Ultrastructural Findings in Noncompaction Prevail with Neuromuscular Disorders

Abstract

Objectives: Little is known about the ultrastructural abnormalities of left ventricular hypertrabeculation/noncompaction (LVHT). This literature review aimed to summarize and discuss ultrastructural abnormalities described in LVHT so far. Methods: The literature search was conducted via MEDLINE using the search terms ‘non-compaction', ‘noncompaction', ‘left ventricular hypertrabeculation', ‘spongy myocardium' in combination with the terms ‘ultra-structural', or ‘electron microscopy'. Results: Altogether, 11 studies reporting ultrastructural investigations of LVHT were retrieved. In these 11 studies, data on 13 patients with LVHT were presented. Ultrastructural abnormalities found in these study patients were generally nonspecific and included an increase in the number of mitochondria (n = 3), abnormally shaped mitochondria (n = 2), distorted cristae (n = 3), sarcomeric derangement (n = 3), immature cardiomyocytes (n = 1), lipid-like inclusions (n = 1), enlarged interstitial spaces (n = 1), increased interstitial collagen (n = 1), or increased glycogen (n = 1). The morphological abnormalities were most prominent in patients with a neuromuscular disorder like Barth syndrome or mitochondrial myopathy. Conclusions: Only in few patients with LVHT, ultrastructural investigations have been performed so far. Ultrastructural abnormalities in LVHT are nonspecific and most prominent in patients with a neuromuscular disorder. There is a strong need to carry out thorough ultrastructural investigations of LVHT to contribute to the understanding of this still unexplained myocardial abnormality.

Studies on Left Ventricular Hypertrabeculation/Noncompaction: The Need for In-Depth Ultrastructural Investigations

“…In LVHT the epicardium is compacted and the endocardium is remarkable in terms of showing an excessive number of trabeculae which are interspersed with deep recesses. As discussed in this issue of Cardiology by Finsterer and Stöllberger [1] endocardial fibrosis has been reported in a number of cases of LVHT, sometimes with elastin deposition. For example, analysis of the heart of a patient with Barth syndrome revealed mitochondrial abnormalities and clear endocardial fibroelastosis.…”

“…The paper by Finsterer and Stöllberger [1] is an interesting and novel literature review that lends particular weight to the association between the morphological abnormalities of LVHT and neuromuscular abnormalities such as Barth syndrome or mitochondrial myopathy. The paper evaluates a number of studies involving neuromuscular abnormalities, including one study on a family with Barth syndrome in addition to another study on a 12-year-old male with Barth syndrome.…”

“…A central theme of the paper by Finsterer and Stöllberger [1] is that there is currently a major need for in-depth ultrastructural investigations of LVHT to further understand this cardiac abnormality. This literature review highlights observations from a relatively small number of ultrastructural studies in the literature and emphasizes key abnormalities including changes in the shape and number of mitochondria, sarcomeric alterations, and other morphological abnormalities such as lipid-like inclusions and enlarged interstitial spaces.…”

“…A key finding across many of the studies analyzed by Finsterer and Stöllberger [1] was a modification in mitochondrial number or morphology. The changes included elongated mitochondria, swollen mitochondria, and disruption of the usual parallel orientation between mitochondria and sarcomeres.…”

“…In conclusion, Finsterer and Stöllberger [1] highlight an important need for ultrastructural analysis in studies on LVHT and this abnormality demonstrates significant influences of developmental regulation as well as important structural features such as sarcomeric dysregulation, endocardial fibroelastosis, and disruption of mitochondrial growth and proliferation that are known to contribute to myocardial dysfunction in these patients.…”