Aerobic training does not alter CRP in apparently healthy, untrained men.

AIM: Regular aerobic exercise may reduce cardiovascular disease (CVD) risk by lowering the concentration of inflammatory markers, such as C-reactive protein (CRP). While studies in diseased populations have shown significant decreases in CRP concentrations with regular aerobic training, little has been conclusively determined regarding the effects of aerobic training on CRP concentrations in apparently healthy, untrained populations. Aim of the study was to examine the effects of a 17-wk half marathon training program (TP) on CRP concentrations, aerobic fitness, and body composition in apparently healthy, untrained men. METHODS: Twenty men (29.3±1.0 y) enrolled as training subjects (TRN) in a 17-wk half marathon TP. An additional 22 men (27.8±1.4 y) served as controls (CON). Fasting blood samples were taken at four time points over the TP and were analyzed for CRP and interleukin-6 (IL-6) concentrations. Aerobic capacity (VO2max) and body fat percent (BF%) were measured before and after the TP. RESULTS: No significant post-training changes in CRP (P=0.70) or IL-6 concentrations (P=0.67) were seen in TRN as a result of the TP, despite significant improvements in VO2max (42.2±1.9 ml∙kg-1∙min⁻¹, P<0.0001) and significant reductions in resting heart rate (P=0.004), BF% (P=0.03), and body mass index (BMI, P=0.05). No significant changes in CRP, VO2max, BMI, or BF% were detected in CON over time. CONCLUSION: Regular aerobic training does not appear to affect CRP concentrations in apparently healthy, untrained men despite significant improvements in bodyweight, BF%, BMI, and VO2max.

Utility of exercise testing to assess athletes for post COVID-19 myocarditis.

Purpose: This study assessed a functional protocol to identify myocarditis or myocardial involvement in competitive athletes following SARS-CoV2 infection. Methods: We prospectively evaluated competitive athletes (n = 174) for myocarditis or myocardial involvement using the Multidisciplinary Inquiry of Athletes in Miami (MIAMI) protocol, a median of 18.5 (IQR 16-25) days following diagnosis of COVID-19 infection. The protocol included biomarker analysis, ECG, cardiopulmonary stress echocardiography testing with global longitudinal strain (GLS), and targeted cardiac MRI for athletes with abnormal findings. Patients were followed for median of 148 days. Results: We evaluated 52 females and 122 males, with median age 21 (IQR: 19, 22) years. Five (2.9%) had evidence of myocardial involvement, including definite or probable myocarditis (n = 2). Three of the 5 athletes with myocarditis or myocardial involvement had clinically significant abnormalities during stress testing including ventricular ectopy, wall motion abnormalities and/or elevated VE/VCO2, while the other two athletes had resting ECG abnormalities. VO2max, left ventricular ejection fraction and GLS were similar between those with or without myocardial involvement. No adverse events were reported in the 169 athletes cleared to exercise at a median follow-up of 148 (IQR108,211) days. Patients who were initially restricted from exercise had no adverse sequelae and were cleared to resume training between 3 and 12 months post diagnosis. Conclusions: Screening protocols that include exercise testing may enhance the sensitivity of detecting COVID-19 related myocardial involvement following recovery from SARS-CoV2 infection.

The ionic mechanism of reperfusion-induced early afterdepolarizations in feline left ventricular hypertrophy.

Left ventricular hypertrophy (LVH) potentiates reperfusion-associated ventricular fibrillation. To study the mechanism responsible, patch-clamp techniques were used to evaluate transmembrane ionic currents during "reperfusion" after a CN(-)-induced metabolic surrogate for ischemia in isolated myocytes from a feline model of experimental LVH. Reperfusion caused the generation of early afterdepolarizations (EADs) from an average take-off potential of -33 mV in LVH cells but not in cells from normal hearts. 10 min after initiating reperfusion of normal cells, action potential duration (APD) at 50% repolarization (APD50) lengthened from 198 +/- 41 to 233 +/- 57 ms whereas in LVH cells APD50 lengthened from 262 +/- 84 to 349 +/- 131 ms (P < 0.05). Among the LVH cells, APD50 lengthening was significantly greater in the cells that had developed EADs. During reperfusion, steady state outward current in the voltage range of the action potential plateau (between -20 and +20 mV) was reduced from the control values in LVH cells but not in normal cells. Reperfusion-related reduction of steady state outward current in LVH cells was abolished under experimental conditions in which L-type Ca2+ current was isolated from other classes of currents whereas it was still observed under the condition in which pure K+ currents could be recorded. Thus, reduction of steady state outward current due to the reduction of outward K+ current over the action potential plateau voltage range appears to be responsible for an excessive prolongation of APD, leading to the development of EADs.

Transverse spread and longitudinal dissociation in the distal A-V conducting system.

Isolated preparations of portions of the canine intraventricular conducting system were studied by microelectrode techniques in order to determine the nature of transverse spread and longitudinal dissociation of impulses in bundle branches and false tendons. Driving stimuli were delivered to an eccentric location on normal conducting tissue, and the arrival times of the propagating impulses were mapped along the length and width of the bundle branch, or along the false tendon ipsilateral and contralateral to the site of stimulation. The difference between the arrival times on the two sides was found to decrease progressively as a function of distance from the site of stimulation, the data suggesting that transverse spread of impulses involves propagation through transverse crossover points between the longitudinally oriented conducting elements. Impulses originating eccentrically became uniformly conducted across the transverse axis of bundle branches 8-15 mm from the level of the stimulating electrode, and of false tendons 2-4 mm from the stimulus site. True longitudinal dissociation, producing conduction maps different from those representing normal transverse propagation, was seen occasionally in tissue having longitudinally oriented strips of abnormal tissue. However, early premature stimulation commonly resulted in longitudinal temporal dissociation of the premature responses, possibly due to functional block in the transverse crossover fibers.

Dynamic behavior and autonomic regulation of ectopic atrial pacemakers.

BACKGROUND: Heart rate (HR) variability reflects the neural regulation of normal pacemaker tissue, but the autonomic nervous regulation of abnormal atrial foci originating outside the sinus node has not been well characterized. We compared the HR variability of tachycardias originating from the ectopic foci and the sinus node. METHODS AND RESULTS: R-R-interval variability was analyzed from 24-hour Holter recordings in 12 patients with incessant ectopic atrial tachycardia (average HR 107+/-14 bpm), 12 subjects with sinus tachycardia (average HR 106+/-9 bpm), and 24 age- and sex-matched subjects with normal sinus rhythm (average HR 72+/-8 bpm). Time- and frequency-domain HR variability measures, along with approximate entropy, short- and long-term correlation properties of R-R intervals (exponents alpha(1) and alpha(2)), and power-law scaling (exponent beta), were analyzed. Time- and frequency-domain measures of HR variability did not differ between subjects with ectopic and sinus tachycardia. Fractal scaling exponents and approximate entropy were similar in sinus tachycardia and normal sinus rhythm, but the short-term scaling exponent alpha(1) was significantly lower in ectopic atrial tachycardia (0.71+/-0.16) than in sinus tachycardia (1.16+/-0.13; P<0.001) or normal sinus rhythm (1.19+/-0.11; P<0.001). Abrupt prolongations in R-R intervals due to exit blocks from the ectopic foci or instability in beat-to-beat R-R dynamics were the major reasons for altered short-term HR behavior during ectopic tachycardias. CONCLUSIONS: HR variability obtained by time- and frequency-domain methods does not differ between ectopic and sinus tachycardias, which suggests that abnormal atrial foci are under similar long-term autonomic regulation as normal pacemaker tissue. Short-term R-R-interval dynamics are altered toward more random behavior in ectopic tachycardia, which may result from a specific autonomic disturbance or an intrinsic abnormality of ectopic atrial pacemakers.

Paired comparisons of efficacy of intravenous and oral procainamide in patients with inducible sustained ventricular tachyarrhythmias.

Thirty-eight patients who had inducible sustained ventricular tachycardia during baseline programmed electrical stimulation underwent electrophysiologic testing after both intravenous and oral administration of procainamide. Each had presented clinically with documented sustained ventricular tachycardia or out of hospital cardiac arrest not associated with acute myocardial infarction. In 23 patients (61%) (Group I) the arrhythmia became noninducible during an intravenous infusion of procainamide. Oral procainamide was subsequently administered and retesting was carried out after dose titration to match plasma concentration at the end of the intravenous study. Among the 23 patients in Group I the mean (+/- SD) plasma procainamide level was 7.2 +/- 2.8 micrograms/ml after intravenous dosing and 7.9 +/- 2.5 micrograms/ml after oral dosing (p = 0.09). In 15 (65%) of the 23 patients, sustained ventricular arrhythmia was inducible on oral therapy with comparable plasma procainamide levels (intravenous = 6.3 +/- 2.1 micrograms/ml, oral = 7.5 +/- 2.1 micrograms/ml). The other eight patients (35%) had concordant responses to repeat testing with comparable intravenous (mean 9.0 +/- 3.3 micrograms/ml) and oral (8.8 +/- 3.1 micrograms/ml) plasma procainamide levels. In the additional 15 patients (Group II) sustained ventricular tachyarrhythmia remained inducible on intravenous procainamide therapy and the patients were retested on oral therapy with similar plasma concentration (p = 0.05). In seven patients (47%) sustained ventricular tachyarrhythmia was noninducible on treatment with oral procainamide (mean plasma level 7.6 +/- 2.7 micrograms/ml) after failure of intravenous procainamide (mean plasma level 10.3 +/- 2.3 micrograms/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac manifestations of cocaine abuse: a cross-sectional study of asymptomatic men with a history of long-term abuse of "crack" cocaine.

OBJECTIVES: The objective of this study was to evaluate the prevalence of cardiac abnormalities in young, asymptomatic long-term "crack" cocaine abusers. BACKGROUND: Although the cardiac complications of cocaine abuse have received widespread attention, the prevalence of cardiac abnormalities in asymptomatic long-term cocaine abusers is unknown. METHODS: History, physical examination, electrocardiogram (ECG) and echocardiogram were performed in 52 consecutive long-term cocaine abusers admitted to a drug rehabilitation program. Findings were compared with those in 14 age-matched normal volunteers and 14 age-matched normotensive patients admitted to a psychiatric service who had a pattern of smoking and alcohol consumption similar to that of the study patients. RESULTS: The ECG findings were abnormal in 29% of cocaine abusers, and included nonspecific ST-T wave changes in 15%, abnormal ST segment elevation in 10%, old inferior infarction in 2%, old anteroseptal infarction in 2% and abnormal precordial R wave progression in 10%. When compared with normal volunteers and control patients, cocaine abusers had increased left ventricular posterior wall thickness (1.12 vs. 0.76 and 0.85 cm, respectively, p < 0.0001), increased septal thickness (1.13 vs. 0.76 and 0.86 cm, p < 0.001) and higher left ventricular mass index (142 vs. 84 and 94 g/m2, p < 0.0001). Left ventricular diastolic filling variables did not differ significantly among the three groups. Diastolic filling variables were similar in cocaine abusers with and without left ventricular hypertrophy, and the prevalence of left ventricular hypertrophy did not differ significantly between those who used no alcohol or < 35 ml/week of alcohol and those who consumed > or = 500 ml/week of alcohol. Left ventricular segmental wall motion abnormalities were present in 11 subjects (21%) and the ejection fraction was decreased (< 0.45) in 2 (4%). CONCLUSIONS: Electrocardiographic and echocardiographic abnormalities are common in long-term cocaine abusers. Despite the frequent occurrence of left ventricular hypertrophy, Doppler-derived diastolic filling pattern was not altered. Concomitant alcohol use did not affect the prevalence of these abnormalities.

Heart rate variability and dispersion of QT interval in patients with vulnerability to ventricular tachycardia and ventricular fibrillation after previous myocardial infarction.

OBJECTIVES: This study was designed to compare QT dispersion measured from the standard 12-lead electrocardiogram and 24-h heart rate variability in patients with vulnerability to either ventricular tachycardia or ventricular fibrillation after a previous myocardial infarction. BACKGROUND: Increased QT interval dispersion and reduced heart rate variability have been shown to be associated with vulnerability to ventricular tachyarrhythmias, but the data have mainly been pooled from patients with presentation of stable ventricular tachycardia and ventricular fibrillation. METHODS: QT dispersion and time domain and two-dimensional vector analysis of heart rate variability were studied in 30 survivors of ventricular fibrillation with a previous myocardial infarction and with inducible unstable ventricular tachyarrhythmia by programmed electrical stimulation and in 30 postinfarction patients with clinical and inducible stable monomorphic sustained ventricular tachycardia. Both of these patient groups were matched, with respect to age, gender and left ventricular ejection fraction, with an equal number of postinfarction control patients without a history of arrhythmic events or inducible ventricular tachyarrhythmia and arrhythmia-free survival during a follow-up period of 2 years. Forty-five age-matched healthy subjects served as normal control subjects. RESULTS: Standard deviation of all sinus intervals and long-term continuous RR interval variability analyzed from Poincaré plots were reduced in patients with vulnerability to ventricular fibrillation (p < 0.001 for both), but not in patients with ventricular tachycardia (p = NS for both), compared with postinfarction control subjects. Corrected QT (QTc) dispersion was significantly broader both in patients with ventricular fibrillation (p < 0.001) and in those with ventricular tachycardia (p < 0.05) than in matched postinfarction control subjects. Heart rate variability performed better than QTc dispersion in predicting vulnerability to ventricular fibrillation. CONCLUSIONS: Increased QT dispersion is associated with vulnerability to both ventricular tachycardia and ventricular fibrillation. Low heart rate variability is specifically related to susceptibility to ventricular fibrillation but not to stable monomorphic ventricular tachycardia, suggesting that the autonomic nervous system modifies the presentation of life-threatening ventricular arrhythmias.

Cardiac arrest in an adolescent with atrial fibrillation and hypertrophic cardiomyopathy.

A 15 year old youth, who presented with out-of-hospital cardiac arrest due to documented ventricular fibrillation, was found to have nonobstructive hypertrophic cardiomyopathy. Electrophysiologic study demonstrated inducible sustained atrial fibrillation with a rapid ventricular response. This rhythm, associated with hypotension and evidence of myocardial ischemia, spontaneously degenerated into ventricular fibrillation. No ventricular arrhythmias were inducible by programmed ventricular stimulation. Therapy with metoprolol and verapamil slowed the ventricular rate during atrial fibrillation and maintained hemodynamic stability, both during follow-up electrophysiologic study and during a subsequent spontaneous episode.

Cellular electrophysiologic changes and "arrhythmias" during experimental ischemia and reperfusion in isolated cat ventricular myocardium.

The cellular electrophysiologic consequences of both regional and global experimental ischemia and reperfusion were studied in the isolated cat myocardium, using conventional microelectrode techniques. Oxygenated Tyrode's solution was perfused through the left anterior descending and circumflex coronary arteries, while the preparation was superfused with Tyrode's solution gassed with 95% nitrogen and 5% carbon dioxide. Electrophysiologic characteristics of endocardial muscle cells were normal during coronary perfusion. When perfusion was discontinued for 30 minutes, resting membrane potential was decreased by 21.6 +/- 4.1%, action potential amplitude was decreased by 29.1 +/- 8.6% and action potential duration was decreased by 54.1 +/- 12.5% (p less than 0.001). Ectopic activity occurred after 5 to 10 minutes of ischemia and was more frequent in regional than in global ischemia (p less than 0.05). Rapid ventricular activity was observed in only 5 (17%) of 29 preparations during ischemia, whereas it occurred in 24 (83%) of 29 preparations during reperfusion. Rapid ventricular activity began 5 to 40 seconds (mean 19) after the start of reperfusion, stopped spontaneously after a mean of 113 +/- 211 seconds and occurred after both regional and global ischemia. The cellular electrophysiologic changes induced by ischemia returned to baseline values within the next 5 minutes. Repeated ischemia and reperfusion runs reproduced the same electrophysiologic changes and rapid ventricular activity. Coronary perfusion with procainamide (20 mg/liter) aggravated the ischemic depressions of action potential amplitude and action potential duration and increased conduction delay during ischemia, but it did not prevent rapid ventricular activity induced by reperfusion. In contrast, verapamil (1 mg/liter) perfusion did not affect the changes in action potential variables during ischemia but prevented reperfusion-induced rapid ventricular activity. Perfusion with calcium ion (Ca2+)-free Tyrode's solution just before ischemia and during reperfusion slowed or prevented reperfusion-induced rapid ventricular activity, without affecting the action potential changes during ischemia. It is concluded that, in these isolated perfused ventricular muscle preparations, different mechanisms may be operative in ischemic and reperfusion arrhythmias and Ca2+ may play an important role in the development of arrhythmias during the reperfusion phase of ischemia/reperfusion sequences.

Reversal of left ventricular intracavitary gradient with intracavitary diastolic regurgitation in hypertrophic obstructive cardiomyopathy.

A 73 year old man presented with angina and nonsustained ventricular tachycardia. Cardiac catheterization revealed the dynamic systolic intracavitary gradient of hypertrophic obstructive cardiomyopathy. Abnormal isovolumetric relaxation resulted in the development of a diastolic gradient from the left ventricular outflow tract to the left ventricular apex accompanied by intracavitary regurgitation of contrast material from the outflow tract to the left ventricular body during left ventriculography. This case provides hemodynamic and angiographic confirmation of abnormal isovolumetric relaxation in this syndrome and insight into its mechanism.

Measurement of heart rate variability: a clinical tool or a research toy?

The objectives of this review are to discuss the diversity of mechanisms that may explain the association between heart rate (HR) variability and mortality, to appraise the clinical applicability of traditional and new measures of HR variability and to propose future directions in this field of research. There is a large body of data demonstrating that abnormal HR variability measured over a 24-h period provides information on the risk of subsequent death in subjects with and without structural heart disease. However, the mechanisms responsible for this association are not completely established. Therefore, no specific therapy is currently available to improve the prognosis for patients with abnormal HR variability. Reduced HR variability has been most commonly associated with a risk of arrhythmic death, but recent data suggest that abnormal variability also predicts vascular causes of death, progression of coronary atherosclerosis and death due to heart failure. A consensus is also lacking on the best HR variability measure for clinical purposes. Time and frequency domain measures of HR variability have been most commonly used, but recent studies show that new analysis methods based on nonlinear dynamics may be more powerful in terms of risk stratification. Before the measurement of HR variability can be applied to clinical practice and used to direct therapy, more precise insight into the pathophysiological link between HR variability and mortality are needed. Further studies should also address the issue of which of the HR variability indexes, including the new nonlinear measures, is best for clinical purposes in various patient populations.

Changes in spontaneous sinus node rate as an estimate of cardiac autonomic tone during stable and unstable ventricular tachycardia.

Changes in sinus node rate were measured as an estimate of reflex control of cardiac autonomic tone during 32 episodes of stable ventricular tachycardia (without loss of consciousness) and 21 episodes of unstable ventricular tachycardia (loss of consciousness requiring electrical cardioversion) in 32 patients without retrograde ventriculoatrial conduction. Sinus node rate was measured before induction of ventricular tachycardia (at 5 s intervals during tachycardia) and 5 s after termination of ventricular tachycardia. It increased from 85 +/- 12 beats/min to a maximum of 109 +/- 25 beats/min during stable ventricular tachycardia (p less than 0.001) and from 82 +/- 15 beats/min to a maximum of 105 +/- 34 beats/min during unstable ventricular tachycardia (p less than 0.001). During unstable ventricular tachycardia, the increase in sinus rate was more abrupt and was followed by a sharp decrease beginning before termination of the tachycardia and resulting in a slower rate after termination (56 +/- 15 beats/min) than before tachycardia (p less than 0.001). Stable ventricular tachycardia resulted in a continuous increase of sinus node rate, which remained higher after termination (102 +/- 15 beats/min) than before tachycardia (p less than 0.001). Autonomic mechanisms responsible for changes in sinus rate were evaluated by reinducing the ventricular tachycardia after beta-adrenergic blockade by propranolol in 10 patients. Intravenous propranolol (mean dose 11 +/- 4 mg) had no effect on the magnitude of increase in sinus rate (+18 +/- 6 beats/min before and +17 +/- 7 beats/min after propranolol).(ABSTRACT TRUNCATED AT 250 WORDS)

Outcome of resuscitation from bradyarrhythmic or asystolic prehospital cardiac arrest.

Previous studies of outcome as a function of the initial electrophysiologic mechanisms recorded at the scene of prehospital cardiac arrest have demonstrated that bradyarrhythmias and asystole have the worst prognosis. In this report, our observations in bradyarrhythmic and asystolic arrests occurring from 1980 to 1982 are compared with those from 1975 to 1978. From 1980 to 1982, 61 (27%) of 225 cardiac arrest events meeting entry criteria for the study were bradyarrhythmic or asystolic. Only 2 (8%) of 24 patients with asystole and 1 (20%) of 5 patients with sinus bradycardia survived prehospital intervention. Only 1 of these 29 patients was discharged from the hospital alive. In contrast, 15 (47%) of 32 patients who presented with idioventricular rhythm at initial contact survived prehospital intervention and were hospitalized, and 8 (25%) of these 32 were ultimately discharged alive. When compared with the 1975 to 1978 patients with bradyarrhythmia and asystole, both prehospital survival (8 versus 30%, p less than 0.001) and survival after hospitalization (0 versus 15%, p less than 0.05) significantly improved, but the improvement occurred predominantly in the subgroup with idioventricular rhythm. Survivors within this subgroup tended to have a prompt response to prehospital pharmacologic interventions that were not available to the 1975 to 1978 group. The response was manifested by return to a sinus mechanism or increase in the rate of idioventricular rhythm. In conclusion, outcome has improved for a specific subgroup of victims of prehospital cardiac arrest with bradyarrhythmia or asystole; the improved outcome may relate to field interventions by rescue personnel at the scene of arrest but the mortality rate is still high.

Electrophysiologic consequences of chronic experimentally induced left ventricular pressure overload.

Cardiac electrophysiologic alterations were evaluated 1 to 8 months after partial supracoronary aortic constriction in cats. This procedure induced left ventricular systolic hypertension and hypertrophy with marked connective tissue infiltration. In situ, premature ventricular complexes were observed during or after vagal slowing of sinus rate in 8 (26%) of the 31 experimental animals, while an additional 3 of the 31 developed ventricular fibrillation. No arrhythmias were recorded in 31 normal or 7 sham-operated cats. In vitro, 29% of the left ventricular preparations from cats with pressure overload and 5% from control cats showed spontaneous ectopic activity. During stimulation at cycle lengths of 800 to 1,000 ms, multiple site impalements of subendocardial muscle cells within fibrotic regions revealed heterogeneous electrical abnormalities. These included short action potential duration, low amplitude action potentials generated from low resting potentials, split upstrokes and electrically silent areas. Impalements in nonfibrotic areas of the left ventricle showed prolongation of muscle action potential duration. Long-term disturbances in cellular electrophysiologic properties may favor the development of arrhythmias and thereby contribute to sudden cardiac death in left ventricular hypertension and hypertrophy.

Relation between heart rate variability and spontaneous and induced ventricular arrhythmias in patients with coronary artery disease.

OBJECTIVES: The aim of this study was to determine the relation between autonomic control of heart rate and the spontaneous occurrence and inducibility of ventricular arrhythmias in patients with coronary artery disease. BACKGROUND: Low heart rate variability increases the risk of arrhythmic events. It is not known whether impaired autonomic heart rate control reflects alterations in functional factors that contribute to the initiation of spontaneous arrhythmias or whether it is the consequence of an anatomic substrate for reentrant tachyarrhythmias. METHODS: Fifty-four patients with coronary artery disease with a history of sustained ventricular tachycardia (n = 25) or cardiac arrest (n = 29) were studied by 24-h ambulatory electrocardiographic recording and by programmed electrical stimulation. Heart rate variability was compared among the patients with and without spontaneous ventricular arrhythmias and with and without inducibility of sustained ventricular tachyarrhythmias. RESULTS: Eight patients had a total of 21 episodes of sustained ventricular tachycardia on Holter recordings. Standard deviation of RR intervals and low frequency and very low frequency components of heart rate variability were significantly blunted in patients with sustained ventricular tachycardias compared with those without repetitive ventricular ectopic activity (p < 0.05, p < 0.01 and p < 0.05, respectively). However, no significant alterations were observed in heart rate variability before the onset of 21 episodes of sustained ventricular tachycardia. Heart rate variability did not differ between the patients with or without nonsustained episodes of ventricular tachycardia. In patients with frequent ventricular ectopic activity, low frequency and very low frequency power components were significantly blunted compared with those with infrequent ventricular ectopic activity (p < 0.01 and p < 0.001, respectively). Heart rate variability did not differ significantly between the patients with and without inducible sustained ventricular tachyarrhythmias. CONCLUSIONS: Impaired very low and low frequency oscillation of heart rate reflects susceptibility to the spontaneous occurrence of ventricular arrhythmias but may not reflect the instantaneous triggers for life-threatening arrhythmias or a specific marker of the arrhythmic substrate for ventricular tachyarrhythmias.

Procainamide pharmacokinetics in patients with acute myocardial infarction or congestive heart failure.

Abnormal procainamide pharmacokinetics (prolonged half-life and decreased volume of distribution) and pharmacodynamics (decreased threshold for the suppression of premature ventricular complexes) have been suggested in patients with acute myocardial infarction or congestive heart failure, or both. To better define procainamide kinetics, 37 patients in the acute care setting received intravenous procainamide (25 mg/min, median dose 750 mg) with peak and hourly blood samples taken over 6 hours. Compared with the 10 control patients, the 12 patients with acute myocardial infarction and the 15 patients with congestive heart failure had normal procainamide pharmacokinetics with respect to half-life (2.3 +/- 1.0, 2.5 +/- 0.9 and 2.6 +/- 0.8 hours, respectively), volume of distribution (1.9 +/- 0.7, 1.8 +/- 0.4 and 1.8 +/- 0.5 liters/kg, respectively), clearance (11.3 +/- 7.5, 9.3 +/- 3.6 and 9.1 +/- 3.5 ml/min per kg, respectively) and unbound drug fraction (66 +/- 9, 66 +/- 9 and 69 +/- 4%, respectively). Low thresholds for greater than 85% premature ventricular complex suppression were confirmed in these patients (median 4.7 micrograms/ml in patients with acute myocardial infarction and 3.3 micrograms/ml in patients with congestive heart failure). Thus, differences in the response of premature ventricular complexes to procainamide reflect electropharmacologic differences dependent on clinical setting rather than pharmacokinetic abnormalities. Furthermore, the reduction of procainamide dosing in patients with acute myocardial infarction or congestive heart failure, based solely on prior kinetic data, may result in inappropriate antiarrhythmic therapy.

Time to first shock and clinical outcome in patients receiving an automatic implantable cardioverter-defibrillator.

The relation between time to first shock and clinical outcome was studied in 60 patients who received an automatic implantable cardioverter-defibrillator (AICD) from August 1983 through May 1988. The mean (+/- SD) patient age was 64 +/- 10 years, 82% were men and the mean ejection fraction was 33 +/- 13%. During follow-up, 38 patients (63%) had one or more shocks; there were no differences in age, gender distribution or ejection fraction at entry between the shock and no shock groups. Among 51 patients with coronary artery disease, 31 (61%) had one or more shocks, whereas all seven patients with cardiomyopathy had one or more shocks (p less than 0.05). Neither of the two patients with idiopathic ventricular fibrillation had shocks. Of the 13 deaths, 12 occurred during post-hospital follow-up and 1 during the index hospitalization. Of the four sudden post-hospital deaths, only one was due to tachyarrhythmia in the absence of acute myocardial infarction. All four sudden deaths and five of eight post-hospital nonsudden deaths occurred in patients who had had one or more appropriate shocks during follow-up. Eight of the nine first appropriate shocks among patients who subsequently died occurred within the first 3 months of follow-up, but the actual deaths were delayed to a mean of 14.1 +/- 13.9 months (p less than 0.05). The mean time to all deaths was 14.8 +/- 13.1 months. The ejection fraction was significantly lower among patients who died than among patients who survived (25 +/- 7% versus 35 +/- 14%, p less than 0.02), but it did not distinguish risk of first shocks.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute and long-term beta-adrenergic blockade for patients with neurocardiogenic syncope.

OBJECTIVES: This study was designed to prospectively evaluate the long-term outcome of drug therapy guided by head-up tilt testing for the management of unexplained syncope and near syncope. BACKGROUND: Head-up tilt testing is used to evaluate patients with unexplained syncope. The validity of acute drug testing and the efficacy of long-term oral therapy for prevention of recurrent syncope have not been investigated in large patient groups. METHODS: We studied 296 consecutive patients with unexplained syncope or near syncope who underwent 80 degrees head-up tilt testing with and without isoproterenol challenge. The efficacy of intravenous and oral beta-blocker therapy was evaluated by repeat testing. Patients with both positive and negative responses to therapy were followed up for rates of recurrence of syncope. RESULTS: A total of 193 patients (65%) had a positive tilt test response; 89% of these 193 required isoproterenol challenge to elicit this response. Patients with a positive tilt test result had lower values for heart rate at rest (mean +/- SD 69 +/- 13 vs. 74 +/- 14 beats/min, p = 0.046) and systolic blood pressure (137 +/- 28 vs. 145 +/- 30 mm Hg, p = 0.0018) at baseline than did the patients with a negative tilt test result. Intravenous propranolol blocked the positive response in 163 (90%) of 181 patients retested. Oral beta-blockers were effective by tilt test criteria in 118 (94%) of 125 patients; 12 (10%) had recurrent clinical symptoms while taking beta-blockers. Eight (42%) of 19 patients who had a negative tilt test response during beta-blocker therapy had recurrent symptoms when they stopped therapy. Three (23%) of 13 patients receiving empiric beta-blocker therapy had recurrent symptoms. The follow-up period for the patients with a positive tilt test result was 28 +/- 11 months (range 5 to 48). CONCLUSIONS: Intravenous propranolol is effective in preventing neurocardiogenic syncope diagnosed during head-up tilt testing and predicts the response to oral beta-blocker therapy. Oral beta-blocker therapy prevents recurrent syncope in the majority of patients. Recurrence of syncope is lowest when efficacy of oral beta-blocker therapy is confirmed by repeat head-up tilt testing.

ST segment tracking for rapid determination of patency of the infarct-related artery in acute myocardial infarction.

OBJECTIVES: This study was designed to test the hypothesis that monitoring the ST segment on a single electrocardiographic (ECG) lead reflecting activity in the infarct zone provides sensitive and specific recognition of reperfusion within 60 min of initiation of therapy in acute myocardial infarction. BACKGROUND: Infarct-related arteries that fail to recanalize early may benefit from immediate rescue angioplasty. Hence, detection of reperfusion has important practical clinical implications. METHODS: Of 41 patients with acute myocardial infarction who had ambulatory ECG (Holter) monitors placed, 38 had adequate ST segment monitoring for 3 h; 35 of the 38 were treated with thrombolytic agents and 3 with primary angioplasty. All patients underwent early coronary angiography and were classified into two groups: Group P (22 patients) had angiographic patency (Thrombolysis in Myocardial Infarction [TIMI] grade 2 or 3 flow), the Group O (16 patients) had persistent occlusion (TIMI grade 0 or 1 flow) of the infarct-related vessel at 60 min from initiation of therapy. The initial ST segment level was defined as the first ST segment level recorded; the peak ST segment level was defined as the highest ST segment level measured during the 1st 60 min. To assess the optimal ST segment recovery criteria for reperfusion, the presence or absence of a > or = 75%, > or = 50% and > or = 25% decrement from initial and peak ST segment levels, sampled and analyzed at 2.5-, 5-, 10-, 15-and 20-min intervals, was correlated with patency of the infarct-related artery at 60 min. RESULTS: ST segment recovery of > or = 50% reduction from peak ST segment levels with sampling rates at < or = 10-min intervals provided the optimal criterion for recognizing coronary artery patency at 60 min (sensitivity 96%, 95% confidence interval [CI] 77% to 99%; specificity 94%, 95% CI 69% to 99%, p < 0.0001). The subgroup of 13 patients in Group P with TIMI grade 3 reperfusion flow all met this criterion (sensitivity 100%, 95% CI 75% to 100%). The use of the initial ST segment level as the baseline for determining the presence of a > or = 50% reduction in ST segment levels within 60 min was less sensitive. Prediction of coronary reperfusion within 60 min of therapy on the basis of a > or = 75% decrement from peak ST segment levels was less sensitive, and the use of a > or = 25% decrement was less specific. CONCLUSIONS: ST segment monitoring of a single lead reflecting the infarct zone provides a reliable method for assessing reperfusion within 60 min of acute myocardial infarction. Optimal criteria for ECG reperfusion include a > or = 50% decrease from peak ST segment levels, with ST segment measurements recorded continuously or at least every 10 min.