Noncompaction Cardiomyopathy (NCC) is a rare cardiomyopathy that features a persistent fetal myocardium, a prominent trabecular meshwork and deep intertrabecular recesses, systolic dysfunction and left ventricular dilatation. There is no consensus on the definition and management of NCC. We report the case of a 64-year-old patient with NCC, with congestive heart failure de novo without known cardiovascular risk factors and family history of sudden cardiac death. An implantable cardioverter-defibrillator was inserted due to the patient’s high risk for sudden cardiac death. Establishing definitive guidelines for the diagnosis of NCC should lead to earlier identification of patients, prompt treatment and improved survival.

Heart Failure, Hypertrabeculation Syndrome, Left Ventricular Noncompaction, Noncompaction Cardiomyopathy, Spongy Myocardium.

Noncompaction Cardiomyopathy (NCC) is a rare cardiomyopathy that features a persistent fetal myocardium, a prominent trabecular meshwork and deep intertrabecular recesses, systolic dysfunction and left ventricular dilatation. There is no consensus on the definition and management of NCC. We report the case of a 64-year-old patient with NCC, with congestive heart failure de novo without known cardiovascular risk factors and family history of sudden cardiac death. An implantable cardioverter-defibrillator was inserted due to the patient’s high risk for sudden cardiac death. Establishing definitive guidelines for the diagnosis of NCC should lead to earlier identification of patients, prompt treatment and improved survival.

Heart Failure, Hypertrabeculation Syndrome, Left Ventricular Noncompaction, Noncompaction Cardiomyopathy, Spongy Myocardium.

While most cases of the patients who develop heart failure on the basis of previous known history of cardiovascular disease, there are rare cases of heart failure that occur without predisposing risk factors. Noncompaction cardiomyopathy (NCC) is characterized by a prominent left ventricular trabecula and deep intertrabecular recesses involving the left ventricle or both cardiac ventricles, resulting in heart failure.

The diagnosis of Noncompaction Cardiomyopathy (NCC) is rare but can be lethal if not recognized. NCC is defined by three main features: the thinning of the compact (C) myocardial layer, a prominent non-compact (NC) trabecular layer, with deep intertrabecular recesses. The ratio of NC to C thickening is at least 2 to 2.3. Finally, Doppler analysis features of blood flow passing through trabecular and crypts [1–3].

64-year-old man with a four-month history of shortness of breath developed further progressing of symptoms, with dyspnea on mild exertion associated with palpitations. Family History was remarkable for multiple first and secondary male family members with nonspecific cardiovascular disease, where his father and brother both suffered sudden cardiac death at young age, at 55 and 43 years of age respectively. The patient’s cardiovascular exam revealed normal S1, S2 heart sounds, no S3 and no murmurs, with bilateral diffuse crackles over the lung fields. Lower extremities featured bilateral pedal edema. Electrocardiogram (ECG) showed a left bundle branch block (Figure 1).

A 2D-Echocardiogram exhibited diastolic dysfunction grade I, mild left ventricular dilation, Left Ventricular Ejection Fraction (LVEF) of 35% by Simpson criteria, and evidence of mesh of endocardial trabeculations. A coronary angiography was normal as well as a 24-hour Holter monitor recording (Figure 2,3).

Cardiac Magnetic Resonance Imaging (MRC) revealed a large diastolic myocardial ratio of non-compacted to compacted thickness suggestive of Noncompaction Cardiomyopathy. An implantation of a cardiac resynchronization defibrillator was performed, and patient was discharged home on chronic anticoagulation (Figure 4,5).

The first account of postnatal persistence of spongy myocardium was a pathological description in 1975 [4]. Two decades later, an isolated, rare myocardial anomaly term “isolated non-compaction of left ventricular myocardium” was recognized, as product of an arrest of the normal compaction process during embryogenesis [5].

Embryogenetic etiologies are key in understanding the pathogenetic mechanisms in the development of NCC. Nonetheless, the description of acquired cases brings into question if it is appropriate to consider arrested maturation as the sole cause in all cases of NCC. It may be part of chronic kidney disease, pregnancy, in young athletes, Sickle Cell Anemia or even hypertension. It is considered that in these cases hemodynamic forces play a great role in disease pathogenesis, and some of these states of NCC may be reversible.

Non-compaction of the left ventricular myocardium is considered a rare form of cardiomyopathy. The true prevalence of NCC is unknown; the prevalence of reported NCC in echocardiography laboratories is between 0.014 and 1.3% [6]. In a retrospective cohort study from the Texas Children’s Hospital echocardiography database NCC accounted for 9.5% of cases, representing the third most frequent cardiomyopathy after ischemic heart disease, idiopathic dilated cardiomyopathy, and valvular disease [7] (Table 1).

Non-compaction of the left ventricular myocardium is a heterogeneous disorder with a sporadic and familial form. Upon identification of an index case of NCC, the familial occurrence rate is estimated at about 30% [8], although 60- 70% of cases appear to be sporadic [9].

There is no single gene defect responsible for NCC; many of the of the genetic phenotypes coincide clinically with cardiomyopathies or genes encoding for sarcomeric proteins, and even for disorders of the mitochondria and cytoskeleton [10–12]. NCC is associated with many genetic conditions, including muscular dystrophies, ion channelopathies that may also cause arrhythmias (e.g. long QT Syndrome), aberrant chromosomal disorders (e.g. trisomies), and as part of metabolic syndromes [13]. In some familial cohorts, several members may present with NCC and others with dilated or hypertrophic cardiomyopathies (Table 2).

The spectrum of the initial presentation of NCC is broad. Major clinical manifestations are symptoms of systolic, diastolic heart failure, and include nonspecific chest pain, arrhythmias like atrial fibrillation, ventricular arrhythmias, sudden cardiac arrest, and thromboembolic events, including stroke.

The electrocardiographic findings are nonspecific for NCC. It can range from entirely normal electrocardiogram to intraventricular conduction delay, left ventricular hypertrophy, and repolarization abnormalities.

The amount of normal myocardium will determine the functional impact of the pathology and the highly variable clinical course. The most severe cases present during the first years of life. At the other end of the severity spectrum are patients with very localized forms of myocardial noncompaction that can be asymptomatic for prolonged periods, with the diagnosis only being made at an old age.

There is much debate regarding the diagnostic criteria for NCC but there may be a predilection for overdiagnosis if criteria are not set strictly enough. For example, remodeling after myocarditis may be misdiagnosed as NCC [14], and similarly with many other well defined clinical entities, caution advised to avoid a diagnosis purely based on visualized estimate of echocardiography.

There is no gold standard test or genetic tests confirmatory of NCC. Multiple modalities may be required for a complete assessment. 2D-Echocardiography is the basic tool for the evaluation of NCC. The classical echocardiographic features of NCC are the presence of multiple prominent trabeculations with deep intertrabecular recesses invaginating deeply into the outer one third of the ventricular myocardium. High resolution imaging of cardiac magnetic resonance (CMR) delivers anatomy in greater detail, as well as functional information of the compacted and noncompacted enhancement for the evaluation of fibrosis (Table 3,4).

Misdiagnosis may be secondary to the presence of compacted papillary muscles of phenomena associated to dilated cardiomyopathy. The diagnostic criteria continue to be debated. It is based on both anatomic and functional characteristics from cardiac Magnetic Resonance Imaging (CMR) or two-dimensional echocardiography (2D-Echo) with the proposed cutoff measures of Non Compacted to Compacted ratio (NC/C) equal or more than 2.23 at the end of systole. Contrast echocardiography enhancing the cardiac wall may be especially helpful. Family history helps in establishing a more precise diagnosis (Table 5).

There is no specific therapy for patients with NCC. There is limited data prospectively assessing specific agents for long-term outcomes in NCC. The standard of care for patients NCC should include evidence-based guideline directed medical therapy for the management of patients with cardiomyopathy, including anticoagulation and primary prevention of sudden cardiac death. The current guidelines for insertion of an implantable cardioverter-defibrillator should be considered in patients with NCC presenting with syncope, symptomatic ventricular arrhythmias or with severely impaired LV systolic function (LVEF<35%).

Another important management goal is the prevention of thromboembolic complications. Anticoagulation should be instituted when a definite left ventricular clot has been identified independent of ventricular systolic function and in patients with atrial fibrillation and or LVEF <40% with high CHA2DS2-VASc score. For the patients who do not fall into either of these categories, risk assessment using the CHA2DS2-VASc score is to be used as guidance and followed by a discussion with the patient regarding the risks and benefits of anticoagulation (Table 6).

Four decades later after its original description, the controversy continues about the etiologic mechanism of NCC, challenging the notion that there is single etiologic mechanism [15]. While morphologic assessment is the only available diagnostic workup, with no single definitive genetic pathway identified, NCC or isolated left ventricular noncompaction remains a diagnostic and management challenge. Consensus for diagnostic criteria are needed as well as further development of patient registries in order to capture data of both clinical and genetic sources. The diagnosis of NCC needs to be established with caution. If a Mendelian association is made, genetic counseling may be considered.

Dr. Milton Carrero for his support in submitting this case for presentation and a special thanks to Dr. Javier Acevedo and Dr. Yandy Miranda and all of those at Mayagüez Medical Center who participated in the management of this challenging case.

This case report was presented as an oral presentation at the American College of Physicians (ACP) Annual Meeting Puerto Rico Chapter 2015 and as a poster presentation at the 22nd World International Cardiology Conference Rome Italy 2017.