Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Apr;27(4):208-213.
doi: 10.1007/s12471-019-1247-0.

Phospholamban cardiomyopathy: a Canadian perspective on a unique population

C C Cheung  1 , J S Healey  2 , R Hamilton  3 , D Spears  4 , M H Gollob  4 , G Mellor  1 , C Steinberg  5 , S Sanatani  6 , Z W Laksman  1 , A D Krahn  7
Affiliations

Phospholamban cardiomyopathy: a Canadian perspective on a unique population

C C Cheung et al. Neth Heart J. 2019 Apr.

Abstract

Introduction: Phospholamban cardiomyopathy is an inherited cardiomyopathy, characterised by a defect in regulation of the sarcoplasmic reticulum Ca2+ pump, often presenting with malignant arrhythmias and progressive cardiac dysfunction occurring at a young age.

Methods: Phospholamban R14del mutation carriers and family members were identified from inherited arrhythmia clinics at 13 sites across Canada. Cardiac investigations, including electrocardiograms, Holter monitoring (premature ventricular complexes, PVCs), and imaging results were summarised.

Results: Fifty patients (10 families) were identified (median age 30 years, range 3-71, 46% female). Mutation carriers were more likely to be older, have low-voltage QRS, T‑wave inversion, frequent PVCs, and cardiac dysfunction, compared to unaffected relatives. Increasing age, low-voltage QRS, T‑wave inversion, late potentials, and frequent PVCs were predictors of cardiac dysfunction (p < 0.05 for all). Older carriers (age ≥45 years) were more likely to have disease manifestations than were their younger counterparts, with disease onset occurring at an older age in Canadian patients and their Dutch counterparts.

Discussion: Among Canadian patients with phospholamban cardiomyopathy, clinical manifestations resembled those of their Dutch counterparts, with increasing age a major predictor of disease manifestation. Older mutation carriers were more likely to have electrical and structural abnormalities, and may represent variable expressivity, age-dependent penetrance, or genetic heterogeneity among Canadian patients.

Keywords: Cardiomyopathy; Genetics; Phospholamban; Sudden cardiac death.

PubMed Disclaimer

Conflict of interest statement

C.C. Cheung, J.S. Healey, R. Hamilton, D. Spears, M.H. Gollob, G. Mellor, C. Steinberg, S. Sanatani, Z.W. Laksman and A.D. Krahn declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Forest plot of predictors of left ventricular dysfunction in R14del-positive patients. (*Statistical significance including age (p = 0.004), low-voltage QRS (p = 0.002), T‑wave inversion (p = 0.012), late potentials (p = 0.009), and frequent premature ventricular complexes (PVCs) (p = 0.002). SAECG signal-averaged ECG)
See this image and copyright information in PMC

References

    1. Schmitt JP, Kamisago M, Asahi M, et al. Dilated cardiomyopathy and heart failure caused by a mutation in phospholamban. Science. 2003;299(5611):1410–1413. doi: 10.1126/science.1081578. - DOI - PubMed
    1. van der Zwaag PA, van Rijsingen IA, Asimaki A, et al. Phospholamban R14del mutation in patients diagnosed with dilated cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy: evidence supporting the concept of arrhythmogenic cardiomyopathy. Eur J Heart Fail. 2012;14(11):1199–1207. doi: 10.1093/eurjhf/hfs119. - DOI - PMC - PubMed
    1. van Rijsingen IA, van der Zwaag PA, Groeneweg JA, et al. Outcome in phospholamban R14del carriers: results of a large multicentre cohort study. Circ Cardiovasc Genet. 2014;7(4):455–465. doi: 10.1161/CIRCGENETICS.113.000374. - DOI - PubMed
    1. Gollob MH, Blier L, Brugada R, et al. Recommendations for the use of genetic testing in the clinical evaluation of inherited cardiac arrhythmias associated with sudden cardiac death: Canadian Cardiovascular Society/Canadian Heart Rhythm Society joint position paper. Can J Cardiol. 2011;27(2):232–245. doi: 10.1016/j.cjca.2010.12.078. - DOI - PubMed
    1. Posch MG, Perrot A, Geier C, et al. Genetic deletion of arginine 14 in phospholamban causes dilated cardiomyopathy with attenuated electrocardiographic R amplitudes. Heart Rhythm. 2009;6(4):480–486. doi: 10.1016/j.hrthm.2009.01.016. - DOI - PubMed

LinkOut - more resources