Heart failure as a substrate and trigger for ventricular tachycardia.

Heart failure (HF) is a major cause of morbidity and mortality with more than 5.1 million individuals affected in the USA. Ventricular tachyarrhythmias (VAs) including ventricular tachycardia and ventricular fibrillation are common in patients with heart failure. The pathophysiology of these mechanisms as well as the contribution of heart failure to the genesis of these arrhythmias is complex and multifaceted. Myocardial hypertrophy and stretch with increased preload and afterload lead to shortening of the action potential at early repolarization and lengthening of the action potential at final repolarization which can result in re-entrant ventricular tachycardia. Myocardial fibrosis and scar can create the substrate for re-entrant ventricular tachycardia. Altered calcium handling in the failing heart can lead to the development of proarrhythmic early and delayed after depolarizations. Various medications used in the treatment of HF such as loop diuretics and angiotensin converting enzyme inhibitors have not demonstrated a reduction in sudden cardiac death (SCD); however, beta-blockers (BB) are effective in reducing mortality and SCD. Amongst patients who have HF with reduced ejection fraction, the angiotensin receptor-neprilysin inhibitor (sacubitril/valsartan) has been shown to reduce cardiovascular mortality, specifically by reducing SCD, as well as death due to worsening HF. Implantable cardioverter-defibrillator (ICD) implantation in HF patients reduces the risk of SCD; however, subsequent mortality is increased in those who receive ICD shocks. Prophylactic ICD implantation reduces death from arrhythmia but does not reduce overall mortality during the acute post-myocardial infarction (MI) period (less than 40 days), for those with reduced ejection fraction and impaired autonomic dysfunction. Furthermore, although death from arrhythmias is reduced, this is offset by an increase in the mortality from non-arrhythmic causes. This article provides a review of the aforementioned mechanisms of arrhythmogenesis in heart failure; the role and impact of HF therapy such as cardiac resynchronization therapy (CRT), including the role, if any, of CRT-P and CRT-D in preventing VAs; the utility of both non-invasive parameters as well as multiple implant-based parameters for telemonitoring in HF; and the effect of left ventricular assist device implantation on VAs.

Ventricular electrical delay as a predictor of arrhythmias in patients with cardiac resynchronization implantable cardioverter defibrillator.

BACKGROUND: Left ventricular (LV) remodeling and clinical response to cardiac resynchronization therapy (CRT) is inversely related to electrical dyssynchrony, measured as LV lead electrical delay (QLV). Presence of atrial or ventricular arrhythmia is correlated with worsening heart failure and LV remodeling. OBJECTIVE: We sought to assess the association of QLV with arrhythmic events in CRT recipients. METHODS: We identified patients implanted with a CRT device at our center. QLV interval was measured and corrected for baseline QRS (cQLV). We performed multivariable Logistic regression to assess the effect of cQLV on the occurrence of atrial/ventricular arrhythmic events. RESULTS: Sixty-nine patients were included in analyses. The cQLV was significantly shorter in patients with atria tachycardia/supraventricular tachycardia (AT/SVT) events compared to patients without AT/SVT events (43.4 ± 22% vs. 60.3 ± 26.7%, p = .006). In contrast, no significant difference in cQLV was observed between patients with and without ventricular tachycardia/fibrillation (VT/VF) events (46.2 ± 25.4% vs. 56 ± 25.7%, p = .13). cQLV was significantly shorter in patients with new onset AT/SVT events compared to those without (38.3 ± 22.2% vs. 55.7 ± 25.7%, p = .028). In contrast, no significant difference in cQLV was observed between patients with and without new onset VT/VF events (44.2 ± 25.2% vs. 56.3 ± 25.5%, p = .069). Following adjusted analyses, cQLV was a significant predictor of AT/SVT, but not for VT/VF. CONCLUSION: cQLV is a simple measure that can identify a vulnerable cohort of CRT patients at increased risk for atrial tachyarrhythmias, and hence can predict reverse remodeling and clinical response to CRT treatment.

Physical activity is associated with positive responses during carotid sinus massage and head-up tilt-table test in patients with unexplained syncope.

AIMS: Physical exercise is known to alter the physiological response to orthostatic stress. This study compared reported physical activity levels in patients with unexplained syncope who did or did not demonstrate positive responses to carotid sinus massage and head-up tilt-table testing. METHODS: We reviewed the records of 1,336 patients with unexplained syncope who underwent carotid sinus massage and head-up tilt-table testing. Patients with positive responses (cases) were compared with patients with negative responses (controls). Multivariable regression analysis was used to identify independent predictors of positive responses to carotid sinus massage and head-up tilt-table testing. RESULTS: Seventy patients had a positive response to carotid sinus massage and 564 patients had a positive response to head-up tilt-table testing. Physical activity was an independent positive predictor of a positive response to both carotid sinus massage {adjusted odds ratio (AOR) 1.86, 95% CI (1.14-3.05); p = 0.01} and head-up tilt-table testing {AOR 1.31, 95% CI (1.04-1.65); P = 0.02} even after adjustment for multiple other factors including age, gender, and other medical conditions. CONCLUSION: Physical activity is associated with greater likelihood of positive responses during carotid sinus massage and head-up tilt-table testing.

Magnesium adjunctive therapy in atrial arrhythmias.

Magnesium (Mg) is an important intracellular ion with cardiac metabolism and electrophysiologic properties. A large percentage of patients with arrhythmias have an intracellular Mg deficiency, which is out of line with serum Mg concentrations, and this may explain the rationale for Mg's benefits as an atrial antiarrhythmic agent. A current limitation of antiarrhythmic therapy is that the potential for cardiac risk offsets some of the benefits of therapy. Mg enhances the balance of benefits to harms by enhancing atrial antiarrhythmic efficacy and reducing antiarrhythmic proarrhythmia potential as well as providing direct antiarrhythmic efficacy when used as monotherapy in patients undergoing cardiothoracic surgery.

Cost-effectiveness of apixaban compared with aspirin for stroke prevention in atrial fibrillation among patients unsuitable for warfarin.

BACKGROUND: Compared with aspirin, apixaban reduces stroke risk in atrial fibrillation (AF) patients unsuitable for warfarin by 63% but does not increase major bleeding. We sought to determine the cost-effectiveness of apixaban versus aspirin. METHODS AND RESULTS: Using the Apixaban versus Acetylsalicylic Acid to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin-K Antagonist Treatment (AVERROES) trial and other studies, we constructed a Markov model to evaluate the costs (2011US$), quality-adjusted life-years (QALYs), and incremental cost-effectiveness of apixaban versus aspirin from the Medicare perspective. Our base-case assumed a 70-year-old AF patient cohort with a CHADS(2) score=2 and a lower-risk of bleeding. We used a 1-month cycle-length and ran separate base-case analyses assuming a trial-length (1-year) and a longer-term (10-year) follow-up. Total costs/patient were $3454 and $1805 for apixaban and aspirin in the trial-length and $44 232 and $50 066 in the 10-year model. Corresponding QALYs were 0.96 and 0.96 in the trial-length and 6.87 and 6.51 in the 10-year model, making apixaban inferior in the first model but dominant in the latter. Conclusions were sensitive to baseline stroke rate in both models, and the monthly cost of major stroke, relative risk of stroke, and prior vitamin-K antagonist use in the life-time model. Probabilistic sensitivity analysis suggested apixaban would only be a cost-effective alternative (<$50 000/QALY) to aspirin 11% of the time in the trial-length model, but cost-effective or dominant 96.7% and 87.5% of iterations in the 10-year model. CONCLUSIONS: In our trial-length model, apixaban was more costly and no more effective than aspirin; however, as follow-up was extended, apixaban became cost-effective and eventually dominant.

Cost-effectiveness of clopidogrel plus aspirin for stroke prevention in patients with atrial fibrillation in whom warfarin is unsuitable.

Guidelines for atrial fibrillation (AF) recommend clopidogrel plus aspirin as an alternative stroke prevention strategy in patients in whom warfarin is unsuitable. A Markov model was conducted from a Medicare prospective using data from the Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events-A (ACTIVE-A) trial and other published studies. Base-case analysis evaluated patients 65 years old with AF, a CHADS(2) (congestive heart failure, 1 point; hypertension defined as blood pressure consistently >140/90 mm Hg or antihypertension medication, 1 point; age ≥75 years, 1 point; diabetes mellitus, 1 point; previous stroke or transient ishemic attack, 2 points) score of 2, and a lower risk for major bleeding. Patients received clopidogrel 75 mg/day plus aspirin or aspirin alone. Patients were followed for up to 35 years. Outcomes included quality-adjusted life-years (QALYs), costs (in 2011 American dollars), and incremental cost-effectiveness ratios. Quality-adjusted life expectancy and costs were 9.37 QALYs and $88,751 with clopidogrel plus aspirin and 9.01 QALYs and $79,057 with aspirin alone. Incremental cost-effectiveness ratio for clopidogrel plus aspirin was $26,928/QALY. With 1-way sensitivity analysis using a willingness-to-pay threshold of $50,000/QALY, clopidogrel plus aspirin was no longer cost effective when the CHADS(2) score was ≤1, major bleeding risk with aspirin was ≥2.50%/patient-year, the relative risk decrease for ischemic stroke with clopidogrel plus aspirin versus aspirin alone was <25%, and the utility of being healthy with AF on combination therapy decreased to 0.95. Monte Carlo simulation demonstrated that clopidogrel plus aspirin was cost effective in 55% and 73% of 10,000 iterations assuming willingness-to-pay thresholds of $50,000 and $100,000/QALY. In conclusion, clopidogrel plus aspirin appears cost-effective compared to aspirin alone for stroke prevention in patients with AF with a CHADS(2) of ≥2 and a lower risk of bleeding.

Effect of cinnamon on glucose control and lipid parameters.

OBJECTIVE: To perform a meta-analysis of randomized controlled trials of cinnamon to better characterize its impact on glucose and plasma lipids. RESEARCH DESIGN AND METHODS: A systematic literature search through July 2007 was conducted to identify randomized placebo-controlled trials of cinnamon that reported data on A1C, fasting blood glucose (FBG), or lipid parameters. The mean change in each study end point from baseline was treated as a continuous variable, and the weighted mean difference was calculated as the difference between the mean value in the treatment and control groups. A random-effects model was used. RESULTS: Five prospective randomized controlled trials (n = 282) were identified. Upon meta-analysis, the use of cinnamon did not significantly alter A1C, FBG, or lipid parameters. Subgroup and sensitivity analyses did not significantly change the results. CONCLUSIONS: Cinnamon does not appear to improve A1C, FBG, or lipid parameters in patients with type 1 or type 2 diabetes.

Monotherapy versus combination therapy with class III antiarrhythmic agents to attenuate transmural dispersion of repolarization: a potential risk factor for torsade de pointes.

Class III antiarrhythmic agents are used for conversion to and maintenance of sinus rhythm from arrhythmias of atrial or ventricular origin. Monotherapy can be limited by adverse events or recurrent arrhythmias. Sotalol, dofetilide, and ibutilide may induce torsade de pointes in 2-8% of patients, whereas amiodarone induces torsade de pointes in less than 1%. We reviewed the literature regarding the possible combination of class III antiarrhythmics and risk for inducing torsade de pointes. Animal studies using amiodarone plus sotalol or d-sotalol suggest that these drug combinations prolong the QTc interval but do not induce torsade de pointes. Similar data extracted from human studies of ibutilide in patients also receiving amiodarone or sotalol showed greater efficacy with combination therapy than with monotherapy, without increased torsade de pointes induction. Reduced transmural dispersion of repolarization with amiodarone and sotalol combination therapy may serve as a mechanism for reducing the risk of torsade de pointes compared with sotalol monotherapy.

Electrocardiographic and hemodynamic effects of coenzyme Q10 in healthy individuals: a double-blind, randomized controlled trial.

BACKGROUND: Coenzyme Q10 (CoQ10) is an endogenous cofactor required for mitochondrial energy production and touted to treat heart failure and prevent statin-induced myopathy. In guinea pig ventricular myocytes, CoQ10 prolongs action potential duration, an effect that might prolong the QTc interval in humans. Additionally, CoQ10 reduced blood pressure in patients with essential hypertension. OBJECTIVE: To determine the electrocardiographic (ECG) and hemodynamic impact of CoQ10 in healthy individuals. METHODS: Healthy volunteers (N = 26; 62% male, age 24 +/- 3 y) were randomized to receive a single dose of CoQ10 50 mg and matching placebo in a crossover fashion with a 7 day washout period between treatments. Twelve-lead ECGs, systolic and diastolic blood pressure, and other hemodynamic parameters (cardiac index and systemic vascular resistance index) were evaluated immediately before (baseline) and 1, 3, 5, and 8 hours after ingestion of the study drug. ECG parameters (P wave and QRS complex duration; PR, QT, QTc, and RR intervals) were measured in lead II by one blinded investigator. For each time point, duplicate blood pressure levels were taken manually and then averaged. Hemodynamic parameters were measured using bioelectrical impedance cardiography. RESULTS: CoQ10 had no effect on any of the evaluated ECG parameters. The maximum postdosing systolic blood pressure showed a statistically significant increase with CoQ10 (117 +/- 10 vs 119 +/- 10 mm Hg; p = 0.037), an effect driven by increases in cardiac index (3.09 vs 2.95 L/min/m(2); p = 0.017). However, blood pressure elevation was most evident at the 5 hour timepoint (116 +/- 10 vs 113 +/- 11 mm Hg; p = 0.049) and was only transient. There were no differences between groups for maximum postdosing diastolic blood pressure. CONCLUSIONS: One dose of CoQ10 does not have any effect on ECG variables and exhibits only mild and transient effect on systolic blood pressure in young, healthy people.

Electrocardiographic and blood pressure effects of the ephedra-containing TrimSpa thermogenic herbal compound in healthy volunteers.

STUDY OBJECTIVE: To determine the effect of an ephedra-containing thermogenic herbal compound (TrimSpa) on rate-corrected QT (QTc) interval duration and systolic blood pressure. DESIGN: Randomized, double-blind, placebo-controlled, crossover, intent-to-treat study. SETTING: Student laboratory at a college of pharmacy. SUBJECTS: Thirteen healthy volunteers (eight men, five women). INTERVENTION: Participants were given TrimSpa, which contains more than 30 ingredients including ephedra 15 mg and caffeine 60 mg, or matching placebo 3 times/day for 7 days in a crossover fashion with a 7-day washout period between treatments. MEASUREMENTS AND MAIN RESULTS: Each subject's QTc interval and systolic blood pressure were measured on days 1, 4, and 7. These measurements were performed immediately before study drug ingestion (baseline) and 0.5, 1, and 3 hours after ingestion. No differences in these variables were found between the TrimSpa and placebo groups. In one subject taking TrimSpa, the QTc interval increased 96 msec from baseline, more than double the largest increase in the placebo group. CONCLUSION: Standard doses of TrimSpa did not induce changes in subjects' QTc intervals or systolic blood pressures. However, because the QTc interval dramatically changed in one subject taking TrimSpa, a large study is needed to determine if the effect is an artifact or if the subject represents a subset of people for whom the drug may pose a risk.

Absence of QTc-interval-prolonging or hemodynamic effects of a single dose of bitter-orange extract in healthy subjects.

STUDY OBJECTIVE: To evaluate the hemodynamic and electrocardiographic effects of a single dose of commercially available bitter-orange dried-fruit extract, which is increasingly being used in dietary supplements. DESIGN: Randomized, double-blind, placebo-controlled, crossover study. SETTING: University of Connecticut, Storrs Campus. SUBJECTS: Eighteen healthy volunteers aged 18 years or older. INTERVENTION: Subjects were given either placebo or bitter-orange dried-fruit extract (450 mg standardized to 27 mg of m- or p-synephrine) in phase 1. The opposite treatment was given during phase 2 after a washout period of at least 7 days. MEASUREMENTS AND MAIN RESULTS: The rate-corrected QT (QTc) interval and blood pressure were measured before dosing and at 1, 3, 5, and 8 hours after dosing. Mean+/-SD values of the maximum postdose values were compared between groups. Subjects receiving bitter-orange extract versus those receiving placebo had similar postdose QTc intervals (402+/-29 vs 403+/-24 msec, p=0.653), systolic blood pressure (114+/-10 vs 115+/-8 mm Hg, p=0.686) and diastolic blood pressure (68+/-9 vs 68+/-8, p=0.879). CONCLUSION: Bitter-orange dried-fruit extract standardized to m- or p-synephrine 27 mg did not significantly alter the QTc interval or blood pressure after a single dose was administered. Future studies are necessary to ensure the safety of this herbal product with multiple doses.

Prevention of fatal arrhythmias in high-risk subjects by fish oil n-3 fatty acid intake.

BACKGROUND: The long-chain n-3 fatty acids in fish have been demonstrated to have antiarrhythmic properties in experimental models and to prevent sudden cardiac death in a randomized trial of post-myocardial infarction patients. Therefore, we hypothesized that these n-3 fatty acids might prevent potentially fatal ventricular arrhythmias in high-risk patients. METHODS AND RESULTS: Four hundred two patients with implanted cardioverter/defibrillators (ICDs) were randomly assigned to double-blind treatment with either a fish oil or an olive oil daily supplement for 12 months. The primary end point, time to first ICD event for ventricular tachycardia or fibrillation (VT or VF) confirmed by stored electrograms or death from any cause, was analyzed by intention to treat. Secondary analyses were performed for "probable" ventricular arrhythmias, "on-treatment" analyses for all subjects who had taken any of their oil supplements, and "on-treatment" analyses only of those subjects who were on treatment for at least 11 months. Compliance with double-blind treatment was similar in the 2 groups; however, the noncompliance rate was high (35% of all enrollees). In the primary analysis, assignment to treatment with the fish oil supplement showed a trend toward a prolonged time to the first ICD event (VT or VF) or of death from any cause (risk reduction of 28%; P=0.057). When therapies for probable episodes of VT or VF were included, the risk reduction became significant at 31%; P=0.033. For those who stayed on protocol for at least 11 months, the antiarrhythmic benefit of fish oil was improved for those with confirmed events (risk reduction of 38%; P=0.034). CONCLUSIONS: Although significance was not achieved for the primary end point, this study provides evidence that for individuals at high risk of fatal ventricular arrhythmias, regular daily ingestion of fish oil fatty acids may significantly reduce potentially fatal ventricular arrhythmias.

Hemodynamic impact of an ephedra-free multicomponent weight-loss supplement.

PURPOSE: The effect of Metabolife Ephedra-Free on blood pressure (BP) and hemodynamics was studied. METHODS: Healthy volunteers were randomly assigned to take a single dose of Metabolife Ephedra-Free or matching placebo and then crossed over to the opposite treatment after a seven-day washout period. BP was measured at baseline and one, three, and five hours after administration. Cardiac index, systemic vascular resistance index (SVRI), and total thoracic fluid content were determined in a subgroup of subjects. RESULTS: Twenty patients (mean +/- S.D. age, 24.8 +/- 1.9 years) completed the study. No significant differences in systolic or diastolic BP were found between the Metabolife Ephedra-Free and placebo groups. In the subgroup (n = 8), SVRI was higher (but not significantly so) in the Metabolife Ephedra-Free group than in the placebo group at one hour (2162.5 +/- 421.1 versus 1934.6 +/- 344.2 dyn x sec x cm(-5) x m(2)); the difference was significant at five hours (1981.6 +/- 293.3 versus 1765.1 +/- 340.3 dyn x sec x cm(-5) x m(2)). CONCLUSION: Single doses of Metabolife Ephedra-Free did not affect BP in healthy young volunteers. SVRI did not exceed the normal range but was elevated at five hours compared with SVRI in placebo recipients.

Electrocardiographic effects of an Ephedra-Free, multicomponent weight-loss supplement in healthy volunteers.

STUDY OBJECTIVE: Metabolife 356, an ephedra-containing weight-loss product, substantially increases the corrected QT (QTc) interval. Metabolife Ephedra Free, a similar supplement, contains caffeine and extracts of green tea, garcinia cambogia, and yerba mate. Its electrocardiographic (ECG) effects are not known. Therefore, we sought to determine the effect of this supplement on the QTc interval. DESIGN: Randomized, double-blind, placebo-controlled, crossover study. SETTING: University of Connecticut, Storrs Campus. SUBJECTS: Twenty healthy volunteers. Intervention. A single capsule containing half the normal recommended dose of Metabolife Ephedra Free or matching placebo was administered in crossover fashion, with a 7-day washout period between treatments. MEASUREMENTS AND MAIN RESULTS: Baseline and three postdose ECG measurements were obtained, and QTc intervals were measured over a 5-hour study period. No significant differences in the QTc interval or other ECG variables were observed between the Metabolife Ephedra Free and placebo groups. CONCLUSION: At half the recommended single dose, Metabolife Ephedra Free does not affect the QTc interval or other ECG variables over 5 hours. Dose-response studies and studies of longer duration should be conducted.

Inappropriate implantable cardioverter defibrillator discharge following consumption of a dietary weight loss supplement.

This report describes the clinical course of a 40-year-old female who experienced repetitive ICD firing after consuming Metabolife 356, a multicomponent dietary weight loss supplement. Following the initiation of Metabolife 356, the patient experienced four shocks over a 3 day period with two 30 J shocks being delivered sequentially. Interrogation of the device revealed atrial tachycardia with 1:1 AV conduction at a rate of 240 beats/min. Metabolife 356 was discontinued and the dosage of sotalol was increased to 120 mg twice daily without recurrence of ICD discharge.

Electrocardiographic and hemodynamic effects of a multicomponent dietary supplement containing ephedra and caffeine: a randomized controlled trial.

CONTEXT: Metabolife 356, a multicomponent dietary supplement containing ephedra and caffeine (DSEC) in addition to several other components, is the top-selling dietary weight loss supplement. Given its common use, anecdotal reports of cardiovascular and cerebrovascular adverse events, and paucity of safety data, further research with this DSEC was warranted. OBJECTIVE: To determine the impact of the DSEC on corrected QT (QTc) interval duration and systolic blood pressure (SBP). DESIGN: Randomized, double-blind, placebo-controlled, crossover study conducted from January to May 2003. SETTING AND PARTICIPANTS: Fifteen healthy volunteers (mean [SD] age, 26.7 [2.52] years; weight, 72.7 [14.93] kg), 6 (40%) of whom were women, recruited from the University of Connecticut, Storrs campus. INTERVENTION: A single dose of the DSEC (containing 19 ingredients including ephedra [12 mg] and caffeine [40 mg]) or matching placebo were administered in a crossover fashion with a 7-day washout period between treatments. MAIN OUTCOME MEASURES: Maximal QTc interval and SBP assessed at 1, 3, and 5 hours after dosing for the DSEC relative to placebo. RESULTS: Individuals receiving the DSEC had a longer maximal QTc interval (mean [SD], 419.4 [11.8] vs 396.1 [15.7] milliseconds; P<.001) and higher SBP (mean [SD], 123.5 [10.98] vs 118.93 [9.62] mm Hg; P =.009) compared with placebo. Participants who received the DSEC were more likely to experience a QTc interval increase of at least 30 milliseconds vs placebo (8 individuals [53.3%] vs 1 individual [6.7%]; relative risk, 2.67 [95% confidence interval, 1.40-5.10]). There were no significant sex-related differences. CONCLUSIONS: The ephedra- and caffeine-containing dietary supplement Metabolife 356 increased the mean maximal QTc interval and SBP. Since the actual ingredient or ingredients in Metabolife 356 responsible for these findings are not known, patients should be instructed to avoid this and similar dietary supplements until more information is known about their safety.

Hemodynamic and electrocardiographic effects of short-term Ginkgo biloba.

OBJECTIVE: To evaluate the immediate and short-term hemodynamic and electrocardiographic effects of Ginkgo biloba (ginkgo). METHODS: Healthy volunteers were randomized to receive ginkgo 120 mg or placebo twice daily for 7 days in this prospective, double blind trial. After at least a 7-day washout period, subjects were crossed over to an additional 7 days of alternate therapy. Blood pressure, heart rate, and 12-lead electrocardiograms were evaluated immediately before (baseline), and at 1, 3, and 5 hours after observed ingestion of study drug on days 1 and 7 of therapy. Electrocardiographic parameters (P wave and QRS complex duration; PR, QT, and QTc intervals) were measured in lead II by a blinded investigator. RESULTS: Ginkgo had no effect on any of the evaluated electrocardiographic parameters at any time point on days 1 or 7. Additionally, no changes in heart rate or systolic and diastolic blood pressure were found between the groups at any time point on any evaluative day. CONCLUSIONS: Commonly used doses of Ginkgo biloba do not have any immediate or short-term effects on blood pressure, heart rate, or electrocardiographic variables in young, healthy volunteers.

Electrocardiographic and hemodynamic effects of Panax ginseng.

OBJECTIVE: To determine whether Panax ginseng ingestion can acutely or chronically alter electrocardiographic parameters: PR, QRS, QT, QTc, and RR intervals, and QT and QTc interval dispersion. Effects of P. ginseng on blood pressure and heart rate also were evaluated. METHODS: This is a prospective, randomized, double-blind, placebo-controlled study of healthy adults at the University of Connecticut. Thirty subjects were randomly allocated to receive 28 days of therapy with either P. ginseng extract 200 mg or placebo. Baseline 12-lead electrocardiograms (ECGs) were obtained. Subsequent ECGs were performed following study drug ingestion at 50 minutes, 2 hours, and 5 hours on days 1 and 28. Blood pressure readings were taken with each ECG. RESULTS: P. ginseng ingestion increased the QTc interval by 0.015 seconds on day 1 at 2 hours compared with the placebo group (p = 0.03). It also reduced diastolic blood pressure from 75 +/- 5 mm Hg at baseline to 70 +/- 6 mm Hg at the same time point (p = 0.02). The observed effects are not believed to be clinically significant. No other statistically significant changes were found in electrocardiographic or hemodynamic variables on days 1 or 28. CONCLUSIONS: P. ginseng, at doses of 200 mg of the extract daily, increases the QTc interval and decreases diastolic blood pressure 2 hours after ingestion in healthy adults on the first day of therapy.