PMID- 15089990
OWN - NLM
STAT- MEDLINE
DCOM- 20040810
LR  - 20151119
IS  - 1045-3873 (Print)
IS  - 1045-3873 (Linking)
VI  - 15
IP  - 4
DP  - 2004 Apr
TI  - First human chronic experience with cardiac contractility modulation by 
      nonexcitatory electrical currents for treating systolic heart failure: mid-term 
      safety and efficacy results from a multicenter study.
PG  - 418-27
AB  - INTRODUCTION: Conventional electrical therapies for heart failure (HF) encompass 
      defibrillation and ventricular resynchronization for patients at high risk for 
      lethal arrhythmias and/or with inhomogeneous ventricular contraction. Cardiac 
      contractility modulation (CCM) by means of nonexcitatory electrical currents 
      delivered during the action potential plateau has been shown to acutely enhance 
      systolic function in humans with HF. The aim of this multicenter study was to 
      assess the chronic safety and preliminary efficacy of an implantable device 
      delivering this novel form of electrical therapy. METHODS AND RESULTS: Thirteen 
      patients with drug-resistant HF (New York Heart Association [NYHA] class III) 
      were consecutively implanted with a device (OPTIMIZER II) delivering CCM biphasic 
      square-wave pulses (20 ms, 5.8-7.7 V, 30 ms after detection of local activation) 
      through two right ventricular leads screwed into the right aspect of the 
      interventricular septum. CCM signals were delivered 3 hours daily over 8 weeks 
      (3-hour phase) and 7 hours daily over the next 24 weeks (7-hour phase). Safety 
      and feasibility of this novel therapy were regarded as primary endpoints. 
      Preliminary clinical efficacy, -as expressed by changes in ejection fraction 
      (EF), NYHA class, 6-minute walking test (6-MWT), peak O(2) uptake (peak VO(2)), 
      and Minnesota Living with HF Questionnaire (MLWHFQ), was assessed at baseline and 
      at the end of each phase. At the end of follow-up (8.8 +/- 0.2 months), all 
      patients were alive, without heart transplantation or need for left ventricular 
      assist device. Serial 24-hour Holter analysis revealed no proarrhythmic effect. 
      No devices malfunctioned or failed for any reason other than end-of-battery life. 
      Throughout the two study phases, EF improved from 22.7 +/- 7% to 28.7 +/- 7% and 
      37 +/- 13% (P = 0.004), 6-MWT from 418 +/- 99 m to 477 +/- 96 m and 510 +/- 107 m 
      (P = 0.002), MLWHFQ from 36 +/- 21 to 18 +/- 12 and 7 +/- 6 (P = 0.002), peak 
      VO(2) from 13.7 +/- 1.1 to 14.9 +/- 1.9 to 16.2 +/- 2.4 (P = 0.037), and NYHA 
      class from 3 to 1.8 +/- 0.4 to 1.5 +/- 0.7 (P < 0.001). CONCLUSION: CCM therapy 
      appears to be safe and feasible. Proarrhythmic effects of this novel therapy seem 
      unlikely. Preliminary data indicate that CCM gradually and significantly improves 
      systolic performance, symptoms, and functional status. CCM therapy for 7 hours 
      per day is associated with greater dispersion near the mean, emphasizing the need 
      to individually tailor CCM delivery duration. The technique appears to be 
      attractive as an additive treatment for severe HF. Controlled randomized studies 
      are needed to validate this novel concept.
FAU - Pappone, Carlo
AU  - Pappone C
AD  - Department of Cardiology, Electrophysiology and Cardiac Pacing Unit, San Raffaele 
      University Hospital, Via Olgettina 60, 20132 Milan, Italy. pappone.carlo@hsr.it
FAU - Augello, Giuseppe
AU  - Augello G
FAU - Rosanio, Salvatore
AU  - Rosanio S
FAU - Vicedomini, Gabriele
AU  - Vicedomini G
FAU - Santinelli, Vincenzo
AU  - Santinelli V
FAU - Romano, Massimo
AU  - Romano M
FAU - Agricola, Eustachio
AU  - Agricola E
FAU - Maggi, Francesco
AU  - Maggi F
FAU - Buchmayr, Gerhard
AU  - Buchmayr G
FAU - Moretti, Giovanni
AU  - Moretti G
FAU - Mika, Yuval
AU  - Mika Y
FAU - Ben-Haim, Shlomo A
AU  - Ben-Haim SA
FAU - Wolzt, Michael
AU  - Wolzt M
FAU - Stix, Guenter
AU  - Stix G
FAU - Schmidinger, Herwig
AU  - Schmidinger H
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cardiovasc Electrophysiol
JT  - Journal of cardiovascular electrophysiology
JID - 9010756
SB  - IM
CIN - J Cardiovasc Electrophysiol. 2004 Apr;15(4):428-9. PMID: 15089991
MH  - Chronic Disease/therapy
MH  - *Defibrillators, Implantable
MH  - Drug Resistance
MH  - Electric Stimulation Therapy/adverse effects/*methods
MH  - Heart Failure/*therapy
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Myocardial Contraction/*physiology
MH  - Prospective Studies
MH  - Risk Factors
MH  - Safety
MH  - Surveys and Questionnaires
MH  - Systole/*physiology
MH  - Treatment Outcome
EDAT- 2004/04/20 05:00
MHDA- 2004/08/11 05:00
CRDT- 2004/04/20 05:00
PHST- 2004/04/20 05:00 [pubmed]
PHST- 2004/08/11 05:00 [medline]
PHST- 2004/04/20 05:00 [entrez]
AID - JCE03580 [pii]
AID - 10.1046/j.1540-8167.2004.03580.x [doi]
PST - ppublish
SO  - J Cardiovasc Electrophysiol. 2004 Apr;15(4):418-27. doi: 
      10.1046/j.1540-8167.2004.03580.x.