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This paper investigates the effects of obesity, socio-economic variables, and individual-specific factors on work productivity across Italian regions. A dynamic panel data with correlated random effects is used to jointly deal with incidental parameters, endogeneity issues, and functional forms of misspecification. Methodologically, a hierarchical semiparametric Bayesian approach is involved in shrinking high dimensional model classes, and then obtaining a subset of potential predictors affecting outcomes. Monte Carlo designs are addressed to construct exact posterior distributions and then perform accurate forecasts. Cross-sectional Heterogeneity is modelled nonparametrically allowing for correlation between heterogeneous parameters and initial conditions as well as individual-specific regressors. Prevention policies and strategies to handle health and labour market prospects are also discussed.

This paper aims to investigate the effects of environmental sources and health statistics on economic growth and other development indicators of interest. With population growth, urbanization, and industrialization of economies, the built environment for human health has emerged as an important and growing driver in interdisciplinary research and evidence-based policy development, improving a country’s growth prospects and the standard of living. A compressed structural Panel Vector Autoregression is used to address these issues. Methodologically, a hierarchical semiparametric Bayesian approach is involved to reduce the dimensionality, overtake variable selection problems, and model stochastic volatility. Policy-relevant strategies are also addressed to investigate causal relationships between sustainability indicators and economic growth.

In Gansbaai (South Africa), at Dyer Island Nature Reserve, a large White shark population is present and can be observed due to the support of local ecotourism operators authorised to reach the field observation sites. Between 2009 and 2019, it was possible to create a database including information about each individual observed. In total, 423 white sharks were sighted during 462 direct observation hours from the boat, that included 220 hours from the diving “cage”. The mean sighting rate was 0.91 (range 0.18–1.53) sharks per hour and sighting rates dramatically declined in the last three years of the study period. Ninety-nine unique Photo-Ids of the dorsal fin were collected and only five re-sightings occurred, which indicate a transient behaviour for the Gansbaai White shark population. The sex ratio showed that females were always prevalent over males throughout the duration of the observations: the ratios were 1:2.2:0.8 for males, females, and unsexed sharks, respectively, and showed the prevalence of immature female individuals (immature: 51 males, 201 females, and 40 unsexed; adults: 49 males, 14 females, and 1 unsexed; undefined maturity: 5 males, 19 females, and 43 unsexed sharks). The predominance of immatures only applies to the females; there were as many immature males (51) as mature (49). The total length for all the individuals was between 150 cm and 500 cm (mean 308 cm, n = 423) with few young-of-the-year and adults recorded, indicating that Gansbaai Area is not a nursery area nor an adult aggregation site, but a seasonal feeding ground. The interannual sighting trend showed a consistent long-term increasing peak (ca. 4–5 years) and this could confirm that, in Gansbaai, the White shark frequency is not affected by ecotourism but, since 2017, a consistent loss of sightings was also due to recorded transient killer whales’ unusual fatal attacks.

The paper develops a computational method to deal with some open issues related to Bayesian model averaging for multiple linear models: overfitting, model uncertainty, endogeneity issues, and missp...

Between the years 2008 and 2013, six annual research expeditions were carried out at Dyer Island (Gansbaai, South Africa) to study the surface behaviour of white sharks in the presence of two passive prey: tuna bait and a seal-shaped decoy. Sightings were performed from a commercial cage-diving boat over 247 h, 250 different white sharks, with a mean total length (TL) of 308 cm, were observed. Of these, 166 performed at least one or more interactions, for a total of 240 interactions with bait and the seal-shaped decoy. In Gansbaai, there is a population of transient white sharks consisting mainly of immature specimens throughout the year. Both mature and immature sharks preferred to prey on the seal-shaped decoy, probably due to the dietary shift that occurs in white sharks whose TL varies between 200 cm and 340 cm. As it is widely confirmed that white sharks change their diet from a predominantly piscivorous juvenile diet to a mature marine mammalian diet, it is possible that Gansbaai may be a hunting training area and that sharks show a discriminate food choice, a strategy that was adopted by the majority of specimens thanks to their ability to visualize energetically richer prey, after having been attracted by the odorous source represented by the tuna bait.

This paper provides new empirical insights in order to give a relevant contribution to the more recent literature on international transmission of shocks among emerging market economies, with a particular emphasis in the most recent recession and postcrisis consolidation. Interdependence, commonality, and heterogeneity in macroeconomic-financial linkages are also identified in order to give new stimulus to the study of international business cycles and policy-making. An extension of a time-varying Structural Panel Bayesian Vector Autoregressive model is developed to deal with model misspecification and unobserved heterogeneity problems when studying multicountry dynamic panels and jointly investigating monetary and fiscal policy effects. The results argue that monetary policy transmission mechanisms and fiscal authority have worked actively among emerging markets but with different actions due to large differences in their financial structure.

This paper provides new empirical insights in order to give a relevant contribution to the more recent literature on international transmission of shocks and on business cycles synchronization across developed economies, with a particular emphasis in the most recent recession and post-crisis consolidation. Interdependence, commonality and heterogeneity in macroeconomic-financial linkages are also identified in order to depict the perplexed nature of modern economies. A time-varying Structural Panel Bayesian Vector Autoregression (SPBVAR) model is developed to deal with model misspecification and unobserved heterogeneity problems when studying multicountry dynamic panels. The results argue for significant synchronization behind a relevant consolidation without delay. Additionally, consolidation is needed to underpin confidence in fiscal solvency at the country level and prevent adverse international externalities. My evidence calls for more integrated macroprudential and financial stability policies. It also shows that, when formulating policies or forecasting, additional transmission channels and economic-institutional issues through which fiscal contractions influence the dynamics of the GDP growth need to be accounted for in muticountry setups.

We review the macroscopic and microscopic anatomy of myocardial disease associated with heart failure (HF) and sudden cardiac death (SCD) and focus on the prevention of SCD in light of its structural pathways. Compared to patients without SCD, patients with SCD exhibit 5- to 6-fold increases in the risks of ventricular arrhythmias and SCD. Epidemiologically, left ventricular hypertrophy by ECG or echocardiography acts as a potent dose-dependent SCD predictor. Dyslipidemia, a coronary disease risk factor, independently predicts echocardiographic hypertrophy. In adult SCD autopsy studies, increases in heart weight and severe coronary disease are constant findings, whereas rates of acute coronary thrombi vary remarkably. The microscopic myocardial anatomy of SCD is incompletely defined but may include prevalent changes of advanced myocardial disease, including cardiomyocyte hypertrophy, cardiomyocyte apoptosis, fibroblast hyperplasia, diffuse and focal matrix protein accumulation, and recruitment of inflammatory cells. Hypertrophied cardiomyocytes express "fetospecific" genetic programs that can account for acquired long QT physiology with risk for polymorphic ventricular arrhythmias. Structural heart disease associated with HF and high SCD risk is causally related to an up-regulation of the adrenergic renin-angiotensin-aldosterone pathway. In outcome trials, suppression of this pathway with combinations of beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, and mineralocorticoid receptor blockers have achieved substantial total mortality and SCD reductions. Contrarily, trials with ion channel-active agents that are not known to reduce structural heart disease have failed to reduce these risks. Device therapy effectively prevents SCD, but whether biventricular pacing-induced remodeling decreases left ventricular mass remains uncertain.

Background: The waveform tilt of bipha- sic shocks yielding the lowest defibrillation threshold (DFT) is not well defined. Some evidence indicates that tilts less than 65% may improve DFTs. Methods: In 57 patients undergoing ICD implanta- tion, DFTs were determined with truncated exponen- tial biphasic waveform tilts at 65%/65% and at 42%/42%. An external defibrillator with custom software was used for testing. The effective capacitance of the defibril- lator was 132-µF for both waveforms. DFTs were de- termined using a binary search method starting with 12 Joules (J). Patients were randomly assigned to ini- tial testing with either one of the two tilts. Thirty patients (Group 1) were tested with a two electrode (active can to RV coil, or SVC coil to RV coil) and 27 patients (Group 2) were tested with a three electrode system (subcutaneous patch or active can + SVC coil to RV coil). Results: Groups 1 and 2 did not differ in age, ejection fraction or antiarrhythmic medications. Group 1 deliv- ered energy DFTs were 10.1 ± 5.5 J with the 65%/65% tilt and 10.1 ± 5.9 J for the 42%/42% tilt (p = 0.92). In group 2 the average DFT for the 65%/65% tilt was 8.4 ± 5.7 J and for the 42%/42% tilt was 8.1 ± 5.3 J (p = 0.70). There were no significant differences in DFTs for either group. The system impedance for Group 1 was 64 ± 12 ohms and for Group 2 was 39 ± 6 ohms (p < 0.0001). Conclusions: We found no differences in DFTs bet- ween 65%/65% tilt and 42%/42% tilt using either 2- or 3-electrode defibrillation systems. Further research is needed to optimize waveforms in order to minimize DFTs, which will result in smaller ICDs and/or greater safety margins for defibrillation.

Implantable cardioverter defibrillators (ICDs) with dual chamber and dual chamber rate responsive pacing may offer hemodynamic advantages for some ICD patients. Separate ICDs and DDDR pacemakers can result in device to device interactions, inappropriate shocks, and underdetection of ventricular fibrillation (VF). The objectives of this study were to compare the VF detection times between the Ventak AV II DR and the Ventak AV during high rate DDDR and DDD pacing and to test the safety of dynamic ventricular refractory period shortening. Patients receiving an ICD were randomized in a paired comparison to pacing at 150 beats/min (DDD pacing) or 175 beats/min (DDDR pacing) during ICD threshold testing to create a "worst case scenario" for VF detection. The VF detection rate was set to 180 beats/min, and VF was induced during high rate pacing with alternating current. The device was then allowed to detect and treat VF. The induction was repeated for each patient at each programmed setting so that all patients were tested at both programmed settings. Paired analysis was performed. Patient characteristics were a mean age of 69 +/- 11 years, 78% were men, coronary artery disease was present in 85%, and a mean left ventricular ejection fraction of 0.34 +/- 0.11. Fifty-two episodes of VF were induced in 26 patients. Despite the high pacing rate, all VF episodes were appropriately detected. The mean VF detection time was 2.4 +/- 1.0 seconds during DDD pacing and 2.9 +/- 1.9 seconds during DDDR pacing (P = NS). DDD and DDDR programming resulted in appropriate detection of all episodes of VF with similar detection times despite the "worst case scenario" tested. Delays in detection may be seen with long programmed ventricular refractory periods which shorten the VF sensing window and may be avoided with dynamic ventricular refractory period shortening.

Background Patients with implantable cardioverter–defibrillators often receive adjunctive antiarrhythmic therapy to prevent frequent shocks. We tested the efficacy and safety of sotalol, a beta-blocker with class III antiarrhythmic effects, for this purpose. Methods In a multicenter trial, patients were stratified according to left ventricular ejection fraction (≤0.30 or >0.30), randomly assigned to double-blind treatment with 160 to 320 mg of sotalol per day (151 patients) or matching placebo (151 patients), and followed for 12 months. Kaplan–Meier analyses of the time to an event were performed. Three end points were used: the delivery of a first shock for any reason or death from any cause, the first appropriate shock for a ventricular arrhythmia or death from any cause, and the first inappropriate shock for a supraventricular arrhythmia or death from any cause. Results Compliance with double-blind treatment was similar in the two groups. There were seven deaths in the placebo group and four in the sot...

Previous work had demonstrated a reduced specificity associated with head-up tilt protocols using high-dose isoproterenol in patients between 20 and 50 years of age. We evaluated the specificity of head-up tilt testing using different isoproterenol infusion doses and administration of nitroglycerin in patients aged >60 years. In addition, whether the same protocols have impact on the sensitivity of the test was also assessed. One hundred sixty subjects were included in this study. Seventy-six were volunteers randomized to either head-up tilt test with low-dose, 3- and 5-microg/min of isoproterenol (group I) or to a protocol including 0.4 mg of sublingual nitroglycerin (group II). In addition, after an upright tilt drug-free state, 58 patients with a history of syncope underwent repeat head-up tilt with increasing doses of isoproterenol infusion, followed by sublingual nitroglycerin if the test result remained negative. The remaining 33 patients were subjected to the nitroglycerin protocol after the drug-free state phase. In the control groups, the incidence of false-positive responses was 88% and 95%, respectively. In patients with syncope after a negative test result during 5 microg of isoproterenol infusion, nitroglycerin administration increased the number of positive responses from 45% to 79%. The percentage of positive tilt in patients undergoing nitroglycerin administration after the drug-free state part of the protocol was 78%. Administration of nitroglycerin was the most significant predictor of a positive upright tilt in patients with syncope. In subjects aged >60 years, head-up tilt protocols with high-dose isoproterenol infusion and nitroglycerin maintained an adequate specificity. In this subset of patients, nitroglycerin seemed to provide a better sensitivity than isoproterenol.

The Jewel 7219D was the first non-thoracotomy implantable cardioverter-defibrillator (ICD) with biphasic shock capability small enough to be placed in the prepectoral subcutaneous position. Size reduction of ICDs is desirable, but safety and efficacy of smaller devices must be demonstrated. Outcomes of patients treated with the Jewel 7219D defibrillator (n = 1,781) and with its precursor model PCD 7217B (n = 2,637) were compared. To use PCD patients (n = 2,637) as historical (n = 2,574) and concurrent controls (n = 63), statistical adjustments using the Cox proportional-hazards regression model were made. Jewel recipients (n = 1,781) treated in 106 US and 32 non-US centers exhibited similar characteristics including a mean age of 59 years, 78% men, ejection fraction of 34%, history of aborted sudden cardiac death in 41%, and coronary artery disease in 70%. Implantation was completed in 1,777 of 1,781 (99.9%) attempts and success with the first electrode configuration and polarity was 89.5%. Kaplan-Meier cumulative first-year survivals for cardiac and all-cause mortality were 98.5% and 93.3%. Complication-free first-year survival for Jewel implants in prepectoral subcutaneous (n = 582), subpectoral submuscular (n = 366), and abdominal (n = 449) positions did not differ (p >0.05). First-year survival free of pocket-related complications exceeded 98% in all locations. Adjusted cardiac and all-cause first-year mortality, and efficacy in terminating spontaneous tachyarrhythmias did not differ between the 2 device groups. In conclusion, the safety and efficacy of Jewel model 7219D in the prepectoral subcutaneous position are at least equal to either those of Jewel models implanted in different positions or to those of the previously extensively characterized PCD 7217B.

Objectives. The objective of this study was to evaluate the feasibility, safety and efficacy of placing implantable cardioverter-defibrillators (ICDs) in the electrophysiology laboratory using conscious sedation with combined hypnotic agents and deep sedation with etomidate. Background. Implantable cardioverter-defibrillators with transvenous leads permit the use of simplified implantation techniques similar to those used for the insertion of permanent pacemakers. However, implantation of ICDs without general anesthesia has thus far gained limited acceptance. Methods. In 162 patients, conscious sedation during ICD placement was achieved with combined intravenous midazolam, morphine and promethazine (Phenergan). Intravenous etomidate was administered to induce deep sedation for defibrillation threshold testing. First-time implantations were in the prepectoral position (n = 142), but some patients with preexisting devices received abdominal implants (n = 20). The results were compared with those of concurrent patients (n = 56) who received prepectoral implants under propofol anesthesia administered by an attending anesthesiologist. Results. The anesthetic protocol was implemented without major intraoperative complications. During deep sedation with etomidate, episodes of apnea, hypoxia or arterial hypotension requiring therapeutic intervention did not occur. During a mean (±SD) follow-up period of 257 ± 140 days (median 227, range 14 to 482), there were, among the 162 patients, a total of two nonsudden cardiac deaths—one 71 days and the other 157 days after the operation. There were two nonsudden deaths in the concurrent control subjects (n = 56)—one 13 days and the other 110 days after the operation. Conclusions. Implantation of ICDs under conscious sedation with combined hypnotic agents and deep sedation with etomidate is a safe and effective procedure with low perioperative morbidity and low long-term complication rates.

This article describes a patient who underwent right ventricular disconnection for medically refractory ventricular tachycardia associated with arrhythmogenic right ventricular dysplasia. After the operation there was no ventricular tachycardia recurrence. Two years after the operation, he received a permanent VVI pacemaker for the symptomatic second-degree AV block. Sensing function of the pacemaker was normal for the normal QRS complexes, but the tiny QRS complexes that appeared after the arrhythmia surgery were not sensed by the pacemaker and therefore caused no problem.

To study the long-term evolution, determinants, and clinical relevance of the conduction abnormalities after orthotopic heart transplantation, 87 patients, followed for a mean of 105 +/- 72 weeks, were divided into 3 groups according to the characteristics of their electrocardiograms compared with their initial electrocardiogram recorded at study entry. The first group consisted of 24 patients whose initial electrocardiogram was normal, and subsequent electrocardiograms remained normal throughout the study. The second group included 27 patients who developed electrocardiographic evidence of progressive conduction system damage. The third group comprised 36 patients whose initial electrocardiogram was abnormal and subsequent electrocardiograms remained unchanged during follow-up. Although the hemodynamic and echocardiographic evaluation of right and left ventricular function were initially similar among the 3 groups, groups 2 and 3 demonstrated a significant deterioration of left ventricular ejection fraction (62 +/- 12% to 55 +/- 16% and 62 +/- 8% to 57 +/- 14%, respectively; p < 0.05) and cardiac index (2.7 +/- 0.6 to 2.3 +/- 0.5 and 3.0 +/- 0.9 to 2.5 +/- 0.9 L/min/m2, respectively; p < 0.05) while patients in group 1 maintained their normal baseline indices. Incidence and progression of coronary artery disease, as well as frequency of rejection episodes, were comparable among the groups. Mortality was higher in the 2 groups with evidence of conduction defects. Sudden death associated with complete heart block (2 patients) or ventricular arrhythmias (3 patients) was exclusively confined to patients with evidence of progressive electrocardiogram abnormalities. We conclude that, following orthotopic heart transplantation, stable or progressive conduction system damage on the electrocardiogram is associated with left ventricular dysfunction and increased mortality. Sudden death is not uncommon among patients demonstrating worsening cardiac conduction and, in some cases, is related to the development of potentially preventable complete heart block.

During the past 10 years numerous studies on the treatment of paroxysmal atrial fibrillation (AF) by right and left atrial ablation procedures have been published. The results of studies based on follow-up periods of a few months have been repeatedly interpreted as providing evidence for curative therapy. However, insufficient focus on the variability of the natural history of paroxysmal AF, the inadequate detection of silent arrhythmic events, the eclectic post-interventional use of antiarrhythmic drugs, and the lack of appropriate control groups make the reports unconvincing. Randomized controlled trials are needed to confirm postulated long-term cure rates for AF.

Background After several days of loading, oral amiodarone, a class III antiarrhythmic, is highly effective in controlling ventricular tachyarrhythmias; however, the delay in onset of activity is not acceptable in patients with immediately life-threatening arrhythmias. Therefore, an intravenous form of therapy is advantageous. This study was designed to compare the safety and efficacy of a high and a low dose of intravenous amiodarone with bretylium, the only approved class III antiarrhythmic agent. Methods and Results A total of 302 patients with refractory, hemodynamically destabilizing ventricular tachycardia or ventricular fibrillation were enrolled in this double-blind trial at 82 medical centers in the United States. They were randomly assigned to therapy with intravenous bretylium (4.7 g) or intravenous amiodarone administered in a high dose (1.8 g) or a low dose (0.2 g). The primary analysis, arrhythmia event rate during the first 48 hours of therapy, showed comparable efficacy between the bretylium group and the high-dose (1000 mg/24 h) amiodarone group that was greater than that of the low-dose (125 mg/24 h) amiodarone group. Similar results were obtained in the secondary analyses of time to first event and the proportion of patients requiring supplemental infusions. Overall mortality in the 48-hour double-blind period was 13.6% and was not significantly different among the three treatment groups. Significantly more patients treated with bretylium had hypotension compared with the two amiodarone groups. More patients remained on the 1000-mg amiodarone regimen than on the other regimens. Conclusions Bretylium and amiodarone appear to have comparable efficacies for the treatment of highly malignant ventricular arrhythmias. Bretylium use, however, may be limited by a high incidence of hypotension.

Adequate spatial resolution of local activation is fundamental for the correct depiction of myocardial activation during ablative treatment of ventricular tachycardia. The widest allowable distances between recording sites that provide an accurate description of the field potential distribution is dictated by the Nyquist sampling theorem. Activation times are derived from the field potentials. However, because of noise intrinsic in activation detection algorithms, closer recording sites may be required than those theoretically computed. The purpose of this study is to examine the spatial frequency spectrum of epicardial activation time sequences computed by common activation detection algorithms, determine which algorithm is least noisy, and derive the recording site density necessary to avoid distortion of the epicardial activation map. Using 40 to 80 electrode linear arrays, monopolar and bipolar electrograms from the epicardium were recorded vertically (base to apex) and horizontally in 11 dogs. Activation times for bipolar electrograms were estimated using Peak, Fastest Zero Crossing, and Morphological algorithms. Activation times for monopolar electrograms were set equal to the time of the fastest negative deflection. Activation time sequences were analyzed using conventional Fourier techniques. Anomalous activation times from serially adjacent bipolar electrograms, which constitute algorithm noise, were studied. Horizontal and vertical interelectrode distances are 3.2 mm and 2.4 mm, respectively. Of the bipolar algorithms, the Morphological algorithm produced the fewest anomalous activation times. Mapping systems having more than 256 channels are required for accurate representation of epicardial activation in a typical 20-kg dog. The endocardial electrode spacing is unknown, but is expected to be at least as dense. Large global mapping systems or regionally dense arrays may offer advantages during catheter ablations for ventricular tachycardia and for studies into the mechanisms of ventricular tachycardia by accurately defining the cardiac activation pattern.

The ability of Holter monitoring to predict clinical events during amiodarone therapy was evaluated in 83 patients with coronary artery disease and inducible monomorphic ventricular tachycardia. Sixty-four patients (77%) had significant ventricular ectopy activity (> or = 10 ventricular premature complexes [VPCs]/hour) at baseline, and 19 (23%) did not; patients were similar in age (63 and 65 years, respectively; p = 0.24) and ejection fraction (31 and 32%, respectively; p = 0.75). Over a mean of 23 +/- 17 months, there was no difference in arrhythmia recurrence (33 and 26%; p = 0.89) or sudden death (16 and 20%; p = 0.94) in patients with and without significant ectopy, respectively. In patients with significant ectopy, amiodarone decreased VPC frequency from baseline to 2 weeks, but not from 2 to 6 weeks. Forty-two patients had > 85% reduction in ectopy at 2 weeks; 20 patients did not. However, this reduction of simple VPCs did not predict a decrease in arrhythmic recurrence (29 vs 40%; p = 0.59) nor sudden death (25 vs 11%; p = 0.56) in patients with and without VPC suppression, respectively. Forty-five patients had Holter monitoring at 6 weeks. Twenty-one patients (47%) had > 95% suppression of ectopy, and 24 did not. Neither the recurrence (38 vs 38%; p = 0.54) nor sudden death (33 vs 13%; p = 0.45) rate was predicted by the degree of VPC suppression. Amiodarone is a powerful suppressant of VPCs, but Holter suppression of this ectopic activity is not predictive of clinical outcome.

Investigations into mechanisms and successful surgical therapy of ventricular tachycardia (VT) depend upon accurate endocardial/epicardial mapping. Deduction of local activation is based upon parameters derived from the field potentiai (FP) (monopolar recording) or its first spatial derivative (bipolar recording). Adequate electrode spacing is an assumption fundamental to the mapping process, but the electrode spacing required for accurate representation of the FP is unknown. The purpose of this work is to derive the electrode spacing necessary to accurately describe the FP on the epicardium. In 11 dogs, electrograms from vertical (V) (base to apex h) bands having 40 electrodes and horizontal (H) bands having 40 to 80 electrodes were sampled at I kHz. The spatial handwidths (BW) were computed according lo two criteria: (1) the frequency yielding 2% mean squared error (MSE) computed at the time of the greatest integrated magnitudes of the Fourier transform; and (2) the highest frequency bounding 95% power computed at each msec throughout the beat. Implied electrode spacings were defined according to the sampling theorem. The 5th percentiles of the implied electrode spacing distributions were used to define the widest interelectrode distance required to prevent spatial aliasing. H-5th percentile and V-5th percentile were, respectively; 2% MSE (3.5 mm, 2.3 mm); 95% power (3.6 mm, 2.3 mm). Thus, a typical 20-kg dog requires more than 250 recording sites for accurate epicardial mapping. Extrapolating to man, these results suggest inadequate electrode density may partially be responsible for incomplete and ambiguous reentry patterns often observed during intraoperutive mapping.

Designation of the time of local activation is fundamental to electrophysiological mapping. In normal myocardium, the minimum slope in extracellular monopolar (MP) electrograms has been linked through simultaneous intracellular and extracellular recordings to phase 0 of the action potential. However, no similar correlation has been demonstrated for a parameter from bipolar (BP) electrograms, now commonly used during electrophysiological studies and intraoperative mapping. The purpose of this work is to compare the activation time, determined according to several common algorithms applied to BP electrograms, with the time of the minimum slope in MP electrograms. Simultaneous normal epicardial MP and BP electrograms were acquired from subjects undergoing surgery for Wolf-Parkinson-White Syndrome and from dogs. The activation time in BP electrograms was defined by four algorithms: (1) peak (P); (2) greatest absolute slope (S); (3) zero crossing of the segment containing the greatest slope (FZC); and (4) morphological (M). Each was compared to the time of the minimum slope in the simultaneously recorded MP response. The incidence of outliers was tabulated. The distribution of activation times computed using each BP algorithm was statistically different from the distribution of activation times derived from MP electrograms. M performed best (absolute difference: 2.6 +/- 2.9 msec; cor coef: 0.9925 in man). The M, P, FZC, and S algorithms produced 3.2%, 3.5%, 4.7% and 4.7% outliers, respectively. The overall performance of a morphologically based algorithm is superior to simplistic BP algorithms based only on slope or peak.(ABSTRACT TRUNCATED AT 250 WORDS)

The purpose of this work is to determine the sensitivity of the estimated time of peaks and maximum slopes, commonly used in activation time computations, to the instant at which sampling is initiated. Based on complex and quickly changing waveforms, 471 monopolar (MP) and bipolar (BP) epicardial responses in man were selected. These were decimated from 10 kHz to simulate sampling at frequencies ranging from 200 Hz to 2,000 Hz. The peak and maximum absolute slope for BP and the minimum slope for MP were computed repeatedly starting at successive 100 microseconds intervals extending throughout the sampling period and compared with these parameters computed from the waveform sampled at 10 kHz. Slopes were estimated using each of four different algorithms. The average greatest shift (AGS) due to variations in sampling onset ranged from 11.2 +/- 3.5 (200 Hz) to 0.3 +/- 0.2 msec (2,000 Hz). For bipolar algorithms, the peak performed better than the slope algorithms (AGS: 5.9 +/- 3.3 to 0.3 +/- 1.0 msec). For MP algorithms, 2 point linear, and 3 and 5 point Lagrange slope estimates performed similarly (AGS: 5.6 +/- 3.3 to 0.3 +/- 0.2 msec); a 5 point least square fit algorithm performed poorly. Sampling MP and BP electrograms below 500 and 400, respectively, often caused maximum shifts greater than 4 msec. Thus, the resolution of the peak and estimated slope is not limited to the sampling period, variations in initiation of sampling can cause significant outliers especially at low sampling rates, and MP electrograms should be sampled faster than BP electrograms for comparable accuracy.

Activation Time Detection for Intraoperative Mapping.Introduction: Local activation determined from monopolar electrograms usually is marked at the time of the minimum slope. In bipolar recordings, the peak, the maximum absolute slope, the baseline crossing of the segment containing the maximum absolute slope, and morphological criteria have been used. The purpose of this work is: (1) to compare activation times determined using these algorithms with activation times corrected by electrophysiologists; and (2) to determine which computerized algorithm requires fewest operator correction of outliers. Methods and Results: Monopolar and bipolar electrograms were collected from the epicardium of subjects undergoing surgery for ventricular tachycardia and Wolff-Parkinson-White syndrome, and the above bipolar and monopolar algorithms were evaluated. The electrophysiologists viewed adjacent channels and evolving isochronal maps but not the computer markings. The morphological algorithm compared most favorably with times marked up by electrophysiologists having an overall average difference of 2.2 ± 3.1 msec. For monopolar data, a five point, least square fit, second-order slope approximation algorithm most closely agreed with the electrophysiologist corrected algorithm (3.2 ± 4.0 msec). The morphological and least square algorithms also produced the fewest outliers (3.1% and 5.7%, respectively). When outliers were removed, bipolar and monopolar discrepancies were reduced to 1.8 ± 1.9 and 2.5 ± 2.3 msec, respectively. Conclusions: Thus, among those algorithms tested, an algorithm based on morphological criteria is best suited for computer determination of bipolar activation times and compares favorably to variations between electrophysiologist corrected and computer marked activation times determined traditionally by the largest negative slope in monopolar data. Identification of outliers using contextual and improved morphological algorithms may improve computerized mapping system performance.

Differentiation between primary and secondary (caused by acute myocardial infarction) ventricular fibrillation has important therapeutic and prognostic implications. The diagnosis of myocardial infarction is based on clinical, ECG, and creatine kinase MB isoenzyme (MBCK) activity. Enzymatic criteria might not be able to confirm the diagnosis of myocardial infarction after recent cardioversion. The routine use of electrophysiologic studies involving the induction and termination of ventricular dysrhythmias provides a setting in which enzyme release as a result of cardioversion alone can be examined. Therefore a systematic investigation of the magnitude and time course of creatine kinase (CK) and MBCK release was performed after termination of ventricular dysrhythmias in 57 patlents undergoing electrophysiologic studies. Of patients requiring external cardioversion, only 50% had an elevation in CK and MBCK activity. Elevation when present correlated with the number of shocks and cumulative energy delivered. The magnitude of MBCK release exceeded 10% of the total CK activity in 9% of observations. Pace-termination of ventricular tachycardia did not result in enzyme release. Arrhythmia characteriatics, coronary artery disease, and left ventricular function did not affect the magnitude of the time course of enzyme release. These data suggest that cardioversion with multipile shocks may result in a component of MBCK release, and thus a false positive diagnosis of primary acute myocardial infarction may be made by relying exclusively on the enzyme release pattern.

Heterotopic heart transplantation has been said to be contraindicated in patients with serious native heart arrhythmias that produce hemodynamic instability. Placement of heterotopic allografts, however, can theoretically act as a biological biventricular assist device to provide hemodynamic support during these unstable rhythms. Further, this operation might beneficially alter the hemodynamic milieu of heart failure such that the arrhythmias are ameliorated. Described is our experience with 4 patients with heart failure receiving heterotopic cardiac allografts, documenting changes in native heart arrhythmia that occurred. These cases demonstrate that heterotopic grafts can adequately sustain hemodynamics during malignant native heart dysrhythmia. We believe native heart ventricular arrhythmias are not a contraindication to heterotopic heart transplantation.

An automatic implantable cardioverter-defibrillator (AICD) was implanted in 40 patients with sudden cardiac arrest (n = 29), sustained monomorphic ventricular tachycardia (n = 10) or recurrent syncope (n = 1) who were unsuitable for direct ablative surgery or had had unsuccessful medical therapy. The effect of patch electrode polarity on the defibrillation threshold was prospectively evaluated. Two large epicardial patches were used. Initial polarity was selected at random. Ventricular fibrillation was induced by direct current and a preestablished defibrillation protocol employed to assess the minimal energy that would reproducibly defibrillate the heart. Nineteen patients had a lower defibrillation threshold with the inferior left ventricular patch as an anode and nine patients had a lower defibrillation threshold with this patch as a cathode. In general, the defibrillation threshold was lower when this patch was used as an anode than when it was used as a cathode (18 +/- 10 versus 22.6 +/- 12.2 J; p less than 0.01). No preoperative variable predicted optimal polarity. Therefore, the effect of patch polarity on defibrillation threshold should be assessed in each patient at the time of AICD implantation so that the safety margin for satisfactory device function can be maximized.

Two parameters commonly used when determining the time of local activation during computerized Intraoperative cardinc mapping are the time of the peak in bipolar electrograms (BP) and the time of the largest negative slope (LNS) in monopoiar electrograms (MP). The dependence of these parameters upon bandwidth was studied. A database of fast MP and BP was compiled from intraoperative recordings collected from epicardial sock arrays in man. Based on 95%, 99% and 99.9% of total signal power, the faandwidths of each response were determined. After removing specified frequencies using the Fourier transform, errors in determining these parameters were computed and characterized with respect to mean square error (MSE), percent power bandwidth and frequency content. The Fourier transform was used for abruptly filter out undesired upper frequencies. Filtering BP at 200 Hz produced a 1-ms shift in the peak in 17.0% of the electrograms, 0.4% of the peaks shifted by 2 ms and none shifted by more than 2 ms. Comparable shifts in the LNS occurred when filtering MP at 400 Hz. Retention of 95% of the power in a BP rarely (0.9%) changed the time of its peak by more than 1 ms. For MP, retention of 99.9% of the power was required for similar performance (3.6%). Thus, although BP have greater signal power in the higher frequencies than MP, a greater bandwidth is required when recording monopolarly in order to preserve the small amount of power necessary to define the time of the LNS with accuracy comparable to determination of the peak in BP.

During a 9-year period 80 patients with drug-resistant sustained ventricular tachycardia underwent direct surgical ablation of arrhythmogenic myocardium. Sixty-nine were male (86%) and 11 female (14%), with 1.9 +/- 1.1 (standard deviation) ventricular tachycardia morphologies per patient. The mean number of drugs failed was 3.7 +/- 1.6 per patient. The preoperative left ventricular ejection fraction was 36.4% +/- 14.4%. Complete preoperative endocardial mapping data (greater than 4 endocardial sites in each ventricular tachycardia) were available for 60 of the 80 patients (75%) and intraoperative endocardial data in the clinical ventricular tachycardia was obtained in 37 (46.3%) of the patients. In 17 patients mapped intraoperatively by computer-assisted techniques, complete epicardial and endocardial data in the clinical ventricular tachycardia were obtained in 14 patients (82.4%). Overall, 73 of 80 (91.3%) had some mapping data available. Hospital mortality occurred in 10 patients (12.5%) at a mean interval of 13.5 days, range 0 to 62 days. Postoperatively the clinical ventricular tachycardia has not recurred in 65 of 70 surviving patients (92.9%). Nonclinical ventricular tachycardia occurred in another four patients. All nine patients with postoperative ventricular tachycardia responded to drugs. The major factors predictive of hospital mortality were prolonged cardiopulmonary bypass (greater than 150 minutes), preoperative ejection fraction less than 31%, and incomplete preoperative mapping. Hospital mortality in patients with an ejection fraction below 31% was significantly associated with a history of amiodarone usage. At 3 years of follow-up, freedom from sudden cardiac death was 95.7%, and 86.7% of patients were free of ventricular tachycardia on no antiarrhythmic drugs. These results suggest that direct ventricular tachycardia operations are an effective form of therapy for patients with sustained monomorphic ventricular tachycardia.

Kapton Arrays for Computerized Mapping. A new technology for intraoperative mapping of the sites of origin and propagation of supraventricular (SVT) and ventricular tachycardia (VT) was implemented and evaluated. Kapton forms a thin, flexible substrate on which copper layers can be bonded, etched, and interconnected similar to a multilayered printed circuit board. Narrow Kapton electrode assemblies with 20 contacts spaced over 113 mm were used to construct epicardial sock electrode arrays (Ep) having 238 electrodes and endocardial balloon electrode arrays (En) having 168 electrodes. These arrays were used for mapping 20 consecutive patients undergoing surgery for SVT or VT. In 10 surgeries for VT, bipolar electrograms from 1,045 Ep and 606 En electrode pairs were examined. Responses were recorded from 88.7% Ep and 94.9% En sites. Of 118 Ep sites not showing a response, 27.1 % were due to poor electrode contact near the apex, or AV groove, and 70.3% approximated unexcitable tissue. Among the 31 En sites showing no response, 35.5% were located about the mitral annulus, and 32.3% over unexcitable tissue. In 10 surgeries for SVT, bipolar electrograms from 1,114 E p electrode pairs were studied. Responses were seen at 94.3% sites. Of the 63 sites not showing a response, 63.5% resulted from poor electrode contact near the apex or AV groove. These electrode arrays, utilizing Kapton strips, have proven highly effective and reliable for computerized intraoperative recording. (J Cardiovasc Electrophysiol, Vol. 1, pp. 496–505, December 1990)

Summary Trials of drug treatment for prevention of sudden arrhythmic death have been disappointing, perhaps because suppressive therapy with arrhythmic agents fails to address the mechanisms leading to electrophysiological failure. We propose that preventive treatment should pay more attention to molecular mechanisms responsible for the progression of cardiac disease to electrophysiological failure. Most sudden cardiac deaths occur in people with atherogenic dyslipidaemias. Our hypothesis is that the pathogenic molecular mechanisms of dyslipidaemias contribute directly to arrhythmogenesis. Proinflammatory-prothrombotic lipid-derived mediators that may play a part in arrhythmogenesis include phospholipids and leucotrienes acting through the platelet-activating-factor and peroxisome proliferator-activated-receptor pathways. There are drugs available to test the hypothesis of dyslipidaemias-specific prevention of electrophysiological failure.

The active can defibrillator has been designed for implantation in the left prepectoral region. Whether this system can be successfully implanted on the right side is unknown. We describe six cases in which placement of the unipolar single lead defibrillation system was successfully attempted in the right prepectoral region due to impediments on the left side. The mean age of the patients was 62 +/- 12 years. Five patients had ischemic heart disease and one idiopathic dilated cardiomyopathy. The endocardial defibrillation electrode was placed in the right ventricle through the right subclavian vein and positioned at the apex in two patients and in the septal position in four patients. Defibrillation threshold testing was performed using a step-up/step-down protocol beginning at 12 J with 3-J increments or decrements. Defibrillation threshold was defined as the lowest energy of the first shock able to terminate ventricular fibrillation. The generator models used were the Medtronic 7218C in 1 patient, the Medtronic 7219C in 3 patients, and the Ventritex Cadet 115 AC in 2 patients. The mean defibrillation threshold was 15 +/- 3 J. The defibrillation thresholds were retested at 1, 3, and 6 months, and showed no significant change in five patients but decreased from 15 J to 12 J in one patient. The presence of impediments on the left side should not preclude attempts to place the unipolar active can system in the right prepectoral region.

The database of the registry for an implantable cardioverter defibrillator was analyzed to determine the efficacy and safety of antitachycardia pacing for the termination of ventricular tachycardia. In 22,339 episodes treated, termination occurred in 94% and acceleration in only 1.4%.

The waveform tilt of biphasic shocks yielding the lowest defibrillation threshold (DFT) is not well defined. Some evidence indicates that tilts less than 65% may improve DFTs.In 57 patients undergoing ICD implantation, DFTs were determined with truncated exponential biphasic waveform tilts at 65%/65% and at 42%/42%. An external defibrillator with custom software was used for testing. The effective capacitance of the defibrillator was 132-microF for both waveforms. DFTs were determined using a binary search method starting with 12 Joules (J). Patients were randomly assigned to initial testing with either one of the two tilts. Thirty patients (Group 1) were tested with a two electrode (active can to RV coil, or SVC coil to RV coil) and 27 patients (Group 2) were tested with a three electrode system (subcutaneous patch or active can + SVC coil to RV coil).Groups 1 and 2 did not differ in age, ejection fraction or antiarrhythmic medications. Group 1 delivered energy DFTs were 10.1 +/- 5.5 J with the 65%/65% tilt and 10.1 +/- 5.9 J for the 42%/42% tilt (p = 0.92). In group 2 the average DFT for the 65%/65% tilt was 8.4 +/- 5.7 J and for the 42%/42% tilt was 8.1 +/- 5.3 J (p = 0.70). There were no significant differences in DFTs for either group. The system impedance for Group 1 was 64 +/- 12 ohms and for Group 2 was 39 +/- 6 ohms (p0.0001).We found no differences in DFTs between 65%/65% tilt and 42%/42% tilt using either 2- or 3-electrode defibrillation systems. Further research is needed to optimize waveforms in order to minimize DFTs, which will result in smaller ICDs and/or greater safety margins for defibrillation.

K.A. Ellenbogen, G.N. Kay, B.L. Wilkoff, eds. 1007 pp, illustrated. Philadelphia, Pa: WB Saunders Company; 2000. $225.00. ISBN 0-7216-7683-9 The second edition of the textbook edited by Ellenbogen, Kay, and Wilkoff has changed its name from Clinical Cardiac Pacing to Clinical Cardiac Pacing and Defibrillation . Although it has grown from 838 to 1007 pages, the number of contributors has declined from 80 to 73 and the number of chapters from 42 to 36. The book has a total of 847 illustrations (average 24/chapter) and 4316 references (average 119/chapter). There has been a considerable renewal of authors—the second edition retains only 32 of the 80 original contributors. As the new title indicates, the editors have …