Atrial fibrillation-induced atrial contractile dysfunction: a tachycardiomyopathy of a different sort.

OBJECTIVE: Although AF-induced atrial contractile dysfunction has significant clinical implications the underlying intracellular mechanisms are poorly understood. METHODS: From the right atrial appendages of 59 consecutive patients undergoing mitral valve surgery (31 in SR, 28 in chronic AF) thin muscle preparations (diameter<0.7 mm) were isolated. Isometric force of contraction was measured in the presence of different concentrations of Ca(2+) and isoprenaline. To assess the function of the sarcoplasmic reticulum, the force-frequency relationship and the post-rest potentiation were studied. The myocardial density of the ryanodine-sensitive calcium release channel (CRC) of the sarcoplasmic reticulum was determined by [3H]ryanodine binding. Myocardial content of SR-Ca(2+)-ATPase (SERCA), phospholamban (Plb), calsequestrin (Cals) and the Na(+)/Ca(2+)-exchanger (NCX) were analyzed by Western blot analysis. Adenylyl cyclase activity was measured with a radiolabeled bioassay using [32P]ATP as a tracer. RESULTS: In 72 muscle preparations of SR patients contractile force was 10.9+/-1.8 mN/mm(2) compared to 3.3+/-0.9 mN/mm(2) (n=48, P<0.01) in AF patients. The positive inotropic effect of isoprenaline was diminished but the stimulatory effect on relaxation and the adenylyl cyclase were not altered in AF patients. The force-frequency relation and the post-rest potentiation were enhanced in atrial myocardium of AF patients. The protein levels of CRC, SERCA, Plb, and Cals were not different between the two groups. In contrast, the Na(+)/Ca(2+)-exchanger was upregulated by 67% in atria of AF patients. CONCLUSIONS: AF-induced atrial contractile dysfunction is not due to beta-adrenergic desensitization or dysfunction of the sarcoplasmic reticulum and thus is based on different cellular mechanisms than a ventricular tachycardia-induced cardiomyopathy. Instead, downregulation or altered function of the L-type Ca(2+)-channel and an increased Ca(2+) extrusion via the Na(+)/Ca(2+)-exchanger seem to be responsible for the depressed contractility in remodeled atria.     

Orthostatic hypertension: Recognizing an underappreciated clinical condition

Orthostatic hypertension refers to an increase in the blood pressure upon assuming an upright posture. This clinical condition has been understudied and is often underappreciated in clinical practice probably because of its unfamiliarity to many clinicians including subspecialists. We report a case of severely symptomatic orthostatic hypertension in a Caucasian female, which was likely secondary to an autonomic dysfunction caused by an underlying vascular adrenergic hypersensitivity and possibly also due to uncontrolled diabetes mellitus (causing baroreflex dysfunction associated with excessive sympathetic stimulation). The case work-up also illustrates a schematic diagnostic and management approach to this rarely encountered clinical entity.     

Atrial fibrillation and congestive heart failure

Atrial fibrillation (AF) and congestive heart failure (CHF) are common cardiac conditions that frequently coexist. There is a complex interplay between the two conditions, with each increasing the morbidity and mortality associated with the other. The management of AF in patients with CHF requires special care because of the increased risk of antiarrhythmic drug therapy in the group. This report reviews current treatment options and assesses the role of the newer therapies of biventricular pacing for CHF and radiofrequency ablation for AF. It also discusses results of the AF-CHF study, which were reported in November 2007.     

Atrial fibrillation and heart failure comorbidity

Atrial fibrillation and heart failure have in common that they mainly occur in older patients and the patients have similar underlying heart diseases. The prevalence of atrial fibrillation in heart failure patients varies from 10% to 30%. There are conflicting data whether the presence of atrial fibrillation is an independent predictor for an increased mortality in heart failure. Optimal medical heart failure therapy can improve outcome and may influence the relationship between atrial fibrillation and survival. Keystones for the management of atrial fibrillation in heart failure patients are the optimal treatment of heart failure, the use of oral anticoagulation, the case-adjusted decision of rhythm or rate control, and the primary prevention of sudden cardiac death. Heart failure patients with atrial fibrillation should receive long-term oral anticoagulation. The two options to treat atrial fibrillation are rhythm control and rate control. Given the findings of randomised trials, rhythm control of atrial fibrillation with the aim to improve survival is not justified in heart failure patients because of uncertainty about the role of atrial fibrillation as a predictor of worse outcomes and the safety of antiarrhythmic drugs. Rhythm control can be attempted, if rate control is chosen and symptoms persist. The indications for rhythm control are to control symptoms, including a deterioration of heart failure related to a loss of atrial contraction. Amiodarone seems to be the drug of choice to maintain sinus rhythm in patients with paroxysmal atrial fibrillation as well as in patients who returned to sinus rhythm after cardioversion. New non pharmacologic approaches for rhythm control such as catheter-based techniques seem to be highly effective. Rate control to prevent rapid atrial fibrillation is an acceptable approach in otherwise asymptomatic heart failure patients. Slowing of the ventricular rate often leads to a moderate improvement in left ventricular function in many patients. Standard therapy for rate control in heart failure patients consists of partial atrioventricular (AV) node blockade with digoxin and a beta-blocker. Amiodarone is also highly effective to reduce ventricular rate in patients with atrial fibrillation. When rate control remains refractory to medical therapy, rate control is achieved with AV node ablation and subsequent pacemaker implantation. Non pharmacological treatments for the primary prevention of sudden cardiac death are the implantation of a defibrillator.     

Atrial fibrillation in heart failure

BACKGROUND: Atrial fibrillation is a common arrhythmia in patients with congestive heart failure caused by left ventricular dysfunction and is associated with significant morbidity and possibly increased mortality rates. It occurs with increasing frequency as the severity of heart failure increases. TREATMENT: As therapeutic options, two basic strategies are available: rhythm control with or without pharmacological manipulation to increase the chance of successful cardioversion and to maintain sinus rhythm, and rate control with anticoagulation. So far, a clear benefit of one of these two strategies over the other has not been demonstrated for patients with atrial fibrillation generally, nor have there been convincing data for the subgroup of heart failure patients. Traditionally, digoxin has been used in patients with heart failure and atrial fibrillation; however, it has no proven potential to restore sinus rhythm and is slow and not very effective in rate control requiring the addition of another rate-limiting agent, preferably a beta-blocker or calcium antagonist. Amiodarone has been evaluated in numerous clinical trials in patients with heart failure and appears to be safe and effective in terms of conversion to sinus rhythm, maintenance of sinus rhythm as well as control of ventricular rate. Dofetilide may be another option in patients with atrial fibrillation and heart failure, although a direct comparison with amiodarone is lacking. The problem with all antiarrhythmic drugs specifically in patients with heart failure is their toxicity. Because of their proarrhythmic effects, Class I antiarrhythmics are contraindicated in patients with heart failure. Torsades de pointes is the most serious adverse effect of sotalol and dofetilide. Amiodaron has less proarrhythmic risk but has numerous non-cardiac toxicities that require frequent monitoring. CONCLUSION: Overall, due to a low efficacy rate and high proarrhythmic risks, an ideal antiarrhythmic agent for patients with atrial fibrillation and heart failure does not exist, and drug selection should be highly individualized. In patients with chronic atrial fibrillation and heart failure, anticoagulation with warfarin for prevention of thromboembolic events is mandatory.     

Atrial natriuretic peptides during experimental atrial tachycardia: role of developing tachycardiomyopathy

INTRODUCTION: Atrial tachycardia and chronic heart failure (CHF) are associated with elevated levels of atrial natriuretic peptide (ANP) and its amino terminal part NT-ANP. Chronic high atrial rates may cause CHF due to a rapid ventricular response. The aim of this study was to establish the contribution of elevated atrial rate and of high ventricular rate, resulting in CHF, on ANP and NT-ANP levels during chronic atrial tachycardia. METHODS AND RESULTS: Thirteen goats (AV-paced group) were subjected to 4 weeks of rapid AV pacing with an atrial and ventricular rate of 240 beats/min. Another five goats (A-paced group) were subjected to 4 weeks of atrial pacing at 240 beats/min while the ventricular rate was kept low and regular at 80 beats/min. Pacing was interrupted only for measurement of right atrial (RA) and left ventricular (LV) diameter and sampling for ANP, NT-ANP, and renin. In the AV-paced group, RA and LV diameter reached 152% and 109% of baseline values, respectively. Both ANP and NT-ANP (8.3 +/- 9.2 pmol/L and 0.5 +/- 0.4 nmol/L at baseline, respectively) increased progressively (53.1 +/- 37.9 pmol/L and 2.0 +/- 0.9 nmol/L, respectively, after 4 weeks). There was a significant correlation between the magnitude of atrial dilation and natriuretic peptide levels after 3 days. In A-paced goats, however, RA and LV diameters did not change. Furthermore, ANP and NT-ANP levels (9.1 +/- 6.0 pmol/L and 0.8 +/- 0.2 nmol/L at baseline, respectively) were unchanged after 4 weeks (5.3 +/- 3.4 pmol/L and 0.6 +/- 0.2 nmol/L, respectively). CONCLUSION: Elevated levels of ANPs during chronic atrial tachycardia are related to a high ventricular rate rather than a high atrial rate alone. Rather than atrial tachycardia, the atrial hemodynamic burden is an important determinant of the sustained ANP response.     

Atrial fibrillation and heart failure in the elderly

Atrial fibrillation (AF) is a common clinical problem in elderly patients and especially in those with heart failure (HF). It is a major risk factor for serious cardiovascular events, such as stroke, HF and premature death. Both the prevalence and incidence of AF increase with age and its prevalence in the United States are estimated at more than 2.2 million, with nearly 75% of patients aged >65?years. Aging-related atrial remodeling with fibrosis, dilation and mitochondrial DNA mutations predispose elderly patients to AF. Current management options for AF, including rate control and anticoagulation therapy, can be successfully applied to the elderly population. New antiarrhythmic and anticoagulation medications such as dronedarone and dabigatran, respectively, can impact the approach to therapy in the elderly. Non-pharmacological options such as catheter-based ablation have also gained prominence and have been incorporated into the guidelines for management of AF. However, more trials in the elderly and very elderly segments are needed to clarify the safety and long-term efficacy of the new treatment options.     

Atrial fibrillation in heart failure: catheter and surgical interventional therapies

Atrial fibrillation and heart failure commonly coexist in the same patient. Each may adversely affect the other. Atrial fibrillation leads to heart failure exacerbation, left ventricular function deterioration and an increase in thrombo-embolic risk. Therapeutic options targeting atrial fibrillation in heart failure patients include pharmacological and non-pharmacological means. Pharmacological therapy is directed at either rate control using nodal blocking agents or rhythm control using anti-arrhythmic agents, of which the options are limited in patients with heart failure. The landmark AF–CHF trial did not show any benefit of rhythm control strategy as opposed to rate control in patients with heart failure and atrial fibrillation. However, patients in this trial as well as in others used mostly amiodarone for rhythm control. This might have negated any positive effects of achieving normal sinus rhythm. Non-pharmacological therapy both for rate and rhythm control is appealing. This includes AV node ablation for rate control, catheter ablation of atrial fibrillation and surgical therapy of atrial fibrillation. This review will address non-pharmacologic treatment of AF in heart failure patients.     

Atrial fibrillation in heart failure: stroke risk stratification and anticoagulation

For an individual patient with both atrial fibrillation and heart failure, stroke risk is one of the most prominent mitigating factors for subsequent morbidity and mortality. Although the CHADS₂ stroke risk score is the most widely used score for risk stratification, it does not take into account the risk factors of vascular disease, female gender, or the age group 65–74 years, for which there is increasing evidence. There is also evidence that diastolic heart failure is as much a risk factor for stroke as systolic heart failure. The new oral anticoagulants dabigatran, rivaroxaban and apixaban appear to be appropriate agents in the heart failure population with atrial fibrillation and risk factors for stroke although there are dose-adjustments for renal insufficiency and these medications are contraindicated in advanced renal disease. As with the atrial fibrillation population as a whole, bleeding risk should be considered for every patient with heart failure prior to making recommendations regarding anticoagulation.     

Atrial fibrillation in patients with heart failure

Atrial fibrillation and heart failure are very common cardiac disorders, and both are associated with symptoms, significant morbidity, and mortality. Studies have attempted to determine the prognostic significance of atrial fibrillation in patients with heart failure. Whether atrial fibrillation is an independent risk factor of mortality remains controversial. Multiple trials using either pharmacologic or nonpharmacologic therapies in an attempt to manage atrial fibrillation have been developed. The purposes of this review are to present an overview of atrial fibrillation in patients with heart failure and to discuss the prevalence, prognostic significance, complications, mechanisms, and trials that have formed the therapies presently used.     

Atrial natriuretic peptide in congestive heart failure

Release of atrial natriuretic peptide (ANP) appears to be a compensatory response in congestive heart failure (CHF) that may counterbalance the adverse effects of stimulated renin-angiotensin and sympathetic nervous systems. We observed increased plasma ANP concentrations in CHF patients in New York Heart Association functional classes II to IV. The fact that such responses already become evident when a patient is in New York Heart Association class II supports the concept that ANP release may counteract the detrimental effects of stimulation of renin and the sympathetic nervous system even in the early phases of heart failure by promoting diuresis and natriuresis, as well as vasodilatation, thus reducing both pre- and afterload. When CHF is severe, however, the counterbalancing effects of ANP may be offset by vasoconstriction and fluid and sodium retention.     

Atrial fibrillation in patients with heart failure: pharmacologic options

Atrial fibrillation is a common arrhythmia in patients with heart failure. The presence of atrial fibrillation deteriorates cardiac function and increases the risk of thromboembolic events. The management of patients with atrial fibrillation in association with heart failure should consist of ventricular rate control, prevention of thromboembolic events, and conversion to normal sinus rhythm. Traditionally, digoxin has been widely used in patients with heart failure and atrial fibrillation; however, it does very little to restore sinus rhythm and requires the addition of another rate-limiting agent to control ventricular rate. The likelihood of successful cardioversion is dependent on the duration of heart failure and the degree of neurohormonal activation. The initiation of antiarrhythmic drug therapy in patients with heart failure should be guided by safety issues as well as consideration of potential benefits vs. risks associated with therapy. Amiodarone has been evaluated in numerous clinical trials and appears to be safe and effective when used in low dosage. Treatment with dofetilide is another option. Comparative studies with oral dofetilide vs. amiodarone are needed to evaluate their efficacy in restoration and maintenance of sinus rhythm in patients with heart failure. Such trials will clearly define the role of dofetilide in the treatment of atrial fibrillation. Routine prophylactic use of antiarrhythmic drug therapy for chronic atrial fibrillation in the setting of heart failure is not recommended due to a low efficacy rate and high proarrhythmic risk. Anticoagulation with warfarin and rate control remain the standard therapy. (c)2001 by CHF, Inc.     

Obstructive coronary atherosclerosis and ischemic heart disease: an elusive link!

In the current pathophysiological model of chronic ischemic heart disease (IHD), myocardial ischemia and exertional angina are caused by obstructive atherosclerotic plaque, and the clinical management of IHD is centered on the identification and removal of the stenosis. Although this approach has been in place for years, several lines of evidence, including poor prognostic impact, suggest that this direct relationship may present an oversimplified view of IHD. Indeed, a large number of studies have found that IHD can occur in the presence or absence of obstructive coronary artery disease and that atherosclerosis is just 1 element in a complex multifactorial pathophysiological process that includes inflammation, microvascular coronary dysfunction, endothelial dysfunction, thrombosis, and angiogenesis. Furthermore, the high recurrence rates underscore the fact that removing stenosis in patients with stable IHD does not address the underlying pathological mechanisms that lead to the progression of nonculprit lesions. The model proposed herein shifts the focus away from obstructive epicardial coronary atherosclerosis and centers it on the microvasculature and myocardial cell where the ischemia is taking place. If the myocardial cell is placed at the center of the model, all the potential pathological inputs can be considered, and strategies that protect the cardiomyocytes from ischemic damage, regardless of the causative mechanism, can be developed.