Yoga as Adjunct Therapy for Chronic Heart Failure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background  Chronic heart failure (CHF) is a prevalent cardiovascular condition that can significantly impact the quality of life and increase mortality risk. Yoga is a mind–body therapy that has been studied as a potential complementary treatment for CHF. However, the effectiveness of yoga in improving outcomes in patients with CHF remains uncertain. Methods  We conducted a systematic review of randomized controlled trials (RCTs) evaluating the effects of yoga on outcomes in patients with CHF. We searched the PubMed, Embase, Scopus, Cochrane Library, and IndMED databases from inception to March 2023. The outcomes of interest were left ventricular ejection fraction (LVEF), cardiac biomarkers, exercise capacity, quality of life, and cardiac function. Results  We identified 11 RCTs that met our inclusion criteria, involving a total of 552 participants. The meta-analysis showed that yoga was associated with significant improvements in peak VO 2 (mean difference [MD]= 3.29; 95% Confidence Interval [CI]: 1.64 to 4.94; I 2 = 0%), exercise capacity (MD=101.54; 95% CI: 6.24 to 196.83; I 2 = 96%), quality of life (MD = –19.99; 95% CI: –25.76 to –14.22; I 2  = 43%), NT-proBNP (MD = –288.78; 95% CI: –492.20 to –85.37; I 2  = 94%), and 6-minute walk test (MD = 101.54; 95% CI: 6.24–196.83; I 2  = 96%), but not in the left ventricular ejection fraction (MD = 4.28; 95% CI: –1.14 to 9.70; I 2  = 93%). Subgroup analysis suggested that the effect of yoga on the quality of life is more pronounced in patients with the “New York Heart Association” (NYHA) class I and II CHF patients and in those who practiced yoga for longer durations. No serious adverse events related to yoga were reported. Most of the included studies were of “low” quality. Conclusion  Current evidence suggests that yoga may be an effective complementary and integrative therapy for improving peak VO 2 exercise capacity, NT-proBNP, and quality of life in patients with CHF. However, the low-quality evidence does not render us to conclude anything beyond doubt or draw any firm clinical recommendation. Future high-quality studies are needed to explore the optimal duration and frequency of yoga practice and its effects on long-term outcomes in this population.


Introduction
According to the American Heart Association/American College of Cardiology guidelines, heart failure (HF) is defined as "a complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill or eject blood." 1 HF is a global epidemic that affects an estimated 23 million people and the leading cause of substantial numbers of morbidity, hospitalizations, mortality, and health care costs, worldwide. 2,3nfectious illnesses and/or dietary deficiencies are no longer the primary causes of death and morbidity in Asian nations, but rather diseases linked to a sedentary lifestyle, such as cardiovascular disease (CVD). 2 According to disease-specific estimates of HF prevalence and incidence rates, the prevalence of HF in India ranges from 1.3 to 4.6 million, with an annual incidence of 491,600 to 1.8 million due to coronary artery diseases, hypertension, obesity, diabetes, and rheumatic heart diseases. 4Reduced physical function, increased dyspnea, and weariness are all signs of HF.The quality of life (QoL) is also reduced in HF patients. 5Despite recent advancements in pharmacologic and device treatment, cardiovascular morbidity and death remain high. 6Likewise, consistent use of conventional medication can lead to various adverse effects.Hence, there is a need for an alternative, nonpharmacologic approach like yoga that may improve physical and psychological function. 5oga is a mind-body practice that incorporates physical postures, breathing methods, and meditation to promote relaxation, stress reduction, and general health and wellbeing.It grew and evolved as a dynamic way of life and spiritual practice in India. 4While the benefits of yoga have been studied in a variety of populations and conditions, its effects on chronic HF remain unclear.However, yoga has gained immense popularity and is considered beneficial in cardiac rehabilitation. 7,8HF is associated with altered autonomic function, resulting in markedly elevated sympathetic activity and blood pressure. 4Yoga has recently gained popularity as a practice in Western culture.Yoga includes breathing exercises, relaxation techniques, and meditation in addition to physical activities.By increasing baroreflex sensitivity and heart rate variability (HRV), lower breathing rate can boost vagal activation and lessen the effect of the sympathetic branch of the autonomous nervous system.Blood pressure and heart rate may drop as vagal involvement increases.Increased systolic stroke volume and enhanced left ventricular ejection fraction (LVEF) may result from load reduction. 94][15] Although an increasing number of studies have been published in the past few years, there is only one systematic review and meta-analysis 16 performed to evaluate the effect of yoga in patients with HF.The review, published in 2014, included two randomized controlled trials (RCTs) and primarily measured peak VO 2 and health-related QoL (HRQoL).It indicates a lack of updated systematic review and meta-analysis in yoga and HF.More-over, several trials have been published since the review was conducted in yoga and CVDs, especially HF.
Given the potential promise of yoga as a complementary and integrative therapy for chronic heart failure (CHF), there is a need for a comprehensive and up-to-date systematic review and meta-analysis of the available evidence.This review aims to synthesize the findings of RCTs that have investigated the effects of yoga on biomarkers and QoL in patients with CHF.By examining the collective evidence, we hope to provide insights into the potential benefits and limitations of yoga as an adjunct therapy for this challenging health condition.

Research Question
What is the effect of yoga on cardiac biomarkers, function, and QoL in individuals with CHF?

Transparency
This review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Eligibility Criteria
Types of studies: RCTs that evaluated the effect of any type of yoga in patients with CHF (systolic and/or diastolic) compared with either standard medical care or other similar interventions, published in English, were included.Furthermore, crossover or non-RCTs, single-group pre-post trials, observational studies, case series, case reports, review articles, surveys, and health news were excluded.
Types of participants: Studies enrolled patients with systolic and/or diastolic HF (aged >18 years) were included in this review.To be eligible, a trial required patients with HF to be randomized to at least one group receiving any type of yoga intervention.CHF is defined as a clinical syndrome characterized by symptoms and/or signs of HF with objective evidence of structural or functional cardiac abnormalities.Yoga intervention could be defined as any practice that involves physical postures (asanas), breathing techniques (pranayamas), meditation (dhyana), and/or relaxation exercises.
Types of outcome measures: The effects of yoga could be evaluated through outcomes like cardiac biomarkers, function, and QoL.Therefore, considering the context, the main outcomes of interest were as follows: • LVEF: It is a measurement of the amount of blood that is pumped out of the left ventricle of the heart with each heartbeat.It is expressed as a percentage and is calculated by dividing the volume of blood pumped out of the left ventricle during systole (the contraction phase) by the total blood volume in the left ventricle at the end diastole (the relaxation phase).In addition, we excluded mental health outcomes, which were not the objective of interest of this study.

Search Methods for Identification of Studies
A rigorous and systematic search strategy was formulated to identify potential articles investigating the impact of yoga on CHF.The search was conducted across multiple electronic databases, including PubMed, Embase, Scopus, Cochrane Library, and IndMED, utilizing appropriate keywords and MeSH terms related to yoga and CHF.The search was not restricted by language; only studies published until March 31, 2023, were included.In addition to the electronic database search, a snowballing technique was utilized to identify other relevant studies by searching through the bibliographies of important articles.The exclusion criteria were appropriately applied to exclude book chapters, abstracts, incomplete reports, case reports, and duplicate records.By adopting such a comprehensive and rigorous approach, only relevant and high-quality studies were considered for inclusion in the synthesis.The search strategy used for PubMed is described in ►Table 1, which is modified and adapted as per the suitability of other databases.

Data Collection and Analysis
Assessment of study eligibility: The identified studies were screened for relevance and eligibility by two independent reviewers, who assessed the titles and abstracts for the inclusion criteria based on the research question.Full-text articles were obtained for studies that met the inclusion criteria or whose relevance was unclear based on the ab-stract.The eligibility of the full-text articles was also assessed independently by two reviewers, and any disagreements were resolved through discussion or with the involvement of a third reviewer.
Data extraction: The relevant data from the eligible studies, such as study characteristics (e.g., author, year, country, sample size), participant characteristics (e.g., age, sex, diagnosis), intervention characteristics (e.g., type, frequency, duration), outcome measures (e.g., biomarkers of HF, QoL), and study results, were independently extracted by two reviewers.Any discrepancies that arose during the data extraction process were resolved through discussion or consultation with a third reviewer.In case of incomplete data reporting in the eligible studies, the corresponding authors were contacted for additional information.The data were considered incomplete if the authors did not respond after successive two reminders.This approach ensures that robust efforts were made to obtain complete data and that the analysis is based on the most comprehensive and accurate information available.
Quality assessment of included studies: To assess the risk of bias (RoB) in individual studies, two reviewers independently utilized the Cochrane collaboration tool for assessing RoB, Version-2 (RoB 2.0). 17The RoB was evaluated across six domains, which include selection bias, performance bias, detection bias, attrition bias, reporting bias, and other biases.
"Selection bias" refers to the way participants are chosen for a study.This review used two criteria to assess selection bias: "random sequence generation" and "allocation concealment.""Adequate random sequence generation" means that participants are placed into groups randomly, and "adequate allocation concealment" means that the researchers could not predict which group a participant would be placed in before or during the study."Performance bias" refers to whether the participants and researchers are aware of which group a participant is in."Adequate blinding" means that neither the participants nor researchers knew which group the participant was in.Although it may be challenging to blind participants and researchers in yoga trials, it is still essential to minimize bias."Detection bias" refers to whether the outcome assessors know which group a participant is in.Adequate blinding of the outcome assessors is essential to Yoga for Chronic Heart Failure Dutta et al. 153 prevent bias."Attrition bias" occurs when some participants drop out of the study, leading to incomplete data.If more than 20% of participants drop out, it can affect the study results, so addressing this with an intention-to-treat analysis is crucial."Reporting bias" occurs when not all the study's outcomes are reported."Other sources of bias" that do not fit into any of these categories are also possible.The RoB was assessed as "low," "unclear," or "high" based on how well these criteria were met.Any disagreements were resolved through discussion among the reviewers.Any discrepancies that arose during the evaluation of RoB were resolved through discussion or consultation with a third reviewer.
Data synthesis and analysis: We first conducted a qualitative synthesis (systematic review) of the included studies.We identified similar and extractable quantitative outcomes across studies and pooled them for quantitative synthesis (meta-analysis).For continuous outcomes (e.g., biomarkers of HF, QoL), we reported the mean difference (MD) with 95% confidence intervals (CIs).The statistical heterogeneities were measured using the I 2 statistic and Cochran's Q test.We used fixed effect and random effect models to estimate the average effect, depending on the amount of heterogeneity exhibited for each outcome.
However, some studies reported the difference from the baseline, rather than the final value score.We pooled the values using the mean difference (unstandardized) method in such cases.Using the mean difference method, we combined studies with change-from-baseline outcomes and studies with final measurement outcomes in a meta-analysis.This is because the mean difference method calculates the difference between two means (e.g., the mean value in the intervention group minus the mean value in the control group) and therefore does not require the outcomes to be standardized.The statistical analyses for this systematic review and meta-analysis were conducted using the "Meta" package in the R software environment (https:// cran.r-project.org/).Specifically, the functions "metacont" and "forest" were utilized to perform the meta-analyses and generate the forest plots, respectively.
Subgroup and sensitivity analysis: In the cases where there was substantial heterogeneity between studies, we conducted subgroup analyses based on participant characteristics (e.g., disease severity), intervention characteristics (e.g., type, frequency, duration), and RoB.This approach helps us to identify potential sources of heterogeneity and provides insights into the factors that may influence the effect of the intervention.
We also conducted sensitivity analyses to explore the impact of individual studies on the overall results.We could assess the results' robustness and identify any influential studies by systematically removing one study at a time and recalculating the pooled effect estimate.This approach helps ensure that the conclusions drawn from the meta-analysis are reliable and not overly influenced by any single study.
Publication bias: We planned to assess publication bias using funnel plots and Egger's test.If there is evidence of publication bias, we would have conducted a trim-and-fill analysis to adjust for the bias.There should be at least 10 studies for publication bias studies in a meta-analysis by the funnel plot test; fewer studies might not give sufficient power to the test and may not detect the real asymmetry. 18n this review, the number of studies on individual outcomes were less than 10.Therefore, publication bias detection was not performed.
The 11 RCTs 4,7-9,19-25 involved 552 participants with CHF.The yoga interventions ranged from 8 to 24 weeks, with an average duration of 12 weeks reported in 70% of the studies.Five studies were conducted in India, 4,20-23 4 in the United States, 7,8,24,25 1 in Sweden, 9 and 1 in Brazil. 19In most trials, yoga intervention was given in the context of standard care, while in two trials, yoga was compared with hydrotherapy 9 and guideline-based therapy. 20The interventions included various compositions of yoga styles, such as meditation, yogic postures (asanas), breathing exercises (pranayama), and relaxation phases.Two studies 19,24,25 exclusively used meditation as an intervention.The control groups received either usual care or an alternative control intervention, such as hydrotherapy.No serious event was reported in any of the trials.We evaluated the effect of yoga on various outcomes in CHF patients through systematic review, with or without meta-analysis (►Table 2).

Left Ventricular Ejection Fraction
Three studies 19,20,22 involving 167 participants evaluated the changes in LVEF after the yogic intervention.Krishna et al 22 showed a significant increase in LVEF in both the yoga and control groups.However, the increase in LVEF was significantly higher in the yoga group compared with the control group.Likewise, a study by Jain et al 20 showed a significant increase in LVEF in the yoga group, whereas the control group showed a nonsignificant increase.On the other hand, Curiati et al 19 showed no significant changes in LVEF in the yoga and control groups.All these studies used 12 weeks of intervention.The study by Curiati et al 19 was not included in the meta-analysis because of a wide baseline difference between groups.However, the pooled effect of the remaining studies did not show any significant improvement in LVEF, with high heterogeneity (I 2 ¼ 93%) and a mean difference of

NT-proBNP
Three studies 20,22,25 reported changes in NT-proBNP after yoga intervention with a total of 175 participants.However, the two similar studies by Jain et al 20 and Krishna et al 22 were included in the meta-analysis.In these studies, NT-proBNP was reported in different units, and the values were converted to pmol/L before analysis.The pooled estimate showed a substantial reduction in NT-proBNP after the yogic intervention (MD ¼ -288.78;95%CI: -492.20 to -85.37;I 2 ¼ 94%; ►Fig.5).
Out of six studies that assessed QoL through MLWHFQ, three reported [19][20][21] significant improvement in the yoga intervention group.In contrast, the other three studies 7,8,25 reflected a nonsignificant improvement in the yoga group compared with the control group.
Among other outcomes of QoL, studies reported a significant increase in the social function domain of SF-36. 25owever, no improvement was observed in QWB-SA, 25 compared with standard care.The effect of yoga was found to be similar to hydrotherapy in changing EQ-5D, EQ-VAS, and disease-specific QoL measured using KCCQ. 9nitially, six studies 7,8,[19][20][21]25 that reported MLwHFQ were included in the meta-analysis. Howver, one study was excluded from the analysis 25 because of the vast dissimilarity in duration and nature of the intervention.Of these, three studies [19][20][21] used 12 weeks of intervention and included the NYHA I and II patients in the study, whereas the two remaining studies 7,8 used 8 weeks of intervention and included the NYHA I, II, and III patients.Both were analyzed as subgroups as well as cumulative. Th first subgroup showed a high heterogeneity (I 2 ¼ 98%) and a mild treatment effect (MD ¼ -15.30; 95%CI: -27.53 to -3.08). Excluing the study by Jain et al, 20 there was a significantly improved treatment effect (MD ¼ -22.24; 95%CI: -27.70 to -16.78), with a substantial reduction in heterogeneity (I 2 ¼ 50%).The second subgroup showed a more robust and significant treatment effect (MD ¼ -13.65; 95%CI: -23.67 to -3.62), with a very insignificant (I 2 ¼ 0%) heterogeneity.The overall effect in all the studies (►Fig.6) was -14.86 (95%CI: -27.01 to -2.70; I  ¼ 97%), and after excluding the study by Jain et al, 20 the pooled estimate improved to -19.99 (95%CI: -25.76 to -14.22;I 2 ¼ 43%; ►Fig.7).

Peak VO 2
Peak VO 2 was reported in three studies 7,8,19 (n ¼ 74) in the unit of mL/kg/min.The overall estimate following the intervention showed a significant improvement in peak VO 2 (MD ¼ 3.29 [95%CI: 1.64-4.94]).The heterogeneity among the studies was reported as very low, with an I 2 value of 0%, which suggests that the pooled result is robust and reliable (►Fig. 8).

Six-Minute Walk Test
Two studies have measured the exercise capacity of HF patients using 6mWT in the unit of meters.The result of Krishna et al's study 21 showed a significant increase in 6mWT distance in the yoga group compared with the control group.Likewise, the study of Jayadevappa et al 25 showed a significant improvement in the 6mWT in the yoga group from baseline to 6 months after treatment compared with the control (health education) group.The meta-analysis showed a significant effect of the intervention in improving the 6mWT (MD ¼ 101.54; 95%CI: 6.24-196.83,I 2 ¼ 96%; ►Fig.9).

Other Outcomes
One study 22 evaluated the effect of 12 weeks of yoga on the Myocardial Performance Index (Tei index).The Tei index is a straightforward, reliable, and independent indicator of heart rate and blood pressure of total cardiac dysfunction in patients with mild to moderate HF.It is calculated as the   In some studies, it has been observed that yoga led to significant improvement in heart rate, 4 increase in highfrequency spectrum and decrease in low-frequency spectrum of HRV, measured through Kubios HRV Version 2.0 software for HRV (Bio-Signal Analysis Group, Finland), 4 reduction in systolic blood pressure (SBP) and diastolic blood pressure (DBP), 4 improvement in rate pressure product (RPP), 4 reduction in hsCRP 7,8,20 and interleukin-6 (IL-6), 7,8 increase in extracellular superoxide dismutase (EC-SOD) activity, 7,8 increase in treadmill time, 7,8 decrease in the minute ventilation/carbon dioxide production (VE/VCO 2 ) slope, 19 and reduction in the norepinephrine level. 19oga did not affect some outcomes like cortisol levels 25 and left ventricular end-diastolic volume index (LVDDi). 19A study reported 9 that the effect of yoga may be similar to hydrotherapy in various outcomes like HRQoL, peripheral oxygen saturation, heart rate, SBP and DBP, high-sensitivity C-reactive protein (hs-CRP), and NT-pro BNP.
Aditee et al 24 assessed the effect of yoga on clinical outcomes in patients with implantable defibrillators for HF.The study showed a reduction in antiarrhythmic use, cumulative atrial fibrillation (AF), persistent AF, sustained VA, ablation for HF, HF hospitalization, and an increase of survival in the yoga group compared with the control group.

Discussion Principal Findings
The systematic review including 11 randomized trials with 552 participants aimed to investigate the effects of yoga as an adjunct therapy for patients with CHF.The principal findings of the review indicate that yoga interventions may have beneficial effects on various outcomes such as QoL, peak VO 2 , exercise capacity, endurance, and a few cardiac biomarkers such as NTproBNP.Subgroup analysis suggested that the effects of yoga on QoL were more pronounced in patients with the NYHA class I and II CHF patients and in those who practiced yoga for longer durations.The review found no significant effect of yoga on LVEF in patients with CHF.However, the evidence is limited, and the quality of the studies included is generally low.

Strengths and Limitations
One of the strengths of this review is that it is based on a comprehensive search of several databases, which included exclusively RCTs.Additionally, the review followed the PRISMA guidelines for conducting and reporting systematic reviews, which enhances its reliability and validity.However, the review has some limitations that need to be considered.One of the main limitations is the small number of studies included in the review, which limits the generalizability of the findings.Moreover, the quality of the studies included in the review is generally low, with several studies having a high RoB.In the meta-analysis, very few studies could be included considering the similarity in individual outcomes.The involved heterogeneity was another concern while interpreting the study results.Only the QoL could be explained a little, using subgroup and sensitivity analyses.The quality of reporting was another issue found in most of the trials, which carries a negative dimension while interpreting such reports.

Comparison with Previous Similar Studies
Our findings are generally consistent with a previous systematic review 16 that reported that yoga might improve peak VO 2 and HRQoL in patients with CHF.However, the previous review has included fewer studies (n ¼ 2), and significant time has elapsed since the review.Our review adds to the literature by including a more comprehensive search of the literature, including a broader range of studies, and evaluating the quality of the studies extensively using validated tools.In contrast to the previous one, this review evaluated the effect of yoga on a broader range of clinical outcomes in CHF patients.

Future Direction and Recommendation
The findings of this review suggest that yoga may have potential benefits as an adjunct therapy for patients with CHF.However, evidence is limited, and the quality of the studies is generally low.Future studies should focus on conducting high-quality RCTs with larger sample sizes to provide more robust evidence on the effects of yoga in patients with CHF.Moreover, future studies should also aim to evaluate the long-term effects of yoga on various outcomes in this population.Given the heterogeneity of yoga interventions used in the studies included in this review, future studies should aim to standardize the interventions to allow for better comparison across studies.In addition, the quality of comprehensive reporting and adverse events must be strengthened in future yoga trials.

Conclusion
This systematic review suggests that yoga may have some benefits as an adjunct therapy for patients with CHF.The review found that yoga interventions may improve QoL, peak VO 2 , exercise capacity, endurance, and cardiac biomarkers.However, the evidence is limited and the quality of the studies included in the review is generally low, which limits the generalizability of the findings.Therefore, future studies should focus on conducting high-quality RCTs with larger sample sizes to provide more robust evidence on the effects of yoga in patients with CHF.Additionally, future studies should aim to standardize the interventions to allow for better comparison across studies and evaluate the long-term effects of yoga on various outcomes in this population.Overall, the findings of this review provide some promising initial evidence for the potential use of yoga as an adjunct therapy for patients with CHF, but further research is needed to evaluate its efficacy and safety beyond any doubt.

Fig. 2
Fig. 2 Risk of bias for individual studies.
Yoga for Chronic Heart Failure Dutta et al. 155
sum of isovolumic contraction and relaxation time divided by the ejection time.The study showed a significant reduction in the Tei index in the yoga group compared with the control group.

Fig. 4
Fig. 4 Forest plot showing the effect of yoga on the left ventricular ejection fraction (LVEF).CI, confidence interval; MD, mean deviation; SD, standard deviation.

Fig. 5
Fig. 5 Forest plot showing the effect of yoga on serum NT-proBNP level.CI, confidence interval; MD, mean deviation; NT-proBNP level, Nterminal prohormone of brain natriuretic peptide; SD, standard deviation.

Fig. 6
Fig. 6 Forest plot showing the effect of yoga on MLwHFQ score (including all the studies).CI, confidence interval; MD, mean deviation; MLwHFQ, Minnesota Living with Heart Failure Questionnaire; SD, standard deviation.

Fig. 7
Fig. 7 Forest plot showing the effect of yoga on MLwHFQ score (revised in sensitivity analysis).CI, confidence interval; MD, mean deviation; MLwHFQ, Minnesota Living with Heart Failure Questionnaire; SD, standard deviation.

Fig. 8
Fig. 8 Forest plot showing the effect of yoga on changing peak VO 2 .CI, confidence interval; MD, mean deviation; SD, standard deviation.

Fig. 9
Fig. 9 Forest plot showing the effect of yoga on 6-minute walk test.CI, confidence interval; MD, mean deviation; SD, standard deviation.