (11). The emerging literature on LVNC shows a complex disease with possible congenital and adult-onset forms that occur in isolation and also in conjunction with neuromuscular abnormalities. Much of what is known about this cardiomyopathy derives from large referral centers in patients presenting with significant symptoms and advanced disease. Disease progression and outcomes for adult patients with incidentally found and asymptomatic LVNC have not been established yet. As such, LVNC’s effect on athletic participation is unknown.
An 18-year-old African-American college football player presented for a preparticipation evaluation. He denied any history of shortness of breath, chest pain, syncope, near-syncope, or palpitations with exercise as well as a family history of sudden cardiac death, myocardial infarction, or congestive heart failure. There was no significant past medical or surgical history. Socially the patient reported history of tobacco and marijuana use. He denied current use. He denied alcohol or other illicit drug use. A 14-point review of systems was completed and was negative.
Upon examination, vital signs were appropriate for his age (blood pressure, 124/68 mm Hg; pulse, 84 bpm; height, 5′9″; weight, 180 lb). Head, eyes, ears, nose, and throat (HEENT) examination result was unremarkable. Neck was supple without thyromegaly, lymphadenopathy, or bruit. Cardiac auscultation revealed regular rate and rhythm without murmur, rub, or gallop when tested in the supine and upright positions. Lungs were clear to auscultation bilaterally. His abdomen was nontender. Bowel sounds were normal and active. There was no hepatosplenomegaly or mass. Skin was without rash. Musculoskeletal and neurological examination results were normal.
The athlete underwent a routine screening protocol performed by the author’s institution including sickle cell trait testing and screening echocardiogram. Sickle cell trait test result was negative. Two-dimensional echocardiogram with Doppler reported normal LV size and systolic function with no regional wall motion abnormalities and an ejection fraction of 65%. Prominent trabeculations involving the middle to apical portion of the LV were reported. This was concerning for ventricular noncompaction, and cardiac magnetic resonance imaging (MRI) was suggested by the interpreting cardiologist.
A cardiac MRI was completed with and without contrast. The LV was found to have normal wall motion, but there was prominent noncompacted myocardium involving the middle and distal lateral wall, distal inferior wall, middle and distal inferolateral wall, and apex. In places, the ratio of noncompacted to compacted myocardium at end-diastole exceeded 2.3:1. There was delayed perfusion in the distal inferolateral wall and apex of the LV, corresponding to the regions of noncompaction. Prominent trabeculations were observed in the right ventricle as well. The four cardiac valves were morphologically unremarkable. No myocardial fibrosis was noted.
An exercise stress test with echocardiogram was then performed for further evaluation. The patient exercised for 13 min and 20 s and accomplished 15.9 METs (104% of predicted exercise tolerance), as per Bruce protocol. He had a resting heart rate of 71 bpm and a peak heart rate of 197 bpm. The patient reported no symptoms before, during, or after exercise. His resting electrocardiogram (ECG) showed normal sinus rhythm without abnormalities. His exercise ECG showed no ischemic ST/T wave changes with exercise, and no arrhythmias were noted. Heart rate recovery at 1 min was 47 bpm. As per the exercise echocardiogram, the patient had a physiological hemodynamic response to exercise and normal LV wall motion response to exercise.
Further testing with 48-h Holter monitor was completed with the athlete participating in all noncontact activities of preseason training camp. Other than a sleeping junctional rhythm, the test was normal with no episodes of supraventricular tachycardia, nonsustained ventricular tachycardia, or ventricular tachycardia. Additionally, the patient reported no symptoms.
This athlete’s final diagnosis was asymptomatic LVNC. No further testing or interventions were performed. The patient was cleared for participation in football with close monitoring and repeat echocardiography to be completed in 1 year. His first year of competition was successful and without complication.
Prevalence and Etiology
LVNC is rare in children and adults, with highest prevalence estimates of 22 per 10,000 in pediatric populations (1) and 1 to 27 per 10,000 in adult populations (33,37,39). In pediatrics, the condition is generally diagnosed in infancy, and in adulthood, it is diagnosed most commonly in 20- to 40-year-old individuals (38). In one large single-center study, LVNC was associated with 2.7% of patients who experienced heart failure and 2% of patients with cardiac transplant (27). However, the prevalence in athletes is unknown.
The etiology of LVNC is unknown. The leading theory to explain LVNC is that there is a malfunction in the embryonic involutionary compaction process with an abnormal arrest in embryonic endomyocardial morphogenesis during fetal development (17). This abnormal development results in a thin compacted epicardial layer and a markedly thickened endocardial layer with numerous trabeculations and deep recesses in the LV. This hypothesis is supported by fetal echocardiography, but definitive proof is lacking (14,21). Alternatively there is an acquired form of LVNC that is reported most often in association with neuromuscular disorders, other cardiac conditions, and chronic renal failure (14,28). LVNC has been linked to mutations in several genes and is thought to have a predominantly autosomal dominant inheritance (19,20,45,47). Approximately 12% to 50% of patients with LVNC have a family history of the same mutation (33,46).
Presentation and Evaluation
The most commonly reported clinical symptoms of LVNC are exertional dyspnea, anginal chest pain, and palpitations (40,44). Syncope also has been reported in athletes with this condition (21) and may occur in 5% of children with LVNC (3). Stöllberger et al., in 2004, reported in a study of 77 patients with LVNC that 13% were asymptomatic (44). Heart failure, arterial hypertension, and a history of diabetes are common in patients with LVNC (40).
In evaluating patients with LVNC, ECG demonstrates nonspecific abnormalities in most cases in both adults and children (33). Further evaluation with Holter monitor testing and loop recording has found both benign conduction abnormalities and life-threatening arrhythmias (8,34). Multiple studies have investigated the potential for life-threatening ventricular arrhythmias, and authors have reported spontaneous and induced torsades de pointes, monomorphic ventricular tachycardia, and ventricular fibrillation (9,14). In 1999, Ichida et al. (19) published their findings on a pediatric sample of 27 patients in which 13 patients were found to have various arrhythmias, the most common of which was premature ventricular contractions (PVC), and found no ventricular tachycardia or fibrillation. They compared their study with other smaller studies, which reported higher rates of ventricular arrhythmias in both adults and children with LVNC. More studies are needed to determine which patients with LVNC are at risk for life-threatening ventricular arrhythmias and sudden cardiac death.
Echocardiography is the method of choice in detection of LVNC (11). Echocardiographic diagnostic criteria for LVNC have been summarized by Jenni et al. (22), Stöllberger et al. (42), and Chin et al. (7) These criteria include a ratio of noncompaction to compaction of greater than 2, the absence of other coexisting cardiac structural abnormalities, at least 4 prominent trabeculations, and recesses supplied by intraventricular blood on color Doppler. The characteristic echocardiographic appearance of LVNC may help distinguish it from other entities such as apical hypertrophic cardiomyopathy or late-stage dilated cardiomyopathy (11). Computed tomography and MRI are useful diagnostically in patients with poor image quality on echocardiography (11). In using a diastolic ratio of noncompacted to compacted layer of greater than 2.3, MRI has been used to distinguish LVNC from healthy volunteers, other cardiomyopathies, and concentric left hypertrophy (35). However, in 2008, Kohli et al. (26) criticized the current diagnostic criteria as too sensitive when their study demonstrated an unexpectedly high percentage of patients with heart failure fulfilling current echocardiographic criteria for LVNC, particularly Black individuals. Thus, further work is needed to truly define LVNC as its own entity and ensure its proper diagnosis.
There are several frequently reported complications of having LVNC. The most common is heart failure and reduced systolic function (3,33). Cardioembolism to either the brain or the periphery also has been reported (11,14). This increased risk is due to several factors including higher rates of atrial fibrillation and/or flutter, formation of thrombi within the intertrabecular recesses, patent foramen ovale, and/or systolic dysfunction (14). However, the increased risk of cardiac thromboembolism is still debated, as some studies have found no increased risk of stroke in patients with LVNC (13,15).
Coronary artery disease and myocardial perfusion abnormalities are under investigation in patients with LVNC. As previously mentioned, stable angina is common in LVNC. However, coronary angiography is usually normal in patients with LVNC. Patients with anginal chest pain but normal coronary arteries are thought to have ischemia due to impaired microvascular flow or dysfunction of coronary microcirculation (8). In a 2002 study by Jenni et al. (23), reversible myocardial ischemia was present in about half of patients with LVNC due to microvascular dysfunction. Positron emission tomography has shown a decrease of coronary flow reserve in both noncompacted and compacted segments of the LV in LVNC, and wall motion abnormalities have been observed in compact segments with decreased coronary flow reserve. These findings, in association with endocardial fibrosis on histological examination, suggest microcirculatory dysfunction in LVNC (4,11). Thus microcirculatory dysfunction and ischemia in LVNC result in myocardial failure and cardiac remodeling, and this could be the cause of the systolic and diastolic LV dysfunction reported commonly in this disease (11).
Treatment of LVNC is focused on prevention and treatment of associated conditions and their progression. Associated conditions include heart failure, central or peripheral embolism, cardiac ischemia, and life-threatening arrhythmias. Risk factors for cerebrovascular accident (CVA) or peripheral embolism include atrial fibrillation, severe systolic dysfunction, and known or previous thrombus formation. These patients should be treated with oral anticoagulation (14). Physicians have used oral anticoagulants in patients with LVNC in whom none of these risk factors are known for primary prevention, and this practice is disputed (14). Atrial fibrillation is common in patients with LVNC, and the American College of Cardiology/American Heart Association/European Society of Cardiology guidelines for atrial fibrillation management can be useful in patients with LVNC (18). Moreover ventricular arrhythmias are of concern in LVNC, but LVNC is not an absolute indication for implantation of a cardioverter-defibrillator in the absence of documented previous ventricular arrhythmia (24). Implantable cardioverter-defibrillator (ICD) should be considered for use in patients with a strong family history of sudden death, high-grade ventricular ectopy on Holter monitoring, and symptoms suggestive of paroxysmal tachyarrhythmias (38). In the case of heart failure and reduced systolic function, traditional therapies including angiotensin converting enzyme (ACE) inhibitors, β blockers, and diuretics are effective (14,38). Patients with LVNC and decompensated heart failure, despite medication optimization, may benefit from cardiac resynchronization therapy or cardiac transplantation (14,41). As related to cardiac ischemia, it is unclear whether an arrest in myocardial maturation prevents adequate growth of cardiac capillaries or if anomalies in microcirculatory development lead to noncompaction, but Song (38) suggested in a 2010 review that treatment of myocyte necrosis and fibrosis will be an important element in treating LVNC in the future.
Outcomes of patients with LVNC are variable. Heart failure and systolic dysfunction may be the most important indicators of patient prognosis (43) followed by thromboembolism, arrhythmias, age, and associated neuromuscular disorders (14). In children, the number of cardiac segments showing LVNC is also a predictor of poor outcome (36). The most common cause of death in patients with LVNC is intractable heart failure or sudden cardiac death (2,14). If symptoms manifest in infancy, the clinical course is usually severe. In adults, there is a minority of patients who experience a mild and favorable clinical course, but the majority of adult patients treated in tertiary care centers have a harsh natural progression of the disease including heart failure, arrhythmias, thromboembolic events, or sudden cardiac death (38).
Although LVNC can present with multiple symptoms, it also has been found in asymptomatic subjects (33). In a prospective study starting in 2005, 156 relatives of 44 patients with LVNC were followed (5). LVNC or dilated cardiomyopathy with prominent trabeculations (noncompacted/compacted ratio 1.0 to 2.0) was found in 41 family members screened, and of these, 28 were asymptomatic. After a mean follow-up of 55 months, 80% of the asymptomatic family members remained asymptomatic. This study also confirmed a familial inheritance pattern of approximately 50% of patients, and they recommended screening all first- and second-degree family members of patients with LVNC (5).
In 2004, Koh et al. described the incidental finding of LVNC in a 36-year-old male undergoing preoperative clearance for spinal surgery (25). Exercise testing and 24-h ECG were completed because of fear of supraventricular or ventricular arrhythmia, and none was detected. Left heart catheterization was performed to look for coronary abnormalities, which were not found. Family members also were screened for the disease, and two older sisters also were found to have asymptomatic LVNC. These three patients were followed for 10 months, and no symptoms had developed by that time.
In a 2012 case report, Cevik and Stainback (6) described a patient with asymptomatic LVNC until progressive shortness of breath developed after his 90th birthday. The authors suggested that this man’s lack of symptom development could be explained by a large retrospective analysis performed in children at Stanford University (36). In the study, echocardiographically calculating the total number of involved segments in each patient provided important prognostic information and could help guide clinical decisions. A larger number of affected segments was associated statistically with poor outcome. In the case study, the 90-year-old patient only had two involved cardiac segments, and the authors attributed his longevity without symptoms to the small number of involved cardiac segments.
In another case series, Nagavalli and Vacek (32) discussed the incidental finding of LVNC while patients were being evaluated for other medical conditions. Their cases included a 56-year-old male with end-stage liver disease and a 78 year-old female admitted with acute coronary syndrome. Although these patients were ill, they did not have the characteristics more commonly found in nonsurvivors of LVNC including significantly larger LV end-diastolic diameter at the time of presentation, New York Heart Association class III/IV, chronic atrial fibrillation, and bundle branch block (33). Nagavalli and Vacek (32) concluded that these cases of LVNC were compatible with other work suggesting a possible benign prognosis for patients with LVNC (12,30,31). Nagavalli and Vacek (32) suggested that older studies included patients in advanced stages and may not represent the true natural history of LVNC and that current echocardiographic criteria for diagnosis may be too sensitive. Moreover they suggested that an incidental finding of LVNC in a patient without symptoms or a family history of unexplained serious cardiac events may not impact survival negatively or require specific management interventions or lifestyle alterations.
With the trend toward increased use of cardiovascular testing during the preparticipation evaluation, more cases of asymptomatic disorders will be uncovered. However, as with incidental LVNC, the natural history of the diagnoses discovered during screening often is poorly understood. As a result, athletes are subjected to the financial and emotional burdens of further testing, restricted participation, and/or exclusion from participation. The ensuing inactivity then carries its own risks of metabolic syndrome and cardiovascular disease. The rhetorical question then must be asked, “Do the benefits of screening outweigh the consequences of discovery?”
The incidental finding of LVNC in an asymptomatic patient is a quagmire. There are currently no evidence-based recommendations on clinical follow-up or interventions. The technology used to identify LVNC has exceeded our understanding of the disease, and previous findings from large tertiary care institutions may not represent the full spectrum of this disease. Further evaluation and intervention in patients with incidental, asymptomatic LVNC may be prudent if the benefits outweigh the risks as determined by age, comorbidities, cardiac function, and family history (32). However at this time, in low-risk individuals, there is insufficient evidence to support limiting athletic participation.
The authors declare no conflicts of interest and do not have any financial disclosures.
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