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.

Relationship of heart rate variability to parasympathetic effect.

BACKGROUND: Baroreflex-mediated parasympathetic stimulation has variable effects on heart rate variability (HRV). We postulated that a quadratic function would describe the relationship between HRV and parasympathetic effect better than a linear function. METHODS AND RESULTS: Twenty-nine normal volunteers (15 women; mean age 39+/-12 years) were studied after beta-adrenergic blockade with intravenous propranolol. Five-minute ECG recordings were made during graded infusions of phenylephrine and nitroprusside to achieve baroreflex-mediated increases and decreases in parasympathetic effect, respectively. Time- and frequency-domain measures of HRV were calculated from the R-R interval tachograms. The R-R interval and the vagal-sympathetic effect (VSE=R-R interval/intrinsic R-R interval) were used as indices of parasympathetic effect. The data were fit to both quadratic and linear models. In each case, the quadratic model (with a negative coefficient for the squared term) was superior to the linear model. There was some evidence that age influenced the responsiveness of the HRV parameters with changing parasympathetic effect, although the regression analysis was significant only in the models for MSSD (P<0.03) and pNN50 (P<0.001). CONCLUSIONS: The relationship between HRV and parasympathetic effect is best described by a function in which there is an ascending limb where HRV increases as parasympathetic effect increases until it reaches a plateau level; HRV then decreases as parasympathetic effect increases. Because there is marked interindividual variation in this relationship, differences in HRV between individuals may reflect differences in this relationship and/or differences in autonomic effects.

Therapeutic developments in sudden cardiac death.

Sudden cardiac death is characterised by the unexpected death of a patient who has been clinically stable. It is frequently due to the development of ventricular tachyarrhythmias. With appropriate treatment, patients can be appropriately resuscitated. Clinically, it is essential to develop treatment strategies to prevent such an episode, as most patients do not survive out-of-hospital cardiac arrest. beta-Blockers are an effective pharmacological therapy in patients following myocardial infarction and in those with congestive heart failure. They may also be effective in other types of heart disease. Anti-arrhythmic agents are not useful as prophylactic drug therapy for reducing mortality in patients at risk for sudden cardiac death. Amiodarone is a notable exception, which may have some benefit, particularly in some subgroups. The implantable cardioverter-defibrillator has emerged as the most effective therapy for preventing sudden cardiac death in high-risk patients. Further work is required to enhance the characterisation of high-risk patients. Genetic analyses in patients with cardiovascular disorders may also identify new approaches to the prevention of sudden cardiac death.

Simultaneous occurrence of atrial fibrillation and atrial flutter.

INTRODUCTION: Early reports suggested that some patients with "atrial fibrillation/flutter" might have atrial fibrillation in one atrium and atrial flutter in the other. However, more recent conceptions of atrial fibrillation/flutter postulate that the pattern is due to a relatively organized (type I) form of atrial fibrillation. We report the occurrence and ECG manifestations of simultaneous atrial fibrillation and flutter in patients undergoing attempted catheter ablation of atrial flutter. METHODS AND RESULTS: In patients undergoing radiofrequency ablation for atrial flutter, an attempt was made to entrain atrial flutter by pacing in the right atrium. The arrhythmias observed occurred following attempts at entrainment, or spontaneously in one case. Twelve transient episodes of simultaneous atrial fibrillation and flutter were observed in five patients. The atrial fibrillation was localized to all or a portion of one atrium, during which the other atrium maintained atrial flutter. In each case, the surface 12-lead ECG reflected the right atrial activation pattern. No patients had interatrial or intra-atrial conduction block during sinus rhythm, suggesting functional intra-atrial block as a mechanism for simultaneous atrial fibrillation/flutter. CONCLUSION: In certain patients, the occurrence of transient, simultaneous atrial fibrillation and flutter is possible. In contrast to prior studies in which it was suggested that left atrial or septal activation determines P wave morphology, the results of the present study show that P wave morphology is determined by right atrial activation. Functional interatrial block appears to be a likely mechanism for this phenomenon.

Electrophysiological and anatomic heterogeneity in evolving canine myocardial infarction.

Although the heterogeneity of electrophysiological properties is increased after myocardial infarction, the degree of this heterogeneity has not been well quantitated and its relationship to the histological changes that occur after infarction has not been carefully examined. The purpose of the present study was to test the hypothesis that alterations in electrophysiological properties in healing canine infarction are related to particular histological changes. Experimental infarction was produced by left anterior descending coronary ligation. Six dogs were used as controls, six were studied 5 days following, and six were studied 8 weeks following infarction. Pacing thresholds, effective refractory periods, and activation-recovery times were determined at 112 sites on the anterior left ventricle using a multiple electrode plaque. Conduction velocity, conduction-heterogeneity index--a measure of conduction disturbance--and histology of the epimyocardium underlying the plaque were assessed. The effective refractory periods and activation-recovery times were greater in both infarction groups, most prominently in the subacute group. In subacute infarction, significant postrepolarization refractoriness was present. In healed infarction, conduction velocity was decreased and the conduction-heterogeneity index was increased compared to controls and subacute infarction. Dispersion of excitability and repolarization was associated with more extensive local scarring. Dispersion of myocardial fiber angles was associated with the conduction-heterogeneity index. Some but not all of the electrophysiological changes noted in the animals with infarction were also seen in sham operated animals. Thus, heterogeneity in repolarization and refractoriness is greatest in the subacute phase of myocardial infarction and is associated with the extent of local cell death. In contrast, disturbances in conduction are greatest in healed infarction and associated with disarray of myocardial fibers.

Uncertainty principle of signal-averaged electrocardiography.

BACKGROUND: Signal-averaged ECG (SAECG) reproducibility is reported to have a component that is independent of residual noise. Methods and Results-In group 1, multiple paired SAECGs were obtained to noise levels of 0.3+/-0.1 and 0.5+/-0.2 microV. For the 0.5- and 0. 3-microV noise recordings, QRS duration (QRSd) was 101.2+/-11.3 and 104.6+/-9.6 ms, respectively (P<0.0001), and the differences in paired QRSd (DeltaQRSd) were normally distributed, with variances of 11.4 and 26.2 ms(2) (P<0.0001). Paired SAECGs were obtained in group 2 patients without and with late potentials; DeltaQRSd variance was 3.3 and 217.9 ms(2) (P<0.0001). In group 3, >/=10 SAECGs were acquired at noise levels of 0.2 to 0.8 microV, in 0.1-microV increments. QRSd increased as noise level decreased. The variance was greater in low-noise (0.2 to 0.4 microV) versus higher-noise (0. 5 to 0.8 microV) recordings. In group 4, SAECGs were analyzed with bidirectional and Bispec filters, with no difference in QRSd between the 2 filters and a normally distributed DeltaQRSd. A computer simulation demonstrated that alterations in the phase relationship of noise to signal results in a normal distribution of signal end points. CONCLUSIONS: Within the acceptable noise range for SAECG, lower noise results in longer QRSd and larger variance, suggesting that more accurate recordings may have less reproducibility. The random timing of noise relative to signal results in the distribution/variance of repeated measurements. Statistical strategies may be used to reduce some of this variance and may enhance the diagnostic utility of SAECG.

Prevention of sudden cardiac death.

Tremendous strides have been made in recent years in the treatment and prevention of sudden cardiac death. Large-scale trials have identified several strategies that may be implemented to improve survival in patients susceptible to sudden cardiac death. In patients who have had a sustained ventricular tachyarrhythmia, the current therapy of choice is an implantable cardioverter defibrillator. For prophylaxis of sudden cardiac death in patients without a previous event, several approaches should be considered. Beta-blockers are an effective pharmacologic therapy in patients after myocardial infarction, and their efficacy has also been demonstrated in patients with congestive heart failure. Antiarrhythmic drugs are not efficacious as prophylactic agents to reduce mortality in these populations. The best therapeutic approach for prophylactic therapy to prevent sudden cardiac death appears to be the implantable cardioverter defibrillator; however, its use can be justified only in patients at high risk for developing sudden cardiac death. Further work is needed to identify the high-risk populations in which this therapy is warranted.

New technique for vagal nerve stimulation.

INTRODUCTION: The vagus nerve travels in a neurovascular bundle with the carotid artery and internal jugular vein. The present study was designed to assess whether transvascular stimulation through the carotid artery of the dog can be used to directly stimulate the vagus nerve and increase parasympathetic tone. METHODS: In five anesthetized dogs, a steerable electrode catheter was positioned under fluoroscopic guidance in the right carotid artery in the mid neck via the femoral artery. Multipolar catheters were positioned transvenously through the femoral vein in the right atrium, across the tricuspid valve to record a His-bundle electrogram, and in the right ventricle. RESULTS: In all five animals, vagal nerve stimulation was successfully achieved with outputs ranging between 10 and 30 mA. Sinus cycle length increased from 473 +/- 113 ms at baseline to 894 +/- 315 ms (P < 0.025) during stimulation from the right carotid artery. There was an increase in the AH interval from 55 +/- 14 to 77 +/- 23 ms (P < 0.03), a shortening of the atrial effective refractory period from 136 +/- 8 to 126 +/- 6 ms (P < 0.01), and a fall in the systolic blood pressure from 135 +/- 20 to 117 +/- 20 mmHg (P < 0.005) with stimulation from the right carotid artery. A prolongation of the AV and VA block cycle lengths and the AV nodal effective refractory period was also noted with stimulation from the right carotid artery. Atrial fibrillation was not induced at baseline in any animal. During stimulation from the right carotid artery, atrial fibrillation was induced in three of five animals and persisted for the duration of stimulation from the right carotid artery. CONCLUSION: Cardiac parasympathetic stimulation can be achieved by positioning a catheter in the neurovascular bundle in the neck adjacent to the vagus nerve with resultant effects on cardiac electrophysiology.

Differential effects of parasympathetic blockade and parasympathetic withdrawal on heart rate variability.

INTRODUCTION: Low heart rate variability (HRV) has been shown to have important prognostic significance in multiple settings. Although this is believed to reflect reduced parasympathetic tone, the physiology of reduced parasympathetic tone has not been elucidated. METHODS AND RESULTS: To evaluate whether parasympathetic withdrawal and partial parasympathetic blockade result in similar changes in HRV, 27 normal volunteers underwent complete beta-adrenergic blockade and then were given (1) graded doses of nitroprusside to achieve baroreflex-mediated parasympathetic withdrawal and (2) low-dose atropine (0.01 mg/kg) to achieve partial parasympathetic blockade. Five-minute ECG recordings were obtained for HRV analysis. In 19 subjects, paired 5-minute recordings from each condition were available with mean RR intervals that differed by < 50 msec (low-dose atropine: 869 +/- 96 msec and nitroprusside 875 +/- 99 msec). The root mean square of the successive RR interval differences was lower following low-dose atropine than following parasympathetic withdrawal with nitroprusside (16 +/- 11 msec vs 22 +/- 15 msec; P < 0.02). During parasympathetic withdrawal, the low-frequency (LF) power was 0.917 +/- 0.602 bpm2 and the high-frequency (HF) power was 0.501 +/- 0.521 bpm2. During partial parasympathetic blockade, the LF and HF powers were significantly lower (0.443 +/- 0.474 bpm2, P < 0.005; and 0.198 +/- 0.207 bpm2, P < 0.02). CONCLUSION: These data confirm that HRV reflects the character of parasympathetic modulation of the heart rate rather than parasympathetic tone per se. Furthermore, this study identifies two distinct physiologic explanations for the finding of low HRV, namely, diminished vagal discharge and resistance of cardiac muscarinic receptors to vagal discharge. Further delineation of the relationships between parasympathetic tone and HRV will allow for better understanding of the pathophysiologic derangements associated with low HRV.

Treatment and prevention of sudden cardiac death: effect of recent clinical trials.

Tremendous strides have been made in recent years in the treatment and prevention of sudden cardiac death. Large scale trials have now established several interventions that may improve survival in patients susceptible to sudden cardiac death. In patients who have had a sustained ventricular tachyarrhythmia, the current therapy of choice is an implantable cardioverter defibrillator. For prophylaxis of sudden cardiac death in patients without a previous event, several approaches should be considered. Beta-Adrenergic blocking agents are an effective pharmacologic therapy in patients following myocardial infarction, and their efficacy has also most recently been demonstrated in patients with congestive heart failure. There is no Vaughan Williams class I or III antiarrhythmic drug that has demonstrated efficacy as a prophylactic agent to reduce mortality in these populations, with the possible exception of amiodarone. The best therapeutic approach for prophylactic therapy to prevent sudden cardiac death appears to be the implantable cardioverter defibrillator; however, its use can be justified only in patients at high risk for developing sudden cardiac death. Further work is needed to identify the high risk populations in which this therapy is warranted.

Inappropriate implantable cardioverter-defibrillator therapy due to the detection of premature ventricular complexes.

Inappropriate shocks delivered by implantable cardioverter-defibrillators may occur in 15%-40% of patients treated with these devices. This article describes a rare cause for inappropriate shocks. Two patients received inappropriate shocks due to the presence of premature ventricular complexes during attempted reconfirmation of ventricular fibrillation. Knowledge of device algorithms for detection and reconfirmation of ventricular fibrillation, designed to have a high degree of sensitivity and therefore lower specificity, allows for reprogramming to avoid further inappropriate shocks.

Resting heart rate is a risk factor for cardiovascular and noncardiovascular mortality: the Chicago Heart Association Detection Project in Industry.

In a prospective cohort study, associations of resting heart rate with risk of coronary, cardiovascular disease, cancer, and all-cause mortality in age-specific cohorts of black and white men and women were examined over 22 years of follow-up. Participants were employees from 84 companies and organizations in the Chicago, Illinois, area who volunteered for a screening examination. Participants included 9,706 men aged 18-39 years, 7,760 men aged 40-59 years, 1,321 men aged 60-74 years, 6,928 women aged 18-39 years, 6,915 women aged 40-59 years, and 1,151 women aged 60-74 years at the baseline examination in 1967-1973. Vital status was ascertained through 1992. For fatal coronary disease, multivariate-adjusted relative risks associated with a 12 beats per minute higher heart rate (one standard deviation) were as follows: for men aged 18-39 years, relative risk (RR) = 1.27 (95% confidence interval (CI) 1.08-1.48); for men aged 40-59 years, RR = 1.13 (95% CI 1.05-1.21); for men aged 60-74 years, RR = 1.00 (95% CI 0.89-1.12); for women aged 40-59 years, RR = 1.21 (95% CI 1.07-1.36); and for women aged 60-74 years, RR = 1.16 (95% CI 0.99-1.37). Corresponding risks for all fatal cardiovascular diseases were similar to those for coronary death alone. Deaths from cancer were significantly associated with heart rate in men and women aged 40-59 years. All-cause mortality was associated with higher heart rate in men aged 18-39 years (RR = 1.11, 95% CI 1.01-1.20), men aged 40-59 years (RR = 1.16, 95% CI 1.11-1.21), and women aged 40-59 years (RR = 1.20, 95% CI 1.13-1.27). Heart rate was not associated with mortality in women aged 18-39 years. In summary, heart rate was a risk factor for mortality from coronary disease, all cardiovascular diseases, and all causes in younger men and in middle-aged men and women, and for cancer mortality in middle-aged men and women.

Sympathovagal balance: how should we measure it?

There are complex interactions between the sympathetic and parasympathetic nervous system inputs to the sinus node. The concept of "sympathovagal balance" reflects the autonomic state resulting from the sympathetic and parasympathetic influences. Despite widespread usage of a variety of heart rate (HR) variability parameters as indexes of sympathovagal balance, no index has been validated as a measure of sympathovagal balance. This study evaluated the utility of HR, HR variability, and a new parameter termed the vagal-sympathetic effect (VSE) as indexes of sympathovagal balance. The ideal parameter had to satisfy the following criteria: 1) the index should vary similarly among subjects in response to different autonomic conditions; 2) the variability in the index among subjects exposed to the same autonomic conditions should be small; and 3) the response of the index to various autonomic conditions should reflect the underlying changes in physiological state and have a meaningful interpretation. Volunteers [8 men, 6 women; mean age 28.5 +/- 4.8 (SD) yr] were evaluated for the effects of sympathetic and parasympathetic stimulation and blockade on HR and HR variability. VSE was defined as the ratio of the R-R interval to the intrinsic R-R interval. VSE and R-R interval consistently changed in the expected directions with parasympathetic and sympathetic stimulation and blockade. A general linearized model was used to evaluate the response of each parameter. VSE and R-R interval had r2 values of 0.847 and 0.852, respectively. Natural logarithm of the low-frequency power had an r2 value of 0.781 with lower r2 values for all the other HR variability parameters. The coefficient of variation was also lowest for each condition tested for the VSE and the R-R interval. VSE and R-R interval best satisfy the criteria for the ideal index of sympathovagal balance. Because it is impractical under most conditions to measure the VSE as the index of sympathovagal balance, the most suitable index is the R-R interval.

Nonsustained ventricular tachycardia in the setting of acute myocardial infarction: tachycardia characteristics and their prognostic implications.

BACKGROUND: Nonsustained ventricular tachycardia (NSVT) has significant prognostic implications in the setting of healing and healed myocardial infarction (MI), but only limited information is available on its importance in the setting of acute MI. We evaluated the prognostic significance of NSVT characteristics in the setting of acute MI. METHODS AND RESULTS: A prospective database was used to identify 112 patients with NSVT within 72 hours of acute MI. A control group was identified matched for age, sex, type of MI, and thrombolytic treatment. Mean age was 64 to 65 years in the 2 groups with 71% to 72% men. Q-wave MI was noted in 52% to 53%, and thrombolytic therapy was administered to 31% to 32% of patients in each group. In-hospital ventricular fibrillation occurred more frequently in the NSVT group (9% versus 0% in the control group; P<0. 001), but total in-hospital (10% versus 4%) and follow-up mortality (10% versus 17%) did not differ between the 2 groups. With a Cox regression model, specific NSVT characteristics were predictive of mortality. The strongest predictor was time from presentation to occurrence of NSVT. Shortest RR interval during NSVT was also a univariate predictor of mortality. Multivariate analysis identified time from presentation to occurrence of NSVT as the strongest predictor of mortality (P<0.0001). The increased relative risk of NSVT was first significant when it occurred 13 hours from presentation and continued to increase as the time from presentation to occurrence of NSVT increased, plateauing at approximately 24 hours with a relative risk of 7.5. CONCLUSIONS: Contrary to prevailing clinical opinion, NSVT that occurs in the setting of acute MI does have important prognostic significance. Specifically, the currently accepted notion that NSVT that occurs within 48 hours of acute MI has no prognostic significance needs to be adjusted. Although NSVT that occurs within the first several hours of presentation does not have an associated adverse prognosis, NSVT that occurs beyond the first several hours after presentation is associated with significant increases in relative risk.

Effects of hormone replacement therapy on QT interval.

We evaluated the electrocardiograms of 208 postmenopausal women (ages 40 to > or = 70 years) without heart disease, medications that could alter the QT interval, use of vaginal estrogens, unknown hormone replacement therapy, or electrocardiographic abnormalities both with (n = 76) and without (n = 132) hormone replacement therapy, and found no significant effects of hormone replacement therapy status on heart rate, QT interval, or the corrected QT interval. Thus, estrogen and/or progesterone effect does not explain the gender differences in myocardial repolarization.

Detection of ventricular fibrillation by transvenous defibrillating leads: integrated versus dedicated bipolar sensing.

INTRODUCTION: Dedicated bipolar sensing has been suggested to be safer than integrated bipolar sensing due to an increased incidence of failure to redetect ventricular fibrillation after an unsuccessful shock with leads that use integrated bipolar sensing. We compared sensing characteristics during ventricular fibrillation of simultaneously recorded dedicated and integrated bipolar electrograms. METHODS AND RESULTS: Thirty patients undergoing transvenous defibrillator implantation with a Transvene lead were studied. Simultaneous recordings were made from the dedicated bipole and the integrated bipole from the distal tip to the coil (interelectrode distance 18.3 mm). The mean detection time and number of undetected beats for the initial episode of ventricular fibrillation were 2804 +/- 569 msec and 0.9 +/- 0.8 using the dedicated recordings and 2938 +/- 546 msec and 1.4 +/- 1.1 (P = 0.026) using the integrated recordings. The mean redetection times and number of undetected beats following a failed first shock (n = 13) were 2468 +/- 225 msec and 0.8 +/- 1.1 for the dedicated recordings and 3042 +/- 498 msec (P < 0.0003) and 4.2 +/- 4.2 (P < 0.005) for the integrated recordings. Frequency analysis of the ventricular fibrillation electrograms demonstrated that the signal energy in the dedicated electrograms was significantly greater than the energy in the integrated electrograms (P < 0.0001). There was a significant negative relationship between detection times and the ventricular fibrillation signal energy. There was no independent effect of recording type (dedicated versus integrated). CONCLUSION: There are only minor differences in detection/redetection of ventricular fibrillation between dedicated and integrated (with tip to coil spacing of 18.3 mm) recording configurations. Detection times during ventricular fibrillation are related to the signal variance or energy recorded. Differences in the sensing performance of the two recording configurations can be explained by the differences in signal energy between the dedicated and integrated recordings that occur during ventricular fibrillation.

Effects of intravenous propranolol on human ventricular strength interval curves.

BACKGROUND: Prior studies on the effects of propranolol on human ventricular refractoriness have yielded occasionally inconsistent results. Most prior studies have examined refractory periods at a single stimulus intensity and without using continuous pacing; thus, the effects of propranolol on repolarization may have not been completely defined. The purpose of the present study was to reevaluate the effects of beta blockade on the human ventricular effective refractory period. METHODS: Strength-interval curves were performed in duplicate in a group of 10 patients to demonstrate their reproducibility. Strength-interval curves were performed before and after intravenous propranolol administration in a second group of 10 patients who had no evidence of structural heart disease. RESULTS: Propranolol increased the absolute refractory period from 208 +/- 9 milliseconds to 212 +/- 10 milliseconds (p = 0.01). However, propranolol decreased the coupling interval at which the strength-interval curve began to show an increase in the stimulus intensity required for capture from 236 +/- 8 milliseconds to 232 +/- 9 milliseconds. This resulted in a decrease of the width of the strength-interval curve from 28.0 +/- 5.1 milliseconds to 20.4 +/- 5.5 milliseconds (p < 0.005). Propranolol also significantly increased the slope of a logarithmic fit of the strength-interval curves. CONCLUSION: Propranolol exerts complex effects on human ventricular refractoriness. Propranolol decreases the width and increases the slope of human strength-interval curve, rather than increasing or decreasing the refractory period. These results have potential implications for antiarrhythmic effects of propranolol.