Role of magnesium in cardiac tachyarrhythmias

The efficacy of magnesium therapy in patients with ventricular tachycardia has previously been reported. Recently completed and ongoing studies validate earlier observations that potassium and magnesium supplementation may control other cardiac arrhythmias, particularly in hypomagnesemic patients. Magnesium treatment is a viable therapeutic option when other antiarrhythmic agents fail to suppress ventricular tachycardia, ventricular fibrillation, multifocal atrial tachycardia, atrial fibrillation and supraventricular tachycardia.     

Herbal medicine: Beneficial effects,side effects,and promising new research in the treatment of arrhythmias

Herbal medications and dietary supplements are unregulated in the United States. The use of these medications has dramatically increased over the past decade. Many of these drugs are biologically active, yet physicians are often unaware their patients are using a traditional remedy. Physicians are frequently unfamiliar with the medications being used and the intended effect, as well as the side-effect profiles that accompany them. Recently, some of the herbal mediations that are commonly used in the general population have been shown to be beneficial for the treatment of arrhythmias. Unfortunately, many more have been shown to be detrimental. In this article, the background behind herbal medication and the degree to which herbal medications are being used is reviewed. Herbal medications known to have beneficial effects in the treatment of arrhythmias, as well as those that have known detrimental effects with regard to cardiac arrhythmias, are highlighted. Finally, research that has been done in this field, focusing on those compounds that have been shown to be biologically active in the treatment of cardiac arrhythmias, are reviewed.     

Fit with good fat? The role of n-3 polyunsaturated fatty acids on exercise performance

N-3 PUFA (n-3) polyunsaturated fatty acids (PUFA) are a family of fatty acids mainly found in oily fish and fish oil supplements. The effects of n-3 PUFA on health are mainly derived from its anti-inflammatory proprieties and its influence on immune function. Lately an increased interest in n-3 PUFA supplementation has reached the world of sport nutrition, where the majority of athletes rely on nutrition strategies to improve their training and performance. A vast amount of attention is paid in increasing metabolic capacity, delaying the onset of fatigue, and improving muscle hypertrophy and neuromuscular function. Nutritional strategies are also frequently considered for enhancing recovery, improving immune function and decreasing oxidative stress. The current review of the literature shows that data regarding the effects of n-3PUFA supplementation are conflicting and we conclude that there is, therefore, not enough evidence supporting a beneficial role on the aforementioned aspects of exercise performance.     

Treatment of ventricular arrhythmias in the coronary patient: What sort of patient? For which rhythm disorder? With Which Procedure?

In the patient with coronary artery disease, complex ventricular arrhygunias and frequent ventricular arrhythmias appear to be independent risk factors for subsequent death, particularly in patients who have had myocardial infarction. M patients with symptomatic arrhythmias, treatment must be instituted and tested during rigorous supervision of the patient. Using both the noninvasive Holter monitoring/exercise test procedure and invasive electrophysiologic testing, a beneficial antiarrhythmic response after institution of antiarrhythmic agents indicates improved prognosis. However, a negative treatment response during programmed stimulation does not necessarily indicate bad prognosis. This is particularly true for testing during amiodarone treatment.

For unselected patients, routine antarrhythmic treatment cannot currently be recommended. Continuing studies will show whether screening for electrical instability of the myocardium, and institution of antiarrhythmic therapy thereafter, win improve overall survival. If patients tolerate β-block-king treatment, this should probably be instituted because reductions In mortality have been found, particularly in high-risk patients.     

Non-antiarrhythmic drugs for the prevention of cardiac arrhythmias.

It is noteworthy that drugs having a significant impact in preventing arrhythmias (atrial or ventricular) are those with no direct specific antiarrhythmic electrophysiologic properties. Specifically, drugs able to interfere with the renin-angiotensin system and the n-3 fatty acids seem to play a relevant role as antiarrhythmics, even if they do not act in the typical manner. Angiotensin-converting enzyme (ACE) inhibitors decrease the incidence of arrhythmias in patients with decreased left ventricular function. The main reduction is linked to a decrease of ventricular arrhythmias, while several studies have suggested that ACE-inhibitors may also decrease the burden of atrial fibrillation. Furthermore, many of angiotensin receptor blockers and spironolactone have been shown to have antiarrhythmic properties. n-3 polyunsaturated fatty acids (PUFAs) are known to be antiarrhythmic as well. Their effects on the fast voltage-dependent sodium current I(NA), inhibition of I(Ca2+) and the K+ channel modulation explain their antiarrhythmic properties. For these reasons the renin-angiotensin system blockade and the n-3 PUFA intake may provide simple and safe protection from cardiac arrhythmias.     

Thiazide treatment of systemic hypertension: effects on serum magnesium and ventricular ectopic activity

Clinical and investigational evidence has proved an association between thiazide-induced electrolyte imbalances and ventricular arrhythmias. It is hypothesized that this increases the potential for sudden unexplained death. Elderly hypertensive patients are at particular risk because of their tendency to have significantly depressed serum magnesium levels, which decrease even further when treated with thiazide diuretics. Potassium supplementation does not effectively restore electrolyte balance unless accompanied by magnesium. Therefore, concomitant administration of potassium and magnesium supplementation appears to be an approach to reducing the risk of arrhythmias and death in thiazide-treated hypertensive patients.     

A review of rhythm disorders in cardiac hypertrophy

Ventricular arrhythmias frequently occur in both experimental and human left ventricular hypertrophy. The mechanism of arrhythmia is not clear but appears to be related to the process of hypertrophy and the accompanying fibrosis rather than to coexistent coronary artery disease or diuretic-induced hypokalemia. Although neither the independent prognostic value of ventricular arrhythmias nor the benefit of antiarrhythmic therapy has been demonstrated in prospective studies involving hypertensive patients, it is possible that appropriate antiarrhythmic therapy may reduce mortality in selected patients with severe hypertrophy.     

Magnesium in congestive heart failure

Magnesium deficit and other electrolyte abnormalities is a frequent disorder in patients with congestive heart failure. Overstimulation of the renin-angiotensin-aldosterone system, long-term administration of diuretics, digoxin, poor oral intake and impaired absorption contribute to these electrolytes abnormalities. Hypomagnesaemia and depletion of intracellular magnesium stores have been held responsible for a variety of cardiovascular and other functional abnormalities, including various arrhythmias, impairment of cardiac contractility, and vasoconstriction. Because sudden death is prevalent in congestive heart failure, a causal relationship between arrhythmias and magnesium deficiency has been proposed. Reportedly, administration of magnesium can suppress ventricular arrhythmias;however, it remains to be elucidated whether administration of magnesium prevents sudden death and improves prognosis of the patients with congestive heart failure. Nevertheless, since magnesium depletion may be prevalent in congestive heart failure and magnesium has anti-arrhythmic and beneficial cardiovascular effects, magnesium should be supplemented to the patients suspected to have its deficiency.     

Vitamins in Aging,Health, and Longevity

Evidence of epidemiological associations of vitamins and disease states have been found for nine vitamins. In observational studies, people with a high intake of antioxidant vitamins by regular diet or as food supplements generally have a lower risk of major chronic disease, such as myocardial infarction or stroke, than people who are low consumers of antioxidant vitamins. Prospectively, folate appears to reduce the incidence of neural tube defects. Vitamin D is associated with a decreased occurrence of fractures when taken with calcium. Zinc, betacarotene, and vitamin E appear to slow the progression of macular degeneration, but do not reduce the incidence. Vitamin E and lycopene may decrease the risk of prostate cancer. In other randomized controlled trials, the apparent beneficial results of a high intake of antioxidant vitamins seen in observational studies have not been confirmed. There is increasing concern from these trials that pharmacological supplementation of vitamins may be associated with a higher mortality risk.     

Herbs and dietary supplements in the prevention and treatment of cardiovascular disease

Herbs and dietary supplements can have significant physiological effects. Garlic (Allium sativum) has shown beneficial lipid effects in a majority of trials; dried garlic preparations are superior to oil preparations. There is preliminary evidence that indicates that hawthorn (Crataegus species) may provide benefit in congestive heart failure. Coenzyme Q also may be of benefit in congestive heart failure. Although observational studies indicate a protective effect of dietary or supplemental vitamin E, controlled trials have not shown a beneficial effect on angina and have been mixed on whether supplementation decreases major cardiac events. Although several observational studies have noted that fish intake protects against cardiovascular disease, prospective studies are less impressive. Fish oil supplementation may have a mild beneficial effect on hypertension, but there is no effect on total cholesterol levels. Trials are inconsistent on whether fish oil reduces restenosis rates following coronary angioplasty. Carnitine appears to have beneficial effects on congestive heart failure and angina; there is also preliminary evidence that arginine may benefit patients with congestive heart failure or angina. Herbs and supplements have been associated with adverse effects and interactions; for example, garlic inhibits platelet aggregation and can cause significant anticoagulation, and the Chinese herb danshen (Salvia miltiorrhiza) appears to potentiate warfarin. Several herbs and supplements hold promise as adjuncts in the prevention and treatment of cardiovascular disease. There is a need for definitive research on the potential risks and benefits of these compounds, including appropriate dosages and formulations, and delineation of adverse events and interactions     

Omega-3 fatty acid supplementation for the prevention of arrhythmias

Fish oil, or omega-3 (n-3) polyunsaturated fatty acid (PUFA), supplements have been purported to produce potential health benefits. One of the strongest supported effects of n-3 PUFAs may be their potential benefits in reducing the risk of sudden cardiac death. This article reviews clinical and mechanistic studies that may explain the effects of these agents on ischemic arrhythmias, sudden death, and atrial fibrillation.     

Dietary Omega-3 Polyunsaturated Fatty Acid Supplementation and Airway Hyperresponsiveness in Asthma

Asthma prevalence continues to increase despite the progress that has been made in the treatment options for asthma. Alternative treatment therapies that reduce the dose requirements of pharmacological interventions would be beneficial, and could potentially reduce the public health burden of this disease. There is accumulating evidence that dietary modification has potential to influence the severity of asthma and reduce the prevalence and incidence of this condition. A possible contributing factor to the increased incidence of asthma in Western societies may the consumption of a pro-inflammatory diet. In the typical Western diet, 20-25-fold more omega (n)-6 polyunsaturated fatty acids (PUFA) than n-3 PUFA are consumed, which results in the release of pro-inflammatory arachidonic acid metabolites. Eicosapentaenoic acid and docosahexaenoic acid are n-3 PUFA derived from fish oil that competitively inhibit n-6 PUFA arachidonic acid (AA) metabolism and this reduce the generation of pro-inflammatory 4-series leukotrienes (LTs) and 2-series prostaglandins (PGs) and production of cytokines from inflammatory cells. These data are consistent with the proposed pathway by which dietary intake of n-3 PUFA modulates lung disease. This article will review the existing information concerning the relationship between n-3 PUFA supplementation and airway hyperresponsiveness in asthma. It includes studies assessing the efficacy of n-3 PUFA supplementation in exercise-induced bronchoconstriction. This review will also address the question as to whether supplementing the diet with n-3 PUFA represents a viable alternative treatment regimen for asthma.     

Dietary Omega-3 Polyunsaturated Fatty Acid Supplementation and Airway Hyperresponsiveness in Asthma

Asthma prevalence continues to increase despite the progress that has been made in the treatment options for asthma. Alternative treatment therapies that reduce the dose requirements of pharmacological interventions would be beneficial, and could potentially reduce the public health burden of this disease. There is accumulating evidence that dietary modification has potential to influence the severity of asthma and reduce the prevalence and incidence of this condition. A possible contributing factor to the increased incidence of asthma in Western societies may the consumption of a pro-inflammatory diet. In the typical Western diet, 20–25-fold more omega (n)-6 polyunsaturated fatty acids (PUFA) than n-3 PUFA are consumed, which results in the release of pro-inflammatory arachidonic acid metabolites. Eicosapentaenoic acid and docosahexaenoic acid are n-3 PUFA derived from fish oil that competitively inhibit n-6 PUFA arachidonic acid (AA) metabolism and this reduce the generation of pro-inflammatory 4-series leukotrienes (LTs) and 2-series prostaglandins (PGs) and production of cytokines from inflammatory cells. These data are consistent with the proposed pathway by which dietary intake of n-3 PUFA modulates lung disease. This article will review the existing information concerning the relationship between n-3 PUFA supplementation and airway hyperresponsiveness in asthma. It includes studies assessing the efficacy of n-3 PUFA supplementation in exercise-induced bronchoconstriction. This review will also address the question as to whether supplementing the diet with n-3 PUFA represents a viable alternative treatment regimen for asthma.     

Pathophysiologic bases for adjunctive therapies in the treatment and secondary prevention of acute myocardial infarction

Postmyocardial infarction (MI) survival has been steadily improving. This improvement has been due, in part, to the actions of the adjunctive medical therapies for the treatment of MI. Aspirin, beta blockers, angiotensin-converting enzyme (ACE) inhibitors, and lipid-lowering agents have been shown to improve survival in the treatment and secondary prevention of MI. Nitrates have beneficial effects as well. These medications complement the reperfusion strategies through different mechanisms. Other adjunctive medical therapies, namely magnesium, antiarrhythmic agents, and calcium-channel blockers, have not been shown to improve mortality with routine post-MI use despite their theoretical benefits.     

Effects of procainamide and disopyramide on long chain acyl carnitine and long chain acyl CoA concentrations in the ischemic heart

Though the efficacies of procainamide and disopyramide in treating arrhythmias are well established, their precise mechanisms of antiarrhythmic action remain unclear. Arrhythmias which occur during acute myocardial ischemia can be explained partly on a metabolic basis. The accumulation of intermediates subsequent to impaired beta-oxidation of free fatty acids has been suggested as a cause of serious arrhythmias. The purpose of this study was to investigate changes in free carnitine, long chain acyl carnitine and long chain acyl CoA concentrations in the ischemic canine heart following the administration of procainamide and disopyramide. The coronary artery was occluded for 40 min and myocardial samples were prepared from both nonischemic and ischemic areas. Procainamide and disopyramide prevented the accumulation of long chain acyl carnitine and long chain acyl CoA in the ischemic myocardium. The results showed that procainamide and disopyramide had beneficial effects on fatty acid metabolism. It was suggested that one of the antiarrhythmic mechanisms of these drugs might be the prevention of the accumulation of fatty acyl derivatives in the ischemic myocardium.     

The Use of ω-3 Poly-Unsaturated Fatty Acids in Heart Failure: A Preferential Role in Patients with Diabetes

Purpose

To review the evidence for a beneficial effect of ω-3 PUFAs in heart failure (HF) and its co-morbidities, their possible preferential effect in diabetes and the potential mechanism for their benefit.

Methods

We summarize the clinical studies which investigated the use of ω-3 PUFAs in patients with HF with an emphasis on diabetes. We briefly summarize the evidence for an effect of ω-3 PUFAs in patients with coronary artery disease (CAD), atrial fibrillation (AF) and ventricular arrhythmias. We also discuss the proposed mechanisms of ω-3 PUFA action in cardiovascular diseases.

Results

While there is emerging evidence for a beneficial effect of ω-3 PUFA supplementation in patients with HF, the evidence for other indications have been variable and conflicting. In HF patients with diabetes, ω-3 PUFAs may have a preferential therapeutic benefit. Randomized controlled trials did not show considerable beneficial effects of ω-3 PUFAs in other conditions such as CAD and AF. In a diabetic and insulin-resistant state, ω-3 PUFAs bind to the G-protein coupled receptor, GPR120, resulting in reduced cytokine production from inflammatory macrophages and improved signaling in adipocytes, leading to a reduction in insulin resistance.

Conclusions

There is promising evidence showing that use of ω-3 PUFA supplementation improves clinical outcomes of HF patients with diabetes. Further clinical trials are needed in this regard.     

Effect of captopril therapy on lymphocyte potassium and magnesium concentrations in patients with congestive heart failure.

Lymphocyte potassium and magnesium were measured before and 3 months after the introduction of captopril in 18 patients taking diuretics for congestive heart failure. Compared to 32 healthy controls, 9 patients who had been on potassium supplements plus frusemide had decreased baseline lymphocyte magnesium and potassium concentrations (p less than 0.01), in spite of similar plasma electrolyte levels. There was a significant (p less than 0.01) increase in both lymphocyte potassium and magnesium levels after 3 months' treatment with captopril and frusemide in these patients. Nine patients who had been taking a potassium-sparing combination diuretic also had an increase in lymphocyte magnesium (p less than 0.05) following the introduction of captopril. Increased intracellular potassium and magnesium may be one mechanism whereby angiotensin-converting enzyme inhibitors reduced arrhythmias and improve survival in patients with congestive heart failure.     

Pilot study of the effects of n-3 polyunsaturated fatty acids on exhaled nitric oxide in patients with stable asthma.

BACKGROUND: The anti-inflammatory effects of n-3 polyunsaturated fatty acids (n-3 PUFA) have been demonstrated both in vitro and in vivo. The results of epidemiological studies suggest that fish consumption has a beneficial effect on lung function and prevalence of asthma. However, data from intervention trials have not revealed a beneficial effect of n-3 PUFA supplementation in patients with established disease. OBJECTIVE: To study the effects of short-term n-3 PUFA supplementation in addition to maintenance therapy on exhaled nitric oxide in asthmatic patients. METHODS: A double-blind, placebo-controlled trial was undertaken in 20 women with asthma. Patients received either a combination of eicosapentaenoic acid and docosahexaenoic acid plus 10 mg vitamin E or placebo twice daily for 2 weeks. The primary outcome measure was the fraction of exhaled nitric oxide (FeNO) and the secondary outcomes were asthma control (score on theAsthma Control Questionnaire [ACQI) and lung function (forced expiratory volume in 1 second [FEV1]). RESULTS: No significant differences were observed in FeNO, ACQ score, or FEV1 between patients receiving n-3 PUFA supplementation and those receiving placebo. CONCLUSIONS: Short-term dietary supplementation with n-3 PUFA in women with stable asthma was not associated with statistically significant changes in FeNO, asthma control, or lung function.     

Do omega-3 polyunsaturated fatty acids reduce risk of sudden cardiac death and ventricular arrhythmias? A meta-analysis of randomized trials

Introduction

Omega-3 polyunsaturated fatty acids (PUFA) have demonstrated to have antiarrhythmic properties. However, randomized studies have shown inconsistent results.

Objective

We aimed to analyze the effect of omega-3 PUFA on preventing potentially fatal ventricular arrhythmias and sudden cardiac death.

Methods

Randomized trials comparing omega-3 PUFA to placebo and reporting sudden cardiac death (SCD) or first implanted cardioverter-defibrillator (ICD) event for ventricular tachycardia or fibrillation were included in this study. A meta-analysis using a random effects model was performed and results were expressed in terms of Odds Ratio (OR) and 95% Confidence Interval (CI) after evaluating for interstudy heterogeneity using I². The reported data were extracted on the basis of the intention-to-treat principle.

Results

A total of 32,919 patients were included in nine trials; 16,465 patients received omega-3 PUFA and 16,454 received placebo. When comparing omega-3 PUFA to placebo, there was nonsignificant risk reduction of SCD or ventricular arrhythmias (OR = 0.82 [95% CI: 0.60–1.21], p = 0.21 I² = 49.7%).

Conclusion

Dietary supplementation with omega-3 PUFA does not affect the risk of SCD or ventricular arrhythmias.     

Antiarrhythmic effect of magnesium sulfate after open heart surgery: effect of blood levels

BACKGROUND: Arrhythmias following cardiac surgery is still a difficult complication to treat. Magnesium sulfate is an effective antiarrhythmic agent with negligible side effects. In this study, effects of magnesium sulfate as a first line antiarrhythmic agent was compared with results of two different well-accepted antiarrhythmic agents. METHODS: One hundred patients with arrhythmia were prospectively randomized to a study and a control group. Lidocaine and amiodarone were accepted as standard antiarrhythmic agents. Patients in study group were received magnesium sulfate routinely as a first line antiarrhythmic agent. Unresponsive arrhythmias were treated with standard antiarrhythmic agents. Control group patients received only standard antiarrhythmics. RESULTS: Magnesium sulfate alone was effective in 56% of the study group whereas 74% of the control group were responsive to standard antiarrhythmics (P=n.s.). In study group, a subgroup analysis according to blood levels of Mg2+ revealed that magnesium sulfate was more effective in patients with low Mg2+ levels (63% for low Mg2+ levels, 55% for normal Mg2+ levels, 36% for high Mg2+ levels) and ventricular arrhythmias (60% for ventricular and 40% for supraventricular arrhythmias), without statistical significance. CONCLUSIONS: Magnesium sulfate is an effective and safe antiarrhythmic agent for arrhythmias developed after open-heart surgery. Its antiarrhythmic effect may relate to its pharmacological properties and unrelated to normalization of the circulating magnesium concentrations. We recommend its use as a first line antiarrhythmic agent without routine measurement of blood levels.