Is T1-Mapping Truly Superior to Late Gadolinium Enhancement-Imaging in Demonstrating Myocardial Fibrosis in Myopathy- and Non-Myopathy Associated Noncompaction?

To the Editor:

With interest we read the article by Zhou et al about 31 left ventricular hypertrabeculation/noncompaction (LVHT) patients who underwent cardiac MRI for evaluation of late gadolinium enhancement (LGE) and T1-mapping.¹ Of these, 14 patients were LGE-positive (LEG+) and 17 were LGE-negative (LGE−).¹ Mean native T1-values were elevated in the LGE− as well as the LGE+ LVHT patients, suggesting that elevated T1 values indicate early fibrosis not visible on LGE imaging.¹ We have the following comments and concerns.

We do not agree with the statement that higher T1-values in LGE+ LVHT patients than in LGE− LVHT patients suggest that T1-mapping is more sensitive than LGE for demonstration of myocardial fibrosis.¹ T1-values are mandatorily elevated in LGE+ LVHT patients because these patients generally have more fibrosis than LGE− LVHT patients.¹

We also do not agree with the statement that LVHT is a genetic cardiomyopathy. Though LVHT has been reported in association with mutations in >40 genes, a causal relation between any of these mutations and the development of LVHT has never been proven. Arguments against a causal relation are that mutations in >40 genes and several chromosomal defects hardly can have the same phenotype, that frequently LVHT does not segregate with a given mutation within a family, that cardiac manifestations in families carrying such mutations are heterogeneous, that LVHT can be acquired, and that in families with an autosomal dominant disease, LVHT may not occur in each generation.²

We also do not agree with the statement that the major clinical presentation of LVHT is heart failure, thromboembolism, or ventricular arrhythmia.³ The major clinical presentation of LVHT is the asymptomatic patient. Heart failure, thromboembolism, or ventricular arrhythmias are complications of LVHT, which may not occur in each patient.

Because LVHT is associated with neuromuscular disorders (NMDs) in up to 80% of the cases,⁴ we should be informed if the 31 included patients were systematically screened for NMDs and how many of these patients indeed had a NMD. In this respect it would be interesting to know if the LGE+ LVHT patients suffered more frequently from a NMD than the LGE− LVHT patients. This is a crucial point because many NMDs develop cardiac involvement in the form of myocardial fibrosis, suggesting that fibrosis associated with LVHT might in fact result from the underlying NMD and not from LVHT.

Table 1 in the paper indicates that the family history was significantly more often positive for LVHT in LGE− LVHT patients as compared with LGE+ LVHT patients.¹ What is the explanation for LGE− LVHT patients more frequently having a positive family history for LVHT than the LGE+ LVHT patients? The finding suggests that LGE− LVHT patients more frequently have a genetic background than LGE+ LVHT patients. Did the LGE− LVHT patients indeed more frequently present with genetic disease than the LGE+ LVHT patients? Was this only the case for the 8 LGE− LVHT patients with a family history positive for LVHT? Were family members of LGE− LVHT patients with LVHT also more frequently LGE− than LGE+? How to explain that LGE+ LVHT patients more frequently presented with chest pain than LGE− LVHT patients? Concerning patients with familial LVHT, which was the trait of inheritance?

Overall, this interesting study should also address the relation between fibrosis due to cardiomyopathy in NMDs and fibrosis due to LVHT. Furthermore, causes other than fibrosis, which could result in elevated T1, such as heart rate or low haemoglobin, should be addressed. Finally, group sizes should be increased to draw final conclusions.

• Josef Finsterer, MD, PhD
• Hospital Rudolfstiftung, Vienna, Austria
• Claudia Stöllberger, MD
• 2^nd Medical Department with Cardiology and Intensive Care Medicine, Hospital Rudolfstiftung, Vienna, Austria

(Released online June 21, 2016)

References

• 1.    Zhou  H,  Lin  X,  Fang  L,  Zhao  X,  Ding  H,  Chen  W, et al. Characterization of compacted myocardial abnormalities by cardiac magnetic resonance with native T1 mapping in left ventricular non-compaction patients: A comparison with late gadolinium enhancement. Circ J 2016; 80: 1210–1216.
• 2.    Finsterer  J,  Zarrouk-Mahjoub  S. Considerations about the genetics of left ventricular hypertrabeculation/non-compaction. Cardiol Young 2015; 25: 1435–1437.
• 3.    Hussein  A,  Karimianpour  A,  Collier  P,  Krasuski  RA. Isolated noncompaction of the left ventricle in adults. J Am Coll Cardiol 2015; 66: 578–585.
• 4.    Stöllberger  C,  Finsterer  J,  Blazek  G. Left ventricular hypertrabeculation/noncompaction and association with additional cardiac abnormalities and neuromuscular disorders. Am J Cardiol 2002; 90: 899–902.