Electrical Changes in Resting, Exercise, and Holter Electrocardiography in Fabry Cardiomyopathy

Abstract

Background: In Fabry cardiomyopathy, little is known about the interaction between its key feature of myocardial replacement fibrosis and changes in resting, Holter, and exercise electrocardiography (−ECG).

Methods and Results: Resting ECG, 24-h Holter ECG, and exercise ECG were performed in 95 patients (50 women) with Fabry disease, staged using cardiac magnetic resonance imaging to measure left ventricular fibrosis. With resting ECG, T alterations were seen in patients with cardiac fibrosis, while time intervals and rhythm were unchanged (except for a longer QRS duration in patients with severe fibrosis). All patients with severe fibrosis showed T inversion, ST alteration, or both. With Holter ECG, maximum and minimum heart rate did not differ with fibrosis severity. Patients without fibrotic tissue showed less ventricular premature beats (VPB) (median 5/24 h) compared to those with mild (median 11/24 h) or severe fibrosis (median 115/24 h; P < 0.05, respectively). Fibrosis was a strong predictor of VPB burden (r ² = 0.5; P < 0.001). During exercise, patients with severe fibrosis had the least increase in systolic blood pressure (sBP) (47 ± 22 mmHg vs. 62 ± 25 mmHg, P < 0.05) and the lowest maximum heart rate (113 ± 18/min; P < 0.05). Patients with mild fibrosis had a high sBP during exercise (198 ± 37 mmHg; P < 0.05). Decreased diastolic blood pressure (>10 mmHg) occurred in some patients with no (3/41) or mild fibrosis (3/34) but not in patients with severe fibrosis (0/20; P < 0.01).

Conclusions: Our data suggest that cardiac replacement fibrosis is responsible for repolarization abnormalities on resting ECG and increased VPB with Holter ECG. During exercise ECG, advanced cardiomyopathy is characterized by chronotropic incompetence with limitations on blood pressure and heart rate increase.

Competing interests: None declared

Appendices

Take-Home

Cardiac replacement fibrosis is responsible for clinical relevant electrical changes and seems to influence exercise intolerance in patients with Fabry disease.

Compliance with Ethics Guidelines

The authors state that the article has not been and will not be published elsewhere in substantially the same form. The submitting author has circulated the article and secured final approval of the version to be peer-reviewed from all coauthors prior to article submission.

This includes confirmation of absence of previous similar or simultaneous publications, their inspection of the manuscript, their substantial contribution to the work, and their agreement to submission.

Conflict of Interest Disclosures

F. Weidemann, J. Krämer, and C. Wanner have received speaker honoraria from Genzyme Corporation and Shire. F. Weidemann and C. Wanner are members of the Fabry Registry European Board of Advisors and have received travel assistance and speaker honoraria. The institution has received research grants from Genzyme Corporation and Shire.

Peter Nordbeck, Stefan Störk, Christian Ritter, and Georg Ertl declare that they have no conflict of interest.

Contributorship Statement

Johannes Krämer, first draft, concept of the manuscript, data interpretation, statistical analysis; Peter Nordbeck, interpretation of the data, concept manuscript, revision manuscript; Stefan Störk, statistical analysis, revision manuscript; Christian Ritter, magnetic resonance imaging, revision manuscript; Georg Ertl, revision manuscript, supervision; Christoph Wanner, interpretation of the data, revision manuscript; Frank Weidemann, interpretation of the data, concept manuscript, revision manuscript, supervision.

Informed Consent

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study. This article does not contain any studies with human or animal subjects performed by the any of the authors.