A SMART Approach to Reducing Atrial Fibrillation Symptoms

Awardee Recipient

  • Michelle L. Dossett, MD, PhD, MPH

    Michelle L. Dossett, MD, PhD, MPH

    Assistant Physician and Instructor in Medicine

    Massachusetts General Hospital and Harvard Medical School

    Dr. Michelle Dossett is board-certified in both internal medicine and integrative medicine. She received her BS in cell and molecular biology as well as her MD and PhD in immunology from the University of Washington in Seattle, Washington. She...


Award

  • 2017 - Pilot Grant

Background

Atrial fibrillation (AF) is the most common cardiac arrhythmia with a lifetime risk of 1 in 6 individuals, and its incidence increases with age (1,2). AF is associated with increased risk of stroke as well as increased risk of cognitive impairment and dementia, regardless of stroke history (3). AF occurs in both permanent and paroxysmal (PAF) forms. Approximately one-third of patients with AF have depression and/or anxiety (4). Among patients with PAF, quality of life as measured by the SF-36 is as low as in patients with significant structural heart disease (e.g., post myocardial infarction or with heart failure) (5). Large epidemiologic studies have demonstrated an association between chronic stress and development of AF (6). Moreover, in patients with PAF, acute stress and negative emotions (e.g., sadness, anger, anxiety, and impatience) increase the likelihood of an AF episode 2-5 fold, whereas happiness decreases the likelihood of AF by 85% (7). The costs of managing AF are high, with direct costs in the U.S. estimated at $10,000-14,000 per patient per year (8). Hospitalizations for AF cost ∼$6.65 billion in 2005, not including hospitalizations for AF sequelae (e.g., bleeding complications or stroke).

Data from a recent single arm, pre-post pilot study of yoga and relaxation techniques for patients with PAF suggests that training in mind-body skills can reduce both symptomatic and asymptomatic AF episodes, symptomatic non-AF episodes, as well as anxiety and depression in this patient population (9). Another study of yoga in patients with implantable cardiac defibrillators (ICDs) demonstrated decreased anxiety and a 32% reduction in ICD-related firing due to ventricular events (10).

Dr. Dossett and colleagues recently completed a small, pre-post study delivering the Benson-Henry Institute’s (BHI) Stress-Management and Resiliency Training (SMART) Program to patients with PAF (n=8). This multimodal resiliency program targets stress with 4 main components: mind-body skills (participants learn a variety of meditation techniques, mini relaxations, walking meditation, and yoga), traditional stress management techniques, healthy lifestyle behaviors (sleep, exercise, nutrition, and social support), and cognitive reappraisal and adaptive coping skills (borrowed from cognitive behavioral therapy, acceptance and commitment therapy, and positive psychology) (11). Study participants had a significant decrease in anxiety and a non-significant trend toward improvement in AF symptoms, perceived stress, depression, and mindfulness.

Negative emotions are known to affect autonomic tone by increasing sympathetic and decreasing vagal activation (6). These components of the autonomic nervous system regulate the fluctuations in cardiac interbeat intervals, also known as heart rate variability (HRV). Loss of complexity in HRV is associated with a variety of diseases, cardiovascular mortality, and aging in general (12,13). One technique that has been widely used to analyze complexity in HRV and other physiologic signals is multiscale entropy (MSE) analysis, with more than 2,400 citations to the original articles published by Dr. Peng and his colleagues (14,15). Recently, MSE of HRV was shown to be an independent predictor of the risk of ischemic stroke in patients with AF (16). Moreover meditation favorably affects HRV complexity (17,18).

Based on what is known about HRV and cardiac disease, and the effects of meditation and yoga on patients with cardiac disease, we hypothesize that mind-body programs, such as the SMART Program, may increase HRV complexity in patients with AF resulting in fewer arrhythmic episodes as well as improvements in mental health. To begin to test this hypothesis, this application seeks to expand on our preliminary findings using a randomized, wait-list controlled trial design to test the effects of the SMART Program on quality of life, mental health, arrhythmia burden, and HRV in patients with PAF. We will deliver the program virtually (via computer video conferencing) to facilitate recruitment and gather preliminary data to help us scale this format to serve a larger population of patients. We plan to use the data gathered from this study to submit an R34 grant to NHLBI (19) to conduct a larger pilot study with a suitable active control group in anticipation of eventually submitting an R01 level grant.

Specific Aims

  1. To determine the effects of the SMART Program on AF-related quality of life, anxiety symptoms and depressive symptoms in patients with PAF.
  2. To determine the effects of the SMART Program on frequency and severity of arrhythmia symptoms in patients with PAF.
  3. To determine the effects of the SMART Program on HRV MSE in patients with PAF.

References

1.     Lloyd-Jones DM, Wang TJ, Leip EP, Larson MG, Levy D, Vasan RS, et al. Lifetime risk for development of atrial fibrillation: the Framingham Heart Study. Circulation. 2004 Aug 31;110(9):1042–6.

2.     Fuster V, Rydén LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA, et al. 2011 ACCF/AHA/HRS focused updates incorporated into the ACC/AHA/ESC 2006 Guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines developed in partnership with the European Society of Cardiology and in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. J Am Coll Cardiol. 2011 Mar 15;57(11):e101-198.

3.     Kalantarian S, Stern TA, Mansour M, Ruskin JN. Cognitive impairment associated with atrial fibrillation: a meta-analysis. Ann Intern Med. 2013 Mar 5;158(5 Pt 1):338–46.

4.     Thrall G, Lip GYH, Carroll D, Lane D. Depression, anxiety, and quality of life in patients with atrial fibrillation. Chest. 2007 Oct;132(4):1259–64.

5.     Dorian P, Jung W, Newman D, Paquette M, Wood K, Ayers GM, et al. The impairment of health-related quality of life in patients with intermittent atrial fibrillation: implications for the assessment of investigational therapy. J Am Coll Cardiol. 2000 Oct;36(4):1303–9.

6.     Lampert R. Behavioral influences on cardiac arrhythmias. Trends Cardiovasc Med. 2016 Jan;26(1):68–77.

7.     Lampert R, Jamner L, Burg M, Dziura J, Brandt C, Liu H, et al. Triggering of symptomatic atrial fibrillation by negative emotion. J Am Coll Cardiol. 2014 Oct 7;64(14):1533–4.

8.     Wolowacz SE, Samuel M, Brennan VK, Jasso-Mosqueda J-G, Van Gelder IC. The cost of illness of atrial fibrillation: a systematic review of the recent literature. EP Eur. 2011 Oct 1;13(10):1375–85.

9.     Lakkireddy D, Atkins D, Pillarisetti J, Ryschon K, Bommana S, Drisko J, et al. Effect of yoga on arrhythmia burden, anxiety, depression, and quality of life in paroxysmal atrial fibrillation: the YOGA My Heart Study. J Am Coll Cardiol. 2013 Mar 19;61(11):1177–82.

10.  Toise SCF, Sears SF, Schoenfeld MH, Blitzer ML, Marieb MA, Drury JH, et al. Psychosocial and cardiac outcomes of yoga for ICD patients: a randomized clinical control trial. Pacing Clin Electrophysiol PACE. 2014 Jan;37(1):48–62.

11.  Park ER, Traeger L, Vranceanu A-M, Scult M, Lerner JA, Benson H, et al. The development of a patient- centered program based on the relaxation response: the Relaxation Response Resiliency Program (3RP). Psychosomatics. 2013 Apr;54(2):165–74.

12.  Goldberger AL, Amaral LAN, Hausdorff JM, Ivanov PC, Peng C-K, Stanley HE. Fractal dynamics in physiology: alterations with disease and aging. Proc Natl Acad Sci U S A. 2002 Feb 19;99 Suppl 1:2466– 72.

13.  Villareal RP, Liu BC, Massumi A. Heart rate variability and cardiovascular mortality. Curr Atheroscler Rep. 2002 Mar;4(2):120–7.

14.  Costa M, Goldberger AL, Peng C-K. Multiscale entropy analysis of complex physiologic time series. Phys Rev Lett. 2002 Aug 5;89(6):068102.

15.  Costa M, Goldberger AL, Peng C-K. Multiscale entropy analysis of biological signals. Phys Rev E Stat Nonlin Soft Matter Phys. 2005 Feb;71(2 Pt 1):021906.

16.  Watanabe E, Kiyono K, Hayano J, Yamamoto Y, Inamasu J, Yamamoto M, et al. Multiscale Entropy of the Heart Rate Variability for the Prediction of an Ischemic Stroke in Patients with Permanent Atrial Fibrillation.PLoS ONE [Internet]. 2015 [cited 2017 Apr 28];10(9). Available from: https://www-ncbi-nlm-nih-gov.ezp- prod1.hul.harvard.edu/pmc/articles/PMC4556684/

17.  Peng CK, Mietus JE, Liu Y, Khalsa G, Douglas PS, Benson H, et al. Exaggerated heart rate oscillations during two meditation techniques. Int J Cardiol. 1999 Jul 31;70(2):101–7.

18.  Peng C-K, Henry IC, Mietus JE, Hausdorff JM, Khalsa G, Benson H, et al. Heart rate dynamics during three forms of meditation. Int J Cardiol. 2004 May;95(1):19–27.

19.  PAR-16-037: NHLBI Clinical Trial Pilot Studies (R34) [Internet]. [cited 2017 Apr 27]. Available from: https://grants.nih.gov/grants/guide/pa-files/PAR-16-037.html

20.  Dusek JA, Otu HH, Wohlhueter AL, Bhasin M, Zerbini LF, Joseph MG, et al. Genomic counter-stress changes induced by the relaxation response. PloS One. 2008;3(7):e2576.

21.  Bhasin MK, Dusek JA, Chang B-H, Joseph MG, Denninger JW, Fricchione GL, et al. Relaxation response induces temporal transcriptome changes in energy metabolism, insulin secretion and inflammatory pathways. PloS One. 2013;8(5):e62817.

22.  Kuo B, Bhasin M, Jacquart J, Scult MA, Slipp L, Riklin EIK, et al. Genomic and clinical effects associated with a relaxation response mind-body intervention in patients with irritable bowel syndrome and inflammatory bowel disease. PloS One. 2015;10(4):e0123861.