295J Contemp Med Sci | Vol. 8, No. 5, September-October 2022: 295–310 Original Biofeedback of Heart Rate Variability in the Treatment of Chronic Diseases: A Systematic Review Saad Majeed Al-Tamimi* Consultant Internist and Cardiologist, College of Dentistry, Al-Farahidi University, Baghdad, Iraq. *Correspondence to: Saad Majeed Al-Tamimi (E-mail: saad65altamimy@yahoo.com) (Submitted: 19 May 2022 – Revised version received: 22 June 2022 – Accepted: 07 July 2022 – Published Online: 26 October 2022) Abstract Background: HRVB (heart rate variability biofeedback) is a non-pharmacological method for chronic diseases evaluation. Methods: Adults chronic sufferers, HRVB as the primary therapy with or without controlled circumstances, and psycho - physiological results as regression analysis were all included in a systematic search. Results: There were 21 publications in overall. HRVB was found to be feasible in chronic patients with no adverse reactions, according to the findings. Significant favourable impacts on hypertension and cardiovascular prognostic, inflammation condition, asthma issues, depression and anxiety, sleeping disruptions, cognitive function, and pain were reported in diverse patient characteristics that could be linked to enhanced quality of life. Increases in treatment practice were accompanied by increases in heart rate variability, implying that HRVB may have a regulatory influence on autonomic function. Conclusions: HRVB has the potential to help individuals with chronic conditions. More research is needed to reinforce these findings as well as identify the most efficient strategy. Keywords: Biofeedback, psychology, heart rate, chronic disease ISSN 2413-0516 Introduction No communicable chronic conditions, such as cardiovascular diseases, malignancy, chronic lung disease, obesity, and mental health problems, had been accountable for about 70% of all mortality globally in 2016, according to the World Health Organization. Their worldwide incidence is rising, and the resulting socially and economically implications are becoming more severe.1 As a result, a fundamental priority for transforming healthcare and lowering health-care expenditures is the effi- ciency and profitability of diseases control. Chronic disorders are often caused by disturbances in the autonomic nervous systems (ANS) balancing, which result in sympathetic sensory overload and a shortage of vasodilatation.2 This dysautonomia can be viewed as a result of disease, but it can also be viewed as a key potential cause in the onset and progression of chronic diseases. Physiological changes such as stress hormone production and secretion (e.g., cor- tisol, norepinephrine), sleeping disturbances, pro-inflamma- tory cytokine production (e.g., IL-6), hypertensions, or immunological malfunction can all lead to health decline and the formation of comorbidity.3 Furthermore, a modelling depending on various epide- miological research found a relationship between reduced vagus nerve function and the aetio-pathogenesis of cardiovas- cular disorders, cancer, and Alzheimer’s disease. Emphasis is being placed on therapies that could boost vagal activity and re-establish independent balancing in this context.4 Heart rate variability (HRV) is an indicator of health that is used to estimate parasympathetic performance and is evalu- ated at resting. Low HRV is a predictor of cardiovascular illness and death risks, while elevated HRV represents the ability of the heart system to respond to internal and extrinsic alterations (e.g., anxiety, activity). Short-term autonomic modulation by the sympathetic nervous system (SNS) and the vagus nerve of the parasympathetic nervous system (PNS) causes cardiac variability.5 Each of those interconnected systems govern heart rate (HR) by increasing or shrinking it in response to physiological processes underlying in short-term HRV management, including baroreflex control and respiratory sinus arrhythmia (RSA). The first enhances HR once BP drops and reduces HR whenever BP rises; the latter enhances HR during intake and reduces HR during expiration.6 Physiological elements (e.g., hormones, inflammatory condition), neuropsychiatric elements (e.g., feelings, anxiety, cognitively regulations), and ecological or health behaviours all have a role in the long-term regulatory frameworks of HRV (e.g., physical exercises, tobacco, alcohol).7 HRV is defined by time fluctuations among each heart- beat and is connected to the electrocardiogram’s RR interval (ECG). ECG or pulse wave measurements are used to deter- mine HRV levels in both the time and frequency domains.8 The root mean squared of consecutive RR interval dis- parities shows largely parasympathetic activity in the tem- poral domain, while the standard deviations of normal-to-normal RR intervals (SDNN) indicates both sym- pathetic and parasympathetic variations on HR. Short-term HRV assessment is mostly focused on the HRV power spec- trum, which is separated into high frequency (HF; 0.15–0.4 Hz) and low frequency (LF; 0.04–0.15 Hz) regions that tend to correspond with various physiological systems in the fre- quency response.9 The HF-band represents respiratory impacts on HR mod- ulation (RSA), which are caused by parasympathetic cardio vagal output, which causes rapid variations in HR. Aside from that, the LF-band correlates to bar reflex activities, which would be a virtuous cycle between sensory receptors and the brainstem that regulates blood pressure through both sympa- thetic and parasympathetic output, resulting in significantly slower fluctuations in HR.10 LF-band, in particular, must be regarded as a representa- tion of the baroreflex activity generated by both sympathetic and parasympathetic HR frequency modulation, rather than as the sole representation of sympathetic stimulation. The mailto:saad65altamimy@yahoo.com 296 J Contemp Med Sci | Vol. 8, No. 5, September-October 2022: 295–310 Biofeedback of Heart Rate Variability in the Treatment of Chronic Diseases: A Systematic Review Original S.M. Al-Tamimi intricacy of the physiological systems included in autonomic cardiovascular responses such as RSA and baroreflex activities should therefore be taken into account when interpreting the HRV power spectral density.11 HRV is controlled by the brainstem, cortical, and sub - cortical regions, and mental function may be altered by HRV due to neuronal interactions between the central autonomic networks and heart activities. According to current studies, the amygdala, insula, and anterior cingulate are all implicated in emotion regulation, implying that emotion and HRV are linked.12 Because vagal outflow prevails during rest due to substan- tial cardio modulator impacts, the authors proposed a neu- rovisceral implementation strategy in which vagal activities promote reciprocal heart-brain connection, implying that HRV may affect cerebral activities.13 Following that, according to McCraty and coworkers’ psychophysiological theory, a particular cardiac rhythm pat- tern emerges once HR synchronises with other oscillatory components including RSA and baroreflex at a particular res- onant frequencies equivalent to 6 breaths/min. Sine wave oscillations of respiration, HR, and BP represent synchronisa- tion of these oscillatory processes and indicate a “coherence condition.” HRV is considerably boosted under these situa- tions, according to the authors, due to increased vagal activa- tion, which could have a good impact on brain activities and, in particular, emotional control. These heart-brain connec- tions caused by vagal afferents and afferents indicate that vagal nerve stimulation has a role in the pathophysiology of chronic disorders and that vagal-activating therapies may be problematic.14 HRVB (heart rate variability biofeedback) is a non-phar- macological method that improves emotional self-regulation and autonomic cardiac modulation by boosting HRV and recovering cardiac vagal function.15 Once breathing is around 6 breaths per minute, the baro- reflex and the breath synchronise, resulting in a unique HRV signal sequence. This cardiac synchronization condition arises at a resonant frequencies of about 0.1 Hz, resulting in large amplitudes in HRV sine wave oscillations and a noticeable peak in the HRV power spectrum’s LF-band. Various researches have looked into the impacts of HRVB on different psychophysiological complaints associated with chronic dis- eases since the late 1990s, and Lehrer has recommended a standardised technique of practice. HRVB has been shown to have good effects on stress in a meta-analysis, while a system- atic review found that HRVB may have advantages for athletic performance.16 The goal of this systematic review was to see if HRVB may be an efficient and realistic non-pharmacological strategy for managing chronic illness sufferers. As a result, we conducted a review of all research involving elderly patients that looked at the impacts of HRVB training on psychophysiological results connected to chronic disorders. Method Search Strategy Publications from the bibliographic resources PubMed/Med- line, Springer Link, and ScienceDirect/Elsevier, that were sub- mitted between 2010 and 2020, were reviewed. Eligibility Criteria All publications that matched the relevant particular needs of the established PICOS criteria relating to demographic, inter- ventions, comparisons, outcomes, as well as research designs have been included in the systematic review: affected individ- uals (over the age of 18) with chronic diseases; accounting the impacts of HRVB as a destined therapies for psychophysiolog- ical diagnoses as regression model; assessing learning out- comes of HRVB from minimally two sessions with guidelines for regulate frequencies respirations at roughly 6 breaths/min; and using a biofeedback equipment showing the HRV in actual time. We included all research strategies and compari- sons methodologies with or without a control group to intro- duce a comprehensive assessment of HRVB interventions for outcome measures. The study involved investigations that used HRVB lonely, HRVB in conjunction with standard treat- ment, or HRVB in conjunction with another non-pharmaco- logical interference, but only if the procedure would include a control group that received the same standard care or non-pharmacological interference, in order to assess the HRVB’s real benefit. Due to potential confounder’s issues in the interpretation of the data, we omitted investigations that coupled HRVB instruction with another non-pharmacolog- ical treatment when the procedure did not provide a control group that permitted us to separate the HRVB different impacts. Data Processing and Study Collection To eliminate unintentional inclusion and exclusion, research screening was performed manually reviewing abstracts and then making revisions depending on the contents of each pub- lication. Publications were initially categorised based on whether or not they fulfilled PICOS requirements; subse- quently, publications that matched our eligibility requirements were documented, with information on procedure, measures, and outcomes. Results Our screening approach turned up 626 papers (PubMed: 95; ScienceDirect: 23; Springer Link: 508), plus three more papers found through sourced citations. Numerous entries were deleted using the selection approach shown in Figure 1 due to duplication (repeated: 39) or because they were not relevant research articles. By implementing the previous reported qual- ifying criteria in this sequence to the final 463 publications, 434 were exempted: Adult people with chronic illnesses, excluding those medical settings such as substance abuse problems (due to the complicated matter concerning behav- ioural problems) and pregnant women (and wasn’t a chronic condition); interventional research of HRVB exercise (2 or more discussions with particular respiration guidelines); and the use of a biofeedback instrument (heartbeat detector or ECG) with real-time HRV monitor. A collection of 21 investigations had been considered, encompassing 883 participants and sample sizes ranging from 13 to 210, with the primary goal of analysing psychophysio- logical results. There were 11 randomised controlled trials, 4 unregulated investigations, and the rest were pilot, feasibility, or laboratory investigations that included a wait-list compar- ison group, an apparently healthy comparison group, a 297J Contemp Med Sci | Vol. 8, No. 5, September-October 2022: 295–310 S.M. Al-Tamimi Original Biofeedback of Heart Rate Variability in the Treatment of Chronic Diseases: A Systematic Review conventional treatment control group, or another interven- tional control subjects. Just trials examining the impacts of HRVB separately have been included in the randomized inves- tigations. The only difference between the intervention and control groups in randomized research was the HRVB treat- ment: HRVB vs. no treatment; HRVB vs. other treatments; HRVB + standard care vs. identical standard care; HRVB + alternative treatment vs. same other interference; HRVB + other interventions vs. same other intervention Table 1 sum- marises them and categorises them by kind of chronic condition. Feasibility in Chronic Patients Adhesion HRVB was evaluated in people with a diagnosis of chronic conditions and in a number of clinical settings. In a one-year longitudinal research, the maximal attrition incidence for HRVB respondents was observed to be about 25%, while assessed employment levels for HRVB everyday routine were over 70%.17 Time limits, transportation challenges, and other factors were mentioned in investigations as factors for Fig. 1 Flow chart for the literature search. 298 J Contemp Med Sci | Vol. 8, No. 5, September-October 2022: 295–310 Biofeedback of Heart Rate Variability in the Treatment of Chronic Diseases: A Systematic Review Original S.M. Al-Tamimi Ta bl e 1. T he b as el in e ch ar ac te ris tic s o f e ac h in cl ud ed st ud y St ud y Sa m pl e St ud y de si gn in g De pe nd en t f as th m a co nt ro l t es to rs a nd fu lfi lm en t t im e He ar t r at e va ria bi lit y bi of ee db ac k in te rv en tio n Vi ab ili ty Si gn ifi ca nt ch an ge s i n he ar t r at e va ria bi lit y bi of ee db ac k co ho rt He ar t r at e va ria bi lit y in ec k di sa bi lit y in de xe s No n- si gn ifi ca nt ou tc om es Ca rd io va sc ul ar d is ea se s Cl im ov e t a l. (2 01 4) Co ro na ry a rt er y di se as es Ag e ra ng ed fr om 45 − 80 • R an do m iz ed co nt ro l T ria l • H ea rt R at e Va ria bi lit y Bi of ee db ac k + st an da rd c ar e (n = 1 3) St an da rd c ar e (n = 1 1) H O SP IT A L A N XI ET Y A N D D EP RE SS IO N SC A LE ; T yp e D pe rs on al ity ; B LO O D PR ES SU RE ; H RV In te rv en tio ns be fo re a nd a fte r 10 tr ai ni ng s (4 5− 60 m in ut es ) t w ic e a w ee k + d ai ly • 7 in di vi du al s w ho ha ve s lip pe d ou t o f th e ne ck im pa irm en t in de x (c ar ee rs a nd ti m e lim ita tio ns ) N ot d et er m in ed • I nc re as e in th e av er ag e co ns is te nc y ra tin g ** co rr el at ed w ith S D N N I • H O SP IT A L A N XI ET Y A N D D EP RE SS IO N SC A LE ; T yp e D pe rs on al ity ; BL O O D PR ES SU RE N ol an e t a l. (2 01 0; 2 01 2) H yp er te ns io n Ag e ra ng ed fr om 3 5 to 64 y ea rs • R an do m iz ed co nt ro l T ria l • H EA RT R AT E VA R- IA BI LI TY B IO FE ED - BA CK (n = 3 5) • A ut og en ic re lie f (n = 3 0) BL O O D P RE SS U RE ; ba ro re fle x se ns iti v- ity ; h ig h- se ns iti vi ty C- re ac tiv e pr ot ei n; IL 6; H RV • I nt er ve nt io ns b ef or e an d af te r O ve r t he c ou rs e of e ig ht w ee ks , t he re w ill b e si x 60 -m in ut e tr ai ni ng se ss io ns a nd a 2 0- m in ut e da ily a st hm a co nt ro l t es t. N ot d et er m in ed • D ay tim e BL O O D P RE S- SU RE ** a nd 2 4 h sy st ol ic BL O O D P RE SS U RE *, a nd pu ls e pr es su re * • I nc re as e of H F po w er ** an d IN TE RB EA T IN TE R- VA L* * du rin g co gn iti ve ta sk • C ha ng es in H F po w er ar e ne ga tiv el y re la te d to in cr ea se s in h ig h- se ns iti vi ty C -r ea ct iv e pr ot ei ns . * , r es po ns iv e- ne ss to b ar or efl ex es * , an d IN TE RB EA T IN TE RV A L* • S en si tiv e to th e ba ro re fle x • C ha ng es in IN TE RL EU - KI N -6 h ad n o eff ec t o n H RV pa ra m et er s or b ar or efl ex re sp on si ve ne ss . Pa tr on e t a l. (2 01 3) Fo llo w in g he ar t su rg er y, th e pa tie nt s’ ag es ra ng ed fr om 5 2 to 6 9. • R an do m iz ed co nt ro l t ria l • H EA RT R AT E VA RI A BI LI TY BI O FE ED BA CK + st re ss m an ag em en ts (n = 1 3) • S tr es s m an ag em en ts (n = 1 3) SP IE LB ER G ER S TA TE A N XI ET Y IN VE N - TO RY ; C EN TE R FO R EP ID EM IO LO G IC A L ST U D IE S- D EP RE S- SI O N S CA LE ; H RV • I nt er ve nt io ns b ef or e an d af te r O ve r t he c ou rs e of tw o w ee ks , t he re w ill b e fiv e 45 -m in ut e tr ai ni ng se ss io ns a nd a 1 5- m in ut e da ily a st hm a co nt ro l as se ss m en t. N ot d et er m in ed • D ep re ss io n (C EN TE R FO R EP ID EM IO LO G IC A L ST U D - IE S- D EP RE SS IO N S CA LE *) • O ve ra ll po w er is in cr ea si ng * *; • C ha ng es in H RV w er e fo un d to b e in ve rs el y re la te d to c ha ng es in de pr es si on * • S PI EL BE RG ER ST AT E A N XI ET Y IN VE N TO RY (C on tin ue d) 299J Contemp Med Sci | Vol. 8, No. 5, September-October 2022: 295–310 S.M. Al-Tamimi Original Biofeedback of Heart Rate Variability in the Treatment of Chronic Diseases: A Systematic Review Ta bl e 1. T he b as el in e ch ar ac te ris tic s o f e ac h in cl ud ed st ud y— Co nt in ue d St ud y Sa m pl e St ud y de si gn in g De pe nd en t f as th m a co nt ro l t es to rs a nd fu lfi lm en t t im e He ar t r at e va ria bi lit y bi of ee db ac k in te rv en tio n Vi ab ili ty Si gn ifi ca nt ch an ge s i n He ar t R at e Va ria bi lit y Bi of ee db ac k co ho rt He ar t r at e va ria bi lit y in ec k di sa bi lit y in de xe s No n- si gn ifi ca nt ou tc om es Yu e t a l. (2 01 8) Co ro na ry a rt er y di se as e Ag e ra ng e 35 − 70 y ea rs • R an do m iz ed co nt ro l t ria l • H EA RT R AT E VA R- IA BI LI TY B IO FE ED - BA CK + s ta nd ar d ca re (n = 1 05 ) • S ta nd ar d ca re (n = 1 05 ) BE CK D EP RE SS IO N IN VE N TO RY ; C H IN ES E H O ST IL IT Y IN VE N - TO RY -S H O RT F O RM ; H RV ; c ar di ov as cu la r pr og no si s • I nt er ve nt io ns b ef or e an d af te r • F ol lo w -u p af te r a ye ar Si x w ee kl y tr ai ni ng se ss io ns • D ro po ut ra te o f 26 .4 7% in th e H EA RT RA TE V A RI A BI LI TY B IO - FE ED BA CK g ro up a nd 34 .4 4% in th e co nt ro l gr ou p • D ep re ss io n (B EC K D EP RE SS IO N IN VE N TO RY to ta l s co re ** ; c og ni tiv e de pr es si on s ub sc al e* *) ; • H os til ity ** (C H IN ES E H O S- TI LI TY IN VE N TO RY -S H O RT FO RM ); • A t t he fo llo w -u p, th e re su lts re m ai ne d th e sa m e; • R ea dm is si on s ar e re du ce d. * an d at fo llo w -u p, e m er - ge nt v in so m ni a in te ns ity in de xt s ** • R es pi ra to ry ra te w as de cr ea se d ** ; • A t t he fo llo w -u p, th e ris e in L F po w er ** w as su st ai ne d • A t t he fo llo w -u p, th er e w as n o di ffe r- en ce b et w ee n th e gr ou ps in te rm s of re du c- in g al l-c au se re ad m is si on s an d al l-c au se am bu la to ry ca re . Ob es ity M ey er e t a l. (2 01 8) In di vi du al s w ith a BM I o f 3 0 or h ig he r ar e co ns id er ed ob es e. T he p ar tic i- pa nt s ra ng ed in a ge fro m 1 8 to 4 5 ye ar s ol d. • P ilo t s tu dy • H EA RT R AT E VA R- IA BI LI TY B IO FE ED - BA CK (n = 1 0) • W ai t- lis t c on tr ol (n = 1 0) PE RC EI VE D S TR ES S SC A LE ; P AT IE N T H EA LT H Q U ES TI O N - N A IR E- D EP RE SS IO N A N D A N XI ET Y; SH O RT F O RM G EN ER A L H EA LT H SU RV EY ; S EL F- EF FI - CA CY ; H RV • I nt er ve nt io ns b ef or e an d af te r • 3 -m on th s fo llo w -u p 6 tr ai ni ng s w ee kl y • E ig ht p eo pl e dr op pe d ou t o f t he in te rv en tio n. • D ep re ss io n (P AT IE N T H EA LT H Q U ES TI O N - N A IR E- D EP RE SS IO N A N D A N XI ET Y* ); • S tr es s (P ER CE IV ED ST RE SS S CA LE *) ; • S el f- effi ca cy (S EL F- EF FI CA CY s um s co re *) ; • Q ua lit y of li fe (B od ily to ta l r an ks * an d m en ta l to ta l g oa ls s co re d* * w er e pr es er ve d at fo llo w -u p on S H O RT F O RM G EN ER A L H EA LT H SU RV EY ) • P oo le d re su lts • S D N N ** p er fo rm an ce im pr ov em en t, to ta l po w er * *; • T he re du ct io n in re sp ira to ry ra te * w as su st ai ne d at th e fo llo w -u p. N ot d et er - m in ed (C on tin ue d) 300 J Contemp Med Sci | Vol. 8, No. 5, September-October 2022: 295–310 Biofeedback of Heart Rate Variability in the Treatment of Chronic Diseases: A Systematic Review Original S.M. Al-Tamimi Ta bl e 1. T he b as el in e ch ar ac te ris tic s o f e ac h in cl ud ed st ud y— Co nt in ue d St ud y Sa m pl e St ud y de si gn in g De pe nd en t f as th m a co nt ro l t es to rs a nd fu lfi lm en t t im e He ar t r at e va ria bi lit y bi of ee db ac k in te rv en tio n Vi ab ili ty Si gn ifi ca nt ch an ge s i n He ar t R at e Va ria bi lit y Bi of ee db ac k co ho rt He ar t r at e va ria bi lit y in ec k di sa bi lit y in de xe s No n- si gn ifi ca nt ou tc om es As th m a Le hr er e t a l. (2 01 8) As th m a Th e pa rt ic i- pa nt s ra ng ed in a ge fro m 2 7 to 4 7 ye ar s ol d. • R A N D O M IZ ED CO N TR O L TR IA L • H EA RT R AT E VA RI A BI LI TY B IO - FE ED BA CK g ro up (n = 3 1) EL EC TR O EN CE PH A - LO G RA M B IO FE ED - BA CK + s oo th in g m us ic + a g ro up o f pe op le e xh al in g at a ra te o f 1 5 br ea th s pe r m in ut e (n = 3 3) M ET AC H O LI N E CH A LL EN G E TE ST ; A ST H M A C O N TR O L TE ST ; A ST H M A Q U A LI TY O F LI FE ; sp iro m et ry a nd im pu ls iv e os ci l- lo m et ry ; e ve ry da y co m pl ai nt s an d m ax im um o ut flo w s; ex pe lle d ni tr ic o xi de • I nt er ve nt io ns b ef or e an d af te r Sh or t p ro to co l ( n = 2 0) : 6 H EA RT R AT E VA RI A BI LI TY BI O FE ED BA CK tr ai ni ng s ov er 1 0 w ee ks + 2 0- m in - ut es p er d ay p ra st hm a co nt ro l t es tic e Lo ng pr ot oc ol (n = 1 1) : 1 0 H EA RT R AT E VA RI A BI LI TY BI O FE ED BA CK te n w ee ks of p ra ct ic e Pl us a d ai ly pr as th m a co nt ro l t es t o f tw en ty m in ut es • 1 9 pe rc en t o f t he to ta l of p at ie nt s  le av e ou t. • A st hm a co m pl ai nt s (A ST H M A C O N TR O L TE ST ** ; A ST H M A Q U A LI TY O F LI FE ** ); • S en si tiv ity o f a irw ay s (M ET AC H O LI N E CH A L- LE N G E TE ST ** ); • F un ct io ni ng o f t he lu ng s (m ax im um v el oc ity * ); • D ys fu nc tio n of th e ai r- w ay s w ith in te rv al s of p oo r as th m a sy m pt om s* (n itr o- ge n di ox id e re le as ed * ) N ot d et er m in ed • J us t a fte r t he r- ap y, th er e w as no d iff er en ce in A ST H M A CO N TR O L TE ST , A ST H M A Q U A L- IT Y O F LI FE , M ET AC H O LI N E CH A LL EN G E TE ST , o r m ax i- m al c irc ul at io n ac ro ss g ro up - in gs ; • T he re is n o di ffe re nc e be - tw ee n a qu ic k an d a le ng th y tr ea tm en t. Ch ro ni c b ra in in ju ry Ki m e t a l. (2 01 3) Ch ro ni c br ai n in ju ry Ag e = 2 3− 63 • P ilo t s tu dy • H EA RT R AT E VA R- IA BI LI TY B IO FE ED - BA CK (n = 1 3) • N o co nt ro l g ro up IN TE G RA TE D V IS U A L A N D A U D IT O RY ; CO N TI N U O U S PE RF O RM A N CE T ES T; BE H AV IO R RA TI N G IN VE N TO RY O F EX EC U TI VE F U N C- TI O N -A D U LT ; H RV • I nt er ve nt io ns b ef or e an d af te r W ee kl y tr ea tm en t o f t en se ss io ns a nd a re si de nt ia l as th m a co nt ro l a ss es s- m en t f ro m s es si on fo ur . • N ot d et er m in ed • N ot d et er m in ed • I m pr ov em en t i n th e co ns is te nc y pr op or tio n* an d th e LF /H F pr op or - tio n ** ; • T he c oh er en t r at io s* an d th e LF /H F ra tio w er e co nn ec te d w ith em ot io na l s ta bi lit y an d ve rb al m em or ie s (B EH AV - IO R RA TI N G IN VE N TO RY O F EX EC U TI VE F U N C- TI O N -A D U LT ) * *; • A tt en tio n (IN TE G RA TE D VI SU A L A N D A U D IT O RY + CO N TI N U O U S PE RF O R- M A N CE T ES T) c or re la te d w ith L F/ H F* * • N ot d et er - m in ed (C on tin ue d) 301J Contemp Med Sci | Vol. 8, No. 5, September-October 2022: 295–310 S.M. Al-Tamimi Original Biofeedback of Heart Rate Variability in the Treatment of Chronic Diseases: A Systematic Review Ta bl e 1. T he b as el in e ch ar ac te ris tic s o f e ac h in cl ud ed st ud y— Co nt in ue d St ud y Sa m pl e St ud y de si gn in g De pe nd en t f as th m a co nt ro l t es to rs a nd fu lfi lm en t t im e He ar t r at e va ria bi lit y bi of ee db ac k in te rv en tio n Vi ab ili ty Si gn ifi ca nt ch an ge s i n He ar t R at e Va ria bi lit y Bi of ee db ac k co ho rt He ar t r at e va ria bi lit y in ec k di sa bi lit y in de xe s No n- si gn ifi ca nt ou tc om es Ch an g et a l. (2 02 0) Ac ut e is ch em ic st ro ke • R A N D O M IZ ED CO N TR O L TR IA L H EA RT R AT E VA RI A BI LI TY BI O FE ED BA CK + st an da rd c ar e (n = 1 9) • S ta nd ar d Ca re (n = 1 9) M IN I-M EN TA L ST A - TU S EX AM IN AT IO N ; H O SP IT A L A N XI ET Y A N D D EP RE SS IO N SC A LE ; H RV • I nt er ve nt io ns b ef or e an d af te r • O ne a nd th re e m on th s 4 da ys o f t ra in in g pr oc es s + 2 0 m in ut es o f d ai ly as th m a m an ag em en t te st in g ov er th re e m on th s. • T hr ee p eo pl e ha d to dr op o ut . • O n- th e- be ds id e tr ai ni ng s es si on s ar e m on ito re d. • A nx ie ty a nd d ep re ss io n (H O SP IT A L A N XI ET Y A N D D EP RE SS IO N S CA LE *) a t 1 an d 3 m on th s • C og ni tiv e fu nc tio ns (M IN I-M EN TA L ST AT U S EX AM IN AT IO N ** ) a t 1 a nd 3 m on th s • D ec re as e of h ea rt ra te * at 1 a nd 3 m on th s; • I nc re as e of S D N N *, RM SS D *, L F* a nd to ta l p ow er * at 1 a nd 3 m on th s N ot d et er - m in ed Ch ro ni c p ai n D ob bi n et a l. (2 01 3) Re fra st hm a co nt ro l te st or y irr ita bl e bo w el s yn dr om e Ag e = 1 8− 60 • H EA RT R AT E VA R- IA BI LI TY B IO FE ED - BA CK (n = 3 1) • H yp no th er ap y (n = 3 0) • R A N D O M IZ ED CO N TR O L TR IA L • I nt er ve nt io ns b ef or e an d af te r • F ol lo w -u p af te r th re e m on th s IR RI TA BL E BO W EL SY N D RO M E SY M PT O M SE VE RI TY S CO RE S; H O SP IT A L A N XI ET Y A N D D EP RE SS IO N S CA LE O ve r t he c ou rs e of tw el ve w ee ks , t he re w ill b e th re e 60 -m in ut e tr ai ni ng c ou rs es a nd a 20 -m in ut e da ily a st hm a co nt ro l a ss es sm en t. • 1 5 dr op ou ts (7 in H EA RT R AT E VA RI A BI LI TY B IO FE ED - BA CK g ro up ) • S ym pt om s (IB SS SS *) a t po st -in te rv en tio n; • A nx ie ty a nd d ep re ss io n (H O SP IT A L A N XI ET Y A N D D EP RE SS IO N S CA LE *) • A t t he fo llo w -u p, th e re su lts re m ai ne d th e sa m e. N ot d et er m in ed • T he re h as be en n o di st in ct io n on th e H O SP IT A L A N XI ET Y A N D D EP RE SS IO N SC A LE a fte r t he tr ea tm en t. W ee ks e t a l. (2 01 5) ≥ 3 m on th s of ch ro ni c di sc om fo rt (fi br om ya lg ia , he ad ac he s, ne ur op at hy , e tc .) 45 to 6 8 ye ar s ol d • R A N D O M IZ ED CO N TR O L TR IA L H EA RT R AT E VA RI - A BI LI TY B IO FE ED - BA CK (n = 1 0) • F ee db ac k fa de (n = 1 0) : f ee db ac k le ve ls w er e sl ow ly re du ce d fro m 90 % to 0 % . 10 -c m v is ua l a na lo g sc al e (V A S) ; P A IN D IS A BI LI TY Q U ES - TI O N N A IR E; 1 1- IT EM TA M PA S CA LE O F KI N ES IO PH O BI A • I nt er ve nt io ns b ef or e an d af te r • F ol lo w -u p af te r th re e m on th s O ve r t he c ou rs e of th re e w ee ks , t he re w ill b e ni ne tr ai ni ng s es si on s. • 6 d ro pp ed o ut o f t he in te rv en tio ns ; • A t t he fo llo w -u p ex am in at io n, th re e w er e m is si ng . • N ot d et er m in ed • N ot d et er m in ed Pa in in te ns ity on V A S, T SK 1 1, PA IN D IS A BI LI - TY Q U ES TI O N - N A IR E (C on tin ue d) 302 J Contemp Med Sci | Vol. 8, No. 5, September-October 2022: 295–310 Biofeedback of Heart Rate Variability in the Treatment of Chronic Diseases: A Systematic Review Original S.M. Al-Tamimi Ta bl e 1. T he b as el in e ch ar ac te ris tic s o f e ac h in cl ud ed st ud y— Co nt in ue d St ud y Sa m pl e St ud y de si gn in g De pe nd en t f as th m a co nt ro l t es to rs a nd fu lfi lm en t t im e He ar t r at e va ria bi lit y bi of ee db ac k in te rv en tio n Vi ab ili ty Si gn ifi ca nt ch an ge s i n He ar t R at e Va ria bi lit y Bi of ee db ac k co ho rt He ar t r at e va ria bi lit y in ec k di sa bi lit y in de xe s No n- si gn ifi ca nt ou tc om es Ca nc er G re en be rg et a l. (2 01 5) N on -s m al l c el l l un g ca nc er (N SC LC ) i s a ty pe o f l un g ca nc er .  Th e pa rt ic ip an ts ’ ag es ra ng ed fr om 46 to 7 1. • I nt er be at in te r- va lli ty fe as ib ili ty an al ys is • H EA RT R AT E VA RI A BI LI TY B IO - FE ED BA CK g ro up (n = 1 6) • T he re is n o co nt ro l gr ou p. H O SP IT A L A N XI ET Y A N D D EP RE SS IO N SC A LE ; P AT IE N T H EA LT H Q U ES TI O N - N A IR E; F A ST H M A CO N TR O L TE ST L; D is - tr es s T he rm om et er an d Pr ob le m A re as • I nt er ve nt io ns b ef or e an d af te r Si x ex er ci se s es si on s (3 0– 45 m in ut es ) th ro ug ho ut c he m ot he r- ap y Pl us a d ai ly a st hm a m an ag em en t a ss es s- m en t o f 2 0 m in ut es • T he re w er e ei gh t ca se s in to ta l; • 1 h ad fi ni sh ed th e pr og ra m ; • H EA RT R AT E VA RI A BI L- IT Y BI O FE ED BA CK d on e du rin g ch em ot he ra py ; • T hr ou gh ou t t ra in in g se ss io ns , t he p ot en tia l to re du ce re sp ira to ry ra te , h ea rt ra te , a nd an xi et y • T he re a re n o st at is tic al an al ys is a va ila bl e. N ot d et er m in ed N ot d et er - m in ed De pr es si on Ca ld w el l e t a l. (2 01 8) M aj or d ep re ss iv e di so rd er (M D D ) i s a ty pe o f d ep re ss io n th at 1 8 to 2 5 ye ar s ol d • R A N D O M IZ ED CO N TR O L TR IA L • H EA RT R AT E VA RI A BI LI TY BI O FE ED BA CK + ps yc ho th er ap y (n = 1 0) • P sy ch ot he ra py (n = 1 0) • N on -d ep re ss ed co nt ro l g ro up (n = 1 1) BE CK D EP RE SS IO N IN VE N TO RY ; H RV • I nt er ve nt io ns b ef or e an d af te r Fi ve s es si on s + 15 –2 0 m in ut es o f a st h- m a sy m pt om s at h om e. O ve r t he c ou rs e of s ix w ee ks , 4 –5 in st an ce s ea ch w ee k N ot d et er m in ed • D ep re ss io n (B D III ** ) • S D N N ** N ot d et er - m in ed H ar to gs e t a l. (2 01 7) M aj or d ep re ss iv e di so rd er (M D D ) T he pa rt ic ip an ts ra ng ed in a ge fr om 2 3 to 6 2 • E xp er im en ta l st ud y • H EA RT R AT E VA R- IA BI LI TY B IO FE ED - BA CK (n = 1 0) • T he re is n o co nt ro l gr ou p BE CK D EP RE SS IO N IN VE N TO RY ; P O SI TI VE O U TC O M E LI ST ; H RV • I nt er ve nt io ns b ef or e an d af te r Ei gh t w ee kl y tr ai ni ng se ss io ns (4 5– 60 m in ut es ) + a d ai ly p ra st hm a co nt ro l t es t o f t w en ty m in ut es • T hr ee fa ilu re s du e to a la ck o f m ot ili ze d vi su al an d au ra l i nt eg ra tio n; • S ev en p eo pl e fin is he d th e en tir e pr og ra m ; • O ne d ep re ss iv e w or se ni ng Fi ve p ar tic ip an ts  h av e ha d cl in ic al b en efi ts : • D ep re ss io n (B D I) • E le m en ts o f r es ili en cy (P O SI TI VE O U TC O M E LI ST Au to no m y ra tin gs ); (H AM D to ta l s co re ** ) • D ur in g th e pr og ra m , th e de gr ee o f c on si st - en cy o f fi ve p ar tic ip an ts im pr ov ed . • T he a ve ra ge H R ha s de cr ea se d * N ot d et er - m in ed (C on tin ue d) 303J Contemp Med Sci | Vol. 8, No. 5, September-October 2022: 295–310 S.M. Al-Tamimi Original Biofeedback of Heart Rate Variability in the Treatment of Chronic Diseases: A Systematic Review Ta bl e 1. T he b as el in e ch ar ac te ris tic s o f e ac h in cl ud ed st ud y— Co nt in ue d St ud y Sa m pl e St ud y de si gn in g De pe nd en t f as th m a co nt ro l t es to rs a nd fu lfi lm en t t im e He ar t r at e va ria bi lit y bi of ee db ac k in te rv en tio n Vi ab ili ty Si gn ifi ca nt ch an ge s i n He ar t R at e Va ria bi lit y Bi of ee db ac k co ho rt He ar t r at e va ria bi lit y in ec k di sa bi lit y in de xe s No n- si gn ifi ca nt ou tc om es Li n et a l. (2 01 9) M aj or d ep re ss iv e di so rd er A ge ra ng ed fro m 2 0 to 7 5 ye ar s. • C as e- co nt ro l st ud y • H EA RT R AT E VA R- IA BI LI TY B IO FE ED - BA CK (n = 2 4) ; • C on tr ol o f t he w ai tin g lis t ( n = 2 4) BE CK A N XI ET Y IN VE N TO RY ; B EC K D EP RE SS IO N IN VE N - TO RY ; P IT TS BU RG H SL EE P Q U A LI TY IN D EX ; P RE -S LE EP A RO U SA L SC A LE ; H RV • I nt er ve nt io ns b ef or e an d af te r • F ol lo w -u p af te r o ne m on th Si x w ee kl y tr ai ni ng s es - si on s (6 0 m in ut es ) P lu s da ily p ra st hm a co nt ro l te st ic e of 1 0 m in ut es • T he re w er e fiv e w ith dr aw al s. • D ep re ss io n (B EC K D EP RE SS IO N IN VE N TO RY to ta l s co re ** , c og ni tiv e de pr es si on *, s om at ic de pr es si on *) ; • A nx ie ty (B EC K A N XI ET Y IN VE N TO RY to ta l s co re ** ); • S le ep (P RE -S LE EP A RO U S- A L SC A LE to ta l s co re *, PI TT SB U RG H S LE EP Q U A LI - TY IN D EX to ta l s co re ** , a nd co gn iti ve a ro us al o f P RE - SL EE P A RO U SA L SC A LE ** ) • A t t he fo llo w -u p, th e re su lts re m ai ne d th e sa m e. • R es pi ra to ry ra te de cr ea se s ** ; • S D N N ** , L F po w er *, L F/ H F* , a nd o ve ra ll po w er * al l i nc re as ed ** ; At th e fo llo w -u p, th e re su lts re m ai ne d th e sa m e. • N o di ffe re nc e be tw ee n gr ou ps fo r PI TT SB U RG H SL EE P Q U A LI TY IN D EX a nd PR E- SL EE P A RO U SA L SC A LE to ta l sc or es Ch ro ni c s tr es s D e Br ui n et a l. (2 01 6) Ch ro ni c st re ss e va lu - at ed fr om P ER CE IV ED ST RE SS S CA LE s co re Ag e ra ng ed fr om 1 8 to 4 0 • R A N D O M IZ ED CO N TR O L TR IA L • H EA RT R AT E VA R- IA BI LI TY B IO FE ED - BA CK (n = 2 5) • M ed ita tio n fo r aw ar en es s (n = 2 7) • P hy si ca l a ct iv ity (n = 2 3) AC S; B EH AV IO R RA TI N G IN VE N TO - RY O F EX EC U TI VE FU N C TI O N -A D U LT ; FF M Q SF ; S EL FC O M - PA SS IO N S CA LE - SH O RT F O RM ; PE N N S TA TE W O RR Y Q U ES TI O N N A IR E • I nt er ve nt io ns b ef or e an d af te r • F ol lo w u p af te r 6 m on th s. O ve r t he c ou rs e of fi ve w ee ks : 1 st w ee k: 1 0 m in - ut es p er d ay 2 nd w ee k = 1 5 m in ut es p er d ay W ee ks 3 –5 = 2 0 m in ut es pe r d ay • T he re w er e 19 w ith dr aw al s in th e H EA RT R AT E VA RI A - BI LI TY B IO FE ED BA CK ca te go ry , i nc lu di ng o ne in th e H EA RT R AT E VA R- IA BI LI TY B IO FE ED BA CK co ho rt (o cc up at io ns an d tim e co ns tr ai nt ); • P ar tic ip an ts w ith an a tt en da nc e ra te of m or e th an 7 0% sh ow ed g re at er g ai ns . • A tt en tio n co nt ro l* (A CS ); • E xe cu tiv e fu nc tio n- in g* (B EH AV IO R RA TI N G IN VE N TO RY O F EX EC U TI VE FU N C TI O N -A D U LT ); • M in df ul a w ar en es s* (F IV E FA CE T M IN D FU LN ES S Q U ES TI O N N A IR E- SH O RT FO RM ); • S el f- co m pa ss io n* (S EL FC O M PA SS IO N S CA LE - SH O RT F O RM ); • W or ry in g* (P EN N S TA TE W O RR Y Q U ES TI O N N A IR E) • W he n co m pa re d to it s pe er s, at te nt io n co nt ro l an d ex ec ut iv e fu nc tio ni ng ha d sm al l i m pa ct v al ue s at fo llo w -u p. N ot d et er m in ed At th e po st - in te rv en tio n an d fo llo w -u p, th er e w as n o su bs ta nt ia l di st in ct io n. (C on tin ue d) 304 J Contemp Med Sci | Vol. 8, No. 5, September-October 2022: 295–310 Biofeedback of Heart Rate Variability in the Treatment of Chronic Diseases: A Systematic Review Original S.M. Al-Tamimi Ta bl e 1. T he b as el in e ch ar ac te ris tic s o f e ac h in cl ud ed st ud y— Co nt in ue d St ud y Sa m pl e St ud y de si gn in g De pe nd en t f as th m a co nt ro l t es to rs a nd fu lfi lm en t t im e He ar t r at e va ria bi lit y bi of ee db ac k in te rv en tio n Vi ab ili ty Si gn ifi ca nt ch an ge s i n He ar t R at e Va ria bi lit y Bi of ee db ac k co ho rt He ar t r at e va ria bi lit y in ec k di sa bi lit y in de xe s No n- si gn ifi ca nt ou tc om es H al lm an e t a l. (2 01 1) St re ss re la te d ch ro ni c ne ck s ho ul de r p ai n Ag e ra ng ed fr om 2 5 to 5 0 ye ar s • P ilo t s tu dy • H EA RT R AT E VA R- IA BI LI TY B IO FE ED - BA CK (n = 1 2) • T he c on tr ol g ro up (n = 1 2) p ar tic ip at - ed in s es si on s 1 an d 10 w ith ou t r ec ei v- in g an y gu id an ce in be tw ee n. Bo rg C R1 0; S TR ES S M ED IC IN E SY M PT O M SC A LE ; H O SP IT A L A N XI ET Y A N D D EP RE SS IO N S CA LE ; SH O RT F O RM G EN ER A L H EA LT H SU RV EY ; N EC K D IS A - BI LI TY IN D EX ; H RV • I nt er ve nt io ns b ef or e an d af te r Te n tr ai ni ng s es si on s ev er y w ee k. N ot d et er m in ed • Q ua lit y of li fe (o n th e SH O RT F O RM G EN ER A L H EA LT H S U RV EY , b od ily pa in *, s oc ia l f un ct io n* , a nd vi ta lit y* *) • L F po w er ** in cr ea se s; LF p ow er *, p N N 50 *, a nd IN TE RB EA T IN TE RV A L * im pr ov e th ro ug ho ut st re ss re co ve ry . • S TR ES S M ED I- CI N E SY M PT O M SC A LE , B or g CR 10 , a nd N EC K D IS A - BI LI TY IN D EX , H O SP IT A L A N XI ET Y A N D D EP RE SS IO N SC A LE Va n de r Z w an et a l. (2 01 5) Ch ro ni c st re ss w as as se ss ed u si ng SC A LE O F PE RC EI VE D ST RE SS T he p ar tic i- pa nt s ra ng ed in a ge fro m 1 8 to 4 0 ye ar s ol d. • R A N D O M IZ ED CO N TR O L TR IA L • H EA RT R AT E VA R- IA BI LI TY B IO FE ED - BA CK (n = 2 6) Ph ys ic al e xe rc is e (n = 2 3) M ed ita tio n fo r aw ar en es s (n = 2 7) D EP RE SS IO N A N XI ET Y ST RE SS SC A LE S; P IT TS BU RG H SL EE P Q U A LI TY IN D EX ; S CA LE S O F PS YC H O LO G IC A L W EL L- BE IN G • I nt er ve nt io ns b ef or e an d af te r • F ol lo w u p af te r s ix m on th s O ve r t he c ou rs e of fi ve w ee ks : 1 st w ee k: 1 0 m in - ut es p er d ay 2 nd w ee k = 1 5 m in ut es p er d ay W ee ks 3 –5 = 2 0 m in ut es pe r d ay • N in e po st -t es t a nd / or fo llo w -u p ex am in a- tio ns w er e m is si ng ; • I nd iv id ua ls w ith a p ar - tic ip at io n ra te o f m or e th an 7 0% s ho w ed gr ea te r g ai ns . • S tr es s* *, a nx ie ty ** , a nd de pr es si on ** (D EP RE SS IO N A N XI ET Y ST RE SS S CA LE S) ; • W el l-b ei ng ** (S CA LE S O F PS YC H O LO G IC A L W EL L- BE IN G ); • S le ep q ua lit y* (P IT TS - BU RG H S LE EP Q U A LI TY IN D EX ); • A t t he fo llo w -u p, th e re su lts re m ai ne d th e sa m e. N ot d et er m in ed • A t p os t- in te r- ve nt io n an d fo llo w -u p, th er e w er e no d iff er - en ce s be tw ee n gr ou ps . Ps yc hi at ric d is or de rs Je st er e t a l. (2 01 8) In di ca tio ns o f ps yc hi at ric d is ea se s (d ep re ss iv e, a nx i- et y, a nd b ip os iti ve ou tc om e lis ta r di so rd er s) T he a ge s of th e pa rt ic ip an ts ra ng ed b et w ee n 63 to 9 6 ye ar s ol d. • E xp er im en ta l st ud y • H EA RT R AT E VA R- IA BI LI TY B IO FE ED - BA CK (n = 2 0) • N o co nt ro l g ro up SP IE LB ER G ER S TA TE A N XI ET Y IN VE N TO RY ; BE CK D EP RE SS IO N IN VE N TO RY ; T RA IL M A KI N G T ES T PA RT A A N D B In te rv en tio ns b ef or e an d af te r O ve r t he c ou rs e of th re e w ee ks , t he re w ill b e si x 30 -m in ut e tr ai ni ng s es - si on s pl us a h om e as th - m a co nt ro l a ss es sm en t tw o tim es p er w ee k. • P ar tic ip an ts h ig h- lig ht ed th e im pa ct o f H EA RT R AT E VA RI A - BI LI TY B IO FE ED BA CK on s tr es s or c on ce rn (6 7% ), de pr es si on o r so rr ow (5 6% ), an d st re ss (4 4% ); or n o be ne fit s of H EA RT R AT E VA RI A BI LI TY B IO FE ED - BA CK o n te ns io n (5 0% ); • A nx ie ty s ym pt om s ar e sl ig ht ly w or se ne d (c om pe tit iv e na tu re o f BF s of tw ar e) o ne p ar - tic ip an t h as c on fir m ed th is. • D ep re ss io n* * (B D III ); • S ta te a nx ie ty ** a nd tr ai t a nx ie ty ** a re tw o ty pe s of a nx ie ty (S PI EL - BE RG ER S TA TE A N XI ET Y IN VE N TO RY ); • A tt en tio n sk ill s (T M T- A ** ) N ot d et er m in ed N ot d et er - m in ed (C on tin ue d) 305J Contemp Med Sci | Vol. 8, No. 5, September-October 2022: 295–310 S.M. Al-Tamimi Original Biofeedback of Heart Rate Variability in the Treatment of Chronic Diseases: A Systematic Review Ta bl e 1. T he b as el in e ch ar ac te ris tic s o f e ac h in cl ud ed st ud y— Co nt in ue d St ud y Sa m pl e St ud y de si gn in g De pe nd en t f as th m a co nt ro l t es to rs a nd fu lfi lm en t t im e He ar t r at e va ria bi lit y bi of ee db ac k in te rv en tio n Vi ab ili ty Si gn ifi ca nt ch an ge s i n He ar t R at e Va ria bi lit y Bi of ee db ac k co ho rt He ar t r at e va ria bi lit y in ec k di sa bi lit y in de xe s No n- si gn ifi ca nt ou tc om es Sc hu m an e t a l. (2 01 8) Po st -T ra um at ic S tr es s D is or de r ( PT SD ).  T he pa rt ic ip an ts ra ng ed in a ge b et w ee n 26 un til 5 0 ye ar s ol d. • P ilo t S tu dy • H EA RT R AT E VA RI A BI LI TY B IO - FE ED BA CK (n = 6 ) Co nt ro lli ng th e w ai tli st w ith br ea th in g te ch - ni qu es (n = 6 ) PT SD C H EC KL IS T FO R TH E D SM 5; H RV • I nt er ve nt io ns b ef or e an d af te r • F ol lo w u p ra ng ed fro m fo ur to 1 6 w ee ks . O ve r t he c ou rs e of 4 w ee ks , O ne s es si on + 10 –1 5 m in ut es tw ic e da ily p ra st hm a co nt ro l te st ic e • T he p ro ce du re w as pe rf or m ed b y te n pe op le ; • D ai ly p ra st hm a m on ito rin g te st ic e pa rt ic ip at io n ra te o f > 70 % ; • S ym pt om s in cl ud e a de cr ea se in in di vi du al s’ irr ita bi lit y, a nx ie ty , a nd sl ee p di st ur ba nc es . • P TS D -s pe ci fic s ym pt om s (P TS D C H EC KL IS T FO R TH E D SM 5* ) m ai nt ai ne d at fo llo w s- up • T he re su lts h av e be en co m bi ne d. • R M SS D * in cr ea se d at th e 16 -w ee k fo llo w -u p N ot d et er - m in ed Ta n et a l. (2 01 1) Po st -T ra um at ic S tr es s D is or de r ( PT SD ).  Th e pa rt ic ip an ts ra ng ed in a ge fr om 2 4 to 6 2 ye ar s ol d. • P ilo t s tu dy • H EA RT R AT E VA R- IA BI LI TY B IO FE ED - BA CK + s ta nd ar d ca re (n = 1 0) • S ta nd ar d ca re (n = 1 0) CL IN IC IA N -A D M IN IS - TE RE D P TS D S CA LE ; PT SD C H EC K- LI ST -S PE CI FI C In te rv en tio ns b ef or e an d af te r O ve r t he c ou rs e of 8 w ee ks , t he re w ill b e 8 tr ai ni ng s es si on s (h al f a n ho ur  e ac h) a nd a 2 0- m in - ut e as th m a co nt ro l t es t tw o tim es p er d ay . • 1 d ro po ut (t ra ns po rt pr ob le m ); • P ar tic ip an ts ra te d th e H EA RT R AT E VA RI A - BI LI TY B IO FE ED BA CK in te rv en tio n as a n 8/ 10 fo r s at is fa st hm a co nt ro l an d th at th ey h ad a pl ea sa nt ti m e. • P TS D -s pe ci fic s ym pt om s (C LI N IC IA N -A D M IN IS TE RE D PT SD S CA LE ** ; P TS D CH EC KL IS T- SP EC IF IC *) N ot d et er m in ed • A t t he e nd o f th e in te rv en - tio n, th er e w as no d iff er en ce be tw ee n th e gr ou ps . Tr ou ss el ar d et a l. (2 01 6) Re m itt ed s ch iz o- ph re ni a Ag e ra ng ed fro m 2 5 to 4 6 ye ar s. • P ilo t s tu dy • H EA RT R AT E VA R- IA BI LI TY B IO FE ED - BA CK (n = 1 0) • N o co nt ro l g ro up SP IE LB ER G ER S TA TE A N XI ET Y IN VE N TO RY ; D ER O G AT IS S TR ES S PR O FI LE ; P O SI TI VE A N D N EG AT IV E SY N D RO M E SC A LE ; W A RW IC K– ED IN - BU RG H M EN TA L W EL L- BE IN G S CA LE ; FR EI BU RG M IN D FU L- N ES S IN VE N TO RY In te rv en tio ns b ef or e an d af te r W ee kl y tr ai ni ng s es si on s of 8 –1 2 ho ur s (o ne h ou r) pl us d ai ly re la xa tio n te ch ni qu es . • N o dr op ou t; • M os t p eo pl e w an t t o re m ai n af te r q ui tt in g; • I n in di vi du al s w ith a hi gh le ve l o f c om - pl ai nt s, th er e ar e m or e be ne fit s. • M in df ul ne ss * (F RE IB U RG M IN D FU LN ES S IN VE N TO RY ); • A nx ie ty s tr es so rs * an d em ot io na l s tr es so r* (D ER O G AT IS S TR ES S PR O FI LE ) N ot d et er m in ed W A RW IC K– ED IN BU RG H M EN TA L W EL L- BE IN G S CA LE , PO SI TI VE A N D N EG AT IV E SY N - D RO M E SC A LE , SP IE LB ER G ER ST AT E A N XI ET Y IN VE N TO RY *< 0. 05 ; * *≤ 0. 01 ; “ N ot d et er m in ed ” i m pl ie s th at th is d at a w as n ot n ot ed in th e st ud y. 306 J Contemp Med Sci | Vol. 8, No. 5, September-October 2022: 295–310 Biofeedback of Heart Rate Variability in the Treatment of Chronic Diseases: A Systematic Review Original S.M. Al-Tamimi withdrawals,18–20 and medical defects.21 Because to significant dropout rates in lung cancer sufferers owing to disease-related health and lifestyle decline or mortality, one procedure was early discontinued.21 Satisfaction Generally, participants were pleased with the stress reduction and positive feeling improvement they experienced while bio- feedback, and the advantages lasted for a long time.17,20,22,23 None of the respondents in any of the research looked at expressed displeasure. Participants with remitted schizo- phrenia readily finished the intervention with no participation requirement, and the majority expressed an incentive to keep afterward due to claimed psychological advantages.23 There was a 67 percent acceptance rating for beneficial effects on anxiety or worry amongst elderly patients with psychiatric conditions, as well as 56 percent satisfaction for state of depres- sion or sorrow and 50 percent satisfaction for stress.22 Adverse Effects HRVB was found to have no major side effects, indicating that it is safe to use in patients with chronic conditions. Other minor side effects were noted, including such anxiety, due to the intrinsic pressure felt by sufferers to fulfil the biofeedback device’s predefined respiratory objectives.22 A familiarisation phase was adopted in a procedure to gradually eliminate the respiratory rating from a natural rhythm of ~14 breaths/min to a goal rate of ~6 breaths/minute to minimise any frustra- tions linked to sluggish breath and hyperventilation.24 Efficacy in Terms of Psychophysiological Results Cardiovascular Disorders and Hypertensive Disorders HRVB was helpful in lowering 24-hour systolic blood pres- sure (–2.1 0.9 mmHg, P = 0.03) and 24-hour pulse pressure (–1.40.6 mmHg, P = 0.02) following 8 weeks of regular practise, according to a randomised controlled trial (RCT) involving 65 participants (autogenic relaxation).25 A trial of 24 patients with atrial fibrillation found no change in blood pressure.18 Since the participants were already on beta-blocker medications when the trial began, all initial systolic and dias- tolic BP readings were within normal ranges through the latter example, which indicates a substantial restriction of the outcomes. As a consequence, HRVB appears to have a benefi- cial effect on blood pressure in hypertensive individuals and cardiovascular prognosis in heart sufferers. Inflammatory Condition In a research of 65 hypertension individuals, a negative rela- tionship between alterations in the inflammatory condition (evaluated by highly sensitive C-reactive proteins and inter- leukin-6) and efferent vagal activity (evaluated by HF power, RR interval, and baroreflex activities) was discovered.26 The researchers hypothesized that increasing efferent vagal action would reduce pro-inflammatory mediators, implying that HRVB could have anti-inflammatory properties. Asthma Disorders All asthma attacks and lung capacity increased in two Rand- omized trials with 94 and 64 participants, respectively, and airway inflammation decreased. When compared to the con- trol group, food and medicine intake was decreased after 10 weeks of daily HRVB practise, indicating that HRVB has a lot of potential in the particular treatment of asthma attacks.27 HRVB was more successful in lowering prescription usage 30 and airways inflammations than electroencephalogram (EEG) biofeedback and standard treatment,27 It was also just as effi- cient as active controls at alleviating asthma attacks,27 bron- chial permeability and lung capacity.27 Anxiety, Depression, and Psychological Response HRVB was found to have substantial favourable impact in 12 of the 15 research that looked at depression as a predictor var- iables; similarly, HRVB was found to have significant positive impacts in 9 of the 12 studies that looked at stress and anxiety. In 12 investigations involving 326 different patient features who suffered from mental illness, depressed mood, tension, and anxiety were considerably reduced,28–30 persistent discom- fort,31 chronic stress,32 psychiatric disorders22,23 and obesity.33 Anxiety and despair levels were reduced over many weeks to a year after HRVB treatment.30–32 Other beneficial psychological consequences were assessed, including greater mindfulness practice, self-compassion, and well-being. In two investigations with a total of 151 patients suf- fering from chronic stress19,32 and one research with ten partic- ipants in remission from schizophrenia, there was a reduction in worry or anger.23 Disruptions in Sleep Three of the four studies that looked at sleep problems found that HRVB improved sleeping patterns in individuals with severe depressed disorders,30 and anxiety symptoms (totalling 162 participants). Increases in sleeping were linked to lower levels of depression30 and stress.32 Characteristics of Post-Traumatic Stress Disorder (PTSD) In three investigations involving 60 patients, PTSD-specific indicators decreased considerably following 4–8 weeks of HRVB therapy. In a research with a small sample size of 20 participants, HRVB was found to be no more efficient than the traditional therapy.20 Cognitive Performances Massive gains in attention skills and executive functioning in individuals afflicted by chronic stress,19 executive function in individuals with mental signs, 38 have been implemented to enhance cognitive capacities. In addition, individuals who had an acute ischemic stroke improved their cognitive function significantly.23,24 Nevertheless, no improvement in cognitive abilities were identified in 13 individuals with persistent brain damage, which is likely owing to the kind of neurological problems.34 Pain 50 participants with irritable bowel syndrome and 24 individ- uals with stress-related chronic neck-shoulder pain improved following HRVB exercise.35 Improvements were sustained three months following HRVB exercise, according to one research.31 A further research, nevertheless, contradicts these 307J Contemp Med Sci | Vol. 8, No. 5, September-October 2022: 295–310 S.M. Al-Tamimi Original Biofeedback of Heart Rate Variability in the Treatment of Chronic Diseases: A Systematic Review findings, finding no substantial pain decrease in patients with diverse chronic pain characteristics.36 There was no informa- tion about the prescriptions and/or use of painkillers. Lifestyle Advancements in quality of life, particularly a rather more active lifestyle and a rise in both social and physical perfor- mance, were found to be linked to a reduction in pain 50 and PTSD-related indicators.17 Discussion Modifications in HRV may Mitigate the Relationship of Interventions The HRVB benefits on HRV were documented in 11 of the 21 investigations in the literature review. The lowered mean HR25 and breathing percentage at rest30,33 all over meetings, as well as the enhanced cohesion proportion throughout sessions,18 showed highest synchronisation between respiratory and car- diovascular processes, recommend that individuals correctly performed HRVB activities and demonstrate the impacts of routine practice. HRV indicators that increased in time, such as SDNN,24,29,30,33 pNN31 or RMSSD,24 and in frequencies, such as overall power,24,30,33 suggested an improvement in cardiac autonomic regulation. 9 Numerous studies have found that higher HRV values are linked to better outcome measures. In patients with chronic brain damage, a higher consistency pro- portion was linked to enhanced affective and psychological functioning.37 In cardiovascular events, greater HF power was linked to lower stress and anxiety levels, as well as lower inflammation condition in hypertensive individuals.26 As a consequence, the authors suggest that by boosting overall HRV and completely overwhelming cardiac vagus nerve activity, HRVB could have inhibitory action on autonomic function implicated in physiological control systems. The cen- tral-autonomic combination of vagal afferents may help to improve psycho - physiological performance in a more cohe- sive and effective process in this manner.38 Furthermore, by optimising and enabling interrelated biological processes, 0.1 Hz oscillations as a resonant frequencies may play a prom- inent part in physical and mental health.39 HRVB could be a potential strategy for managing a broad variety of ailments conditions and their effects by increasing vagal heart activity.40 Troublesome Explanation of HRV The HF power reflects PNS arousal while spontaneous breathing at resting (about 10–15 breaths/min), while the LF power mostly indicates baroreflex action influenced by both SNS and PNS. Whereas an elevation in HF strength indicates an elevation in PNS arousal, a rise in LF power may result in a rise in baroreceptor regulation controlled by ANS control and cannot clearly differentiate synchronous from parasympa- thetic involvement. The findings of HRV in the spectral domain in the research used in this study were characterized as the reinstitution of cardiac vagal regulation, expressed in either HF or LF regions. Furthermore, the effect of respiratory rate on HRV radio spectrum demonstrates that for a respira- tory rate under 9 breaths/min, vagal activities may pass over into the LF-band.41-43 Latest discoveries reveal that parasympa- thetic inhibition can remove HRV power in the LF-band in healthy persons beneath slow breathing conditions, showing the importance of cardiac vagal activity throughout a limited range of frequencies of 4–9 breaths/minute.44 In this respect, some studies propose increasing the frequencies limitation between the HF and LF bands from 0.15 Hz to 0.1 Hz to account for the particular effects of slow breathing on the HRV frequency distribution as well as the complicated interactions among PNS and SNS signalling heart-brain connections.39 Numerous technical features of HRV signal acquisition, including such monitoring length, instrument employed (ECG or pulse sensor), HRV variables evaluated, and respira- tory circumstances, vary between procedures. Ventilation was not measured in any of the procedures, therefore not deter- mined on breathing rate, tidal volume, or intake to exhalation ratios was supplied, although their recognised impacts on HRV.45 Respiratory variables should be observed to interpret the data more precisely because variations in rhythms of respi- ration may alter the HRV power spectrum as a potential medi- ator.43 Other variables that may play a role in HRV regulation, such as medicine and physically activities,46 must also be taken into account. As a consequence, studies relating to the increase of HRV indices must be regarded with caution, as they do not show a direct cause-and-effect connection among HRVB and ANS control. HRVB Versus Other Interventions The known methods implementations were also explored as component of this systematic review. HRVB was largely effec- tive when opposed to normal care or waiting listing controlled trials47,29,30,33,35 but not when contrasted to active controls that included various non-pharmacological treatments.19,27,31,32 Autogenic relaxing, progressive muscle relaxation, electroen- cephalogram biofeedback,27 hypnotherapy, 50 mindfulness training, and physical activity19,32 have all been shown to improve psycho - physiological results. HRV indicators were not enhanced by any of the other non-pharmacological treat- ments utilised as a controlled group, indicating HRVB’s dis- tinct abilities on autonomic cardiac modulation (Table 1). Whenever HRVB is used in conjunction with regular care, the findings demonstrate that it can be used as an adjunctive therapy for clinical patients. Nevertheless, since of potential confounders, we eliminated some of the studies that show promising prospects for integrated non-pharmacological ther- apies in chronic illness treatment, such as physically exercises, healthcare management,48 or relaxation techniques.49 Guidelines for HRVB Training Regimes The majority of the regimens we looked at gave 4–12 moni- tored workshops with ongoing home practise. Home practise was created to strengthen diaphragmatic breathing instruc- tions and enhance HRV responsiveness, whereas monitored training were offered to ensure that HRVB activities were completed. The authors discovered a dose-response relation- ship between HRVB practise and symptomatology decrease19,32 implying the need of consistent practise and the presence of a practise barrier at which HRVB can deliver the desired results. We may estimate that optimum practise should comprise at least one monitored workshop accompanied by consistent home practise of at least 10 minutes daily for four weeks depending on the examined publications. This finding is con- sistent with previously reported HRVB protocol guidelines, which suggest 5 monitored sessions with 20-minute daily 308 J Contemp Med Sci | Vol. 8, No. 5, September-October 2022: 295–310 Biofeedback of Heart Rate Variability in the Treatment of Chronic Diseases: A Systematic Review Original S.M. Al-Tamimi practises.50 Patients may choose shorter practise hours if they are concerned about dropping out due to time constraints. HRVB practise, on the other hand, is likely to be helpful when tailored to the patient’s profiles and skills, with the option of providing more monitored sessions and extended procedures as needed. Guidelines for HRVB Training Programs The researchers of the examined procedures have offered a series of findings: To prevent minor side effects, provide a familiarisation phase of slow breathing activities at the start of the treatment (anxiety or breathlessness);47,24 practice the slow abdomen breathing exercises by introducing pursed-lips abdominal breathing with slightly delayed exhale;24 and, all through the session, gradually reduce the amount of time sub- jected to optical biofeedback in order to develop full inde- pendence in HRVB practise.36 Lehrer’s methodology includes a brief anti-hyperventilation warning (“In hopes of avoiding hyperventilation during the timed respiration activity, kindly eliminate exceedingly breathing techniques.”).50 Participants who are new to 0.1 Hz respiration must be given instructions to “breathe superficially and spontaneously.” Even though it has been demonstrated that an participant’s HR frequencies range makes it easier to enter cardiac coherence phase,51 HRVB has often been established on roughly 6 breaths/min. In terms of the inhalation/exhalation proportion (i/e), a lower i/e ratio appears to result in enhanced relaxing, reducing stress, mindfulness, and good energy in participants 68, and a 1/2 proportion could boost baroreflex responsiveness.52 Others’ findings, on the other hand, demonstrate that a 1/1 ratio is more beneficial than extended exhalation (40 percent intake and 60 percent expiration) in increasing HRV.53 As a result, more research is required to explain these various issues and to find the best beneficial breathing technique. Future Studies Possibilities Our findings are consistent with earlier studies that show HRVB has a favourable impact on clinical results and demon- strate that HRVB is a viable and prospective treatment option for people with chronic conditions.40,54,55 The researchers con- cluded that HRVB could help restore autonomic heart control and emotional self-control, as evidenced by the positive asso- ciation between clinical results and HRV indicators.26,37,34,56 Given the role of the autonomic nervous system in pathogen- esis6 and the fact that HRV is a measure of cardiac morbidity, a potential regulating impact of HRVB on functional status provides attractive alternative therapy possibilities. Our research is hampered by the lack of risk-of-bias evaluation of the included research, despite the fact that it gives a qualitative summary of HRVB outcomes and methods. Given the diver- sity of procedures employed in HRVB studies, subsequent papers should emphasise analysing risk of bias, evaluating the significance of every report’s results, and doing meta-analyses to get more firm conclusions on the possible impact of HRVB. Further controlled trials are needed to much more pre- cisely assess the efficacy of HRVB in comparison to standard treatment and effective control circumstances (e.g., relaxation, mindfulness meditation, physical exercise). As potential con- founders, respiratory rhythm (incidence, peak flow, and inspi- ration to exhalation ratio), physical activity, and medications should all be observed.46 As according respiratory rate and HRV signals collection, the various time and frequency parameters of HRV should be properly analysed.42 Investiga- tors may be inspired by a beautiful study whose findings were released after the comprehensive study’s eligibility deadline.57 It was carried out on depressed patients, and the procedure was based on a very thorough medication regimen that included a 5-week HRVB intervention during psychiatric inpatient recovery. The findings demonstrated an increase in HRV-LF amplitude and consistency ratios, as well as a reduc- tion in depression scores and resting breathing rate, indicating that physicians have great potential. Different analysis tech- niques to enhance the extracting included in HRV must be prepared and implemented in the future for a reliable estima- tion of functional connectivity utilising HRV. Quantitative evaluations of HRVB’s impact on sympathetic cardiac control could possibly be more useful.58 Lastly, in future investiga- tions, established protocols for both treatment procedures and data collection should be observed to improve the effect of meta-analyses and review articles.43 Conclusion The efficacy of HRVB as an adjunctive therapy in patients with chronic conditions is highlighted in this comprehensive review. Because of the wide range of individuals and results, it’s hard to draw mechanical generalizations about how HRVB affects intervention effects. HRVB may have a regula- tory influence on autonomic heart control by enhancing HRV and recovering vagal functionality, according to our findings. The enhanced vagal flow may therefore impact brain activities and improve emotional self-regulation, implying that HRVB could be useful as a supplemental remedy for various of chronic conditions. Considering the excellent benefits of HRVB on psychophysiological results across a variety of patient characteristics, it’s apparent that HRVB has a bright future in the treatment of chronic disor- ders. Confirming these findings, clarifying the understanding of the HRV power spectrum, and determining the most effec- tive strategy in chronic disease management will require more research. Conflict of Interest None.  References 1. Lehrer P, Kaur K, Sharma A, Shah K, Huseby R, Bhavsar J, et al. Heart rate variability biofeedback improves emotional and physical health and performance: A systematic review and meta analysis. Applied Psychophysiology and Biofeedback. 2020;45(3):109–29. 2. Reneau M. Heart rate variability biofeedback to treat fibromyalgia: an integrative literature review. 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