Effectiveness and safety of traditional herbal medicine on cardiac arrhythmic condition: A systematic review and meta-analysis of randomized control clinical trial
The prevalence of heart disease is increasing. The overall prevalence of arrhythmia was 1%. The incidence rate was observed to significantly increase with age, with a prevalence of 8% in individuals of advanced age (over 80 years).  Atrial fibrillation (AF), the most common arrhythmia, is a major factor associated with fatal cardiovascular conditions such as ischemic heart disease, cardiovascular disease, and heart failure, without appropriate management.  Arrhythmias include various diseases with an abnormal heartbeat, such as AF, paroxysmal supraventricular tachycardia, sinus arrhythmia, ectopic atrial rhythm or wandering pacemaker, atrial premature beat, ventricular premature beat, ventricular tachycardia, and AV block.  In conventional medicine, factor IIa (thrombin) inhibitors (dabigatran) and factor Xa inhibitors (xaban) are used to prevent embolisms caused by arrhythmias. Drug therapies for the management of arrhythmias include lidocaine, amiodarone, and propafenone.  Non-pharmacological therapies for the management of arrhythmias include pacemakers, catheter ablation, and implantable cardioverter-defibrillators.  However, these standard treatments have several limitations. Drug therapy is associated with problems such as necessitating lifetime medication for symptom management, rather than curative intent, or adverse effects associated with the drug itself.  Even in non-pharmacological therapies such as surgery, if a pacemaker is used, there is a risk of side effects such as making imaging impossible, significantly impeding daily life, and increasing the risk of bleeding.  Therefore, the demand for alternative therapies for managing arrhythmias is gradually increasing. In East Asian countries, various complementary and alternative therapies are used to manage arrhythmias.  In East Asian traditional medical records, arrhythmia diseases are already known as slow (迟脉), hesitant (涩脉), skipping (促脉), knotted (结脉), and regularly intermittent pulses (大脉) through pulse diagnosis method from ancient times. In addition, various therapeutic approaches have been suggested, including acupuncture, herbal medicine, and moxibustion.  A recent study reported the significance of acupuncture and moxibustion in arrhythmias.  As such, systematic literature reviews on acupuncture and moxibustion treatment have been continuously published, and research evidence has expanded. However, for traditional herbal medicine (THM) treatment, a systematic literature review of the overall THM for various arrhythmic diseases is still insufficient. Only 1 meta-analysis of specific herbal medicines has been conducted.  Therefore, this study aimed to examine the effectiveness and adverse events of THM in various arrhythmias in randomized clinical trials (RCTs) using a systematic literature review and meta-analysis methodology. This study examined comprehensive and up-to-date knowledge of THM for arrhythmias for further clinical research and practice. Furthermore, we propose suggestions for future studies by examining the clinical outcome variables and methodological flaws associated with the existing studies.   We conducted a systematic literature review and meta-analysis according to the Cochrane manual.  The study protocol was prepared according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines.  The study protocol was registered in the Open Science Framework (OSF. io). ( https://osf.io/7r8kn/ ). This study was a systematic review of the existing literature and did not require institutional review board approval. 2.1. Eligible criteria for study selection 2.1.1. Definition of disease Arrhythmia is a condition in which the heart beats irregularly or an abnormal heartbeat appears.  In this study, the arrhythmias were primary, and their sub-classifications included tachycardia, bradycardia, AF, ventricular premature contraction, ventricular tachycardia, sinus dysfunction, and atrioventricular conduction block.  However, secondary arrhythmias occurring due to coronary artery disease, cardiac hypertrophy, and hyperthyroidism were excluded. Patients with arrhythmias after percutaneous coronary intervention were excluded.  All symptom classifications (syndrome differentiation) in traditional East Asian medicine were permitted. 2.1.2. Types of interventions and comparators The THM treatment group included herbal medicine monotherapy and combination therapy with Western medicine (WM). Various formulations are available for different types of herbal medicines, such as pills, decoctions, powders, and extracts; however, the administration route is limited to oral drugs. Interventions involving other routes, such as injections, external treatment, intraperitoneal injection, intravenous injection, intramuscular injection, or fumigation treatment, were excluded. In single medicinal herbs, if herbal medicines were not included in the East Asian country’s Pharmacopoeia (such as the Korean or Chinese Pharmacopoeia), the research was excluded. For combination therapy with Western and herbal medicines, we included only studies that adopted the same WM between the intervention and control groups. In addition, non-pharmacological treatments such as acupuncture and moxibustion were excluded from this study to explore the effect of THM alone, not with acupuncture nor moxibustion. 2.1.3. Types of outcome measurements No restrictions exist on the type of clinical outcomes. We extracted every clinical outcome adopted in each clinical trial, including the total effective rate (TER), heart rate (HR) change, electrocardiogram change, and Holter 24-h electrocardiogram results. After investigating the clinical outcomes of each study, a meta-analysis was performed on the outcomes commonly used in several studies. 2.2. Searching strategy and database We searched the core electronic databases MEDLINE (via PubMed) ( https://www.ncbi.nlm.nih.gov/pubmed ) and the Cochrane Library ( https://www.cochranelibrary.com/ ) and Embase ( https://www.embase.com ). In addition, we searched Chinese and Korean DBs such as the China National Knowledge Infrastructure ( http://gb.oversea.cnki.net/Kns55/ ), DBpia ( www.dbpia.co.kr ), Korean Studies Information Service System ( http://kiss.kstudy.com/ ), OASIS ( https://oasis.kiom.re.kr/ ), and RISS ( http://www.riss.kr/index.do ). No restrictions exist on the language of the research papers, and the initial search period included publications up to September 2022. With time elapsed since the initial document search, a new search was conducted with a reference point of the end of April 2024.The search strategy and results for each database are described in Supplementary 1A, Supplemental Digital Content, http://links.lww.com/MD/M750 and 1B, Supplemental Digital Content, http://links.lww.com/MD/M751 . 2.3. Data collection and analysis 2.3.1. Inclusion and exclusion criteria Inclusion criteria Research on herbal medicine alone or combination treatment with conventional medication. A study targeting patients diagnosed with primary arrhythmias. A study in which the study design corresponds to a randomized comparative clinical trial. Administration routes were orally prescribed herbal medicine. Exclusion criteria Non-RCT designs such as animal experiments, case report papers, and review papers. When an invasive herbal medicine administration method was used (pharmacopuncture). Secondary arrhythmias due to organic causes (arrhythmias due to postoperative arrhythmias, heart failure, myocardial infarction, or hyperthyroidism). Research restricted to a specific subgroup (age). 2.3.2. Literature selection For studies found in the search, duplicate literature was removed using Endnote X9 (Clarivate Analytics, London, United Kingdom). For primary selection, 2 independent authors (J.A. and H.C.) reviewed the titles and abstracts and selected suitable studies. Full texts of the selected primary studies were reviewed and confirmed. In the case of discrepancies, a final decision was made via discussion. Issues that remained unresolved after discussion were assessed by a third reviewer (J.L.). 2.3.3. Data extraction and management In the final included studies after the selection process, the data extraction and risk-of-bias assessment results were extracted to Excel (Microsoft, Redmond, WA). Data extraction was performed based on the year of publication, study design method, diagnostic criteria, general characteristics of the participants, intervention method of the intervention and control groups, outcome evaluation index, and outcome measurement value. 2.4. Quality assessment The risk-of-bias assessment was performed using the Cochrane collaboration’s “Risk of bias” tool applied to randomized comparative clinical studies (RCTs), referring to Cochrane’s systematic literature review guidelines.  The risk of bias was evaluated for each item: random sequence generation, allocation concealment, blinding of the participants and personnel, blinding of the outcome assessments, incomplete outcome data, selective reporting, and other sources of bias.  The risk-of-bias was independently evaluated by 2 researchers (J.A. and H.C.) after discussing the evaluation criteria in advance. If a consensus was not reached, a third researcher (J.L.) intervened. 2.5. Meta-analysis A meta-analysis was performed to quantitatively synthesize treatment effects by combining several clinical studies on the clinical effects of herbal medicine treatment for arrhythmias. The RevMan (Review Manager version 5.4.1, Cochrane, UK) program was used for meta-analysis. A meta-analysis was conducted when the study design, intervention method, and evaluation tool were appropriate for the quantitative synthesis of studies based on heterogeneity. The risk ratio (RR) was used for dichotomous outcomes, whereas weighted mean differences and 95% confidence intervals (CIs) were used for continuous outcomes. To assess the heterogeneity between studies based on the Higgins I 2 statistic, an I 2 > 50% indicated heterogeneity between studies. If considerable heterogeneity was identified, a random-effects model was used to synthesize the results.  2.6. Publication bias A funnel plot was used to visually inspect publication bias in the included studies. Eggar’s test was used to analyze publication bias.   2.1.1. Definition of disease Arrhythmia is a condition in which the heart beats irregularly or an abnormal heartbeat appears.  In this study, the arrhythmias were primary, and their sub-classifications included tachycardia, bradycardia, AF, ventricular premature contraction, ventricular tachycardia, sinus dysfunction, and atrioventricular conduction block.  However, secondary arrhythmias occurring due to coronary artery disease, cardiac hypertrophy, and hyperthyroidism were excluded. Patients with arrhythmias after percutaneous coronary intervention were excluded.  All symptom classifications (syndrome differentiation) in traditional East Asian medicine were permitted. 2.1.2. Types of interventions and comparators The THM treatment group included herbal medicine monotherapy and combination therapy with Western medicine (WM). Various formulations are available for different types of herbal medicines, such as pills, decoctions, powders, and extracts; however, the administration route is limited to oral drugs. Interventions involving other routes, such as injections, external treatment, intraperitoneal injection, intravenous injection, intramuscular injection, or fumigation treatment, were excluded. In single medicinal herbs, if herbal medicines were not included in the East Asian country’s Pharmacopoeia (such as the Korean or Chinese Pharmacopoeia), the research was excluded. For combination therapy with Western and herbal medicines, we included only studies that adopted the same WM between the intervention and control groups. In addition, non-pharmacological treatments such as acupuncture and moxibustion were excluded from this study to explore the effect of THM alone, not with acupuncture nor moxibustion. 2.1.3. Types of outcome measurements No restrictions exist on the type of clinical outcomes. We extracted every clinical outcome adopted in each clinical trial, including the total effective rate (TER), heart rate (HR) change, electrocardiogram change, and Holter 24-h electrocardiogram results. After investigating the clinical outcomes of each study, a meta-analysis was performed on the outcomes commonly used in several studies.   Arrhythmia is a condition in which the heart beats irregularly or an abnormal heartbeat appears.  In this study, the arrhythmias were primary, and their sub-classifications included tachycardia, bradycardia, AF, ventricular premature contraction, ventricular tachycardia, sinus dysfunction, and atrioventricular conduction block.  However, secondary arrhythmias occurring due to coronary artery disease, cardiac hypertrophy, and hyperthyroidism were excluded. Patients with arrhythmias after percutaneous coronary intervention were excluded.  All symptom classifications (syndrome differentiation) in traditional East Asian medicine were permitted.   The THM treatment group included herbal medicine monotherapy and combination therapy with Western medicine (WM). Various formulations are available for different types of herbal medicines, such as pills, decoctions, powders, and extracts; however, the administration route is limited to oral drugs. Interventions involving other routes, such as injections, external treatment, intraperitoneal injection, intravenous injection, intramuscular injection, or fumigation treatment, were excluded. In single medicinal herbs, if herbal medicines were not included in the East Asian country’s Pharmacopoeia (such as the Korean or Chinese Pharmacopoeia), the research was excluded. For combination therapy with Western and herbal medicines, we included only studies that adopted the same WM between the intervention and control groups. In addition, non-pharmacological treatments such as acupuncture and moxibustion were excluded from this study to explore the effect of THM alone, not with acupuncture nor moxibustion.   No restrictions exist on the type of clinical outcomes. We extracted every clinical outcome adopted in each clinical trial, including the total effective rate (TER), heart rate (HR) change, electrocardiogram change, and Holter 24-h electrocardiogram results. After investigating the clinical outcomes of each study, a meta-analysis was performed on the outcomes commonly used in several studies.   We searched the core electronic databases MEDLINE (via PubMed) ( https://www.ncbi.nlm.nih.gov/pubmed ) and the Cochrane Library ( https://www.cochranelibrary.com/ ) and Embase ( https://www.embase.com ). In addition, we searched Chinese and Korean DBs such as the China National Knowledge Infrastructure ( http://gb.oversea.cnki.net/Kns55/ ), DBpia ( www.dbpia.co.kr ), Korean Studies Information Service System ( http://kiss.kstudy.com/ ), OASIS ( https://oasis.kiom.re.kr/ ), and RISS ( http://www.riss.kr/index.do ). No restrictions exist on the language of the research papers, and the initial search period included publications up to September 2022. With time elapsed since the initial document search, a new search was conducted with a reference point of the end of April 2024.The search strategy and results for each database are described in Supplementary 1A, Supplemental Digital Content, http://links.lww.com/MD/M750 and 1B, Supplemental Digital Content, http://links.lww.com/MD/M751 .   2.3.1. Inclusion and exclusion criteria Inclusion criteria Research on herbal medicine alone or combination treatment with conventional medication. A study targeting patients diagnosed with primary arrhythmias. A study in which the study design corresponds to a randomized comparative clinical trial. Administration routes were orally prescribed herbal medicine. Exclusion criteria Non-RCT designs such as animal experiments, case report papers, and review papers. When an invasive herbal medicine administration method was used (pharmacopuncture). Secondary arrhythmias due to organic causes (arrhythmias due to postoperative arrhythmias, heart failure, myocardial infarction, or hyperthyroidism). Research restricted to a specific subgroup (age). 2.3.2. Literature selection For studies found in the search, duplicate literature was removed using Endnote X9 (Clarivate Analytics, London, United Kingdom). For primary selection, 2 independent authors (J.A. and H.C.) reviewed the titles and abstracts and selected suitable studies. Full texts of the selected primary studies were reviewed and confirmed. In the case of discrepancies, a final decision was made via discussion. Issues that remained unresolved after discussion were assessed by a third reviewer (J.L.). 2.3.3. Data extraction and management In the final included studies after the selection process, the data extraction and risk-of-bias assessment results were extracted to Excel (Microsoft, Redmond, WA). Data extraction was performed based on the year of publication, study design method, diagnostic criteria, general characteristics of the participants, intervention method of the intervention and control groups, outcome evaluation index, and outcome measurement value.   Inclusion criteria Research on herbal medicine alone or combination treatment with conventional medication. A study targeting patients diagnosed with primary arrhythmias. A study in which the study design corresponds to a randomized comparative clinical trial. Administration routes were orally prescribed herbal medicine. Exclusion criteria Non-RCT designs such as animal experiments, case report papers, and review papers. When an invasive herbal medicine administration method was used (pharmacopuncture). Secondary arrhythmias due to organic causes (arrhythmias due to postoperative arrhythmias, heart failure, myocardial infarction, or hyperthyroidism). Research restricted to a specific subgroup (age).   For studies found in the search, duplicate literature was removed using Endnote X9 (Clarivate Analytics, London, United Kingdom). For primary selection, 2 independent authors (J.A. and H.C.) reviewed the titles and abstracts and selected suitable studies. Full texts of the selected primary studies were reviewed and confirmed. In the case of discrepancies, a final decision was made via discussion. Issues that remained unresolved after discussion were assessed by a third reviewer (J.L.).   In the final included studies after the selection process, the data extraction and risk-of-bias assessment results were extracted to Excel (Microsoft, Redmond, WA). Data extraction was performed based on the year of publication, study design method, diagnostic criteria, general characteristics of the participants, intervention method of the intervention and control groups, outcome evaluation index, and outcome measurement value.   The risk-of-bias assessment was performed using the Cochrane collaboration’s “Risk of bias” tool applied to randomized comparative clinical studies (RCTs), referring to Cochrane’s systematic literature review guidelines.  The risk of bias was evaluated for each item: random sequence generation, allocation concealment, blinding of the participants and personnel, blinding of the outcome assessments, incomplete outcome data, selective reporting, and other sources of bias.  The risk-of-bias was independently evaluated by 2 researchers (J.A. and H.C.) after discussing the evaluation criteria in advance. If a consensus was not reached, a third researcher (J.L.) intervened.   A meta-analysis was performed to quantitatively synthesize treatment effects by combining several clinical studies on the clinical effects of herbal medicine treatment for arrhythmias. The RevMan (Review Manager version 5.4.1, Cochrane, UK) program was used for meta-analysis. A meta-analysis was conducted when the study design, intervention method, and evaluation tool were appropriate for the quantitative synthesis of studies based on heterogeneity. The risk ratio (RR) was used for dichotomous outcomes, whereas weighted mean differences and 95% confidence intervals (CIs) were used for continuous outcomes. To assess the heterogeneity between studies based on the Higgins I 2 statistic, an I 2 > 50% indicated heterogeneity between studies. If considerable heterogeneity was identified, a random-effects model was used to synthesize the results.    A funnel plot was used to visually inspect publication bias in the included studies. Eggar’s test was used to analyze publication bias.   3.1. Study selection Among the 2921 articles, 82 were selected. The literature selection process was described using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow chart criteria (Fig. ). 3.2. Characteristics of the included studies All clinical studies were published in China. The general characteristics of the included studies are summarized in Table . 3.2.1. Included disease Of the 82 studies, 20 were conducted without categorizing specific arrhythmias using the word “arrhythmia.” In the remaining studies, 13 had AF or paroxysmal AF, 21 had bradycardia arrhythmia or sinus bradycardia, 9 had rapid arrhythmia or tachyarrhythmia, and 19 had ventricular arrhythmia or premature ventricular contractions (Table ). 3.2.2. Interventions Fifteen studies used a combination therapy group (THM and WM) and the control as the WM alone group. In the 59 RCTs, the THM-alone group (treatment group) was compared with the WM-alone group (control group). Eight studies compared the THM and WM groups with the Placebo THM and WM groups. Regarding conventional medications, propafenone was used in 14 RCTs, amiodarone in 13, atropine in seven, beta-blockers in five, mexiletine in six, salbutamol in one, ethmozine in one, and methotrexate in one. Six studies did not mention specific WM drugs in the control group and only mentioned that they used standard treatments. Detailed information on the herbal prescriptions, treatment duration, and composition of the herbal medicines is shown in Supplementary 2A, Supplemental Digital Content, http://links.lww.com/MD/M752 and 2B, Supplemental Digital Content, http://links.lww.com/MD/M753 . The most frequently used medicinal herb for arrhythmia treatment was Ophiopogonis Radix (Maidong, 麦冬, 64 times), Radix Astragali (Huangqi, 黄芪, 32 times), Ginseng Radix et Rhizoma (Renshen, 人蔘, 32 times), Salviae Miltiorrhizae Radix et Rhizoma (Danshen, 丹参, 32 times), Glycyrrhizae Radix et Rhizoma Praeparata cum Melle (Zhigancao, 炙甘草, 29 times), and Schisandrae Fructus (Wuweizi, 五味子, 27 times). 3.2.3. Treatment regimen Of the 78 studies in which dose information was specified, 35 reported doses 3 times per day (TID), 37 twice per day (bid), and six four times per day (QID). Among the 79 studies, 2 weeks were adopted in 13 RCTs, 3 weeks in 3 RCTs, 1 month in 44 RCTs, 1–2 months in 2 RCTs, 2 months in 4 RCTs, and 3 months in 10 RCTs. One study implemented treatments for 16 weeks (4 months), and 2 studies used treatments for 6 months (Table ). 3.2.4. Applied outcomes TER was the most common clinical outcome variable (77 RCTs) and HR (26 RCTs). Among studies that used Holter electrocardiography, 13 measured the number of premature ventricular contractions (PVC). Among the studies using electrocardiography, 7 measured PR time, 5 measured QRS time, and 8 measured QTc time. Three studies measured the total HR over 24 hours, and 1 study measured the size of the left ventricle using ultrasound. Three studies measured HR variability, 2 measured tachycardia, and one measured general arrhythmia (Table ). 3.3. Clinical effectiveness of herbal medicine in cardiac arrhythmia TER was used as the primary outcome measure. To analyze the treatment effect, the literature was classified into separate diseases such as arrhythmia, sinus bradycardia, tachycardia, AF, and PVC. The results were classified by comparing the effects of HM + WM versus placebo HM + WM, HM + WM versus WM, and HM versus WM. 3.3.1. (Unspecified) arrhythmia Among 20 RCTs for the unspecified arrhythmia subtype, the TER of the HM-only group or the HM + WM combined group was significantly higher than that of the WM group (RR: 1.20, 95% CI: 1.13–1.26, I 2 = 0%). In the HM versus WM design (19 RCTs), TER in the HM group was significantly higher than that in the WM group (RR: 1.20, 95% CI: 1.12–1.28). Only 1 study compared HM + WM with WM alone. The TER of the HM combined group was significantly higher than that of the WM group (RR: 1.20, 95% CI: 1.02–1.40) (Fig. ). The meta-analysis results for HR are represented in Supplementary 3A, Supplemental Digital Content, http://links.lww.com/MD/M754 . 3.3.2. Premature ventricular contractions Among the 18 RCTs for PVC treatment, the TER of the HM-only group or the HM + WM combined group was significantly higher than that of the WM group (RR: 1.29, 95% CI: 1.15–1.33). In 14 RCTs comparing HM and WM, the TER was significantly higher in the HM group (RR, 1.24; 95% CI: 1.15–1.33). In the HM + WM versus WM alone group design (4 RCTs), the TER of the combined group was higher than that of the WM alone group (RR: 1.45, 95% CI: 1.07–1.95) (Fig. ). The HR was not significantly different (Supplementary 3B, Supplemental Digital Content, http://links.lww.com/MD/M754 ). In 10 RCTs, the number of PVC was measured using a 24-h Holter electrocardiogram. The HM group or HM + WM combined group showed fewer times on average than that of the WM group (MD: −453.24, 95% CI: −592.38 to −314.09) (Fig. ). Liang 2020’s study discussed only the average number of PVCs and did not provide the standard deviation; thus, they were excluded from the meta-analysis. In the HM versus WM design (8 RCTs), the number of PVCs was less than that in the WM group (MD: −355.90, 95% CI: −488.32 to −223.47). In the HM + WM versus the WM design, the difference was not significant. 3.3.3. Sinus bradycardia Among the 18 studies targeting patients with bradycardia, the TER of the HM group was significantly higher than that of the WM group (15 RCTs) or the placebo HM group (3 RCTs) (RR: 1.26, 95% CI 1.17–1.36). In 15 RCTs comparing HM versus WM designs, the TER was higher in the HM group (RR, 1.22; 95% CI: 1.16–1.29). In the 3 RCTs using HM + WM versus placebo HM + WM designs, the TER was not significantly different (Fig. ). HR was measured in 12 RCTs among the 18 RCTs involving patients with bradycardia. The HR of the HM group was significantly higher than that of the WM group (6 RCTs) or the placebo HM group (3 RCTs). (MD: 5.25, 95% CI: 2.64–7.85). In 9 RCTs using the HM versus WM design, the HR was higher in the HM group than that in the WM group (MD: 6.07, 95% CI: 2.37–9.7). In 3 RCTs using HM + WM versus placebo HM + WM design, HR was higher in the HM group (MD: 3.07, 95% CI: 0.78–5.35) (Fig. ). 3.3.4. Tachycardia The overall meta-analysis of 9 RCTs revealed that HM treatment resulted in a higher TER than that in the control group (RR, 1.23; 95% CI: 1.15–1.32). In the HM versus WM group design (5 RCTs), the HM group showed a higher TER than that of the WM group (RR: 1.19, 95% CI: 1.09–1.29). In the case of the HM + WM versus WM group design (3 RCTs), TER was higher in the HM + WM group than that in the WM group (RR: 1.29, 95% CI: 1.12–1.48). In 1 study comparing HM + WM versus HM placebo + WM, the TER in the HM group was higher than that in the placebo HM group (RR: 1.86, 95% CI 1.24–2.79) (Fig. ). Outcome variables using electrocardiogram and HR variability, such as PR time, QT time, standard deviation of all NN intervals, and standard deviation of the averages of NN intervals, are represented in Supplementary 3C–G, Supplemental Digital Content, http://links.lww.com/MD/M754 . 3.3.5. Atrial fibrillation Thirteen studies included patients with AF. In 12 RCTs, the TER, HM alone, or HM + WM group showed better TER than that in the control group (RR: 1.17, 95% CI: 1.07–1.27). In the HM versus WM group design, TER was higher than that in the WM group (RR: 1.21, 95% CI: 1.04–1.41). In the HM + WM versus WM design, TER was higher in the HM + WM group than that in the WM group (RR: 1.13, 95% CI: 1.03–1.24) (Fig. ). Six studies used the HR/min as the outcome. HM with WM or HM alone showed decreased HR/min (RR: −6.97, 95% CI: −10.77 to −3.17). In 3 RCTs that adopted the HM versus WM design, the HM group had a lower HR than that of the WM group (RR: −7.93, 95% CI: −14.42 to −1.43). In the other 3 RCTs that used the HM + WM versus WM design, the HM + WM group showed less HR than that of the WM group (RR: −5.93, 95% CI: −11.29 to −0.64) (Fig. ). Decreased HR can be interpreted that HM has a positive effect of HM on AF.  3.4. Safety Among the 82 studies included in this review, only 37 reported adverse events. Of the 37 studies, 11 reported no adverse events in either the intervention or control group. Adverse reactions were reported in 26 studies, 6 of which reported no adverse effects in the intervention group. Among the side effects reported in the treatment group, nausea was the most common (7 cases), followed by gastrointestinal discomfort (4 cases), dizziness (4 cases), headache (3 cases), dry mouth (3 cases), anorexia (dyspepsia) (3 cases), and constipation (2 cases). The adverse effects of individual studies are reported in detail in Table . No serious adverse events associated with HM were reported. 3.5. Risk of bias The overall risk of bias across the articles reviewed in this study is shown in Figure and Supplementary 4, Supplemental Digital Content, http://links.lww.com/MD/M755 . As many studies have compared herbal medicine monotherapy, herbal medicine, and Western medicine combination therapy, the risk of bias for blinding was “high.” In addition, many studies often graded allocation concealment and random sequence generation as “unclear” due to ambiguous descriptions. The risk of bias was “low” for the remaining items. 3.6. Publication bias Publication bias was evaluated by visual inspection using a funnel plot (Supplementary 5A–O, Supplemental Digital Content, http://links.lww.com/MD/M756 ). Visual inspection revealed that the possibility of publication bias was relatively low.   Among the 2921 articles, 82 were selected. The literature selection process was described using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow chart criteria (Fig. ).   All clinical studies were published in China. The general characteristics of the included studies are summarized in Table . 3.2.1. Included disease Of the 82 studies, 20 were conducted without categorizing specific arrhythmias using the word “arrhythmia.” In the remaining studies, 13 had AF or paroxysmal AF, 21 had bradycardia arrhythmia or sinus bradycardia, 9 had rapid arrhythmia or tachyarrhythmia, and 19 had ventricular arrhythmia or premature ventricular contractions (Table ). 3.2.2. Interventions Fifteen studies used a combination therapy group (THM and WM) and the control as the WM alone group. In the 59 RCTs, the THM-alone group (treatment group) was compared with the WM-alone group (control group). Eight studies compared the THM and WM groups with the Placebo THM and WM groups. Regarding conventional medications, propafenone was used in 14 RCTs, amiodarone in 13, atropine in seven, beta-blockers in five, mexiletine in six, salbutamol in one, ethmozine in one, and methotrexate in one. Six studies did not mention specific WM drugs in the control group and only mentioned that they used standard treatments. Detailed information on the herbal prescriptions, treatment duration, and composition of the herbal medicines is shown in Supplementary 2A, Supplemental Digital Content, http://links.lww.com/MD/M752 and 2B, Supplemental Digital Content, http://links.lww.com/MD/M753 . The most frequently used medicinal herb for arrhythmia treatment was Ophiopogonis Radix (Maidong, 麦冬, 64 times), Radix Astragali (Huangqi, 黄芪, 32 times), Ginseng Radix et Rhizoma (Renshen, 人蔘, 32 times), Salviae Miltiorrhizae Radix et Rhizoma (Danshen, 丹参, 32 times), Glycyrrhizae Radix et Rhizoma Praeparata cum Melle (Zhigancao, 炙甘草, 29 times), and Schisandrae Fructus (Wuweizi, 五味子, 27 times). 3.2.3. Treatment regimen Of the 78 studies in which dose information was specified, 35 reported doses 3 times per day (TID), 37 twice per day (bid), and six four times per day (QID). Among the 79 studies, 2 weeks were adopted in 13 RCTs, 3 weeks in 3 RCTs, 1 month in 44 RCTs, 1–2 months in 2 RCTs, 2 months in 4 RCTs, and 3 months in 10 RCTs. One study implemented treatments for 16 weeks (4 months), and 2 studies used treatments for 6 months (Table ). 3.2.4. Applied outcomes TER was the most common clinical outcome variable (77 RCTs) and HR (26 RCTs). Among studies that used Holter electrocardiography, 13 measured the number of premature ventricular contractions (PVC). Among the studies using electrocardiography, 7 measured PR time, 5 measured QRS time, and 8 measured QTc time. Three studies measured the total HR over 24 hours, and 1 study measured the size of the left ventricle using ultrasound. Three studies measured HR variability, 2 measured tachycardia, and one measured general arrhythmia (Table ).   Of the 82 studies, 20 were conducted without categorizing specific arrhythmias using the word “arrhythmia.” In the remaining studies, 13 had AF or paroxysmal AF, 21 had bradycardia arrhythmia or sinus bradycardia, 9 had rapid arrhythmia or tachyarrhythmia, and 19 had ventricular arrhythmia or premature ventricular contractions (Table ).   Fifteen studies used a combination therapy group (THM and WM) and the control as the WM alone group. In the 59 RCTs, the THM-alone group (treatment group) was compared with the WM-alone group (control group). Eight studies compared the THM and WM groups with the Placebo THM and WM groups. Regarding conventional medications, propafenone was used in 14 RCTs, amiodarone in 13, atropine in seven, beta-blockers in five, mexiletine in six, salbutamol in one, ethmozine in one, and methotrexate in one. Six studies did not mention specific WM drugs in the control group and only mentioned that they used standard treatments. Detailed information on the herbal prescriptions, treatment duration, and composition of the herbal medicines is shown in Supplementary 2A, Supplemental Digital Content, http://links.lww.com/MD/M752 and 2B, Supplemental Digital Content, http://links.lww.com/MD/M753 . The most frequently used medicinal herb for arrhythmia treatment was Ophiopogonis Radix (Maidong, 麦冬, 64 times), Radix Astragali (Huangqi, 黄芪, 32 times), Ginseng Radix et Rhizoma (Renshen, 人蔘, 32 times), Salviae Miltiorrhizae Radix et Rhizoma (Danshen, 丹参, 32 times), Glycyrrhizae Radix et Rhizoma Praeparata cum Melle (Zhigancao, 炙甘草, 29 times), and Schisandrae Fructus (Wuweizi, 五味子, 27 times).   Of the 78 studies in which dose information was specified, 35 reported doses 3 times per day (TID), 37 twice per day (bid), and six four times per day (QID). Among the 79 studies, 2 weeks were adopted in 13 RCTs, 3 weeks in 3 RCTs, 1 month in 44 RCTs, 1–2 months in 2 RCTs, 2 months in 4 RCTs, and 3 months in 10 RCTs. One study implemented treatments for 16 weeks (4 months), and 2 studies used treatments for 6 months (Table ).   TER was the most common clinical outcome variable (77 RCTs) and HR (26 RCTs). Among studies that used Holter electrocardiography, 13 measured the number of premature ventricular contractions (PVC). Among the studies using electrocardiography, 7 measured PR time, 5 measured QRS time, and 8 measured QTc time. Three studies measured the total HR over 24 hours, and 1 study measured the size of the left ventricle using ultrasound. Three studies measured HR variability, 2 measured tachycardia, and one measured general arrhythmia (Table ).   TER was used as the primary outcome measure. To analyze the treatment effect, the literature was classified into separate diseases such as arrhythmia, sinus bradycardia, tachycardia, AF, and PVC. The results were classified by comparing the effects of HM + WM versus placebo HM + WM, HM + WM versus WM, and HM versus WM. 3.3.1. (Unspecified) arrhythmia Among 20 RCTs for the unspecified arrhythmia subtype, the TER of the HM-only group or the HM + WM combined group was significantly higher than that of the WM group (RR: 1.20, 95% CI: 1.13–1.26, I 2 = 0%). In the HM versus WM design (19 RCTs), TER in the HM group was significantly higher than that in the WM group (RR: 1.20, 95% CI: 1.12–1.28). Only 1 study compared HM + WM with WM alone. The TER of the HM combined group was significantly higher than that of the WM group (RR: 1.20, 95% CI: 1.02–1.40) (Fig. ). The meta-analysis results for HR are represented in Supplementary 3A, Supplemental Digital Content, http://links.lww.com/MD/M754 . 3.3.2. Premature ventricular contractions Among the 18 RCTs for PVC treatment, the TER of the HM-only group or the HM + WM combined group was significantly higher than that of the WM group (RR: 1.29, 95% CI: 1.15–1.33). In 14 RCTs comparing HM and WM, the TER was significantly higher in the HM group (RR, 1.24; 95% CI: 1.15–1.33). In the HM + WM versus WM alone group design (4 RCTs), the TER of the combined group was higher than that of the WM alone group (RR: 1.45, 95% CI: 1.07–1.95) (Fig. ). The HR was not significantly different (Supplementary 3B, Supplemental Digital Content, http://links.lww.com/MD/M754 ). In 10 RCTs, the number of PVC was measured using a 24-h Holter electrocardiogram. The HM group or HM + WM combined group showed fewer times on average than that of the WM group (MD: −453.24, 95% CI: −592.38 to −314.09) (Fig. ). Liang 2020’s study discussed only the average number of PVCs and did not provide the standard deviation; thus, they were excluded from the meta-analysis. In the HM versus WM design (8 RCTs), the number of PVCs was less than that in the WM group (MD: −355.90, 95% CI: −488.32 to −223.47). In the HM + WM versus the WM design, the difference was not significant. 3.3.3. Sinus bradycardia Among the 18 studies targeting patients with bradycardia, the TER of the HM group was significantly higher than that of the WM group (15 RCTs) or the placebo HM group (3 RCTs) (RR: 1.26, 95% CI 1.17–1.36). In 15 RCTs comparing HM versus WM designs, the TER was higher in the HM group (RR, 1.22; 95% CI: 1.16–1.29). In the 3 RCTs using HM + WM versus placebo HM + WM designs, the TER was not significantly different (Fig. ). HR was measured in 12 RCTs among the 18 RCTs involving patients with bradycardia. The HR of the HM group was significantly higher than that of the WM group (6 RCTs) or the placebo HM group (3 RCTs). (MD: 5.25, 95% CI: 2.64–7.85). In 9 RCTs using the HM versus WM design, the HR was higher in the HM group than that in the WM group (MD: 6.07, 95% CI: 2.37–9.7). In 3 RCTs using HM + WM versus placebo HM + WM design, HR was higher in the HM group (MD: 3.07, 95% CI: 0.78–5.35) (Fig. ). 3.3.4. Tachycardia The overall meta-analysis of 9 RCTs revealed that HM treatment resulted in a higher TER than that in the control group (RR, 1.23; 95% CI: 1.15–1.32). In the HM versus WM group design (5 RCTs), the HM group showed a higher TER than that of the WM group (RR: 1.19, 95% CI: 1.09–1.29). In the case of the HM + WM versus WM group design (3 RCTs), TER was higher in the HM + WM group than that in the WM group (RR: 1.29, 95% CI: 1.12–1.48). In 1 study comparing HM + WM versus HM placebo + WM, the TER in the HM group was higher than that in the placebo HM group (RR: 1.86, 95% CI 1.24–2.79) (Fig. ). Outcome variables using electrocardiogram and HR variability, such as PR time, QT time, standard deviation of all NN intervals, and standard deviation of the averages of NN intervals, are represented in Supplementary 3C–G, Supplemental Digital Content, http://links.lww.com/MD/M754 . 3.3.5. Atrial fibrillation Thirteen studies included patients with AF. In 12 RCTs, the TER, HM alone, or HM + WM group showed better TER than that in the control group (RR: 1.17, 95% CI: 1.07–1.27). In the HM versus WM group design, TER was higher than that in the WM group (RR: 1.21, 95% CI: 1.04–1.41). In the HM + WM versus WM design, TER was higher in the HM + WM group than that in the WM group (RR: 1.13, 95% CI: 1.03–1.24) (Fig. ). Six studies used the HR/min as the outcome. HM with WM or HM alone showed decreased HR/min (RR: −6.97, 95% CI: −10.77 to −3.17). In 3 RCTs that adopted the HM versus WM design, the HM group had a lower HR than that of the WM group (RR: −7.93, 95% CI: −14.42 to −1.43). In the other 3 RCTs that used the HM + WM versus WM design, the HM + WM group showed less HR than that of the WM group (RR: −5.93, 95% CI: −11.29 to −0.64) (Fig. ). Decreased HR can be interpreted that HM has a positive effect of HM on AF.    Among 20 RCTs for the unspecified arrhythmia subtype, the TER of the HM-only group or the HM + WM combined group was significantly higher than that of the WM group (RR: 1.20, 95% CI: 1.13–1.26, I 2 = 0%). In the HM versus WM design (19 RCTs), TER in the HM group was significantly higher than that in the WM group (RR: 1.20, 95% CI: 1.12–1.28). Only 1 study compared HM + WM with WM alone. The TER of the HM combined group was significantly higher than that of the WM group (RR: 1.20, 95% CI: 1.02–1.40) (Fig. ). The meta-analysis results for HR are represented in Supplementary 3A, Supplemental Digital Content, http://links.lww.com/MD/M754 .   Among the 18 RCTs for PVC treatment, the TER of the HM-only group or the HM + WM combined group was significantly higher than that of the WM group (RR: 1.29, 95% CI: 1.15–1.33). In 14 RCTs comparing HM and WM, the TER was significantly higher in the HM group (RR, 1.24; 95% CI: 1.15–1.33). In the HM + WM versus WM alone group design (4 RCTs), the TER of the combined group was higher than that of the WM alone group (RR: 1.45, 95% CI: 1.07–1.95) (Fig. ). The HR was not significantly different (Supplementary 3B, Supplemental Digital Content, http://links.lww.com/MD/M754 ). In 10 RCTs, the number of PVC was measured using a 24-h Holter electrocardiogram. The HM group or HM + WM combined group showed fewer times on average than that of the WM group (MD: −453.24, 95% CI: −592.38 to −314.09) (Fig. ). Liang 2020’s study discussed only the average number of PVCs and did not provide the standard deviation; thus, they were excluded from the meta-analysis. In the HM versus WM design (8 RCTs), the number of PVCs was less than that in the WM group (MD: −355.90, 95% CI: −488.32 to −223.47). In the HM + WM versus the WM design, the difference was not significant.   Among the 18 studies targeting patients with bradycardia, the TER of the HM group was significantly higher than that of the WM group (15 RCTs) or the placebo HM group (3 RCTs) (RR: 1.26, 95% CI 1.17–1.36). In 15 RCTs comparing HM versus WM designs, the TER was higher in the HM group (RR, 1.22; 95% CI: 1.16–1.29). In the 3 RCTs using HM + WM versus placebo HM + WM designs, the TER was not significantly different (Fig. ). HR was measured in 12 RCTs among the 18 RCTs involving patients with bradycardia. The HR of the HM group was significantly higher than that of the WM group (6 RCTs) or the placebo HM group (3 RCTs). (MD: 5.25, 95% CI: 2.64–7.85). In 9 RCTs using the HM versus WM design, the HR was higher in the HM group than that in the WM group (MD: 6.07, 95% CI: 2.37–9.7). In 3 RCTs using HM + WM versus placebo HM + WM design, HR was higher in the HM group (MD: 3.07, 95% CI: 0.78–5.35) (Fig. ).   The overall meta-analysis of 9 RCTs revealed that HM treatment resulted in a higher TER than that in the control group (RR, 1.23; 95% CI: 1.15–1.32). In the HM versus WM group design (5 RCTs), the HM group showed a higher TER than that of the WM group (RR: 1.19, 95% CI: 1.09–1.29). In the case of the HM + WM versus WM group design (3 RCTs), TER was higher in the HM + WM group than that in the WM group (RR: 1.29, 95% CI: 1.12–1.48). In 1 study comparing HM + WM versus HM placebo + WM, the TER in the HM group was higher than that in the placebo HM group (RR: 1.86, 95% CI 1.24–2.79) (Fig. ). Outcome variables using electrocardiogram and HR variability, such as PR time, QT time, standard deviation of all NN intervals, and standard deviation of the averages of NN intervals, are represented in Supplementary 3C–G, Supplemental Digital Content, http://links.lww.com/MD/M754 .   Thirteen studies included patients with AF. In 12 RCTs, the TER, HM alone, or HM + WM group showed better TER than that in the control group (RR: 1.17, 95% CI: 1.07–1.27). In the HM versus WM group design, TER was higher than that in the WM group (RR: 1.21, 95% CI: 1.04–1.41). In the HM + WM versus WM design, TER was higher in the HM + WM group than that in the WM group (RR: 1.13, 95% CI: 1.03–1.24) (Fig. ). Six studies used the HR/min as the outcome. HM with WM or HM alone showed decreased HR/min (RR: −6.97, 95% CI: −10.77 to −3.17). In 3 RCTs that adopted the HM versus WM design, the HM group had a lower HR than that of the WM group (RR: −7.93, 95% CI: −14.42 to −1.43). In the other 3 RCTs that used the HM + WM versus WM design, the HM + WM group showed less HR than that of the WM group (RR: −5.93, 95% CI: −11.29 to −0.64) (Fig. ). Decreased HR can be interpreted that HM has a positive effect of HM on AF.    Among the 82 studies included in this review, only 37 reported adverse events. Of the 37 studies, 11 reported no adverse events in either the intervention or control group. Adverse reactions were reported in 26 studies, 6 of which reported no adverse effects in the intervention group. Among the side effects reported in the treatment group, nausea was the most common (7 cases), followed by gastrointestinal discomfort (4 cases), dizziness (4 cases), headache (3 cases), dry mouth (3 cases), anorexia (dyspepsia) (3 cases), and constipation (2 cases). The adverse effects of individual studies are reported in detail in Table . No serious adverse events associated with HM were reported.   The overall risk of bias across the articles reviewed in this study is shown in Figure and Supplementary 4, Supplemental Digital Content, http://links.lww.com/MD/M755 . As many studies have compared herbal medicine monotherapy, herbal medicine, and Western medicine combination therapy, the risk of bias for blinding was “high.” In addition, many studies often graded allocation concealment and random sequence generation as “unclear” due to ambiguous descriptions. The risk of bias was “low” for the remaining items.   Publication bias was evaluated by visual inspection using a funnel plot (Supplementary 5A–O, Supplemental Digital Content, http://links.lww.com/MD/M756 ). Visual inspection revealed that the possibility of publication bias was relatively low.   4.1. Summary of findings This study investigated RCTs of herbal prescriptions for arrhythmias. A total of 82 studies were included in this systematic review and meta-analysis. Our results showed that the TER for unclassified arrhythmias, PVC, sinus bradycardia, tachycardia, and AF was higher in the HM group than that in the control group. The results of the analysis of the individual arrhythmia types were as follows. The number of 24-h PVCs was significantly lower in the intervention group than that in the control group. In patients with sinus bradycardia, the HR was higher in the intervention group than that in the control group. In studies involving patients with tachycardia, the HR was significantly lower in the HM group than that in the control group. Additionally, autonomic parameters, such as standard deviation of all NN intervals, were higher in the intervention group than that in the control group. In studies of patients with AF, the HR and ECG indices related to the risk of AF were lower in the intervention group than those in the control group. No serious adverse events associated with the herbal medicine treatments have been reported. 4.2. Debates: implication for clinical practice and theoretical basis Arrhythmia is one of the 3 major heart diseases with an increasing incidence worldwide. Western medical treatments for arrhythmia include anticoagulants and antiarrhythmic drugs. If the drugs are ineffective, radiofrequency catheter ablation or pacemakers are used. Amiodarone is a widely used conventional medication to treat tachycardia; however, it has been associated with adverse effects, such as sinus bradycardia and toxicity in several studies.  Non-pharmacological treatment for arrhythmia may lead to complications, such as postoperative infections, and can cause difficulties in postoperative magnetic resonance imaging. Moreover, the eligibility criteria for non-pharmacological treatment are limited.  However, traditional East Asian medicines have a long history of treating cardiac disease. Various studies have reported the effects of herbal medicine, acupuncture, moxibustion, and external preparations for the treatment of symptoms related to arrhythmias, such as fatigue, chest pain, and anxiety.  However, previous systematic reviews and meta-analyses of herbal medicines on arrhythmias only investigated individual-specific herbal prescriptions or a certain subtype of arrhythmia, leading to a lack of a comprehensive overview of arrhythmia treatment with HTM.  Therefore, this study provides quantitative evidence on the effects of herbal medicines on arrhythmia treatment for clinicians. The results of this study will be helpful in the decision-making of traditional medicine physicians treating cardiac disorders. However, our study did not focus on specific subgroups (by sex or age). Therefore, further studies are warranted to identify subgroup effects. Regarding safety, among the 37 studies, only 11 reported no adverse events in either the intervention or control group. Most reported adverse events were digestive system side effects, and no serious adverse events were observed. The herbs most commonly used for treating arrhythmia include Opiopogonis radix (Maidong), Radix Astragali (Huangqi), Ginseng Radix et Rhizoma (Renshen), Salviae Miltiorrhizae (Danshen), Glycyrrhizae Radix et Rhizoma Praeparata cum Melle (Zhigancao), and Schisandrae Fructus (Wuweizi). These medicinal herbs are widely used in TEAM to manage heart diseases. Sheng-Mai-San, a representative TCM prescription for cardiac disease composed of Maidong, Renshen, and Wuweiz, is effective against myocardial ischemic injury.  Renshen is well known for its effects on cardiovascular diseases, including arrhythmia, by regulating Ca 2+ channels.  Zhigancao acts on the HERG (K+) channels of cardiomyocytes to control abnormal heartbeats, such as tachycardia. Wuweizi regulates NCOR2 and NFAT expression to repair heart cell damage. Gosam contains oxymatrine, which protects blood vessels and acts on calcium and potassium channels, thereby improving heart function.  4.3. Suggestions for further research In most studies, the only reported outcome variable was TER, and no specific clinical outcome was adequate for specific arrhythmia subtypes. Disease-specific clinical endpoints that require long-term follow-up should be included in RCTs.  In future studies, long-term follow-up of clinical endpoints related to AF, such as cardiac death, stroke, heart failure, hospitalization, and emergency room visits, should be considered. Moreover, various core outcome sets have been developed for herbal medicine studies on heart disease.  Future herbal medicine studies should adopt core outcome sets related to AF. In a few studies, inappropriate electrophysiological indices were used. Increased PR and QTc times on ECG were associated with increased AF risk. However, in such cases, PR and QTc time are used as indicators of risk rather than as indicators of treatment effects.  In our review, studies used PR and QTc time to determine the effect of herbal medicine on AF, which is not an appropriate index for the treatment effect. Autonomic parameters such as HR variability, which are associated with long-term prognosis, can be considered. In future studies, qualitative research methodologies should be considered to explain changes in the QoL and satisfaction of participants, which will promote an in-depth understanding of the effects and expectations of TEAM management.  Several problems have been identified in disease diagnosis. In our meta-analysis, 20 studies defined arrhythmia without specific definitions or subtypes, such as AF and sinus bradycardia. In future studies, arrhythmia subtypes should be classified in greater detail. Regarding the treatment regimens, most studies adopted standardized and semi-standardized prescriptions. Therefore, more pragmatic clinical trials on the effects of traditional medicine therapy are needed.  Several studies have not mentioned adverse events, emphasizing the importance of reporting the safety of the intervention. Cases have been reported in which the indiscriminate use of THM without proper diagnosis and prescription by a traditional practitioner resulted in liver damage. Furthermore, future studies should conduct adverse event reporting using standardized questionnaires to distinguish cases or concerns regarding DILI from existing natural medicines.  4.4. Limitations and strengths This study has several limitations. We did not analyze the specific formulation effects of herbal medicines such as liquids, extracts, and powders. In future studies, we could adopt a network meta-analysis method to explore the treatment effects according to the formulation and administration route. However, we did not compare the effects of the herbal prescriptions. Based on these results, we evaluated the effects of each herbal medicine using a network meta-analysis method in further study. In addition, only a small number of studies on the specific outcomes of specific arrhythmia subtypes were included. Finally, the follow-up periods of the included studies were relatively short. Real-world studies are required to overcome the limitations associated with the length of each clinical trial. However, this study had several strengths. To the best of our knowledge, this is the first study to comprehensively review the effects and safety of various herbal medicines on AF. In a previous study on sinus bradycardia, only 6 herbal prescriptions were investigated.  In previous studies, only specific herbal prescriptions were evaluated, whereas various herbal prescriptions were included in this study. In other studies, there were certain flaws in the search strategy that just used “AF” and “Chinese Medicine” as the search terms to generate search formulas, which limited the number of studies included.  In our study, a wider range of search strategies was applied.   This study investigated RCTs of herbal prescriptions for arrhythmias. A total of 82 studies were included in this systematic review and meta-analysis. Our results showed that the TER for unclassified arrhythmias, PVC, sinus bradycardia, tachycardia, and AF was higher in the HM group than that in the control group. The results of the analysis of the individual arrhythmia types were as follows. The number of 24-h PVCs was significantly lower in the intervention group than that in the control group. In patients with sinus bradycardia, the HR was higher in the intervention group than that in the control group. In studies involving patients with tachycardia, the HR was significantly lower in the HM group than that in the control group. Additionally, autonomic parameters, such as standard deviation of all NN intervals, were higher in the intervention group than that in the control group. In studies of patients with AF, the HR and ECG indices related to the risk of AF were lower in the intervention group than those in the control group. No serious adverse events associated with the herbal medicine treatments have been reported.   Arrhythmia is one of the 3 major heart diseases with an increasing incidence worldwide. Western medical treatments for arrhythmia include anticoagulants and antiarrhythmic drugs. If the drugs are ineffective, radiofrequency catheter ablation or pacemakers are used. Amiodarone is a widely used conventional medication to treat tachycardia; however, it has been associated with adverse effects, such as sinus bradycardia and toxicity in several studies.  Non-pharmacological treatment for arrhythmia may lead to complications, such as postoperative infections, and can cause difficulties in postoperative magnetic resonance imaging. Moreover, the eligibility criteria for non-pharmacological treatment are limited.  However, traditional East Asian medicines have a long history of treating cardiac disease. Various studies have reported the effects of herbal medicine, acupuncture, moxibustion, and external preparations for the treatment of symptoms related to arrhythmias, such as fatigue, chest pain, and anxiety.  However, previous systematic reviews and meta-analyses of herbal medicines on arrhythmias only investigated individual-specific herbal prescriptions or a certain subtype of arrhythmia, leading to a lack of a comprehensive overview of arrhythmia treatment with HTM.  Therefore, this study provides quantitative evidence on the effects of herbal medicines on arrhythmia treatment for clinicians. The results of this study will be helpful in the decision-making of traditional medicine physicians treating cardiac disorders. However, our study did not focus on specific subgroups (by sex or age). Therefore, further studies are warranted to identify subgroup effects. Regarding safety, among the 37 studies, only 11 reported no adverse events in either the intervention or control group. Most reported adverse events were digestive system side effects, and no serious adverse events were observed. The herbs most commonly used for treating arrhythmia include Opiopogonis radix (Maidong), Radix Astragali (Huangqi), Ginseng Radix et Rhizoma (Renshen), Salviae Miltiorrhizae (Danshen), Glycyrrhizae Radix et Rhizoma Praeparata cum Melle (Zhigancao), and Schisandrae Fructus (Wuweizi). These medicinal herbs are widely used in TEAM to manage heart diseases. Sheng-Mai-San, a representative TCM prescription for cardiac disease composed of Maidong, Renshen, and Wuweiz, is effective against myocardial ischemic injury.  Renshen is well known for its effects on cardiovascular diseases, including arrhythmia, by regulating Ca 2+ channels.  Zhigancao acts on the HERG (K+) channels of cardiomyocytes to control abnormal heartbeats, such as tachycardia. Wuweizi regulates NCOR2 and NFAT expression to repair heart cell damage. Gosam contains oxymatrine, which protects blood vessels and acts on calcium and potassium channels, thereby improving heart function.    In most studies, the only reported outcome variable was TER, and no specific clinical outcome was adequate for specific arrhythmia subtypes. Disease-specific clinical endpoints that require long-term follow-up should be included in RCTs.  In future studies, long-term follow-up of clinical endpoints related to AF, such as cardiac death, stroke, heart failure, hospitalization, and emergency room visits, should be considered. Moreover, various core outcome sets have been developed for herbal medicine studies on heart disease.  Future herbal medicine studies should adopt core outcome sets related to AF. In a few studies, inappropriate electrophysiological indices were used. Increased PR and QTc times on ECG were associated with increased AF risk. However, in such cases, PR and QTc time are used as indicators of risk rather than as indicators of treatment effects.  In our review, studies used PR and QTc time to determine the effect of herbal medicine on AF, which is not an appropriate index for the treatment effect. Autonomic parameters such as HR variability, which are associated with long-term prognosis, can be considered. In future studies, qualitative research methodologies should be considered to explain changes in the QoL and satisfaction of participants, which will promote an in-depth understanding of the effects and expectations of TEAM management.  Several problems have been identified in disease diagnosis. In our meta-analysis, 20 studies defined arrhythmia without specific definitions or subtypes, such as AF and sinus bradycardia. In future studies, arrhythmia subtypes should be classified in greater detail. Regarding the treatment regimens, most studies adopted standardized and semi-standardized prescriptions. Therefore, more pragmatic clinical trials on the effects of traditional medicine therapy are needed.  Several studies have not mentioned adverse events, emphasizing the importance of reporting the safety of the intervention. Cases have been reported in which the indiscriminate use of THM without proper diagnosis and prescription by a traditional practitioner resulted in liver damage. Furthermore, future studies should conduct adverse event reporting using standardized questionnaires to distinguish cases or concerns regarding DILI from existing natural medicines.    This study has several limitations. We did not analyze the specific formulation effects of herbal medicines such as liquids, extracts, and powders. In future studies, we could adopt a network meta-analysis method to explore the treatment effects according to the formulation and administration route. However, we did not compare the effects of the herbal prescriptions. Based on these results, we evaluated the effects of each herbal medicine using a network meta-analysis method in further study. In addition, only a small number of studies on the specific outcomes of specific arrhythmia subtypes were included. Finally, the follow-up periods of the included studies were relatively short. Real-world studies are required to overcome the limitations associated with the length of each clinical trial. However, this study had several strengths. To the best of our knowledge, this is the first study to comprehensively review the effects and safety of various herbal medicines on AF. In a previous study on sinus bradycardia, only 6 herbal prescriptions were investigated.  In previous studies, only specific herbal prescriptions were evaluated, whereas various herbal prescriptions were included in this study. In other studies, there were certain flaws in the search strategy that just used “AF” and “Chinese Medicine” as the search terms to generate search formulas, which limited the number of studies included.  In our study, a wider range of search strategies was applied.   Various herbal medicines have clinical advantages in improving arrhythmia-related symptoms. Herbal medicine combination therapy may be an effective addition to the currently available conventional arrhythmia medications without severe adverse events. Therefore, future studies should adopt disease-specific outcome variables. Considering the low methodological quality of individual studies, large-scale, long-term follow-up, and rigorous clinical studies on the effects of herbal medicine on arrhythmia are warranted. Our results provide useful fundamental data for future study design by researchers and decision-making by clinicians.   This paper was modified from research projects included in the thesis of the first author, Jae-yoon Ahn, translated into English and submitted.   Data curation: Jae-yoon Ahn, Hongmin Chu. Methodology: Jungtae Leem. Supervision: Jungtae Leem. Writing – original draft: Jae-yoon Ahn, Hongmin Chu. Writing – review & editing: Jong-Min Yun, Jungtae Leem.      