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Biomedical subjects

F J Venditti

Publications and source records attributed to F J Venditti.

At least 19 recordsLinked to original sources

The class III antiarrhythmic effect of sotalol exerts a reverse use-dependent positive inotropic effect in the intact canine heart.

OBJECTIVES: We sought to study the rate related effects of sotalol on myocardial contractility and to test the hypothesis that the class III antiarrhythmic effect of sotalol has a reverse use-dependent positive inotropic effect in the intact heart. BACKGROUND: Antiarrhythmic drugs exert significant negative inotropic effects. Sotalol, a beta-adrenergic blocking agent with class III antiarrhythmic properties, may augment contractility by virtue of its ability to prolong the action potential duration (APD). METHODS: In 10 anesthetized dogs, measurements of left ventricle (LV) peak (+)dP/dt and simultaneous endocardial action potentials were made during baseline conditions and after sequential administration of esmolol and sotalol. In addition, electrical and mechanical restitution curves were constructed at a basic pacing cycle length of 600 ms by introducing a test pulse of altered cycle length ranging from 200 ms to 2,000 ms. RESULTS: In the steady state pacing experiments, sotalol prolonged the APD in a reverse use-dependent manner; such an effect was not seen with esmolol. At cycle lengths exceeding 400 ms, LV (+)dP/dt was significantly higher with sotalol than it was with esmolol. There was a direct relation between APD and LV (+)dP/dt with sotalol (r = 0.46, p < 0.001), but there was no significant relation between APD and LV (+)dP/dt with esmolol (r = 0.27, p = NS). Results in the single beat (restitution) studies were qualitatively similar to the steady state results; APD (at cycle length >400 ms) and LV (+)dP/dt (at cycle length >600 ms) were significantly higher with sotalol than they were with esmolol. CONCLUSIONS: The reverse use-dependent prolongation of APD by sotalol is associated with a positive inotropic effect.

Action Potentials↗

Electrical alternans during rest and exercise as predictors of vulnerability to ventricular arrhythmias.

This investigation was performed to evaluate the feasibility of detecting repolarization alternans with the heart rate elevated with a bicycle exercise protocol. Sensitive spectral signal-processing techniques are able to detect beat-to-beat alternation of the amplitude of the T wave, which is not visible on standard electrocardiogram. Previous animal and human investigations using atrial or ventricular pacing have demonstrated that T-wave alternans is a marker of vulnerability to ventricular arrhythmias. Using a spectral analysis technique incorporating noise reduction signal-processing software, we evaluated electrical alternans at rest and with the heart rate elevated during a bicycle exercise protocol. In this study we defined optimal criteria for electrical alternans to separate patients from those without inducible arrhythmias. Alternans and signal-averaged electrocardiographic results were compared with the results of vulnerability to ventricular arrhythmias as defined by induction of sustained ventricular tachycardia or fibrillation at electrophysiologic evaluation. In 27 patients alternans recorded at rest and with exercise had a sensitivity of 89%, specificity of 75%, and overall clinical accuracy of 80% (p <0.003). In this patient population the signal-averaged electrocardiogram was not a significant predictor of arrhythmia vulnerability. This is the first study to report that repolarization alternans can be detected with heart rate elevated with a bicycle exercise protocol. Alternans measured using this technique is an accurate predictor of arrhythmia inducibility.

Adolescent↗

Undersensing of ventricular fibrillation in a noncommitted nonthoracotomy cardioverter defibrillator system.

OBJECTIVE: Evaluation of the impact of undersensing on VF detection time and the relationship of undersensing to the programmed shock energy. BACKGROUND: Failure to reconfirm an ongoing arrhythmia due to undersensing by a noncommitted ICD might prolong the time to therapy. METHODS: We measured initial detection times and redetection times at predischarge and at 2 and 6 months in 29 patients (22 men, mean age 60 years) with a noncommitted nonthoracotomy ICD. Telemetry data and output markers were used to analyze each induction. RESULTS: Undersensing leading to failure to reconfirm was present in 44 (11.1%) of 398 episodes of sustained VF and prolonged significantly the median initial detection time from 2.3 seconds (25th and 75th percentiles: 2 and 2.6 s, respectively) to 5.45 seconds (4.3 and 7.35 s, P < 0.0001). One episode required external defibrillation after reconfirmation failure occurred during charging; the total detection time prior to shock was 46 seconds. In a subset of 87 episodes with failed first shocks, the initial detection time was 2.3 seconds (2.1 and 2.8 s) and the redetection time 3 seconds (2.5 and 4.77 s, P < 0.0001). The presence of undersensing prolonged the redetection from 2.6 seconds (2.35 and 3.1 s) to 5.4 seconds (4.53 and 7.35 s, P < 0.0001). Undersensing was more prevalent during the redetection period (P = 0.004) and in episodes of sustained VF in which the first shock energy was higher than 15 J (19.7% vs 5.8%, P < 0.0001). CONCLUSIONS: In this automatic defibrillator system, undersensing occurs in 11% of the sustained VF inductions and prolongs detection time significantly. Redetection is longer than initial detection mostly due to the presence of undersensing, the frequency of which is proportional to the programmed energy. The clinical significance of this finding is unknown.

Cardiac Pacing, Artificial↗

Combined use of non-thoracotomy cardioverter defibrillators and endocardial pacemakers.

OBJECTIVE: To study the potential interactions in patients with endocardial permanent pacemakers and non-thoracotomy implantable cardioverter defibrillator (ICD) systems. DESIGN: Case series and cohort study. SETTING: Tertiary referral centre. PATIENTS: Fifteen consecutive patients with both endocardial pacemakers (12 dual chamber and three single chamber) and non-thoracotomy ICD systems. MAIN OUTCOME MEASURES: Detection inhibition of induced ventricular fibrillation; double counting; and pacemaker function after shocks. In the evaluation of detection inhibition, 124 VF inductions were analysed for detection duration compared with induced VF episodes in controls with an ICD but without a pacemaker. RESULTS: Two patients (13%) showed detection inhibition of VF and required pacemaker system change at the time of the ICD implant. With the final lead position, despite frequent pacemaker undersensing of VF, ICD detection of VF was not inhibited during any induction, and neither initial detection nor redetection times for VF were different from controls. Double/triple counting of pacemaker artefact and evoked electrogram was noted in three patients (20%). In two, this was remedied during the implantation procedure, and in the other it was abolished when amiodarone treatment was discontinued. Pacemaker function was affected by ICD discharges in two patients, one who showed postshock atrial undersensing and loss of capture, and another whose pacemaker reverted to VVI mode. CONCLUSIONS: When careful testing is performed at implantation to detect and remedy device interactions, non-thoracotomy ICD treatment and endocardial pacemakers can be used safely in combination.

Adult↗

Impact of reduced heart rate variability on risk for cardiac events. The Framingham Heart Study.

BACKGROUND: Although heart rate variability (HRV) is altered in a variety of pathological conditions, the association of reduced HRV with risk for new cardiac events has not been studied in a large community-based population. METHODS AND RESULTS: The first 2 hours of ambulatory ECG recordings obtained on subjects of the Framingham Heart Study who were free of clinically apparent coronary heart disease or congestive heart failure were reprocessed to assess HRV. Five frequency-domain measures and three time-domain measures were obtained. The associations between HRV measures and the incidence of new cardiac events (angina pectroris, myocardial infarction, coronary heart disease death, or congestive heart failure) were assessed with proportional hazards regression analyses. There were 2501 eligible subjects with a mean age of 53 years. During a mean follow-up of 3.5 years, cardiac events occurred in 58 subjects. After adjustment for age, sex, cigarette smoking, diabetes, left ventricular hypertrophy, and other relevant risk factors, all HRV measures except the ratio of low-frequency to high-frequency power were significantly associated with risk for a cardiac event (P = .0016 to .0496). A one-standard deviation decrement in the standard deviation of total normal RR intervals (natural log transformed) was associated with a hazard ratio of 1.47 for new cardiac events (95% confidence interval of 1.16 to 1.86). CONCLUSIONS: The estimation of HRV by ambulatory monitoring offers prognostic information beyond that provided by the evaluation of traditional cardiovascular disease risk factors.

Adult↗

Determinants of heart rate variability.

OBJECTIVES: This study sought to examine clinical determinants of heart rate variability and to report normative reference values for eight heart rate variability measures. BACKGROUND: Although the clinical implications of heart rate variability have been described, clinical determinants and normative values of heart rate variability measures have not been studied systematically in a large community-based population. METHODS: The first 2 h of ambulatory electrocardiographic recordings obtained in Framingham Heart Study subjects attending a routine examination were reprocessed for heart rate variability. Recordings with transient or persistent nonsinus rhythm, premature beats > 10% of total beats, < 1-h recording time or processed time < 50% of recorded time were excluded; subjects receiving antiarrhythmic medications also were excluded. Among five frequency domain and three time domain measures that were obtained, low frequency power (0.04 to 0.15 Hz), high frequency power (0.15 to 0.40 Hz) and the standard deviation of total normal RR intervals based on 2-h recordings were selected for the principal analyses. Variables with potential physiologic effects or possible technical influences on heart rate variability measures were chosen for multiple linear regression analysis. Normative values, derived from a subset of healthy subjects, were adjusted for age and heart rate. RESULTS: There were 2,722 eligible subjects with a mean age (+/-SD) of 55 +/- 14 years. Three separate multiple linear regression analyses revealed that higher heart rate, older age, beta-adrenergic blocking agent use, history of myocardial infarction or congestive heart failure, diuretic use, diastolic blood pressure > or = 90 mm Hg, diabetes mellitus, consumption of three or more cups of coffee per day and smoking were associated with lower values of one or more heart rate variability measures, whereas longer processed time, start time in the morning, frequent supraventricular and ventricular premature beats, female gender and systolic blood pressure > or = 160 mm Hg were associated with higher values. Age and heart rate were the major determinants of all three selected heart rate variability measures (partial R2 values 0.125 to 0.389). Normative reference values for all eight heart rate variability measures are presented. CONCLUSIONS: Age and heart rate must be taken into account when assessing heart rate variability.

Adult↗

Circadian variation in defibrillation energy requirements.

BACKGROUND: Reports have demonstrated a circadian variation in the incidence of acute myocardial infarction, ventricular arrhythmias, and sudden cardiac death. We tested the hypothesis that a similar circadian variation exists for defibrillation energy requirements in humans. METHODS AND RESULTS: We reviewed the time of defibrillation threshold (DFT) measurements in 134 patients with implantable cardioverter-defibrillators (ICDs) who underwent 345 DFT measurements. The DFT was determined in 130 patients at implantation, in 121 at a 2 months, and in 94 at 6 months. All patients had nonthoracotomy systems. The morning DFT (8 AM to 12 noon) was 15.1 +/- 1.2 J compared with 13.1 +/- 0.9 J in the midafternoon (12 noon to 4 PM) and 13.0 +/- 0.7 J in the late afternoon (4 to 8 PM), P < .02. In a separate group of 930 patients implanted with an ICD system with date and time stamps for each therapy, we reviewed 1238 episodes of ventricular tachyarrhythmias treated with shock therapy. To corroborate the hypothesis that energy requirements for arrhythmia termination vary during the course of the day, we plotted the failed first shock frequency for all episodes per hour. There was a significant peak in failed first shocks in the morning compared with other time intervals (P = .02). CONCLUSIONS: There is a morning peak in DFT and a corresponding morning peak in failed first shock frequency. This morning peak resembles the peaks seen in other cardiac events, specifically sudden cardiac death. These findings have important implications for appropriate ICD function, particularly in patients with marginal DFTs.

Aged↗

Classification of death in antiarrhythmia trials.

OBJECTIVES: We sought to develop and apply a new scheme for the classification of death to be used in trials of antiarrhythmia treatments. BACKGROUND: Because presently accepted classifications of death do not fully describe or tabulate all significant aspects of terminal events, nor do they consider unique aspects of arrhythmia investigations, a new classification scheme that addresses these issues is desirable. METHODS: A classification scheme of deaths that occur in antiarrhythmia trials was developed using the following categories: 1) primary organ cause (cardiac [arrhythmic, nonarrhythmic or unknown], noncardiac or unknown); 2) temporal course (sudden, nonsudden or unknown); 3) documentation (witnessed, monitored [yes, no or unknown]); 4) operative relation (preoperative, perioperative or postoperative); and 5) system relation (procedure related, pulse generator related and lead related [yes, no or unknown]). RESULTS: The classification scheme was used in a clinical trial of a new implantable cardioverter-defibrillator (1,250 patients, of whom 79 died) and used in an application for device market approval. Application of the classification to data reported using an older classification scheme is demonstrated. CONCLUSIONS: We propose a descriptive classification scheme that 1) fully describes and tabulates all significant aspects of terminal events; 2) incorporates previously used categorizations of death and new categorizations that address unique aspects of arrhythmia investigations; and 3) tabulates sufficient data to allow comparison with other studies. Events in a clinical trial of implantable defibrillator therapy were classified using the new classification scheme.

Arrhythmias, Cardiac↗

Morning peak in ventricular tachyarrhythmias detected by time of implantable cardioverter/defibrillator therapy. The CPI Investigators.

BACKGROUND: A morning peak in occurrence of sudden cardiac death has been identified in epidemiological studies, but the studies are subject to selection bias, with the exclusion of unwitnessed deaths, which are more likely to occur at night. The recent availability of implantable cardioverter/defibrillators that record the time of ventricular tachyarrhythmias requiring either pacing or shock therapy provides an opportunity to clarify the timing of ventricular tachyarrhythmias predisposing to sudden cardiac death. Analysis of the timing of arrhythmias in different patient subgroups, such as patients with poor left ventricular function, may provide further insight into the mechanism of onset of sudden cardiac death. METHODS AND RESULTS: We studied patients in whom a cardioverter/defibrillator (Ventak PRx) was implanted between September 1990 and September 1993 in US centers. Events that could be timed occurred in 483 patients. With an RR cycle length of 240 ms as a cutoff, corresponding to a heart rate of 250 beats per minute, episodes were categorized as rapid (n = 1217) or less rapid (n = 9266) ventricular tachyarrhythmias. A higher proportion of both rapid and less rapid ventricular tachyarrhythmias began in the late morning compared with other times of the day. The subgroup of patients with ejection fraction < 20% at the time of implantation demonstrated a more uniform 24-hour distribution of tachycardias < or = 250 beats per minute than patients with higher left ventricular ejection fraction. CONCLUSIONS: Further investigation of the late morning peak and of precipitants of ventricular tachyarrhythmias by use of data from the implantable cardioverter/defibrillator may provide insight into the pathophysiological mechanisms causing sudden cardiac death.

Circadian Rhythm↗

Increase in defibrillation threshold in non-thoracotomy implantable defibrillators using a biphasic waveform.

We have previously reported a chronic increase in defibrillation threshold in a non-thoracotomy implantable cardioverter-defibrillator (ICD) system using monophasic waveforms. To determine if this phenomenon is related to the lead system or the waveform used, we studied the chronic defibrillation threshold in consecutive patients receiving an ICD capable of delivering biphasic waveforms with the same lead system previously evaluated. Twenty-five patients received an ICD with biphasic shock waveform and have been followed for 4 to 15 months. All have undergone defibrillation threshold measurements using the identical testing protocol with biphasic waveforms at implant and at 2 months. Coronary artery disease was present in 15, idiopathic dilated cardiomyopathy in 9, and valvular heart disease in 1. The presenting arrhythmia was ventricular fibrillation in 11, ventricular tachycardia in 10, and syncope with inducible ventricular tachycardia in 4. The configuration of the shocking electrodes was randomized; the lead-only configuration was used in 14 patients (56%), and a subcutaneous patch was used in the remaining patients. Mean defibrillation threshold using a step-down technique was 9.8 +/- 1.0 J at implant, 13.2 +/- 1.6 J at 2 months, and 12.4 +/- 1.5 J at 6 months (p = 0.01 by analysis of variance). There was no change in clinical status, cardiac size, radiographic lead position, or impedance between implant and 2 months. These findings suggest the increase in defibrillation threshold in this ICD system is not related to the type of waveform used, but rather is a feature of non-thoracotomy as opposed to epicardial electrodes.

Adult↗

The role of coronary revascularization in recipients of an implantable cardioverter-defibrillator.

The impact of adjuvant coronary revascularization was studied in a group of 138 recipients of an implantable cardioverter-defibrillator, all of whom had ischemic heart disease as the cause of their arrhythmias. Patients chosen for revascularization had more severe anatomic, symptomatic, or physiologic evidence of active ischemia. There were no operative deaths among 23 patients who actually underwent coronary artery bypass combined with cardioverter-defibrillator implantation; however, operative mortality by the intention-to-treat principle was 8% (2/25). Total cardiac survival was better for patients who underwent revascularization than for those patients who had "high-risk" characteristics and did not undergo revascularization. Stratified subgroup analysis demonstrated significant survival advantages favoring revascularization in patients with three-vessel or left main coronary artery disease, class III or IV angina, and an ejection fraction greater than 25%. Multivariate analysis revealed that low ejection fraction and left main coronary artery disease were independent predictors of decreased survival.

Adult↗

Transvenous versus transthoracic cardioverter-defibrillator implantation. A comparative analysis of morbidity, mortality, and survival.

The hypothesis that transvenous implantation of a cardioverter-defibrillator is associated with less morbidity than use of a transthoracic approach was investigated in a retrospective series of 146 patients. None of these patients had concomitant heart procedures, and the preoperative characteristics of the two groups were similar. When analyzed by actual technique used (transvenous, 57 patients; transthoracic, 89 patients) and by the intention-to-treat method (transvenous, 65 patients, 8 of whom actually underwent thoracotomy; thoracotomy, 81 patients), transvenous implantation was associated with a lower incidence of postoperative respiratory complications and atrial fibrillation. Total cardiac mortality and freedom from sudden cardiac death in the transvenous and transthoracic groups were comparable at 2 years.

Aged↗

Transvenous cardioverter defibrillators: cost implications of a less invasive approach.

To assess the economic impact of a transvenous lead system for an implantable cardioverter defibrillator (ICD), we evaluated the hospital charges for two groups of patients: group I patients (n = 23) underwent implantation of an ICD generator with an epicardial lead system via a thoracotomy and group II patients (n = 25) underwent implantation of the same generator using transvenous leads. There was no difference in demographics between the two groups. There was a 15% decrease in total charges for the transvenous group compared to the thoracotomy group ($54,142 vs $63,359, P < 0.05). Evaluation of the component charges revealed that the decline could be attributed to a reduction in implant ($27,328 vs $29,285, P < 0.02) and convalescent charges ($7,703 vs $15,179, P < 0.01) for the transvenous group. There was a corresponding decrease in length of stay for the transvenous group (22 vs 29 days, P < 0.05) largely secondary to a 38% reduction in convalescent length of stay (8 vs 13 days, P < 0.05). We conclude that the use of transvenous lead systems for the ICD results in a significant reduction in hospital charges as well as hospital length of stay.

Aged↗

The associations of levels of serum potassium and magnesium with ventricular premature complexes (the Framingham Heart Study).

There are conflicting data regarding the impact of serum potassium and magnesium levels on susceptibility to ventricular premature complexes (VPCs) in the clinical setting. The associations of serum potassium and magnesium levels with the prevalence of complex or frequent (> 30/hour, multiform or repetitive) VPCs were examined after adjusting for age, sex, smoking, caffeinated coffee consumption, alcohol consumption, and left ventricular mass in Framingham Offspring Study subjects who were free of clinically apparent heart disease. There were 3,327 eligible subjects (mean age 44 years). Complex or frequent VPCs were present in 183 subjects (5.5%). When age-adjusted prevalences of complex or frequent VPCs were compared among quartiles of serum potassium and magnesium using a trend test, lower potassium (p = 0.002) and lower magnesium (p = 0.010) levels were associated with higher prevalence rates of arrhythmia. In logistic regression analyses that included potassium and magnesium simultaneously, potassium (p = 0.0021) and magnesium (p = 0.0311) levels were inversely associated with the occurrence of complex or frequent VPCs after adjustment for age, sex, smoking, coffee and alcohol consumption, diuretic use, and systolic blood pressure. These associations remained significant after accounting for left ventricular mass. A 1 SD decrement in potassium (0.48 mEq/liter) or magnesium (0.16 mEq/liter) level was associated with a 27% (95% confidence interval 6% to 51%) and a 20% (95% confidence interval 3% to 41%) greater odds of complex or frequent VPCs, respectively. Lower levels of serum potassium and magnesium were concurrently associated with higher prevalence rates of ventricular arrhythmias.

Adult↗

Advances in ICD lead systems.

We have presented both technical and clinical data indicating that transvenous lead systems are comparable to standard epicardial ICD systems with respect to efficacy. In addition there may be a reduction in morbidity when compared with the standard epicardial implant. We have shown for the Endotak and Transvene systems that each has its own idiosyncrasies, advantages, and disadvantages. Other lead systems are too early in their clinical evaluations for such definitive statements to be made. Regarding long-term reliability, the issues of mechanical integrity of the insulation and conductor materials, as well as the stability (or otherwise) of sensing and defibrillating characteristics remains to be determined for all lead systems. Similarly, compatibility between lead systems and pulse generators made by different manufacturers cannot be assumed, but needs to be prospectively examined in rigorous clinical trials.

Defibrillators, Implantable↗

Rise in chronic defibrillation thresholds in nonthoracotomy implantable defibrillator.

BACKGROUND: To establish the chronic stability of defibrillation thresholds (DFTs) in a transvenous cardioverter/defibrillator (TCD) system, we studied 37 consecutive patients with TCD systems implanted for > 6 months. METHODS AND RESULTS: DFT was measured by a step-down method at implant and 2 and 6 months later. The mean ejection fraction was 34.5 +/- 14.3%. Coronary artery disease with previous myocardial infarction was present in 31 patients. The mean DFT rose from 13.3 +/- 4.3 J at implant to 16.5 +/- 4.7 J at 2 months (P < .001) and 17.6 +/- 5.4 J at 6 months (P < .0001). ANOVA revealed a statistically significant rise in DFT over time (P < .0005). At 2 months, 25 patients had a rise in DFT, and 14 had a rise > or = 5 J. The observed rise at 2 months persisted in 19 patients. A chronic rise, defined as > or = 5 J rise at 6 months, occurred in 17 patients. Univariate analysis of clinical as well as implant variables revealed no predictors of a rise in DFT in this group. CONCLUSIONS: We conclude that there is a significant rise in DFT at 2 and 6 months in this TCD system. Although the chronic threshold remained well within the available energy range of the pulse generator, this observation has important implications for implantation guidelines, programming, and future pulse generator development for TCD patients.

Aged↗

Reduced heart rate variability and mortality risk in an elderly cohort. The Framingham Heart Study.

BACKGROUND: The prognostic implications of alterations in heart rate variability have not been studied in a large community-based population. METHODS AND RESULTS: The first 2 hours of ambulatory ECG recordings obtained on original subjects of the Framingham Heart Study attending the 18th biennial examination were reprocessed to assess heart rate variability. Subjects with transient or persistent nonsinus rhythm, premature beats > 10% of total beats, < 1 hour of recording time, processed time < 50% of recorded time, and those taking antiarrhythmic medications were excluded. The associations between heart rate variability measures and all-cause mortality during 4 years of follow-up were assessed. There were 736 eligible subjects with a mean age (+/- SD) of 72 +/- 6 years. The following five frequency domain measures and three time domain measures were obtained: very-low-frequency power (0.01 to 0.04 Hz), low-frequency power (0.04 to 0.15 Hz), high-frequency power (0.15 to 0.40 Hz), total power (0.01 to 0.40 Hz), the ratio of low-frequency to high-frequency power, the standard deviation of total normal RR intervals, the percentage of differences between adjacent normal RR intervals that are > 50 milliseconds, and the square root of the mean of the squared differences between adjacent normal RR intervals. During follow-up, 74 subjects died. In separate proportional hazards regression analyses that adjusted for relevant risk factors, very-low-frequency power (P < .0001), low-frequency power (P < .0001), high-frequency power (P = .0014), total power (P < .0001), and the standard deviation of total normal RR intervals (P = .0019) were significantly associated with all-cause mortality. When all eight heart rate variability measures were assessed in a stepwise analysis that included other risk factors, low-frequency power entered the model first (P < .0001); thereafter, none of the other measures of heart rate variability significantly contributed to the prediction of all-cause mortality. A 1 SD decrement in low-frequency power (natural log transformed) was associated with 1.70 times greater hazard for all-cause mortality (95% confidence interval of 1.37 to 2.09). CONCLUSIONS: The estimation of heart rate variability by ambulatory monitoring offers prognostic information beyond that provided by the evaluation of traditional risk factors.

Aged↗