Douglas P. Zipes

Indiana University-Purdue University School of Medicine, Indianapolis, Indiana, United States

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Publications (584)5031.15 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The document was approved by the American College of Cardiology Board of Trustees in August 2015 and Executive Committee in September 2015, the American Heart Association Science Advisory and Coordinating Committee in August 2015 and Executive Committee in September 2015, and by the Heart Rhythm Society Board of Trustees in August 2015. For the purpose of transparency, disclosure information for the ACC Board of Trustees, the board of the convening organization of this document, is available at: The American College of Cardiology requests that this document be cited as follows: Zipes DP, Calkins H, Daubert JP, Ellenbogen KA, Field ME, Fisher JD, Fogel RI, Frankel DS, Gupta A, Indik JH, Kusumoto FM, Lindsay BD, Marine JE, Mehta LS, Mendes LA, Miller JM, Munger TM, Sauer WH, Shen WK, Stevenson WG, Su WW, Tracy CM, Tsiperfal A. ACC/AHA/HRS advanced training statement on clinical cardiac electrophysiology (a revision of the ACC/AHA 2006 update of the clinical competence statement on invasive electrophysiology studies, catheter ablation, and cardioversion). J Am Coll Cardiol 20XX; XX:xxx-xx. This article is copublished in Circulation: Arrhythmia and Electrophysiology and HeartRhythm Journal. Copies: This document is available on the World Wide Web sites of the American College of Cardiology (, American Heart Association (, and Heart Rhythm Society ( For copies of this document, please contact Elsevier Inc. Reprint Department, fax (212) 633-3820, email Permissions: Multiple copies, modification, alteration, enhancement, and/or distribution of this document are not permitted without the express permission of the American College of Cardiology. Requests may be completed online via the Elsevier site (
    Heart rhythm: the official journal of the Heart Rhythm Society 09/2015; DOI:10.1016/j.hrthm.2015.09.014 · 5.08 Impact Factor
  • Circulation Arrhythmia and Electrophysiology 09/2015; DOI:10.1161/HAE.0000000000000014 · 4.51 Impact Factor
  • Douglas P Zipes
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    ABSTRACT: J. Rod Gimbel (1) has provided a well-reasoned and erudite commentary on the shortcomings of our present cardiac implantable electronic devices. Basically, he argues that pacemakers should provide antitachycardia pacing (ATP) as they did years ago, while implantable cardioverter defibrillators (ICDs) that deliver painful and mostly unwanted shocks should be programmable to have shock delivery turned off, while preserving high rate ATP. Both can be accomplished in a keystroke (or two) should the "Big Three" device companies choose to do so. Importantly, newer ICD treatment algorithms have significantly reduced spurious shock delivery, but it does seems reasonable in some patients to be able to deactivate the shock while preserving high rate ATP. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Pacing and Clinical Electrophysiology 03/2015; 38(6). DOI:10.1111/pace.12620 · 1.13 Impact Factor
  • Mark J. Shen · Douglas P. Zipes
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    ABSTRACT: "Heart failure is an increasingly prevalent disease with high mortality and public health burden. It is associated with autonomic imbalance characterized by sympathetic hyperactivity and parasympathetic hypoactivity. Evolving novel interventional and device-based therapies have sought to restore autonomic balance by neuromodulation. Results of preclinical animal studies and early clinical trials have demonstrated the safety and efficacy of these therapies in heart failure. This article discusses specific neuromodulatory treatment modalities individually-spinal cord stimulation, vagus nerve stimulation, baroreceptor activation therapy, and renal sympathetic nerve denervation." Copyright © 2015 Elsevier Inc. All rights reserved.
    Heart Failure Clinics 02/2015; 11(2). DOI:10.1016/j.hfc.2014.12.010 · 1.84 Impact Factor
  • Douglas P Zipes
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    ABSTRACT: Advances in treating cardiac arrhythmias include autonomic manipulation, drugs, imaging, devices, and genetics. I have selected articles published in 2014 that further our knowledge in each area, and which are representative of other important articles that could not be cited. Highlighting five diverse areas emphasizes the complexity of treating arrhythmias.
    Nature Reviews Cardiology 12/2014; 12(2). DOI:10.1038/nrcardio.2014.211 · 9.18 Impact Factor
  • Hiroshi Morita · Douglas P Zipes · Shiho T Morita · Jiashin Wu
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    ABSTRACT: Background: The junction between the coronary sinus (CS) musculature and both atria contributes to initiation of atrial tachyarrhythmias. The current study investigated the effects of CS isolation from the atria by radiofrequency catheter ablation on the induction and maintenance of atrial fibrillation (AF). Methods and results: Using an optical mapping system, we mapped action potentials at 256 surface sites in 17 isolated and arterially perfused canine atrial tissues containing the entire musculature of the CS, right atrial septum, posterior left atrium, left inferior pulmonary vein, and vein of Marshal. Rapid pacing from each site before and after addition of acetylcholine (0.5 μmol/L) was applied to induce AF. Epicardial radiofrequency catheter ablation at CS-atrial junctions isolated the CS from the atria. Rapid pacing induced sustained AF in all tissues after acetylcholine. Microreentry within the CS drove AF in 88% of preparations. Reentries associated with the vein of Marshall (29%), CS-atrial junctions (53%), right atrium (65%), and pulmonary vein (76%) (frequently with 2-4 simultaneous circuits) were additional drivers of AF. Radiofrequency catheter ablation eliminated AF in 13 tissues before acetylcholine (P<0.01) and in 5 tissues after acetylcholine. Radiofrequency catheter ablation also abbreviated the duration of AF in 12 tissues (P<0.01). Conclusions: CS and its musculature developed unstable reentry and AF, which were prevented by isolation of CS musculature from atrial tissue. The results suggest that CS can be a substrate of recurrent AF in patients after pulmonary vein isolation and that CS isolation might help prevent recurrent AF.
    Circulation Arrhythmia and Electrophysiology 11/2014; 7(6). DOI:10.1161/CIRCEP.114.001578 · 4.51 Impact Factor
  • Douglas P Zipes
    Circulation 11/2014; 130(19):e169. DOI:10.1161/CIRCULATIONAHA.114.013654 · 14.43 Impact Factor
  • Douglas P. Zipes
  • Douglas P Zipes
    Heart rhythm: the official journal of the Heart Rhythm Society 09/2014; 11(9):1501-1502. DOI:10.1016/j.hrthm.2014.07.013 · 5.08 Impact Factor
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    Jeffrey J Goldberger · Richard L Popp · Douglas P Zipes
    The Lancet 08/2014; 384(9943). DOI:10.1016/S0140-6736(14)61303-9 · 45.22 Impact Factor
  • Mark J Shen · Douglas P Zipes
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    ABSTRACT: The autonomic nervous system plays an important role in the modulation of cardiac electrophysiology and arrhythmogenesis. Decades of research has contributed to a better understanding of the anatomy and physiology of cardiac autonomic nervous system and provided evidence supporting the relationship of autonomic tone to clinically significant arrhythmias. The mechanisms by which autonomic activation is arrhythmogenic or antiarrhythmic are complex and different for specific arrhythmias. In atrial fibrillation, simultaneous sympathetic and parasympathetic activations are the most common trigger. In contrast, in ventricular fibrillation in the setting of cardiac ischemia, sympathetic activation is proarrhythmic, whereas parasympathetic activation is antiarrhythmic. In inherited arrhythmia syndromes, sympathetic stimulation precipitates ventricular tachyarrhythmias and sudden cardiac death except in Brugada and J-wave syndromes where it can prevent them. The identification of specific autonomic triggers in different arrhythmias has brought the idea of modulating autonomic activities for both preventing and treating these arrhythmias. This has been achieved by either neural ablation or stimulation. Neural modulation as a treatment for arrhythmias has been well established in certain diseases, such as long QT syndrome. However, in most other arrhythmia diseases, it is still an emerging modality and under investigation. Recent preliminary trials have yielded encouraging results. Further larger-scale clinical studies are necessary before widespread application can be recommended.
    Circulation Research 03/2014; 114(6):1004-21. DOI:10.1161/CIRCRESAHA.113.302549 · 11.02 Impact Factor
  • John C Lopshire · Douglas P Zipes
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    ABSTRACT: Spinal cord stimulation with implantable devices has been used worldwide for decades to treat regional pain conditions and cardiac angina refractory to conventional therapies. Preclinical studies with spinal cord stimulation in experimental animal models of heart disease have described interesting effects on cardiac and autonomic nervous system physiology. In canine and porcine animals with failing hearts, spinal cord stimulation reverses left ventricular dilation and improves cardiac function, while suppressing the prevalence of cardiac arrhythmias. In this paper, we present further canine studies that determined the optimal site and intensity of spinal cord stimulation that produced the most robust and beneficial clinical response in heart failure animals. We then explore and discuss the clinically relevant aspects and potential impediments that may be encountered in translating spinal cord stimulation to human patients with advanced cardiac disease.
    Journal of Cardiovascular Translational Research 02/2014; 7(3). DOI:10.1007/s12265-014-9547-7 · 3.02 Impact Factor
  • Circulation 01/2014; 129(4):516-26. DOI:10.1161/CIRCULATIONAHA.113.007149 · 14.43 Impact Factor
  • Douglas P Zipes
    Circulation 01/2014; 129(1):101-11. DOI:10.1161/CIRCULATIONAHA.113.005504 · 14.43 Impact Factor
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    ABSTRACT: On the basis of the current state of knowledge of PEA, in conjunction with its increased prevalence compared with tachyarrhythmic cardiac arrests, its historically poor outcome, and emerging suggestions that opportunities for better outcomes may be feasible, the working group made a series of recommendations that constitute a road map for future research. The workshop participants produced a working definition of the PEA syndrome and, on the basis of the literature, support the differentiation of primary and secondary forms of PEA. It was recognized that many different experimental and clinical conditions may lead to the PEA syndrome. However, it is not clear whether there is a final common pathway at the cellular level for each of these conditions. Traditional experimental models of the PEA syndrome differ substantially from conditions in the majority of clinical cases. The Oregon SUDS, the Cardiac Arrest Registry to Enhance Survival, the Resuscitation Outcomes Consortium, and surveillance data on medication use before arrest suggest that there may be important patient “host factors” associated with PEA as the initial documented cardiac arrest rhythm. These observations are intriguing, but it is not clear whether these associations signal a causal relationship that may provide insight into the pathophysiological mechanisms underlying PEA. Several relatively simple and inexpensive modalities, potentially useful for further PEA classification, are readily available. Echocardiographic and end-tidal carbon dioxide observations provide real-time insight into the potential causes and prognosis of PEA, but little is known about the hemodynamics during clinical resuscitation. Therefore, methods to estimate the inotropic status and systemic vascular resistance during resuscitation would be potentially useful. The working group makes the following recommendations: 1. Develop a taxonomic classification of the known experimental and clinical conditions associated with PEA. 2. Conduct future experimental and clinical studies and report them using this taxonomic classification. 3. Identify new experimental models that better mimic the clinical conditions leading to the syndrome of PEA to elucidate the intracellular pathways that result in the syndrome of PEA. Development and refinement of such models should be a high priority, contributing to the design of pilot studies in humans. 4. Capture and analyze accurate additional data elements in existing and future cardiac arrest surveillance, notably prior illnesses and current medications, to further elucidate the relationship between patient host factors and the initial documented cardiac arrest rhythm. 5. Collect genetic, proteomic, and biomarker data on both experimental models and clinical subjects that may lead to a better understanding of the pathophysiology of PEA. 6. Obtain real-time hemodynamic information during resuscitation, particularly when PEA occurs, to guide pharmacological management. Perform noninvasive technologies such as bioimpedance and bioreactance in experimental cardiac arrest and PEA models to determine whether they can track hemodynamics accurately enough during low-flow states to be of potential use clinically. For those with promising results, consider conducting clinical studies of hemodynamically guided pharmacological intervention (eg, vasoconstrictor/vasodilator/inotropic therapy) during PEA. 7. Consider the merits of pilot testing of PEA-specific interventions in humans on the basis of promising experimental data such as synchronized mechanical chest compression and vasodilator therapy. 8. Conduct experimental and pilot clinical studies focusing on earlier application of therapeutic hypothermia, particularly when initiated during ongoing resuscitation.
    Circulation 12/2013; 128(23):2532-41. DOI:10.1161/CIRCULATIONAHA.113.004490 · 14.43 Impact Factor
  • Heart rhythm: the official journal of the Heart Rhythm Society 09/2013; DOI:10.1016/j.hrthm.2013.09.056 · 5.08 Impact Factor
  • Takeshi Ueyama · Douglas P Zipes · John C Lopshire · Jiashin Wu
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    ABSTRACT: BACKGROUND: Ischemia suppresses action potentials (AP) by elevating interstitial K(+) and activating KATP channels, and alters cytosolic Ca(2+) transients (CaT) via metabolic inhibition. OBJECTIVE: This study tested the hypothesis that AP and CaT respond to ischemia with different spatiotemporal courses and patterns. METHODS: Thirty-four transmural wedges were isolated from canine left ventricular free walls, perfused arterially, and stained with voltage and Ca(2+)-sensitive dyes. Twenty-eight wedges underwent 15 min of arterial occlusion during pacing at a cycle length (PCL) of 300 (n=19) or 600ms (n=9). Six other wedges had sequential reduction of perfusion flow from full to 50%, 25%, and 10% at 300ms PCL. AP and CaT were recorded on the cut-exposed transmural surfaces with an optical mapping system. RESULTS: Although ischemia suppressed APs, it enhanced CaT to 150±10% (more in the endocardium than epicardium) and induced CaT alternans during the first 2 min of arterial occlusion, and then suppressed CaT (PCL: 300ms). Enhancement of CaT (to 159±23%) also occurred during low flow (25%) perfusion (PCL: 300ms). Faster suppression of AP than of CaT occurred with subepicardial preference. After 15 min arterial occlusion, AP and CaT remained in only small regions during 300 ms PCL, but were preserved in most regions during 600ms PCL. CONCLUSIONS: Early ischemia induced a surge and alternans in CaT and caused its dissociation from AP both in time course of suppression and in spatial distribution. These results suggested there were different cellular regulatory mechanisms of AP and of CaT in responding to ischemia from arterial occlusion.
    Heart rhythm: the official journal of the Heart Rhythm Society 05/2013; 10(8). DOI:10.1016/j.hrthm.2013.05.021 · 5.08 Impact Factor
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    ABSTRACT: Background: The risks of sports participation for implantable cardioverter-defibrillator (ICD) patients are unknown. Methods and results: Athletes with ICDs (age, 10-60 years) participating in organized (n=328) or high-risk (n=44) sports were recruited. Sports-related and clinical data were obtained by phone interview and medical records. Follow-up occurred every 6 months. ICD shock data and clinical outcomes were adjudicated by 2 electrophysiologists. Median age was 33 years (89 subjects <20 years of age); 33% were female. Sixty were competitive athletes (varsity/junior varsity/traveling team). A pre-ICD history of ventricular arrhythmia was present in 42%. Running, basketball, and soccer were the most common sports. Over a median 31-month (interquartile range, 21-46 months) follow-up, there were no occurrences of either primary end point-death or resuscitated arrest or arrhythmia- or shock-related injury-during sports. There were 49 shocks in 37 participants (10% of study population) during competition/practice, 39 shocks in 29 participants (8%) during other physical activity, and 33 shocks in 24 participants (6%) at rest. In 8 ventricular arrhythmia episodes (device defined), multiple shocks were received: 1 at rest, 4 during competition/practice, and 3 during other physical activity. Ultimately, the ICD terminated all episodes. Freedom from lead malfunction was 97% at 5 years (from implantation) and 90% at 10 years. Conclusions: Many athletes with ICDs can engage in vigorous and competitive sports without physical injury or failure to terminate the arrhythmia despite the occurrence of both inappropriate and appropriate shocks. These data provide a basis for more informed physician and patient decision making in terms of sports participation for athletes with ICDs.
    Circulation 05/2013; 127(20):2021-2030. DOI:10.1161/CIRCULATIONAHA.112.000447 · 14.43 Impact Factor
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    Sami Viskin · Arthur A M Wilde · Andrew D. Krahn · Douglas P Zipes
    Journal of the American College of Cardiology 04/2013; 62(4). DOI:10.1016/j.jacc.2013.04.009 · 16.50 Impact Factor
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    ABSTRACT: OBJECTIVES: To determine the availability of quinidine in the world. BACKGROUND: Quinidine is the only oral medication that is effective for preventing life-threatening ventricular arrhythmias due to Brugada syndrome and idiopathic ventricular fibrillation. However, because of its low price and restricted indication, this medication is not marketed in many countries. METHODS: We conducted a world survey of quinidine availability by contacting professional medical societies and arrhythmia specialists worldwide. Physicians were e-mailed questionnaires requesting information concerning the quinidine preparation available at their hospital. We also requested information concerning cases of adverse arrhythmic events resulting from quinidine unavailability. RESULTS: A total of 273 physicians from 131 countries provided information regarding quinidine availability: Quinidine is readily available in only 19 (14%) countries. In contrast, this medication is not accessible in 99 (76%) countries and is available but only through specific regulatory processes that require 4-30 days for completion in 13 (10%) countries. We were able to gather information concerning 22 patients who had serious arrhythmias probably related (10 cases) or possibility related (12 cases) to the absence of quinidine, including 2 fatalities possibly due to quinidine unavailability. CONCLUSIONS: The lack of quinidine accessibility is a serious medical hazard at the global level.
    Journal of the American College of Cardiology 04/2013; 61(23). DOI:10.1016/j.jacc.2013.02.077 · 16.50 Impact Factor

Publication Stats

23k Citations
5,031.15 Total Impact Points


  • 1974–2015
    • Indiana University-Purdue University School of Medicine
      • Department of Medicine
      Indianapolis, Indiana, United States
    • Masonic Medical Research Laboratory
      Utica, New York, United States
  • 2014
    • Northeast Ohio Medical University
      رافينا، أوهايو, Ohio, United States
  • 1973–2014
    • Indiana University-Purdue University Indianapolis
      • • Department of Medicine
      • • Department of Radiology
      • • Krannert Institute of Cardiology
      Indianapolis, Indiana, United States
  • 2013
    • Starship Children's Hospital
      Окленд, Auckland, New Zealand
    • Tel Aviv Sourasky Medical Center
      • Department of Cardiology
      Tell Afif, Tel Aviv, Israel
  • 2011
    • Mayo Clinic - Rochester
      Rochester, Minnesota, United States
  • 2008
    • American Heart Association
      Dallas, Texas, United States
  • 2007
    • Taipei Veterans General Hospital
      • Cardiology Division
      T’ai-pei, Taipei, Taiwan
  • 2006
    • University of California, San Francisco
      San Francisco, California, United States
    • Case Western Reserve University
      Cleveland, Ohio, United States
  • 1995–2006
    • San Francisco VA Medical Center
      San Francisco, California, United States
  • 2005
    • Indiana University Bloomington
      Bloomington, Indiana, United States
  • 1989–2004
    • Cornell University
      • Biomedical Sciences
      Ithaca, NY, United States
    • University of Texas Medical School
      Houston, Texas, United States
  • 2001–2003
    • University of Pavia
      Ticinum, Lombardy, Italy
    • European Society of Cardiology
      Provence-Alpes-Côte d'Azur, France
    • National Heart, Lung, and Blood Institute
      Maryland, United States
  • 2002
    • Marion County Health Department
      Indianapolis, Indiana, United States
    • Georgetown University
      • Department of Medicine
      Washington, D. C., DC, United States
    • Fondazione Salvatore Maugeri IRCCS
      Ticinum, Lombardy, Italy
  • 1995–2002
    • American College of Cardiology
      Washington, Washington, D.C., United States
  • 2000
    • National Institutes of Health
      Maryland, United States
  • 1999
    • Riley Hospital for Children
      Indianapolis, Indiana, United States
  • 1992–1999
    • Indiana University East
      Ричмонд, Indiana, United States
  • 1998
    • Minneapolis Heart Institute
      Minneapolis, Minnesota, United States
  • 1984–1996
    • Richard L. Roudebush VA Medical Center
      Indianapolis, Indiana, United States
  • 1983–1984
    • University of Iowa
      • • Division of Cardiovascular Medicine
      • • Department of Internal Medicine
      Iowa City, Iowa, United States
    • University of Minnesota Duluth
      Duluth, Minnesota, United States
    • University of Illinois at Chicago
      • Section of Cardiology
      Chicago, IL, United States
  • 1982–1984
    • Indianapolis Zoo
      Indianapolis, Indiana, United States
    • Government of Ontario, Canada
      Guelph, Ontario, Canada
  • 1981
    • The University of Western Ontario
      London, Ontario, Canada
  • 1975
    • Marion General Hospital
      Marion, Indiana, United States