title: Diffuse fibrosis leads to a decrease in unipolar voltage: Validation in a swine model of premature ventricular contraction-induced cardiomyopathy.
abstract: BACKGROUND
  Frequent premature ventricular contractions (PVCs) may lead to dilated cardiomyopathy. A leftward shift in the unipolar voltage distribution in patients with cardiomyopathy has also been described and attributed to increased fibrosis.
  
  
  OBJECTIVE
  We established a swine model of PVC-induced cardiomyopathy and assessed (1) whether an increase in left ventricular fibrosis occurs and (2) whether increased fibrosis leads to a leftward shift in the unipolar voltage distribution.
  
  
  METHODS
  Ten swine underwent implantation of ventricular pacemakers; 6 programmed to deliver a 50% PVC burden and 4 controls without pacing. Voltage maps were acquired at baseline and after 14 weeks of ventricular bigeminy.
  
  
  RESULTS
  In the PVC group, left ventricular ejection fraction decreased from 67% ± 7% to 44% ± 15% (P < .05) with no change in controls (71% ± 6% to 73% ± 4%; P = .56). The fifth percentile of the bipolar and unipolar voltage distribution at baseline was 1.63 and 5.36 mV, respectively. In the control group, after 14 weeks of pacing there was no significant change in % bipolar voltage <1.5 mV (pre 1.2% vs post 2.2%; P = .34) or % unipolar voltage <5.5 mV (pre 4.0% vs post 3.5%; P = .20). In the PVC group, there was a significant increase in % unipolar voltage <5.5 mV (5.4% vs 12.6%; P < .01), with a leftward shift in the unipolar voltage distribution. Histologically, % fibrosis was increased in the PVC group (control 1.8% ± 1.3% vs PVC 3.4% ± 2.6%; P < .01).
  
  
  CONCLUSIONS
  PVC-induced cardiomyopathy in swine leads to an increase in interstitial fibrosis and a leftward shift in the unipolar voltage distribution. These findings are consistent with findings in humans with PVC-induced cardiomyopathy.
authors.affiliation: Section of Cardiac Electrophysiology, Department of Medicine, University of California, San Francisco, San Francisco, California.
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Section of Cardiac Electrophysiology, Department of Medicine, University of California, San Francisco, San Francisco, California.
authors.forename: Dolkun
authors.initials: D
authors.lastname: Rahmutula
authors.affiliation: Section of Cardiac Electrophysiology, Department of Medicine, University of California, San Francisco, San Francisco, California.
authors.forename: Srikant
authors.initials: S
authors.lastname: Duggirala
authors.affiliation: Section of Cardiac Electrophysiology, Department of Medicine, University of California, San Francisco, San Francisco, California.
authors.forename: Babak
authors.initials: B
authors.lastname: Nazer
authors.affiliation: Section of Cardiac Electrophysiology, Department of Medicine, University of California, San Francisco, San Francisco, California.
authors.forename: Qizhi
authors.initials: Q
authors.lastname: Fang
authors.affiliation: Section of Cardiac Electrophysiology, Department of Medicine, University of California, San Francisco, San Francisco, California.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Olgin
authors.affiliation: Section of Cardiac Electrophysiology, Department of Medicine, University of California, San Francisco, San Francisco, California.
authors.forename: Richard
authors.initials: R
authors.lastname: Sievers
authors.affiliation: Section of Cardiac Electrophysiology, Department of Medicine, University of California, San Francisco, San Francisco, California. Electronic address: egerstenfeld@medicine.ucsf.edu.
authors.forename: Edward P
authors.initials: EP
authors.lastname: Gerstenfeld
mesh_terms: D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D022062:Electrophysiologic Techniques, Cardiac / Q000379:methods; D055724:Electrophysiological Phenomena; D005355:Fibrosis; D006801:Humans; D008955:Models, Cardiovascular; D012720:Severity of Illness Index; D013318:Stroke Volume; D013552:Swine; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D018879:Ventricular Premature Complexes / Q000150:complications / Q000503:physiopathology
keywords: Cardiomyopathy; Electroanatomic mapping; Fibrosis; Premature ventricular contraction; Voltage mapping