Coronary vasospasm induced by painful compression of the brachial artery following coronary angiography.

We report the occurrence of coronary vasospasm following forceful compression of the brachial artery after coronary angiography.

Determinants of label non-adherence to non-vitamin K oral anticoagulants in patients with newly diagnosed atrial fibrillation.

Aims: To evaluate the extent and determinants of off-label non-vitamin K oral anticoagulant (NOAC) dosing in newly diagnosed Dutch AF patients. Methods and results: In the DUTCH-AF registry, patients with newly diagnosed AF (<6 months) are prospectively enrolled. Label adherence to NOAC dosing was assessed using the European Medicines Agency labelling. Factors associated with off-label dosing were explored by multivariable logistic regression analyses. From July 2018 to November 2020, 4500 patients were registered. The mean age was 69.6 ± 10.5 years, and 41.5% were female. Of the 3252 patients in which NOAC label adherence could be assessed, underdosing and overdosing were observed in 4.2% and 2.4%, respectively. In 2916 (89.7%) patients with a full-dose NOAC recommendation, 4.6% were underdosed, with a similar distribution between NOACs. Independent determinants (with 95% confidence interval) were higher age [odds ratio (OR): 1.01 per year, 1.01-1.02], lower renal function (OR: 0.96 per ml/min/1.73 m2, 0.92-0.98), lower weight (OR: 0.98 per kg, 0.97-1.00), active malignancy (OR: 2.46, 1.19-5.09), anaemia (OR: 1.73, 1.08-2.76), and concomitant use of antiplatelets (OR: 4.93, 2.57-9.46). In the 336 (10.3%) patients with a reduced dose NOAC recommendation, 22.9% were overdosed, most often with rivaroxaban. Independent determinants were lower age (OR: 0.92 per year, 0.88-0.96) and lower renal function (OR: 0.98 per ml/min/1.73 m2, 0.96-1.00). Conclusion: In newly diagnosed Dutch AF patients, off-label dosing of NOACs was seen in only 6.6% of patients, most often underdosing. In this study, determinants of off-label dosing were age, renal function, weight, anaemia, active malignancy, and concomitant use of antiplatelets.

Exchange biased delta-E effect enables the detection of low frequency pT magnetic fields with simultaneous localization.

Delta-E effect sensors are based on magnetoelectric resonators that detune in a magnetic field due to the delta-E effect of the magnetostrictive material. In recent years, such sensors have shown the potential to detect small amplitude and low-frequency magnetic fields. Yet, they all require external magnetic bias fields for optimal operation, which is highly detrimental to their application. Here, we solve this problem by combining the delta-E effect with exchange biased multilayers and operate the resonator in a low-loss torsion mode. It is comprehensively analyzed experimentally and theoretically using various kinds of models. Due to the exchange bias, no external magnetic bias fields are required, but still low detection limits down to [Formula: see text] at 25 Hz are achieved. The potential of this concept is demonstrated with a new operating scheme that permits simultaneous measurement and localization, which is especially desirable for typical biomedical inverse solution problems. The sensor is localized with a minimum spatial resolution of 1 cm while measuring a low-frequency magnetic test signal that can be well reconstructed. Overall, we demonstrate that this class of magnetic field sensors is a significant step towards first biomedical applications and compact large number sensor arrays.

Selection of patients for cardiac resynchronisation therapy (CRT) in an unselected heart failure population.

BACKGROUND: In patients with chronic heart failure (CHF), the presence of conduction delay across the myocardium is a well-known feature. During recent years an increasing number of CHF patients have been treated with cardiac resynchronisation therapy (CRT). So far in many protocols patients have been selected using the criteria of left ventricular ejection fraction (LVEF) ≤35% concomitant with signs of widening of the QRS on the surface electrocardiogram, either with or without left bundle branch block (LBBB) morphology. METHODS: In this article we discuss which of the patients admitted with CHF to a regular cardiology practice could be candidates for this therapy. Data were obtained from January 2000 to December 2004 on a total of 861 CHF patients, of whom 309 had an LVEF ≤35%. Of these patients, 123 patients showed a QRS width >120 msec, while 81 patient had a QRS width >140 msec. In total, 89 patients had an LBBB morphology on the electrocardiogram, while 21 patients had univentricular pacing devices in situ. In those patients with an LVEF >35%, QRS width was 108±27msec. CONCLUSION: A substantial number of patients presenting with CHF in a regular cardiology practice are suitable candidates for CRT therapy according to currently used criteria of QRS width and LVEF. This number could be increased even more if recent information concerning intraventricular conduction delay in CHF patients with less widening of the QRS complex were to be applied, as judged by echocardiographic techniques.

Practical implications of having a dedicated heart failure programme.

BACKGROUND: The prevalence of heart failure (HF) is gaining epidemic proportions. Recent data stress the importance of multidisciplinary strategies for the management of HF patients, but the practical consequences of such programmes remain unclear. OBJECTIVE: To describe our experience with a dedicated heart failure programme involving two HF nurses and a cardiologist. METHOD: All patients admitted to the cardiology department with NYHA class III-IV heart failure were included. After admission, patients received optimal medical therapy according to current guidelines, and extensive instructions from a dedicated HF nurse. On discharge they were given comprehensive lists of medications and symptoms, and a weighing list. They were advised to call a nurse in case of questions or problems. RESULTS: 861 patients were included: 63% >75 years, 47% with LVEF >45%. From 2000 onwards, the number of patients admitted once a year increased but seemed to level off in 2004. Most phone calls involved weight changes as well as general physical complaints. In 1266 (46%) of calls, the medication change was a consequence of a problem raised by the patient. The nurse received and answered almost all phone calls. CONCLUSION: The patient group will grow substantially during the first years of the programme, but the number of patients seen in the outpatient clinic appears to stabilise after five years. Many issues regarding the care of these patients can be handled by the HF nurse.

Production of follistatin in porcine endothelial cells: differential regulation by bacterial compounds and the synthetic glucocorticoid RU 28362.

Follistatin (FS) is the specific binding protein of activin; it has a broad tissue distribution and is also found in serum. The ovary has the highest level of FS expression, but ovariectomy does not cause a permanent reduction in the serum FS level. Therefore, the source of FS in serum is still elusive. As a regulatable, nongonadal source of serum FS could influence ovarian and pituitary-derived hormone secretion and thus reproductive function, we searched for a source of extragonadal FS expression that might contribute to the FS protein level in serum. We found that endothelial cells from blood vessels express FS messenger RNA (mRNA) and protein; therefore, we studied the regulation of steady state levels of FS mRNA in porcine endothelial cells from aorta (AEC) and brain microvessels (BMVEC) in tissue culture. For detection of FS mRNA, a specific 32P-radiolabeled antisense probe and a S1-nuclease protection assay were used. FS steady state levels of AEC decreased with time in culture, i.e. postconfluent AEC had lower FS mRNA levels than confluent cultures, which, in turn, had lower FS mRNA levels than subconfluent cell cultures. FS mRNA levels in AEC were induced by increasing concentrations of FCS and stimulated by 30 micrograms/ml endothelial cell growth supplement. FS mRNA levels in AEC and BMVEC increased approximately 20-fold within 4 h during incubation of the cells with 100 nM phorbol 12-myristate, 13-acetate, whereas 0.5 nmol/ml forskolin tested in AEC for between 4-48 h had no significant effect. Furthermore, 0.1 microM ocadaic acid, an inhibitor of serine/threonine phosphatases 1 and 2A, caused a significant increase in FS mRNA levels. FS mRNA levels in AEC were not significantly affected by various concentrations of porcine FSH, epidermal growth factor, or retinoic acid for between 4-48 h. Treatment of the cells with 0.01-10 micrograms/ml bacterial lipopolysaccharides (LPS) caused a dose-dependent increase (up to 10-fold) in FS mRNA steady state level in AEC, whereas 1-1000 nM RU 28362, a synthetic glucocorticoid, inhibited FS mRNA steady state levels in a dose-dependent manner. The induction of FS mRNA with 1 microgram/ml LPS was completely blocked by 100 nM RU 28362, and the stimulatory effects of LPS were only visible after 4 h of treatment, not after 24 or 48 h. The same effects were observed with BMVEC. We, furthermore, analyzed FS protein secretion of AEC by Western blotting and demonstrated that FS proteins were secreted into the culture medium upon stimulation with LPS. None of these treatments had an obvious effect on the ratio of the two different forms of FS mRNA (FS 344:FS 317). Besides the expression of FS mRNA in AEC and BMVEC, FS mRNA is also expressed in uncultured plexus choroideus epithel and meninges, and FS protein is found in human cerebrospinal fluid. From this study it is concluded that 1) endothelial cells from different tissues produce FS mRNA; 2) the FS mRNA levels of AEC and BMVEC are subjected to regulation by FCS, endothelial cell growth supplement, bacterial LPS, and the glucocorticoid RU 28362; 3) phosphatases and the protein kinase C-dependent, but not the protein kinase A-dependent, pathway are involved in regulating the steady state levels of FS mRNA in AEC and BMVEC; and 4) endothelial cells produce and secrete FS protein and are thus a likely source of FS in serum.

Electrophysiologic mechanisms of perpetuation of atrial fibrillation.

The presence of an excitable gap during atrial fibrillation (AF), although short and variable, may be of potential importance for the development of alternative techniques for termination of AF by rapid pacing. Also the notion that perpetuation of AF may be partly dependent on macroreentry around the natural atrial orifices, may provide a new therapeutic option for the permanent cure of AF by interrupting the anatomical circular pathways in the atria by radiofrequency ablation. In our opinion the rapidly growing understanding of the electrophysiologic mechanisms of AF certainly warrants some optimism about the possibility of cure of AF in the near future without causing too much discomfort and without carrying on unacceptable risk.

Effects of verapamil, diltiazem and disopyramide on sinus function: a comparison with bepridil.

Cardiac drugs known to affect sinus function mostly exhibit negative chronotropic activity. However, impulse conduction within the sinus node can also be influenced. Recently we studied the direct effects of bepridil on rabbit sinus function. It appeared that sinoatrial impulse conduction was depressed markedly with drug concentrations that did not affect sinus automaticity. In the present study the direct effects of verapamil, diltiazem and disopyramide on rabbit sinus function and atrial conduction properties were studied. Verapamil (8.8 x 10(-8) M) reduced the sinoatrial impulse conduction velocity by 35% and prolonged sinoatrial refractoriness by 36%. On the other hand, the sinus rate and atrial conduction parameters were hardly affected. Diltiazem (5 x 10(-6) M) exerted similar actions on the sinoatrial impulse conduction velocity and caused a simultaneous reduction in the sinus rate of 48%. Atrial conduction remained unaffected. Disopyramide (5 x 10(-5) M) depressed both the atrial and nodal conduction properties markedly, whereas the sinus rate was reduced moderately, by almost 20%. Thus, verapamil, diltiazem and disopyramide act differently on sinus function and atrial conduction, whereby the predominant effect of verapamil and diltiazem on sinoatrial conduction properties favours the occurrence of a sinus exit block.

[Anisotropy and reentrant ventricular tachycardia: experimental model in the isolated rabbit heart]. / Anisotropía y taquicardia ventricular por reentrada: modelo experimental en el corazón aislado de conejo.

The purpose of this study was to study the role of anisotropic distribution of conduction velocity in the initiation and perpetuation of ventricular tachycardia in an experimental model of sustained reentrant ventricular tachycardia in the Langendorff perfused rabbit heart. The hearts of 30 rabbits were used in the study. The right ventricle, the interventricular septum and the endocardial and intramural layers of the left ventricle were destroyed by freezing. In the surviving epicardial layer an obstacle was created using a cryoprobe. Thus, the final preparation consisted of a perfused ring of epicardium in the left ventricle. In 27 of 30 experiments programmed electrical stimulation induced sustained reentrant excitation around the obstacle. The cycle length of the tachycardia ranged from 128 to 197 ms in different experiments (mean 162 +/- 17 ms). During tachycardia in some segments of the ring the impulse propagated parallel to fiber orientation at a mean conduction velocity of 61 +/- 7 cm/s whereas in other segments of the ring the impulse propagated perpendicular to fiber orientation at a mean conduction velocity of 22 +/- 4 cm/s. An excitable gap was present during all episodes of tachycardia. In conclusion, conduction velocity during reentrant tachycardia depends on the relation between direction of propagation and fiber orientation. This anisotropic distribution of conduction velocity can play an important role in the initiation and perpetuation of ventricular tachycardia.

Local vascular complications after use of the hemostatic puncture closure device Angio-Seal.

BACKGROUND: As an alternative to manual pressure techniques new systems for achieving arterial hemostasis after cardiac catheterization were developed. Here we report about the diagnosis and therapy of femoral artery complications after use of the closure device Angio-Seal, consisting of an intraarterial anchor and extravascular collagen plug. PATIENTS AND METHODS: Angio-Seal was deployed in 350 patients undergoing cardiac catheterization. Vascular investigations after device application consisted of ankle/brachial-pressure-index measurement, duplex sonography, and angiography. RESULTS: Vascular complications occurred in 10 of 350 patients. In two patients complete occlusions of the superficial femoral artery required immediate vascular surgery. Stenoses of the superficial (five patients) and the common (three patients) femoral arteries were diagnosed in 8 cases. Of these 10 patients eight were obese, in 2 cases there was a further catheterization with Angio-Seal device application via the same femoral approach. Until now six patients underwent successful surgery: in 4 cases the whole Angio-Seal device was located intraarterially, there was 1 case of intima-dissection, and 1 case remained unclear due to a diagnostic delay of 7 months. In three patients with stenoses of the common femoral arteries without hemodynamic relevance no therapy was required. CONCLUSIONS: Occlusions or stenoses of femoral arteries after use of Angio-Seal can be diagnosed easily by duplex sonography. All hemodynamic relevant complications (n = 7 of 350 [2%]) concerned a puncture of superficial femoral arteries. In these patients vascular surgery seems to be an adequate therapy.

Incidence of cutaneous vasoactivity in patients with anemia and pulmonary hypoxia.

BACKGROUND: In cutaneous laser Doppler flow (LDF)-recordings, various forms of flowmotion or vasoactivity can be observed. It is still a matter of dispute, whether flowmotion is a phenomenon of physiological or pathophysiological conditions. Therefore, we tested the hypothesis of increased vasoactivity being typical for patients with various degrees of acute and chronic anemia as well as with chronic obstructive pulmonary disease (COPD). PATIENTS AND METHODS: We examined 12 healthy controls, 14 patients with COPD with a PO2 below 60 mmHg, 16 patients with chronic and 7 patients with acute anemia with an Hb below 12 g/dl. We used a simple LDF-technique on the dorsum of the forefoot. The regularity of blood flow frequencies was determined by calculation of the coefficient of variation. RESULTS: Periods without vasoactivity (i.e. constant flow pattern) were 21% in normal controls, 7% in patients with COPD and 2% in patients with acute or chronic anemia. Mean frequencies in the four groups varied between 3.8 and 4.8 cpm, with significant changes only in the group with acute blood loss. However, vasoactivity was significantly more regular in the COPD- and anemia-groups as compared to normal controls, with coefficients of variation of 47.4% for controls, 31.8% for COPD- and 29.3% for chronic and 35.1% for acute anemia-patients. CONCLUSIONS: The present paper shows that cutaneous vasoactivity is more regular in the three examined clinical entities of systemic tissue hypo-oxygenation, i.e. chronic and acute anemia and severe COPD as compared to healthy control subjects. Therefore, we hypothesize that increased vasoactivity constitutes a regulatory defense mechanism in cases of reduced oxygenation, by improving microcirculatory blood flow distribution.

Dronedarone in patients with atrial fibrillation.

Dronedarone is a recently developed new class III antiarrhythmic drug which possesses electrophysiological properties of all four Vaughan-Williams classes. An important difference with amiodarone is that it does not contain an iodine component and therefore lacks the iodine-related adverse effects. Based on currently available data, dronedarone can not be recommended as first-line therapy for either rhythm or rate control. We recommend to initiate rhythm or rate control with drugs as indicated in the 2006 guidelines of the ESC and other organisations. As amiodarone, dronedarone can be given to patients for whom standard drug therapy is not effective, or limited by (severe) side effects, although it is less effective than amiodarone. Nevertheless, it may be considered to give dronedarone initially to patients who would otherwise have received amiodarone, since the latter has more severe side effects than the former drug. The daily dosage of dronedarone is oral administration, 400 mg twice daily. Dronedarone is contraindicated in patients with impaired left ventricular function (NYHA class III/IV) and haemodynamic instability. (Neth Heart J 2010;18:370-3.).

Standardised pre-hospital care of acute myocardial infarction patients: MISSION! guidelines applied in practice.

Background. To improve acute myocardial infarction (AMI) care in the region 'Hollands-Midden' (the Netherlands), a standardised guideline-based care program was developed (MISSION!). This study aimed to evaluate the outcome of the pre-hospital part of the MISSION! program and to study potential differences in pre-hospital care between four areas of residency.Methods. Time-to-treatment delays, AMI risk profile, cardiac enzymes, hospital stay, in-hospital mortality, and pre-AMI medication was evaluated in consecutive AMI patients (n=863, 61±13years, 75% male) transferred to the Leiden University Medical Center for primary percutaneous coronary intervention (PCI).Results. Median time interval between onset of symptoms and arrival at the catheterisation laboratory was 150 (interquartile range [IQR] 101-280) minutes. The alert of emergency services to arrival at the hospital time was 48 (IQR 40-60) minutes and the door-to-catheterisation laboratory time was 23 (IQR 13-42) minutes. Despite significant regional differences in ambulance transportation times no difference in total time from onset of symptoms to arrival at the catheterisation room was found. Peak troponin T was 3.33 (IQR 1.23-7.04) µg/l, hospital stay was 2 (IQR 2-3) days and in-hospital mortality was 2.3%. Twelve percent had 0 known risk factors, 30% had one risk factor, 45% two to three risk factors and 13% had four or more risk factors. No significant differences were observed for AMI risk profiles and medication pre-AMI. Conclusions. This study shows that a standardised regional AMI treatment protocol achieved optimal and uniformly distributed pre-hospital performance in the region 'Hollands-Midden', resulting in minimal time delays regardless of area of residence. Hospital stay was short and in-hospital mortality low. Of the patients, 88% had ≥1 modifiable risk factor. (Neth Heart J 2010;18:408-15.).

Sinus node automaticity during atrial fibrillation in isolated rabbit hearts.

BACKGROUND: It is still unclear what role the sinus node may play in the genesis or perpetuation of atrial fibrillation. Therefore, we studied the electrical activity in different regions of the sinus node during atrial fibrillation. METHODS AND RESULTS: In Langendorff-perfused rabbit hearts, paroxysms of atrial fibrillation were induced by burst pacing. Standard microelectrode techniques were used to record transmembrane potentials from different regions of the sinus node. We found that during atrial fibrillation, a high degree (5:1) of sinoatrial entrance block was present that protected the pacemaker fibers in the center of the sinus node against the high rate of fibrillatory impulses. As a result, the true pacemaker fibers in the center of the node were activated with only a slightly higher average rate than during sinus rhythm. Spontaneous diastolic depolarization was still present but was modulated by electrotonic depolarizations due to intranodal conduction block of atrial fibrillatory impulses. Incidentally, phase 4 depolarization resulted in the generation of spontaneous action potentials in the sinus node. However, the high activation rate in the sinoatrial border during atrial fibrillation prevented these spontaneous impulses to exit from the sinus node. Because of the minimal degree of sinus node overdrive suppression (9%) and the presence of concealed automaticity during atrial fibrillation, spontaneous termination of atrial fibrillation was promptly followed by resumption of normal sinus rhythm. CONCLUSIONS: During atrial fibrillation, sinus automaticity still is present in the center of the sinus node and hardly overdrive suppressed due to a high degree of sinoatrial entrance block.

Experimental models of arrhythmias: toys or truth?

In this communication two new experimental models of atrial fibrillation are described. One model (artificial maintenance of atrial fibrillation in conscious goats) points to the electrophysiological changes caused by prolonged atrial fibrillation. It shows that within 24 h of atrial fibrillation the atrial refractory period becomes markedly shortened and the duration of atrial fibrillation markedly prolonged. In the other model, experimentally induced atrial fibrillation in the dog is regionally entrained by local rapid pacing. However, termination of atrial fibrillation by local overdrive pacing was never observed. The possible implication of these new experimental models for prevention and treatment of clinical atrial fibrillation are discussed.

Proarrhythmic effects of flecainide. Experimental evidence for increased susceptibility to reentrant arrhythmias.

BACKGROUND: The goal of this study was to investigate the nature and electrophysiological mechanisms of the proarrhythmic effects of flecainide in Langendorff-perfused rabbit hearts. METHODS AND RESULTS: A thin layer of epicardium was obtained by an endocardial cryotechnique in 10 Langendorff-perfused rabbit hearts. Six other hearts were kept intact. Programmed electrical stimulation using up to three closely coupled premature stimuli and burst pacing was used to test the inducibility of arrhythmias both during control and administration of 1 micrograms/ml flecainide. During control, in the thin layer of epicardium, application of one to three premature stimuli induced nonsustained ventricular tachycardia in out of 10 hearts, and burst pacing induced nonsustained ventricular tachycardia in four hearts and sustained ventricular tachycardia in two hearts. During administration of 1 microgram/ml flecainide, application of one to three premature stimuli induced sustained ventricular tachycardia in five hearts, and burst pacing induced sustained ventricular tachycardia in nine hearts. All tachycardias were based on circus movement of the impulse around arcs of functional block. During administration of flecainide, different locations of the arc of block could be found in the same heart, leading to different reentrant circuits with different cycle lengths. In the control group of six intact hearts, application of up to three closely coupled premature stimuli in all cases induced ventricular fibrillation both during control and administration of flecainide. CONCLUSIONS: Flecainide alters propagation of the impulse in thin surviving layers of myocardium in a manner that facilitates the induction of functionally determined reentry.

Mapping of reset of anatomic and functional reentry in anisotropic rabbit ventricular myocardium.

BACKGROUND: Premature stimulation is used to characterize the reentrant circuit during ventricular tachycardia (VT) in patients. The goal of this study was to compare the effects of premature stimulation on functional and anatomic reentrant VT. METHODS AND RESULTS: In 18 Langendorff-perfused rabbit hearts, thin layers of anisotropic left ventricular subepicardium were created by a cryoprocedure. In 8 hearts, rapid pacing induced reentry around a line of functional conduction block; in 10 hearts, reentry occurred around a fixed epicardial obstacle created by a cryoprobe. The cycle lengths (CL) of functional and anatomic VT were 110 +/- 10 and 167 +/- 17 milliseconds, respectively. During anatomic VT, the excitable gap measured 43% of the CL and premature stimuli could always reset VT (44 +/- 12 milliseconds). During early premature beats, conduction of the orthodromic wave was slightly depressed, but anatomic VT was never terminated. Reset curves at different sites in the ventricle revealed three different response types, both determined by and characterizing the spatial and temporal relation between pacing and recording sites. Premature stimulation during functional VT revealed a local excitable gap at the pacing site measuring 27% of the cycle length of VT. However, in only 3 of 8 hearts, premature stimuli could reset functional VT by 8%. In 5 VTs, advancement of the paced activation was fully compensated by prolongation of the return cycle, and VT was not reset. Due to slow conduction both toward and inside the circuit, the paced orthodromic wave lost its prematurity already within a distance of 6 to 10 mm from the pacing site. CONCLUSIONS: Both during anatomic and functional reentry, an excitable gap is present in the reentrant circuit. Three different response curves reveal the localization of the pacing and recording sites in the circuit. Anatomic VT can always be reset by premature stimuli, whereas in 5 of 8 hearts, functional VT could not be reset. In the other 3 hearts, VT could only be reset for less than 7% to 11% of the VT interval. Therefore, it seems very unlikely that clinical VT based on functional reentry can be reset.

Entrainment of reentrant ventricular tachycardia in anisotropic rings of rabbit myocardium. Mechanisms of termination, changes in morphology, and acceleration.

BACKGROUND: Entrainment of ventricular tachycardia can either terminate or change the rate and/or morphology of ventricular tachycardia. The purpose of this study was to elucidate the underlying mechanisms by mapping of entrainment of ventricular tachycardia. METHODS AND RESULTS: In 10 Langendorff-perfused rings of anisotropic rabbit left ventricular epicardium created by a cryoprocedure, ventricular tachycardia with a cycle length of 167 +/- 17 milliseconds was induced by incremental pacing. During transient entrainment (10 stimuli), the circulating wave was extinguished by collision with the paced antidromic wave, whereas ventricular tachycardia was reset by the paced orthodromic wave. At shorter pacing intervals, the site of collision shifted deeper into the circuit. Entrainment at high rates (104 +/- 11 milliseconds) resulted in either termination (n = 54), a change in morphology (n = 8), or acceleration (n = 6) of ventricular tachycardia. Termination of ventricular tachycardia was due to complete (84%) or partial (16%) block of the paced orthodromic wave. Partial block induced microreentry within the circuit, resulting in a reflected echo wave that terminated ventricular tachycardia. A change in morphology of ventricular tachycardia was due to reversion of the direction of propagation of the circulating wave around the obstacle. Acceleration of ventricular tachycardia was caused by double-wave reentry induced by block of the paced antidromic wave. In 28 cases, the sequence of activation during entrainment was not stable but changed from beat to beat due to varying arcs of conduction block. Block occurred predominantly (86%) during slow transverse propagation. Before termination, local oscillations in interval occurred, resulting in a shortening of the last local interval at the site of block by 10 +/- 6 milliseconds. CONCLUSIONS: Termination of ventricular tachycardia by entrainment was due either to complete orthodromic block or to a reflected echo wave. A change in morphology occurred when the direction of the circulating wave reversed. Acceleration of ventricular tachycardia was due to initiation of double-wave reentry. All changes were preceded by conduction block during one or more stimuli at one or multiple sites in the circuit. Block occurred predominantly during slow transverse propagation and was preceded by local oscillations in interval at the site of block.