David L. Ross

Prognostic significance of ventricular tachycardia and fibrillation induced at programmed stimulation and delayed potentials detected on the signal-averaged electrocardiograms of survivors of acute myocardial infarction.

The relative prognostic significance of ventricular tachycardia and ventricular fibrillation inducible at programmed stimulation within 1 month of acute myocardial infarction was compared in a prospective study of 403 clinically well survivors of transmural infarction who were 65 years old or younger. The prognostic significance of delayed potentials on the signal-averaged electrocardiogram was also examined in a subset of 306 patients without bundle branch block. Among the study patients, 20% had inducible ventricular tachycardia, 14% had inducible ventricular fibrillation, and 66% had no inducible arrhythmias. The 2 year probability of remaining free from cardiac death or nonfatal ventricular tachycardia or fibrillation was 0.73 for those with inducible ventricular tachycardia, 0.93 for those with inducible ventricular fibrillation, and 0.92 for those with no inducible arrhythmias. The cycle length of inducible ventricular tachycardia was 230 msec or more in 70% of the patients with inducible tachycardia who died. Of the patients studied by signal-averaged electrocardiography, 26% had delayed potentials. At 2 years, the probability of remaining free from cardiac death or nonfatal ventricular tachycardia or fibrillation was 0.73 for patients with delayed potentials and 0.95 for patients with no delayed potentials. There was a significant correlation (p less than .001) between the presence of delayed potentials and the ability to induce ventricular tachycardia. In conclusion, in survivors of recent infarction who have not had spontaneous ventricular tachycardia or fibrillation, inducible tachycardia (but not inducible fibrillation) at programmed stimulation predicts a significant risk of death or spontaneous tachycardia or fibrillation. A similar risk is found for patients with delayed potentials on the signal-averaged electrocardiogram.

Curative surgery for atrioventricular junctional (“AV Nodal”) reentrant tachycardia

A new surgical approach was studied prospectively in 10 consecutive patients with atrioventricular (AV) junctional reentrant tachycardia. The aim was to abolish tachycardia yet preserve normal AV conduction. On the basis of electrophysiologic study before operation, patients were classified as type A (ventriculoatrial [VA] intervals during tachycardia less than or equal to 40 ms) (seven patients) or type B (VA intervals greater than 40 ms) (three patients). Dual AV junctional pathways were demonstrable with single extrastimulus testing in seven patients before operation. Endocardial mapping during tachycardia at surgery revealed earliest atrial activation anteromedial to the AV node in type A patients and posterior to the node in the type B patients. The perinodal atrium in the region of earliest atrial activation during tachycardia was carefully disconnected from the AV node. After operation, AV junctional reentrant tachycardia was not inducible at comprehensive electrophysiologic study in any patient, and no clinical recurrences have occurred during a follow-up period of 2 to 14 months (mean 8 +/- 4). Normal AV conduction was preserved in all cases. Anterograde slow AV junctional pathway conduction was abolished in five of seven cases. Retrograde His to atrium conduction time was prolonged in type A patients but the capacity for retrograde VA conduction remained excellent. Retrograde His to atrium conduction was interrupted or severely compromised in the type B patients. These data show that there are at least two types of AV junctional reentry. Perinodal atrium appears to be part of the reentrant circuit in human AV junctional reentry. Although the most consistent effect of surgery was on the retrograde limb of the circuit, anterograde slow pathway conduction was also modified. AV junctional reentry is surgically curable with a high success rate.

EHRA/HRS/APHRS expert consensus on ventricular arrhythmias.

Christian Torp Pedersen (EHRA Chairperson, Denmark), G. Neal Kay (HRS Chairperson, USA), Jonathan Kalman (APHRS Chairperson, Australia), Martin Borggrefe (Germany), Paolo Della-Bella (Italy), Timm Dickfeld (USA), Paul Dorian (Canada), Heikki Huikuri (Finland), Youg-Hoon Kim (Korea), Bradley Knight (USA), Francis Marchlinski (USA), David Ross (Australia), Frédéric Sacher (France), John Sapp (Canada), Kalyanam Shivkumar (USA), Kyoko Soejima (Japan), Hiroshi Tada (Japan), Mark E. Alexander (USA), John K. Triedman (USA), Takumi Yamada (USA), and Paulus Kirchhof (Germany)

Compensatory changes in atrial volumes with normal aging: is atrial enlargement inevitable?

OBJECTIVES The aim of this study was to evaluate left atrial volume and its changes with the phases (active and passive) of atrial filling, and to examine the effect of normal aging on these parameters and pulmonary vein (PV) flow patterns. BACKGROUND Atrial volume change with normal aging has not been adequately described. Pulmonary vein flow patterns have not been volumetrically evaluated in normal aging. Combining atrial volumes and PV flow patterns obtained using transthoracic echocardiography could estimate shifts in left atrial mechanical function with normal aging. METHODS A total of 92 healthy subjects, divided into two groups: Group Y (young <50 years) and Group O (old > or =50 years), were prospectively studied. Maximal (Vol(max)) and minimal (Vol(min)) left atrial volumes were measured using the biplane method of discs and by three-dimensional echocardiographic reconstruction using the cubic spline interpolation algorithm. The passive filling, conduit, and active emptying volumes were also estimated. Traditional measures of atrial function, mitral peak A-wave velocity, velocity time integral (VTI), atrial emptying fraction, and atrial ejection force were measured. RESULTS As age increased, Vol(max), Vol(min), and total atrial contribution to left ventricle (LV) stroke volume were not significantly altered. However, the passive emptying volume was significantly higher (14.2 +/- 6.4 ml vs. 11.6 +/- 5.7 ml; p = 0.03) whereas the active emptying volume was lower (8.6 +/- 3.7 ml vs. 10.2 +/- 3.8 ml; p = 0.04) in Group Y versus Group O. Pulmonary vein flow demonstrated an increase in peak diastolic velocity (Group Y vs. Group O) with no corresponding change in diastolic VTI or systolic fraction. CONCLUSIONS Normal aging does not increase maximum (end-systolic) atrial size. The atrium compensates for changes in LV diastolic properties by augmenting active atrial contraction. Pulmonary vein flow patterns, although diastolic dominant using peak velocity, demonstrated no volumetric change with aging.

Cholesterol-lowering effects of plant sterol esters differ in milk, yoghurt, bread and cereal.

Objective: To measure the relative effects of each of four phytosterol ester-enriched low-fat foods (bread, breakfast cereal, milk and yoghurt) on serum lipids, plasma phytosterols and carotenoids.Design: Three research centres undertook a randomised, incomplete crossover, single-blind study consisting of four treatment periods of 3 weeks each, one of which was a control period. Each sterol-enriched test food provided 1.6 g/day of phytosterols as sterol esters.Setting: General Community.Subjects: In all 58, free-living men and women with mean age (s.d.) 54 (8) y, moderately elevated plasma total cholesterol 6.2 (0.7) mmol/l and body mass index 26.2 (3.0) kg/m2.Main outcome measures: Serum lipids, plasma phytosterols and carotenoids.Results: Serum total and LDL cholesterol levels were significantly lowered by consumption of phytosterol-enriched foods: milk (8.7 and 15.9%) and yoghurt (5.6 and 8.6%). Serum LDL cholesterol levels fell significantly by 6.5% with bread and 5.4% with cereal. They were both significantly less efficacious than sterol-enriched milk (P<0.001). Plasma sitosterol increased by 17–23% and campesterol by 48–52% with phytosterol-enriched milk and bread. Lipid-adjusted β-carotene was lowered by 5–10% by sterols in bread and milk, respectively.Conclusions: This is the first study to demonstrate that cholesterol-lowering effects of plant sterol esters may differ according to the food matrix. Plant sterols in low-fat milk was almost three times more effective than in bread and cereal. Despite phytosterol-enriched cereal products resulting in lower serum cholesterol reductions compared to sterol-enriched milk, the detection of similar changes in plasma phytosterols demonstrated that such products still delivered and released phytosterols to the gut.

Routine programmed electrical stimulation in survivors of acute myocardial infarction for prediction of spontaneous ventricular tachyarrhythmias during follow-up: Results, optimal stimulation protocol and cost-effective screening

Of 3,286 consecutive patients treated for acute myocardial infarction, electrophysiologic testing was performed in 1,209 survivors (37%) free of significant complications at the time of hospital discharge to determine their risk of spontaneous ventricular tachyarrhythmias during follow-up. Sustained monomorphic ventricular tachycardia was inducible by programmed electrical stimulation in 75 (6.2%). Antiarrhythmic therapy was not routinely prescribed regardless of the test results. During the 1st year of follow-up, 14 infarct survivors (19%) with inducible ventricular tachycardia experienced spontaneous ventricular tachycardia or fibrillation in the absence of new ischemia compared with 34 (2.9%) of those without inducible ventricular tachycardia (p less than 0.0005). During the extended follow-up period (median 28 months) of those with inducible ventricular tachycardia, 19 (25%) had a spontaneous electrical event; 37% of these first events were fatal. These results suggest that the most cost-effective strategy for predicting arrhythmia will be obtained by restricting electrophysiologic testing to infarct survivors whose left ventricular ejection fraction is less than 40% and using a stimulation protocol containing four extrastimuli. Electrophysiologic testing is the single best predictor of spontaneous ventricular tachyarrhythmias during follow-up in infarct survivors. The majority (94%) with a negative test benefit from the more reliable reassurance that all is well, whereas the 25% risk of electrical events in those with inducible ventricular tachycardia justifies a prospective trial of effective prophylactic antiarrhythmic interventions.

Risk to Patients From Radiation Associated With Radiofrequency Ablation for Supraventricular Tachycardia

BACKGROUND Radiofrequency ablation may be associated with prolonged fluoroscopy times. Previous studies have calculated radiation risks by measuring the radiation dose at a limited number (6) of body sites. This is an inherently inaccurate measure. Our study aimed to quantify more precisely patient-related radiation risks associated with radiofrequency ablation for supraventricular tachycardia. METHODS AND RESULTS Nine female patients having radiofrequency ablation for supraventricular tachycardia were studied. The radiation dose was determined at 41 body sites in each patient with the use of thermoluminescent dosimeters and was correlated with that measured simultaneously with a Diamentor dose-area product meter. The estimated mean organ doses (mGy) per 60 minutes of fluoroscopy were: lungs 30.8; bone marrow 4.3; left breast 5.1; right breast 3. 5; and thyroid 2.4. From the average organ doses, the estimated mean total lifetime excess risk of a fatal malignancy was 294 per million cases (0.03%) per 60 minutes of fluoroscopy. The risk calculation from the Diamentor dose-area product and thermoluminescent dosimeters were similar, suggesting that radiation dose was measured accurately. The estimated risk of radiation-induced malignancy increased with increasing body mass index (P=0.03). CONCLUSIONS Prolonged fluoroscopy during radiofrequency ablation may potentially cause a small increase in the lifetime risk of fatal malignancy, with lung malignancy being most likely. This risk is small only with the use of techniques and x-ray equipment optimized to keep radiation as low as possible. The risk is increased in obese patients.

What is the best predictor of spontaneous ventricular tachycardia and sudden death after myocardial infarction

BackgroundDeath during the first year after myocardial infarction is most commonly due to spontaneous ventricular tachycardia (VT) or fibrillation (VF). The purpose of this study was to compare, in a single cohort of patients, the values of inducible VT, delayed ventricular activation, low left ventricular ejection fraction, high-grade ventricular ectopy, and ST segment displacement on exercise in predicting electrical events (witnessed instantaneous death and spontaneous VT or VF) during the first year after myocardial infarction. Methods and ResultsThree hundred sixty one patients aged less than 71 years underwent electrophysiological study, signal-averaged electrocardiogram, gated blood-pool scan, 24 hour ambulatory electrocardiographic monitoring, and exercise testing 1-2 weeks after myocardial infarction and were then followed up for at least 1 year. There were 34 deaths (eight witnessed instantaneous, 26 other), and nine patients survived one or more episodes of spontaneous VF or VT. Patients with inducible VT were 15.2 times more likely to suffer electrical events than patients without inducible VT. No proportional-hazards model excluding inducible VT was as good a predictor of electrical events as was inducible VT alone. ConclusionsInducible VT at electrophysiological study was the single best predictor of spontaneous VT and sudden death after myocardial infarction. (Circulation 1991;83:756–763)

Fibroblasts Can Be Genetically Modified to Produce Excitable Cells Capable of Electrical Coupling

Background—Cardiac conduction occurs in an electrical syncytium of excitable cells connected by gap junctions. Disruption of these electrophysiological properties causes conduction slowing or block. Depending on the location of affected cells within the heart, this has the potential to result in clinical syndromes such as atrioventricular block. With a view to developing gene therapy strategies for repairing cardiac conduction defects, we sought to establish whether the phenotype of fibroblasts can be modified by gene transfer to produce cells capable of electrical excitation and coupling. Methods and Results—High-titer lentiviral vectors encoding MyoD, a myogenic transcription factor, and connexin43, a gap junction protein, were produced by established methods. Human dermal fibroblasts (HDFs) were efficiently (>80%) transduced at a multiplicity of infection of 50. HDFs transduced with the MyoD-encoding vector underwent myogenic conversion, as evidenced by myotube formation and detection of muscle-specific proteins. Importantly, calcium transients indicative of membrane excitability were observed in MyoD-induced myotubes after loading with a calcium-sensitive dye and electrical stimulation. Transients from adjacent myotubes displayed different excitation thresholds, indicating an absence of coupling between cells, consistent with skeletal muscle biology. In contrast, simultaneous transduction of HDFs with MyoD and connexin43-encoding vectors resulted in the appearance of transients in adjacent myotubes with identical thresholds, indicative of electrical coupling. Notably, dye transfer studies confirmed gap junctional intercellular communication. Conclusions—Fibroblasts can be genetically modified to produce excitable cells capable of electrical coupling. These observations strengthen the prospect of developing gene-based strategies for repairing cardiac conduction defects.

Comparison of epicardial and endocardial linear ablation using handheld probes.

BACKGROUND The optimal technique for producing linear radiofrequency thermal lesions in myocardial tissue is unclear. We compared epicardial ablation on the beating heart with endocardial ablation after cardioplegia. METHODS Radiofrequency lesions were produced using a multielectrode malleable handheld probe in ovine myocardium with three wall thicknesses. Detailed analysis of lesion dimensions was used to assess the effects of site of ablation, muscle thickness, and duration of ablation. RESULTS After epicardial atrial ablation, myocardial lesions were detected in all sections without macroscopically visible epicardial fat (n = 10), but only 43% (6/14) of sections with epicardial fat. Three of 24 atrial epicardial sections (13%) and 92% (23/25) of endocardial atrial lesion sections were clearly transmural. In thicker tissues lesion depth was independent of endocardial (right ventricle: 3.9 +/- 1.1 mm, left ventricle: 3.8 +/- 0.7 mm) or epicardial (right ventricle: 3.4 +/- 0.6 mm, left ventricle: 4.3 +/- 0.9 mm) ablation site. Epicardial lesions are less deep in thinner areas of myocardium (p = 0.003). Lesions were all wider than they were deep. There was no significant increase in lesion depth with the increase in ablation duration from 1 to 2 minutes. CONCLUSIONS Lesions were unlikely to be transmural with either technique when the wall thickness was greater than about 4 mm. Epicardial fat has an important negative effect on epicardial lesion formation. Where epicardial fat is absent epicardially produced lesions penetrate less deeply when the wall thickness is small, possibly due to endocardial cooling by circulating blood. Prolongation of the duration of ablation from 1 to 2 minutes does not significantly increase lesion depth.