Salt supplementation in the management of orthostatic intolerance: Vasovagal syncope and postural orthostatic tachycardia syndrome.

Salt supplementation is a common non-pharmacological approach to the management of recurrent orthostatic syncope or presyncope, particularly for patients with vasovagal syncope (VVS) or postural orthostatic tachycardia syndrome (POTS), although there is limited consensus on the optimal dosage, formulation and duration of treatment. Accordingly, we reviewed the evidence for the use of salt supplementation to reduce susceptibility to syncope or presyncope in patients with VVS and POTS. We found that short-term (~3 months) salt supplementation improves susceptibility to VVS and associated symptoms, with little effect on supine blood pressure. In patients with VVS, salt supplementation is associated with increases in plasma volume, and an increase in the time taken to provoke a syncopal event during orthostatic tolerance testing, with smaller orthostatic heart rate increases, enhanced peripheral vascular responses to orthostatic stress, and improved cerebral autoregulation. Responses were most pronounced in those with a baseline sodium excretion <170 mmol/day. Salt supplementation also improved symptoms, plasma volume, and orthostatic responses in patients with POTS. Salt supplementation should be considered for individuals with recurrent and troublesome episodes of VVS or POTS without cardiovascular comorbidities, particularly if their typical urinary sodium excretion is low, and their supine blood pressure is not elevated. The efficacy of the response, in terms of the improvement in subjective and objective markers of orthostatic intolerance, and any potential deleterious effect on supine blood pressure, should be routinely monitored in individuals on high salt regimes.

Overview of management of atrial fibrillation in symptomatic elderly patients: pharmacologic therapy versus AV node ablation.

Atrial fibrillation is an abnormal heart rhythm affecting the upper chambers of the heart in which uncoordinated electrical depolarizations lead to ineffective contractions. Approximately five million patients in the US have atrial fibrillation, and this number is expected to double to 10 million over the next 30 years. Advancing age is a major risk factor for the development of atrial fibrillation; new cases of atrial fibrillation are diagnosed in men over age 80 at the rate of 2% per year. Although several drugs are available for management of atrial fibrillation, the efficacy of these drugs may be limited in elderly patients. In this review, we provide an overview of management of atrial fibrillation, with special emphasis on pharmacologic therapy versus arteriovenous (AV) node ablation in symptomatic elderly patients.

Epidemiology of reflex syncope.

Cost-effective diagnostic approaches to reflex syncope require knowledge of its frequency and causes in different age groups. For this purpose we reviewed the available literature dealing with the epidemiology of reflex syncope. The incidence pattern of reflex syncope in the general population and general practice is bimodal with peaks in teenagers and in the elderly. In the young almost all cases of transient loss of consciousness are due to reflex syncope. The life-time cumulative incidence in young females ( congruent with 50 %) is about twice as high as in males ( congruent with 25 %). In the elderly, cardiac causes, orthostatic and postprandial hypotension, and the effects of medications are common, whereas typical vasovagal syncope is less frequent. In emergency departments, cardiac causes and orthostatic hypotension are more frequent especially in elderly subjects. Reflex syncope, however, remains the most common cause of syncope, but all-cause mortality in subjects with reflex syncope is not higher than in the general population. This knowledge about the epidemiology of reflex syncope can serve as a benchmark to develop cost-effective diagnostic approaches.

Database Conference January 27-30, 2000, Washington D.C.--Do existing databases answer clinical questions about geriatric cardiovascular disease and stroke?

EXECUTIVE SUMMARY: Most randomized, controlled trials evaluating the effectiveness of pharmaceutical, surgical, and device interventions for the prevention and treatment of cardiovascular disease have excluded patients over 75 years of age. Consequently, the use of these therapies in the older population is based on extrapolation of safety and effectiveness data obtained from younger patients. However, there are many registries and observational databases that contain large amounts of data on patients 75 years of age and older, as well as on younger patients. Although conclusions from such data are limited, it is possible to define the characteristics of patients who did well and those who did poorly. The goal of this conference was to convene the principal investigators of these databases, and others in the field of geriatric cardiology, to address questions relating to the safety and effectiveness of treatment interventions for several cardiovascular conditions in the elderly. Seven committees discussed the following topics: (I) Risk Factor Modification in the Elderly; (II) Chronic Heart Failure; (III) Chronic Coronary Artery Disease: Role of Revascularization; (IV) Acute Myocardial Infarction; (V) Valve Surgery in the Elderly; (VI) Electrophysiology, Pacemaker, and Automatic Internal Cardioverter Defibrillators Databases; (VII) Carotid Endarterectomy in the Elderly. The chairs of these committees were asked to invite principal investigators of key databases in each of these areas to discuss and prepare a written statement concerning the available safety and efficacy data regarding interventions for these conditions and to identify and prioritize areas for future study. The ultimate goal is to stimulate further collaborative outcomes research in the elderly so as to place the treatment of cardiovascular disease on a more scientific basis.

Intra-atrial conduction block along the mitral valve annulus during accessory pathway ablation: evidence for a left atrial "isthmus".

INTRODUCTION: We observed a change in the atrial activation sequence during radiofrequency (RF) energy application in patients undergoing left accessory pathway (AP) ablation. This occurred without damage to the AP and in the absence of a second AP or alternative arrhythmia mechanism. We hypothesized that block in a left atrial "isthmus" of tissue between the mitral annulus and a left inferior pulmonary vein was responsible for these findings. METHODS AND RESULTS: Electrophysiologic studies of 159 patients who underwent RF ablation of a left free-wall AP from 1995 to 1999 were reviewed. All studies with intra-atrial conduction block resulting from RF energy delivery were identified. Fluoroscopic catheter positions were reviewed. Intra-atrial conduction block was observed following RF delivery in 11 cases (6.9%). This was evidenced by a sudden change in retrograde left atrial activation sequence despite persistent and unaffected pathway conduction. In six patients, reversal of eccentric atrial excitation during orthodromic reciprocating tachycardia falsely suggested the presence of a second (septal) AP. A multipolar coronary sinus catheter in two patients directly demonstrated conduction block along the mitral annulus during tachycardia. CONCLUSION: An isthmus of conductive tissue is present in the low lateral left atrium of some individuals. Awareness of this structure may avoid misinterpretation of the electrogram during left AP ablation and may be useful in future therapies of atypical atrial flutter and fibrillation.

Congenital long QT syndromes and Brugada syndrome: the arrhythmogenic ion channel disorders.

Congenital long QT syndromes (LQTS) and Brugada syndrome are hereditary disorders of cardiac ion channels which result in life-threatening cardiac arrhythmias or sudden cardiac death in patients with anatomically normal hearts. The pathogenesis of these dramatic events has been partially elucidated with the identification of the individual ion channels involved and understanding of the effect of some disease-causing mutations on the membrane currents and action potential. The clinical spectrum of congenital LQTS is broader than previously thought and involves certain patients previously diagnosed with idiosyncratic drug-induced proarrhythmia. The initial treatment for congenital LQTS patients involves beta-blockers in most cases. Indications for implantable cardioverter-defibrillator (ICD) or pace-maker (PM) implantation in selected individuals continue to evolve.

Long-term survival after ablation of the atrioventricular node and implantation of a permanent pacemaker in patients with atrial fibrillation.

BACKGROUND: In patients with atrial fibrillation that is refractory to drug therapy, radio-frequency ablation of the atrioventricular node and implantation of a permanent pacemaker are an alternative therapeutic approach. The effect of this procedure on long-term survival is unknown. METHOD: We studied all patients who underwent ablation of the atrioventricular node and implantation of a permanent pacemaker at the Mayo Clinic between 1990 and 1998. Observed survival was compared with the survival rates in two control populations: age- and sex-matched members of the Minnesota population between 1970 and 1990 and consecutive patients with atrial fibrillation who received drug therapy in 1993. RESULTS: A total of 350 patients (mean [+/-SD] age, 68+/-11 years) were studied. During a mean of 36+/-26 months of follow-up, 78 patients died. The observed survival rate was significantly lower than the expected survival rate based on the general Minnesota population (P<0.001). Previous myocardial infarction (P<0.001), a history of congestive heart failure (P=0.02), and treatment with cardiac drugs after ablation (P=0.03) were independent predictors of death. Observed survival among patients without these three risk factors was similar to expected survival (P=0.43). None of the 26 patients with lone atrial fibrillation died during follow-up (37+/-27 months). The observed survival rate among patients who underwent ablation was similar to that among 229 controls with atrial fibrillation (mean age, 67+/-12 years) who received drug therapy (P=0.44). CONCLUSIONS: In the absence of underlying heart disease, survival among patients with atrial fibrillation after ablation of the atrioventricular node is similar to expected survival in the general population. Long-term survival is similar for patients with atrial fibrillation, whether they receive ablation or drug therapy. Control of the ventricular rate by ablation of the atrioventricular node and permanent pacing does not adversely affect long-term survival.

Is sinus node modification appropriate for inappropriate sinus tachycardia with features of postural orthostatic tachycardia syndrome?

Inappropriate sinus tachycardia and postural orthostatic tachycardia are ill-defined syndromes with overlapping features. Although sinus node modification has been reported to effectively slow the sinus rate, long-term clinical response has not been adequately assessed. Furthermore, whether patients with postural orthostatic tachycardia would benefit from sinus node modification is unknown. The study prospectively assessed the short- and long-term clinical outcomes of seven consecutive female patients with postural orthostatic tachycardia syndrome and inappropriate sinus tachycardia who were treated with sinus node modification. The study was conducted in a tertiary care center. The electrophysiological and clinical responses were prospectively assessed as defined by autonomic function testing, including Valsalva maneuver, deep breathing, tilt table testing, and quantitative sudomotor axonal reflex testing. Among the study population (mean age was 41+/-6 years), 5 (71%) patients had successful sinus node modification. At baseline, heart rates were 101+/-12 beats/min before modification and 77+/-9 beats/min after modification (P = 0.001). With isoproterenol, heart rates were 136+/-9 and 105+/-12 beats/min (P = 0.002) before and after modification, respectively. The mean heart rate during 24-hour Holter monitoring was also significantly reduced: 96+/-9 and 72+/-6 beats/min (P = 0.005) before and after modification, respectively. Despite the significant reduction in heart rate, autonomic symptom score index (based on ten categories of clinical symptoms) was unchanged before (15.6+/-4.1) and after (14.6+/-3.6) sinus node modification (P = 0.38). Sinus rate can be effectively slowed by sinus node modification. Clinical symptoms are not significantly improved after sinus node modification in patients with inappropriate sinus tachycardia and postural orthostatic tachycardia. A primary subtle autonomic disregulation is frequently present in this population. Sinus node modification is not recommended in this patient population.

Syncope in the elderly: new trends in diagnostic approach and nonpharmacologic management.

Syncope in the elderly is an important health care issue because of the large patient population, challenging diagnostic and therapeutic approaches, and potentially devastating consequences. Significant comorbidity and atypical clinical presentations render a precise determination of the cause of syncope difficult. Recent studies suggest that noninvasive tests, such as carotid sinus massage or tilt-table testing, can be helpful in the diagnostic workup. It has been shown that permanent pacemaker therapy benefits elderly patients with carotid sinus hypersensitivity, and younger patients with recurrent vasovagal syncope. The implantable wireless loop recorder can be effective in documenting transient arrhythmias as causes of syncope in selected patients. Elderly patients with syncope and a low ejection fraction are at increased risk of sudden death due to malignant ventricular arrhythmia. Electrophysiologic study and electrophysiology-guided therapy should be considered in this segment of the population.

Epidemiology and natural history of atrial fibrillation: clinical implications.

With a substantial impact on morbidity and mortality, the growing "epidemic" of atrial fibrillation (AF) intersects with a number of conditions, including aging, thromboembolism, hemorrhage, hypertension and left ventricular dysfunction. Currently, the epidemiology and natural history of AF govern all aspects of its clinical management. The ongoing global investigative efforts toward understanding AF are also driven by epidemiologic findings. New developments, by affecting the natural history of the disease, could eventually alter the nature of decision making in patients with AF. The crucial issue of rate versus rhythm control awaits completion of the AF Follow-up Investigation of Rhythm Management trial. The processes of electrical and structural remodeling that perpetuate AF appear to be reversible. In the era of functional genomics, the molecular basis of this ubiquitous arrhythmia is in the process of being defined. Unraveling the molecular genetics of AF might provide new insights into the structural and electrical phenotypes resulting from genetic mutations and, as such, new approaches to treatment of this arrhythmia at the ion channel and cellular levels. Thus, current adverse trends are superimposed on a background of a rapidly developing knowledge base and potentially exciting new therapeutic options. Consequently, an understanding of the epidemiology and natural history of AF is crucial to the future allocation of resources and the utilization of an expanding range of therapies aimed at reducing the impact of this disease on a changing patient population.

Potassium channel openers: therapeutic potential in cardiology and medicine.

Potassium (K(+)) channel openers (KCOs) define a class of chemically diverse agents that share a common molecular target, the metabolism-regulated ATP-sensitive K(+) (K(ATP)) channel. In view of the unique function that K(ATP) channels play in the maintenance of cellular homeostasis, this novel class of ion channel modulators adds to existent pharmacotherapy with potential in promoting cellular protection under conditions of metabolic stress. Indeed, experimental studies have demonstrated broad therapeutic potential for KCOs, including roles as cardioprotective agents, vasodilators, bronchodilators, bladder relaxants, anti-epileptics, insulin secretagogues and promoters of hair growth. However, clinical experience with these drugs is limited and their place in patient management needs to be fully established.

Role of programmed ventricular stimulation and implantable cardioverter defibrillators in patients with idiopathic dilated cardiomyopathy and syncope.

The aim of this study was to evaluate the role of programmed ventricular stimulation and ICDs in patients with idiopathic dilated cardiomyopathy and syncope. Between 1990 and 1998, 54 (mean age 67+/-11 years, 76% men) patients presented with idiopathic dilated cardiomyopathy and syncope. An electrophysiological study was done in 37 of the 54 patients: 10 had inducible sustained monomorphic ventricular tachycardia, 12 had conduction system disease or neurocardiogenic syncope, and 15 had a normal study. Overall, 17 patients received an ICD, 15 patients received a pacemaker, and 22 patients received no device. Nine of the 15 patients with a negative electrophysiological study eventually received an ICD: 3 because they were considered high risk and 6 because of recurrent syncope or presyncope. In the 17 patients who received an ICD, incidence of appropriate shocks at 1 and 3 years was 47% and 74%, respectively, in the inducible sustained monomorphic ventricular tachycardia group, and 40% and 40%, respectively, in the group without inducible sustained monomorphic ventricular tachycardia (P = 0.29, log-rank test). In conclusion, programmed ventricular stimulation is not useful in risk stratification of patients with idiopathic dilated cardiomyopathy and syncope and may delay necessary ICD implantation.

Electrophysiologic characteristics of diverse accessory pathway locations of antidromic reciprocating tachycardia.

This study assessed antidromic reciprocating tachycardia (ART) in patients with paraseptal accessory pathways (APs). Previous clinical experience suggests that paraseptal APs are unable to serve as the anterograde limb during ART. Based on the reentry wavelength concept, we hypothesized that anatomic location of a paraseptal AP may not preclude occurrence of ART. If wavelength criteria were met due to prolonged conduction time retrogradely in the atrioventricular node or anterogradely in the AP, ART may be sustained. All patients who had ART in the electrophysiologic laboratory at our institution (1991 to 1998) were studied. Based on fluoroscopically guided electrophysiologic mapping and radiofrequency ablation, AP location was classified as paraseptal, posterior, or lateral. Conduction time and refractoriness measurements were made for all components of the ART circuit. Of 24 patients with ART, 5 (21%) had ART utilizing a paraseptal AP. Anterograde conduction time through the AP and retrograde atrioventricular nodal conduction time were significantly longer in patients with paraseptal versus lateral pathways. Isoproterenol was required for ART induction in 38% of patients with a posterior AP, 36% with lateral AP location, but not in patients with a paraseptal AP. There were no significant differences in tachycardia cycle length or refractoriness of anterograde and/or retrograde components of the macroreentry circuit between the 3 pathway locations. Thus, ART can occur in patients with a paraseptal AP. Slower anterograde pathway conduction, or retrograde atrioventricular nodal conduction renders the wavelength critical for completion of the antidromic re-entrant circuit.

Vasovagal syncope.

BACKGROUND: Vasovagal syncope is the most common type of syncope and is one of the most difficult types to manage. PURPOSE: This article reviews the status of mechanisms, diagnosis, and management of vasovagal syncope. DATA SOURCES: MEDLINE search for English-language and German-language articles on vasovagal syncope published up to June 1999. STUDY SELECTION: Case reports and series, clinical trials, research investigations, and review articles from peer-reviewed journals. DATA EXTRACTION: Findings were summarized and discussed individually. Summaries were made in table format. Statistical analysis of combined data was inappropriate because of differences among studies in patient selection, testing, and follow-up. DATA SYNTHESIS: The population of patients with vasovagal syncope is highly heterogeneous. Triggers of vasovagal syncope are likely to be protean, and many potential central and peripheral triggers have been identified. The specific mechanisms underlying the interactions among decreased preload, sympathetic and parasympathetic modulation, vasodilation, and cardioinhibition remain unknown. Tilt-table testing is a widely used diagnostic tool. The test results should be interpreted in the context of patients' clinical presentations and with an understanding of the sensitivity and specificity of the test. Assessment of therapeutic outcomes has been difficult, primarily because of patient heterogeneity, the large number of pharmacologic agents available for therapy, and the sporadic nature of the syndrome complex. CONCLUSIONS: Vasovagal syncope is a common clinical syndrome that has complex and variable mechanisms and is difficult to manage. Advancements are being made in laboratory investigations of its triggering mechanisms. Randomized, controlled trials of pharmacologic and nonpharmacologic interventions are needed. Mechanism-targeted therapeutic trials may improve clinical outcomes.

Low concentrations of 17beta-estradiol protect single cardiac cells against metabolic stress-induced Ca2+ loading.

OBJECTIVES: The main objective of the present study was to determine whether low physiological levels of estrogen directly protect cardiac cells against metabolic stress. BACKGROUND: The beneficial effect of estrogens on the cardiovascular system has been traditionally ascribed to decrease in peripheral vascular resistance and to an antiatherogenic action. Whether physiological concentrations of 17beta-estradiol (E2) are also able to protect cardiomyocytes against metabolic insult directly is unknown. METHODS: Isolated ventricular cardiomyocytes were loaded with the Ca2+-sensitive fluorescent dye Fluo-3 and imaged by a digital epifluorescence imaging system. In cardiac cells preincubated with hormones and/or drugs for 8 h, metabolic stress was induced by addition and removal of 2,4-dinitrophenol (DNP). RESULTS: In cardiomyocytes, a 3-min-long exposure to chemical hypoxia, followed by reoxygenation, produced intracellular Ca2+ loading independently of gender (female: 729 +/- 88 nmol/liter; male: 778 +/- 97 nmol/liter). Pretreatment with E2 (10 nmol/liter) significantly reduced the magnitude of hypoxia/reoxygenation-induced Ca2+ loading in female (E2-treated: 298 +/- 39 nmol/liter; untreated: 729 +/- 88 nmol/liter), but not in male (E2-treated: 1029 +/- 177 nmol/liter; untreated: 778 +/- 97 nmol/liter) cardiac cells. The protective action of E2 was not mimicked by the inactive estrogen stereoisomer, 10 nmol/liter 17alpha estradiol (17alpha estradiol-treated: 886 +/- 122 nmol/liter; untreated: 729 +/- 88 nmol/liter), and was abolished by tamoxifen (1 micromol/liter), which acts as an antagonist of E2 on estrogen receptors (E2 plus tamoxifen-treated: 702 +/- 98 nmol/liter; untreated: 729 +/- 88 nmol/liter). CONCLUSIONS: In a gender-dependent manner, E2 directly protects cardiac cells against hypoxia-reoxygenation injury through an estrogen receptor-mediated mechanism. Such property of E2 may contribute to cardioprotection in the female gender.

Distinct hemodynamic profiles in patients with vasovagal syncope: a heterogeneous population.

OBJECTIVE: The objective was to investigate mechanisms of vasovagal syncope by identifying laboratory techniques that characterize cardiovascular profiles in patients with vasovagal syncope. BACKGROUND: The triggering mechanisms of vasovagal syncope are complex. The patient population is likely heterogeneous. We hypothesized that distinct hemodynamic profiles are definable with provocative maneuvers. METHODS: Three groups of subjects were matched for age and gender: 16 patients with a history of syncope and an inducible vasovagal response during passive tilt table testing (70 degrees, 45 min, group I), 16 with a history of syncope, negative passive tilt table testing but positive isoproterenol tilt table testing (0.05 microg/kg per min, 70 degrees, 10 min, group II), and 16 control subjects. Beat-to-beat hemodynamic functions were determined noninvasively by photo-plethysmography and impedance cardiography. RESULTS: At baseline, hemodynamic functions were not different among the three groups (supine). In response to tilt before any symptoms developed, total peripheral resistance decreased 9% +/- 14% in group I from baseline supine to tilt position but increased 27% +/- 18% in group II and 28% +/- 17% in controls (p < 0.001). Responses to isoproterenol were not significantly different between group II and controls in supine position. In response to tilt during isoproterenol infusion before any symptoms developed, total peripheral resistance decreased 24% +/- 20% in group II and increased 20% +/- 48% in controls (p = 0.002). CONCLUSIONS: Group I patients may have impaired ability to increase vascular resistance during orthostatic stress. The inability to overcome isoproterenol-induced vasodilatation during tilt is important in triggering a vasovagal response in group II patients. These data suggest that the population with vasovagal response is heterogeneous. Distinct hemodynamic profiles in response to various provocative maneuvers are definable with noninvasive, continuous monitoring techniques.

First evidence of premature ventricular complex-induced cardiomyopathy: a potentially reversible cause of heart failure.

Tachycardia-induced cardiomyopathy is a well-recognized and reversible condition, but left ventricular dysfunction due to frequent isolated premature ventricular complexes (PVCs) has not been reported. We observed resolution of dilated cardiomyopathy in a patient after a focal source of PVCs was eliminated by radiofrequency ablation. In a subset of patients with heart failure, PVC-induced cardiomyopathy may be a potentially reversible cause of left ventricular dysfunction.