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.

Global right atrial mapping of human atrial flutter: the presence of posteromedial (sinus venosa region) functional block and double potentials : a study in biplane fluoroscopy and intracardiac echocardiography.

BACKGROUND: Previous studies of atrial flutter have found linear block at the crista terminalis; this was thought to predispose the patient to the arrhythmia. More recent observations, however, have demonstrated crista conduction. We sought to characterize the posterior boundary of atrial flutter. METHODS AND RESULTS: Patients with counterclockwise flutter (n=20), clockwise flutter (n=3), or both (n=5) were studied using two 20-pole catheters. Biplane fluoroscopy determined catheter positions. During counterclockwise flutter, craniocaudal activation occurred along the entire lateral and posterior right atrial walls. Septal activation proceeded caudocranially. In all patients, a line of block was seen in the posteromedial (sinus venosa) right atrium; this was manifested by the presence of double potentials where the upward and downward activations collided. Anatomic location was confirmed by intracardiac echocardiography in 9 patients. In patients with clockwise flutter, the line of block and double potentials were seen in the same location during counterclockwise flutter, but the activation sequence around the line of block was reversed. Pacing near the site of double potentials during sinus rhythm excluded a fixed line of block, and premature atrial complexes demonstrated functional block with manifest double potentials. In 2 patients, posterior ectopy organized to subsequently initiate isthmus-dependent atrial flutter. CONCLUSIONS: (1) A functional line of block is seen at the posteromedial (sinus venosa region) right atrium during counterclockwise and clockwise atrial flutter. (2) All lateral wall right atrial activation can be uniform during flutter, without linear block or double potentials in the region of the crista terminalis. (3) Activation at the site of posteromedial right atrial functional block can organize to subsequently initiate isthmus-dependent atrial flutter.

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.

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.

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.

Relation between mode of pacing and long-term survival in the very elderly.

OBJECTIVES: This study analyzes the relationship between pacing mode and long-term survival in a large group of very elderly patients (> or = 80 years old). BACKGROUND: The relationship between pacing mode and long-term survival is not clear. Because the number of very elderly who are candidates for pacing is increasing, issues related to pacemaker (PM) use in the elderly have important clinical and economic implications. METHODS: We retrospectively reviewed 432 patients (mean age, 84.5+/-3.9 years) who received their initial PM (ventricular in 310 and dual chamber in 122) between 1980 and 1992. Follow-up was complete (3.5+/-2.6 years). Observed survival was estimated by the Kaplan-Meier method. Age- and gender-matched cohorts from the Minnesota population were used for expected survival. Log-rank test and Cox regression hazard model were used for univariate and multivariate analyses. RESULTS: Patients with ventricular PMs appeared to have poor overall survival compared with those with dual-chamber PMs. Observed survival after PM implantation in high grade atrioventricular block (AVB) patients was significantly worse than expected survival of the age- and gender-matched population (p < 0.0001), whereas observed survival of patients with sinus node dysfunction was not significantly different from expected survival of the matched population (p = 0.413). By univariate analysis, ventricular pacing in patients with AVB appeared to be associated with poor survival compared with dual-chamber pacing (hazard ratio [HR] 2.08; 95% confidence interval [CI] 1.33 to 3.33). After multivariate analysis, this difference was no longer significant (HR 1.41; 95% CI 0.88 to 2.27). Independent predictors of all-cause mortality were number of comorbid illnesses, New York Heart Association functional class, left ventricular depression and older age at implant. Pacing mode was not an independent predictor of overall survival. Older age at implantation, diabetes mellitus, dementia, history of paroxysmal atrial fibrillation and earlier year of implantation were independent predictors of ventricular pacemaker selection. CONCLUSIONS: After PM implantation, long-term survival among very elderly patients was not affected by pacing mode after correction of baseline differences. Selection bias was present in pacing mode in the very elderly, with ventricular pacing selected for sicker and older patients, perhaps partly explaining the apparent "beneficial impact on survival" observed with dual-chamber pacing.

Utility of a single-stage isoproterenol tilt table test in adults: a randomized comparison with passive head-up tilt.

OBJECTIVES: This study was conducted to develop a time-efficient tilt table test. BACKGROUND: Current protocols of tilt table testing are quite time-consuming. This study was designed to assess the diagnostic value, tolerance and procedural time of a single-stage isoproterenol tilt table protocol. METHODS: A single-stage isoproterenol tilt table test was compared with the passive tilt table test. The study was prospectively designed in a randomized and crossover fashion. RESULTS: The study population consisted of 111 patients with a history of syncope (mean age 55 +/- 20 years). Of the total, 62 patients (56%; 95% confidence interval, 46% to 65%) had a positive vasovagal response during isoproterenol tilt table testing and 35 (32%; 23% to 41%) during passive tilt table testing (p = 0.002). The mean procedural times of the study population were 11.7 +/- 3.6 min and 36.9 +/- 13.3 min for isoproterenol and passive tilt table testing, respectively (p < 0.001). All patients tolerated single-stage isoproterenol testing. In the 23 control subjects (mean age 34 +/- 11 years), the apparent specificities were 91% (72% to 99%) and 83% (61% to 99%) for passive and single-stage tilt table testing, respectively. CONCLUSIONS: The single-stage isoproterenol tilt table test was more effective in inducing a positive vasovagal response in an adult population than the standard passive tilt table test, and it significantly reduced the procedural time. The increase in positive yield was associated with a moderate decrease in apparent specificity. These observations support the conclusion that single-stage tilt table testing could be a reasonable diagnostic option in patients undergoing syncope evaluation.

Adenosine: potential modulator for vasovagal syncope.

OBJECTIVES: This study examined the hypothesis that adenosine could provoke a vasovagal response in susceptible patients. Mechanisms of the vasovagal response were further explored by studying the adenosine-mediated reactions. BACKGROUND: Increased sympathetic activity is frequently observed before vasovagal syncope. Recent studies have demonstrated that adenosine, in addition to its direct bradycardiac and vasodilatory effects, can increase sympathetic discharge by activating cardiovascular afferent nerves. METHODS: The effects of adenosine and head-up tilt-table testing with or without isoproterenol were prospectively evaluated in 85 patients examined for syncope after negative results of electrophysiologic testing (51 men and 34 women, mean [+/- SD] age 61 +/- 17 years). Adenosine bolus injections of 6 mg and 12 mg were sequentially administered to patients in the upright position. The same protocol was implemented in 14 normal control subjects (7 men and 7 women, mean [+/- SD] age 38 +/- 10 years). RESULTS: Transient hypertension or tachycardia was observed in 57 (67%) and 20 (24%) patients after administration of 6 mg and 12 mg of adenosine, respectively, during the immediate phase (first 15 s), suggesting direct sympathetic activation. Hypotension and reflex tachycardia were observed in all patients during the delayed phase (15 to 60 s after adenosine injection), suggesting baroreceptor unloading. A vasovagal response was induced in 22 (26%) and 29 (34%) patients after adenosine administration and during tilt-table testing. Inducibility of a vasovagal response by these two methods was comparable (p = 0.12). Of the control subjects, one (7%) had a vasovagal response after adenosine administration and one (7%) had a positive response during tilt-table testing. CONCLUSIONS: These observations support the idea that adenosine is an endogenous modulator of the cardiac excitatory afferent nerves. Sympathetic activation by adenosine can be direct (i.e., cardiac excitatory afferent nerves) and indirect (i.e., vasodilation and reflex sympathetic activation). Adenosine could be an important modulator in triggering a vasovagal response in susceptible patients during examination for syncope.

Reconstitution of the solubilized cardiac sarcoplasmic reticulum potassium channel. Identification of a putative Mr approximately 80 kDa polypeptide constituent.

Recent evidence has indicated that potassium ion movement through sarcoplasmic reticulum (SR) K+ channels is an important countercurrent for Ca2+ release from SR. We used Chaps-solubilized SR vesicles and sucrose density gradient centrifugation to identify components of the canine cardiac SR K+ channel. To overcome the difficulty of the absence of a high-affinity specific ligand, we have successfully applied the planar lipid bilayer reconstitution technique to identify and functionally assay for the solubilized SR K+ channel. We found that Chaps solubilization of the channel did not change the protein's functional properties. The cardiac SR K+ channel sediments as a 15-20S protein complex. A polypeptide of Mr approximately 80 kDa was found to specifically comigrate with the 15-20S gradient fractions and might be a major constituent of the cardiac SR K+ channel.

Postural tachycardia syndrome (POTS).

In orthostatic intolerance, the patient develops symptoms while standing that are relieved when the patient assumes a supine position. Different degrees of orthostatic intolerance exist, but not a system of grading severity. We have developed a system that grades the severity of orthostatic intolerance by the three-pronged criteria of the rapidity of development and the severity of orthostatic symptoms, the ability of the subject to withstand orthostatic stresses, and the degree of interference with daily living. In this article, this system is presented, and one disorder, postural tachycardia syndrome (POTS), is examined in some detail.

Population-based study of the incidence of sudden unexplained death in epilepsy.

OBJECTIVE: To determine the population-based incidence of sudden unexplained death in epilepsy (SUDEP) and to determine the risk of SUDEP compared with the general population. BACKGROUND: Prior studies of SUDEP have described a wide range of incidence and have suffered from selection bias and other methodologic limitations. A population-based study of the incidence of SUDEP has never been performed. Furthermore, the risk of sudden death in the epilepsy population has not been compared with that of the general population. METHODS: All deaths in persons whose epilepsy was diagnosed between 1935 and 1994 in Rochester, MN, were reviewed. The rate of SUDEP was compared with the expected rate of sudden death in the general population for patients age 20 to 40 years to determine the standardized mortality ratio (SMR). RESULTS: We identified nine cases of SUDEP. SUDEP accounted for 8.6% (7 of 81) of the deaths in persons 15 to 44 years of age. The incidence of SUDEP was 0.35 per 1,000 person-years. SMR for SUDEP was 23.7 (95% confidence interval, 7.7 to 55.0) compared with the general population. CONCLUSIONS: The incidence of SUDEP in our study was 0.35 per 1,000 person-years. SUDEP was responsible for 1.7% of deaths in our cohort. SUDEP is a rare cause of death in the epilepsy population but exceeds the expected rate of sudden death in the general population by nearly 24 times.

Long-term survival after permanent pacemaker implantation for sick sinus syndrome.

In this population-based study, long-term survival and prognostic factors were examined in 148 patients, 55 men and 93 women, from Olmsted County, Minnesota, who had permanent pacemaker implantation for sick sinus syndrome between 1969 and 1991. The overall survival for patients who had received a permanent pacemaker for sick sinus syndrome was significantly worse than that of an age- and sex-matched control population (p < 0.0001). The increased mortality was attributable at least in part to the presence of structural heart disease in patients with sick sinus syndrome who had undergone permanent pacemaker implantation (82 of 148 patients, 55%). Survival of patients with isolated sick sinus syndrome was comparable (p = 0.6729), whereas in patients with structural heart disease it was significantly worse than expected (p < 0.0001). Symptoms were eliminated or improved in 116 patients (78%) after pacemaker implantation. Multivariate analysis identified congestive heart failure, valvular heart disease, history of stroke or transient ischemic attack, and age as independent risk factors for mortality. However, there was a trend toward decreased survival in patients who had received ventricular pacing compared with those who had received dual-chamber pacing, but this difference did not reach statistical significance (p = 0.0556). The mode of pacing was not an independent risk factor (p = 0.23). The observed survival of patients aged < 80 years was significantly worse than expected (p < 0.0001), whereas that of patients aged > or = 80 years was similar to the expected (p = 0.22).

Long-term survival after pacemaker implantation for heart block in patients > or = 65 years.

Permanent pacing can prevent recurrent symptoms and reduce mortality in elderly patients with symptomatic high-degree atrioventricular (AV) block. However, long-term survival with respect to comparable control subjects has not been well defined. In our study, relative long-term survival and prognostic predictors after permanent pacemaker implantation for symptomatic high-degree AV block were assessed among all residents of Olmsted County, Minnesota, who were > or = 65 years old. Of the 154 patients, 77 were men and 77 were women (mean age 80 +/- 7 years). Follow-up was 0.1 to 19.8 years (mean 4.2 +/- 2.8). Sixty-nine patients had isolated AV block and 85 had coexisting heart disease. Observed survival at 1, 3, 5, and 10 years was 85%, 68%, 52%, 21%, and 72%, 50%, 31%, 11% for patients with isolated AV block and patients with coexisting heart disease, respectively (p = 0.006). Observed survival in patients 65 to 79 years old with isolated AV block was comparable to age- and sex-matched cohorts (p = 0.53), but in patients aged > or = 80 years, it was less than that for control subjects (p = 0.014). In patients with coexisting heart disease, observed survival was less than that for control subjects in patients 65 to 79 years old (p < 0.001) and > or = 80 years (p < 0.001). Multivariate analysis identified congestive heart failure, chronic obstructive pulmonary disease, age, syncope, insulin-dependent diabetes mellitus, and male gender as independent predictors of increased mortality.

Value and limitations of two-dimensional echocardiography in predicting myocardial infarct size.

To investigate the quantitative relations between the severity of regional wall motion abnormalities and segmental infarct size and between the severity of overall left ventricular dysfunction and global infarct size, a clinicopathologic study was undertaken of 30 patients who had a 2-dimensional (2-D) echocardiogram within 7 days before death. The severity of regional wall motion abnormalities was graded for each segment with a 2-D echocardiographic 14-segment model. The severity of global left ventricular dysfunction was calculated as the mean of the visualized regional wall motion scores. On pathologic examination of autopsy specimens, segmental infarct size was estimated as a percentage of the segmental cross-sectional area. The global infarct size was expressed as a percentage of the total left ventricular mass. At the segmental level, regional wall motion score was positively correlated (r = 0.53) with the segmental infarct size. The sensitivity and specificity of detecting infarcted segments by abnormal wall motion scores were 81 and 71%, respectively. All dyskinetic segments revealed infarct size of greater than or equal to 10%. The wall motion score index was positively correlated (r = 0.52) with the global infarct size. The mean global infarct size was 7% for the 8 patients with a wall motion score index of less than 2, which was significantly lower than the mean of 27% for the 22 patients with a wall motion score index of greater than or equal to 2 (p less than 0.001). A 2-D echocardiogram is sensitive and specific in detecting infarcted segments and can be useful in quantitating myocardial damage after myocardial infarction.

Sudden unexpected nontraumatic death in 54 young adults: a 30-year population-based study.

The objective of this study was to evaluate the incidence and correlates of sudden unexpected nontraumatic death among young adults in a well-surveyed population. The incidence and pathogenesis of sudden unexpected nontraumatic death in a young adult population (aged 20 to 40 years old) have not been well defined. All residents 20 to 40 years old from Olmsted County, Minnesota, who had nontraumatic sudden death between 1960 and 1989 were included. Histologic and gross cardiac specimens were examined. The incidence of sudden death was estimated based on the ratio of number of observed events to relative census data for the Olmsted County population from the last 3 decades. Statistical comparisons between age decades were obtained with the chi-square test. Incidence trends were tested using Poisson regression. Of the 54 subjects, 19 were women (4.1/10(5) population annually) and 35 were men (8.7/10(5) population annually). An increase in incidence of sudden death was evident in men. Causes of death included coronary artery disease, noncardiovascular disease, suspected primary arrhythmia, vascular disease, myocarditis, hypertrophic cardiomyopathy, and unknown causes. Gross and histologic features suggestive of right ventricular dysplasia were found in 9 subjects (17%), but 6 of these 9 had other established causes of death. Of the 27 sudden deaths between 1980 and 1989, 9 (33%) had a history of cocaine abuse. A trend in increasing incidence of sudden death in young men is noted. A high prevalence of cocaine abuse was observed in young adults who died suddenly. Histologic features of right ventricular dysplasia were prevalent but were not necessarily the primary cause of death.

Hemodynamic analysis during isoproterenol-induced vasovagal syncope.

An isoproterenol-mediated increase in cardiomotor tone and a decrease in afterload contribute to the induction of vasovagal syncope. Contrary to conventional belief, a significant decrease in preload is not observed immediately before isoproterenol-induced syncope.

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.

Mechanisms of adenosine-mediated actions on cellular and clinical cardiac electrophysiology.

OBJECTIVE: To provide insights into the molecular mechanisms of adenosine-mediated cardiac cellular electrophysiology and how information about these mechanisms can be used to facilitate diagnostic and therapeutic approaches to various clinical arrhythmias. DESIGN: A review of (1) adenosine metabolism and receptors in the cardiac system, (2) adenosine-mediated signal transduction pathways in the regulation of cellular electrophysiology in various cardiac cell types, and (3) the clinical usefulness of adenosine in cardiac electrophysiology is presented. RESULTS: The effects of adenosine on cardiac electrophysiologic properties are consequences of complex interactions among the specific cardiac target structures, the density and type of adenosine receptors, and the effector systems. The easy application of adenosine and its short half-life, favorable side-effects profile, and electrophysiologic properties make it an excellent diagnostic and therapeutic tool for the initial assessment of various tachyarrhythmias. CONCLUSION: The direct adenosine-activated KACh (potassium acetylcholine) channel signal transduction system explains the effects of adenosine on the sinus node, atrioventricular node, and atrial myocardium. The indirect adenosine-inhibited adenylate cyclase system accounts for its negative inotropic effects on the catecholamine-entrained contractility in atrial and ventricular myocardium. Because of the recent purification and cloning of adenosine receptors and subunits of G proteins, additional adenosine-mediated electrophysiologic mechanisms can be explored.

Survivors of acute myocardial infarction: who is at risk for sudden cardiac death?

Coronary artery disease is the leading cause of death in the United States. Approximately half of the deaths attributable to coronary artery disease are sudden cardiac deaths. A logical approach to prevention of sudden death is to identify those who are at risk and then to initiate effective therapy. Left ventricular dysfunction, frequent ventricular ectopic activity, nonsustained ventricular tachycardia, and late potentials have been identified as markers for increased risk of sudden cardiac death. The sensitivity and specificity of these risk factors vary, and the positive predictive power is less than satisfactory. The value of invasive electrophysiologic testing for risk stratification in the general postinfarction patient population remains unclear. In addition to these diagnostic difficulties, prevention of sudden death also has been limited by imperfect efficacy and potential lethal effects of the currently available antiarrhythmic agents. Automatic implantable defibrillators are effective for aborting sudden death; however, the potential for more general use of automatic defibrillators in asymptomatic but high-risk postinfarction patients has not been evaluated.