PMID- 29635323
OWN - NLM
STAT- MEDLINE
DCOM- 20190604
LR  - 20190604
IS  - 2047-2412 (Electronic)
IS  - 2047-2404 (Linking)
VI  - 20
IP  - 1
DP  - 2019 Jan 1
TI  - Myocardial fibrosis as an early feature in phospholamban p.Arg14del mutation 
      carriers: phenotypic insights from cardiovascular magnetic resonance imaging.
PG  - 92-100
LID - 10.1093/ehjci/jey047 [doi]
AB  - AIMS: The p.Arg14del founder mutation in the gene encoding phospholamban (PLN) is 
      associated with an increased risk of malignant ventricular arrhythmia (VA) and 
      heart failure. It has been shown to lead to calcium overload, cardiomyocyte 
      damage, and eventually to myocardial fibrosis. This study sought to investigate 
      ventricular function, the extent and localization of myocardial fibrosis and the 
      associations with ECG features and VA in PLN p.Arg14del mutation carriers. 
      METHODS AND RESULTS: Cardiovascular magnetic resonance (CMR) data of 150 mutation 
      carriers were analysed retrospectively. Left ventricular (LV) and right 
      ventricular (RV) volumes, mass, and ejection fraction were measured. The extent 
      of late gadolinium enhancement (LGE) was expressed as a percentage of myocardial 
      mass. All standard ECG parameters were measured. Occurrence of VA was analysed on 
      ambulatory 24-h and/or exercise electrocardiography, if available. Mean age was 
      40 +/- 15 years, 42% males, and 7% were index patients while 93% were 
      pre-symptomatic carriers identified after family cascade screening. Mean LV 
      ejection fraction (LVEF) and RV ejection fraction were 58 +/- 9% and 55 +/- 9%, 
      respectively. LV-LGE was present in 91% of mutation carriers with reduced LVEF 
      (<45%) and in 30% of carriers with preserved LVEF. In carriers with positive 
      LV-LGE, its median extent was 5.9% (interquartile range 3.2-12.7). LGE was mainly 
      observed in the inferolateral wall. Carriers with inverted T-waves in the lateral 
      ECG leads more often had LV-LGE (P < 0.01) than carriers without. Finally, the 
      presence of LV-LGE, but not attenuated R-waves and inverted lateral T-waves, was 
      independently associated with VA. CONCLUSION: LV myocardial fibrosis is present 
      in many PLN p.Arg14del mutation carriers, and who still have a preserved LVEF. It 
      is seen predominantly in the LV inferolateral wall and corresponds with 
      electrocardiographic repolarization abnormalities. Although preliminary, 
      myocardial fibrosis was found to be independently associated with VA. Our 
      findings support the use of CMR with LGE early in the diagnostic work-up.
FAU - Te Rijdt, Wouter P
AU  - Te Rijdt WP
AD  - Department of Clinical and Experimental Cardiology, University of Groningen, 
      University Medical Center Groningen, Groningen, the Netherlands.
AD  - Netherlands Heart Institute (Nl-HI), Utrecht, the Netherlands.
AD  - Department of Genetics, University of Groningen, University Medical Center 
      Groningen, Groningen, the Netherlands.
FAU - Ten Sande, Judith N
AU  - Ten Sande JN
AD  - Netherlands Heart Institute (Nl-HI), Utrecht, the Netherlands.
AD  - Department of Clinical and Experimental Cardiology, Heart Center, University of 
      Amsterdam, Academic Medical Center, Amsterdam, the Netherlands.
FAU - Gorter, Thomas M
AU  - Gorter TM
AD  - Department of Clinical and Experimental Cardiology, University of Groningen, 
      University Medical Center Groningen, Groningen, the Netherlands.
FAU - van der Zwaag, Paul A
AU  - van der Zwaag PA
AD  - Department of Genetics, University of Groningen, University Medical Center 
      Groningen, Groningen, the Netherlands.
FAU - van Rijsingen, Ingrid A
AU  - van Rijsingen IA
AD  - Department of Clinical and Experimental Cardiology, Heart Center, University of 
      Amsterdam, Academic Medical Center, Amsterdam, the Netherlands.
FAU - Boekholdt, S Matthijs
AU  - Boekholdt SM
AD  - Department of Clinical and Experimental Cardiology, Heart Center, University of 
      Amsterdam, Academic Medical Center, Amsterdam, the Netherlands.
FAU - van Tintelen, J Peter
AU  - van Tintelen JP
AD  - Department of Clinical Genetics, University of Amsterdam, Academic Medical 
      Center, Amsterdam, the Netherlands.
FAU - van Haelst, Paul L
AU  - van Haelst PL
AD  - Department of Cardiology, Antonius Hospital, Sneek, the Netherlands.
AD  - Roche Diagnostics, Basel, Switzerland.
FAU - Planken, R Nils
AU  - Planken RN
AD  - Department of Radiology, University of Amsterdam, Academic Medical Center, 
      Amsterdam, the Netherlands.
FAU - de Boer, Rudolf A
AU  - de Boer RA
AD  - Department of Clinical and Experimental Cardiology, University of Groningen, 
      University Medical Center Groningen, Groningen, the Netherlands.
FAU - Suurmeijer, Albert J H
AU  - Suurmeijer AJH
AD  - Department of Pathology, University of Groningen, University Medical Center 
      Groningen, Groningen, the Netherlands.
FAU - van Veldhuisen, Dirk J
AU  - van Veldhuisen DJ
AD  - Department of Clinical and Experimental Cardiology, University of Groningen, 
      University Medical Center Groningen, Groningen, the Netherlands.
FAU - Wilde, Arthur A M
AU  - Wilde AAM
AD  - Department of Clinical and Experimental Cardiology, Heart Center, University of 
      Amsterdam, Academic Medical Center, Amsterdam, the Netherlands.
FAU - Willems, Tineke P
AU  - Willems TP
AD  - Department of Radiology, University of Groningen, University Medical Center 
      Groningen, Groningen, the Netherlands.
FAU - van Dessel, Pascal F H M
AU  - van Dessel PFHM
AD  - Department of Clinical and Experimental Cardiology, Heart Center, University of 
      Amsterdam, Academic Medical Center, Amsterdam, the Netherlands.
AD  - Department of Cardiology, Medisch Spectrum Twente, Enschede, the Netherlands.
FAU - van den Berg, Maarten P
AU  - van den Berg MP
AD  - Department of Clinical and Experimental Cardiology, University of Groningen, 
      University Medical Center Groningen, Groningen, the Netherlands.
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PL  - England
TA  - Eur Heart J Cardiovasc Imaging
JT  - European heart journal. Cardiovascular Imaging
JID - 101573788
RN  - 0 (Calcium-Binding Proteins)
RN  - 0 (Contrast Media)
RN  - 0 (Organometallic Compounds)
RN  - 0 (phospholamban)
RN  - 6HG8UB2MUY (Meglumine)
RN  - L0ND3981AG (gadoterate meglumine)
SB  - IM
MH  - Adult
MH  - Calcium-Binding Proteins/*genetics
MH  - Cardiomyopathies/*diagnostic imaging/*genetics
MH  - Contrast Media
MH  - Electrocardiography
MH  - Female
MH  - Fibrosis/pathology
MH  - Genetic Predisposition to Disease
MH  - Humans
MH  - Image Interpretation, Computer-Assisted
MH  - Magnetic Resonance Imaging, Cine/*methods
MH  - Male
MH  - Meglumine
MH  - Middle Aged
MH  - Mutation
MH  - Myocardium/*pathology
MH  - Netherlands
MH  - Organometallic Compounds
MH  - Phenotype
MH  - Retrospective Studies
MH  - Tachycardia, Ventricular/diagnostic imaging/genetics
MH  - Ventricular Dysfunction, Left/*diagnostic imaging/*genetics
EDAT- 2018/04/11 06:00
MHDA- 2019/06/05 06:00
CRDT- 2018/04/11 06:00
PHST- 2017/05/03 00:00 [received]
PHST- 2018/03/12 00:00 [accepted]
PHST- 2018/04/11 06:00 [pubmed]
PHST- 2019/06/05 06:00 [medline]
PHST- 2018/04/11 06:00 [entrez]
AID - 4964011 [pii]
AID - 10.1093/ehjci/jey047 [doi]
PST - ppublish
SO  - Eur Heart J Cardiovasc Imaging. 2019 Jan 1;20(1):92-100. doi: 
      10.1093/ehjci/jey047.