Plasmatic BRAF-V600E allele fraction as a prognostic factor in metastatic colorectal cancer treated with BRAF combinatorial treatments.

BACKGROUND: Combination of a BRAF inhibitor (BRAFi) and an anti-epidermal growth factor receptor (EGFR), with or without a MEK inhibitor (MEKi), improves survival in BRAF-V600E-mutant metastatic colorectal cancer (mCRC) over standard chemotherapy. However, responses are heterogeneous and there are no available biomarkers to assess patient prognosis or guide doublet- or triplet-based regimens. In order to better characterize the clinical heterogeneity observed, we assessed the prognostic and predictive role of the plasmatic BRAF allele fraction (AF) for these combinations. PATIENTS AND METHODS: A prospective discovery cohort including 47 BRAF-V600E-mutant patients treated with BRAFi-anti-EGFR ± MEKi in clinical trials and real-world practice was evaluated. Results were validated in an independent multicenter cohort (n= 29). Plasmatic BRAF-V600E AF cut-off at baseline was defined in the discovery cohort with droplet digital PCR (ddPCR). All patients had tissue-confirmed BRAF-V600E mutations. RESULTS: Patients with high AF have major frequency of liver metastases and more metastatic sites. In the discovery cohort, median progression-free survival (PFS) and overall survival (OS) were 4.4 and 10.1 months, respectively. Patients with high BRAF AF (≥2%, n = 23) showed worse PFS [hazard ratio (HR) 2.97, 95% confidence interval (CI) 1.55-5.69; P = 0.001] and worse OS (HR 3.28, 95% CI 1.58-6.81; P = 0.001) than low-BRAF AF patients (<2%, n = 24). In the multivariable analysis, BRAF AF levels maintained independent significance. In the validation cohort, high BRAF AF was associated with worse PFS (HR 3.83, 95% CI 1.60-9.17; P = 0.002) and a trend toward worse OS was observed (HR 1.86, 95% CI 0.80-4.34; P = 0.15). An exploratory analysis of predictive value showed that high-BRAF AF patients (n = 35) benefited more from triplet therapy than low-BRAF AF patients (n = 41; PFS and OS interaction tests, P < 0.01). CONCLUSIONS: Plasmatic BRAF AF determined by ddPCR is a reliable surrogate of tumor burden and aggressiveness in BRAF-V600E-mutant mCRC treated with a BRAFi plus an anti-EGFR with or without a MEKi and identifies patients who may benefit from treatment intensification. Our results warrant further validation of plasmatic BRAF AF to refine clinical stratification and guide treatment strategies.

Sex and gender perspectives in colorectal cancer.

Historically women were frequently excluded from clinical trials and drug usage to protect unborn babies from potential harm. As a consequence, the impact of sex and gender on both tumour biology and clinical outcomes has been largely underestimated. Although interrelated and often used interchangeably, sex and gender are not equivalent concepts. Sex is a biological attribute that defines species according to their chromosomal makeup and reproductive organ, while gender refers to a chosen sexual identity. Sex dimorphisms are rarely taken into account, in either preclinical or clinical research, with inadequate analysis of differences in outcomes according to sex or gender still widespread, reflecting a gap in our knowledge for a large proportion of the target population. Underestimation of sex-based differences in study design and analyses has invariably led to 'one-drug' treatment regimens for both males and females. For patients with colorectal cancer (CRC), sex also has an impact on the disease incidence, clinicopathological features, therapeutic outcomes, and tolerability to anticancer treatments. Although the global incidence of CRC is higher in male subjects, the proportion of patients presenting right-sided tumours and BRAF mutations is higher among females. Concerning sex-related differences in treatment efficacy and toxicity, drug dosage does not take into account sex-specific differences in pharmacokinetics. Toxicity associated with fluoropyrimidines, targeted therapies, and immunotherapies has been reported to be more extensive for females with CRC than for males, although evidence about differences in efficacy is more controversial. This article aims to provide an overview of the research achieved so far into sex and gender differences in cancer and summarize the growing body of literature illustrating the sex and gender perspective in CRC and their impact in relation to tumour biology and treatment efficacy and toxicity. We propose endorsing research on how biological sex and gender influence CRC as an added value for precision oncology.

Respiratory variability of sinus node activation in humans: insights from ultra-high-density mapping.

PURPOSE: Experimental data suggest that shifts in the site of origin of the sinus node (SN) correlate with changes in heart rate and P wave morphology. The direct visualization of the effect of respiration on SN electrical activation has not yet been reported in humans. We aimed to measure the respiratory shifting of the SN activation using ultra-high-density mapping. METHODS: Sequential right atrial (RA) activation mapping during sinus rhythm (SR) was performed. Three maps were acquired for each patient: basal end-expiratory (Ex), end-inspiratory (Ins), and end-expiratory under isoproterenol (Iso). The earliest activation site (EAS) was defined as the earliest unipolar electrograms (EGM) with a QS pattern and was localized with respect to the ostium of the superior vena cava (SVC; negative values if EAS inside the SVC). RESULTS: In 20 patients, 49 maps in SR were acquired (20 Ex, 19 Ins, and 10 Iso). Expiratory (944 ± 227 ms) and inspiratory (946 ± 227 ms) SR cycle lengths were similar, but shortened under isoproterenol (752 ± 302 ms). Activation was unicentric in 33 maps and multicentric in 16: 4 during Ins, 10 during Ex, and 2 Iso. EAS location was significantly more cranial in expiration than in inspiration (0.27 ± 12.1 vs 5 ± 11.51 mm, p = 0.01). Iso infusion tends to induce a supplemental cranial shift (-4.07 ± 15.83 vs 0.27 ± 12.7 mm, p = 0.21). EAS were found in SVC in 22.7% of maps (30% Ex, 21% Ins, and 8% Iso). CONCLUSION: Inspiration induces a significant caudal shift of the earliest sinus activation. In one-third of the cases, sinus rhythm earliest activation is inside the SVC.

Magnetic navigation and voltage mapping guided implantation of a pacemaker atrial lead in a previously unpaceable patient.

We report successful implantation of the atrial pacing lead in a patient in whom such operation had previously failed with the manual approach. Right atrial (RA) electro-anatomical voltage mapping was used to identify an area suitable for pacing and magnetic navigation to allow exhaustive RA exploration leading to successful RA lead screwing.

Accelerated idioventricular rhythm requiring catheter ablation in a child: The dark side of a benign arrhythmia.

A 12 year-old boy, with no history of cardiac disease, was referred to our department for evaluation of an incessant accelerated idioventricular rhythm (AIVR) complicated with severe left ventricular (LV) dysfunction and cardiogenic shock. Extensive diagnostic work-up failed to reveal any structural heart disease. During electrophysiological study, AIVR originated from the right ventricular endocardial anterior wall and was successfully ablated using remote magnetic navigation. LV function showed complete recovery four weeks after the procedure. This case highlights a life-threatening evolution of an arrhythmia generally presented as a benign entity in children.

Catheter ablation of typical atrial flutter: a randomized comparison of 2 methods for determining complete bidirectional isthmus block.

BACKGROUND: Complete bidirectional isthmus conduction block (CBIB) was initially assessed by sequential detailed activation mapping at both sides of the ablation line during proximal coronary sinus and anteroinferior right atrium pacing. Mapping only the ablation line ("on-site" atrial potential analysis) was recently reported as a means of CBIB identification. The study was designed to compare these 2 techniques prospectively regarding the diagnosis of CBIB. METHODS AND RESULTS: In 76 consecutive patients (mean age, 63.4+/-10.5 years), typical atrial flutter ablation was performed using either the activation mapping technique (group I) or on-site atrial potential analysis (group II). Criteria for CBIB using on-site atrial potential analysis was the recording of parallel, widely spaced double atrial potentials along the ablation line. The CBIB criterion was retrospectively searched using the alternative technique at the end of the procedure. In successful patients, the mean radiofrequency delivery duration was longer in group II (845+/-776 versus 534+/-363 s; P:=0.03). On-site, clear-cut, widely spaced double atrial potentials and activation mapping suggesting CBIB were concomitantly observed in only 47 patients (54%), and ambiguous/atypical double potentials were recorded in 31 patients (39%). CONCLUSIONS: Although feasible, the on-site atrial potential analysis seemed to be inferior to the classic activation mapping technique, mainly because of the ambiguity of electrogram interpretation along the ablation line. However, when combined with the activation mapping technique, it provided additional information regarding isthmus conduction properties in some cases. Therefore, optimally, both methods should be used concomitantly.

Atrioatrial conduction after orthotopic heart transplantation.

OBJECTIVES: In two patients with orthotopic heart transplantation, the surface electrocardiogram suggested interaction between the donor right atrium and the recipient right atrium. An electrophysiologic investigation was performed to assess possible atrioatrial conduction. BACKGROUND: After orthotopic heart transplantation, both recipient and donor atrial activities are usually independent, but in humans they may synchronize for short periods during exercise. METHODS: Electrophysiologic recordings were made using standard techniques. The atrial electrode locations (anterior for the donor and posterior for the recipient right atria) were confirmed by fluoroscopy. Incremental and programmed donor and recipient right atrial pacing protocols were performed. RESULTS: Unidirectional conduction between native and graft atria occurred in both patients. This phenomenon was evident at rest, during normal sinus rhythm and at various pacing rates, resulting in frequent atrial bigeminy and trigeminy. CONCLUSIONS: Possible atrioatrial conduction after orthotopic heart transplantation may potentially be arrhythmogenic for the chamber where extrasystoles occur. This should be taken into account in attempting to devise new pacing modes if both atria are rendered electrically common.

Catheter ablation of atrioatrial conduction as a cure for atrial arrhythmia after orthotopic heart transplantation.

OBJECTIVES: We present three patients in whom atrial arrhythmia was treated by ablation of electrical conduction across a surgical suture line. BACKGROUND: Conduction across the suture line separating the donor and native right atria has recently been described after orthotopic heart transplantation. METHODS: Mapping and pacing of both grafted and recipient right atrium was performed to assess the relation between both atria and its relevance to clinical arrhythmia, prior to successful radiofrequency at the site of electrical communication. RESULTS: In cases 1 and 3, atrioatrial conduction was bidirectional. In both, two types of P waves were observed during sinus rhythm. In case 2, conduction from the recipient to the grafted atrium yielded a very particular surface ECG pattern of atrial extrasystole. The block being unidirectional, the recipient atrial sinus rhythm was not perturbed and behaved like an atrial parasystole. Ablation was performed during sinus rhythm in case 1, recipient right atrial pacing in case 2 and grafted right atrial pacing in case 3 at the site with the shortest conduction time to the other tissue. At the successful ablation site multiple component potentials were recorded. Respectively, 1, 4 and 2 radiofrequency pulses were followed by total atrioatrial conduction interruption. No tachycardia could be induced at the end of the procedure and late follow-up was event free. CONCLUSIONS: The existence of arrhythmogenic atrioatrial conduction should be taken into account when evaluating atrial arrhythmias in the transplanted heart because it is potentially curable by radiofrequency catheter ablation.

Entrainment of circus movement tachycardia utilizing an accessory pathway with long retrograde conduction times during ventricular and atrial stimulation.

An unusual case is presented in which a circus movement tachycardia incorporating an accessory pathway with long retrograde conduction time was transiently entrained. Overdrive high right atrial stimulation produced entrainment without atrial fusion since collision of anterograde and retrograde impulses took place within the accessory pathway. Tachycardia termination occurred when, at a faster pacing rate, an atrial impulse that collided in the accessory pathway was blocked at the atrioventricular (AV) node. In contrast, the entrainment seen during right ventricular apical stimulation was characterized by the occurrence of both fusion and collision within the ventricles. The tachycardia was terminated when a pure paced impulse that collided in the normal pathway was blocked in a retrograde direction in the accessory pathway. These data indicate that: 1) transient entrainment of this arrhythmia (circus movement tachycardia) can be identified by the classical criteria used to diagnose it, provided that fusion and collision occur within the ventricles; and 2) the accessory pathway is the weak link for tachycardia termination only during ventricular pacing since the AV node is the weak link during atrial stimulation.

Cellular electrophysiologic changes and "arrhythmias" during experimental ischemia and reperfusion in isolated cat ventricular myocardium.

The cellular electrophysiologic consequences of both regional and global experimental ischemia and reperfusion were studied in the isolated cat myocardium, using conventional microelectrode techniques. Oxygenated Tyrode's solution was perfused through the left anterior descending and circumflex coronary arteries, while the preparation was superfused with Tyrode's solution gassed with 95% nitrogen and 5% carbon dioxide. Electrophysiologic characteristics of endocardial muscle cells were normal during coronary perfusion. When perfusion was discontinued for 30 minutes, resting membrane potential was decreased by 21.6 +/- 4.1%, action potential amplitude was decreased by 29.1 +/- 8.6% and action potential duration was decreased by 54.1 +/- 12.5% (p less than 0.001). Ectopic activity occurred after 5 to 10 minutes of ischemia and was more frequent in regional than in global ischemia (p less than 0.05). Rapid ventricular activity was observed in only 5 (17%) of 29 preparations during ischemia, whereas it occurred in 24 (83%) of 29 preparations during reperfusion. Rapid ventricular activity began 5 to 40 seconds (mean 19) after the start of reperfusion, stopped spontaneously after a mean of 113 +/- 211 seconds and occurred after both regional and global ischemia. The cellular electrophysiologic changes induced by ischemia returned to baseline values within the next 5 minutes. Repeated ischemia and reperfusion runs reproduced the same electrophysiologic changes and rapid ventricular activity. Coronary perfusion with procainamide (20 mg/liter) aggravated the ischemic depressions of action potential amplitude and action potential duration and increased conduction delay during ischemia, but it did not prevent rapid ventricular activity induced by reperfusion. In contrast, verapamil (1 mg/liter) perfusion did not affect the changes in action potential variables during ischemia but prevented reperfusion-induced rapid ventricular activity. Perfusion with calcium ion (Ca2+)-free Tyrode's solution just before ischemia and during reperfusion slowed or prevented reperfusion-induced rapid ventricular activity, without affecting the action potential changes during ischemia. It is concluded that, in these isolated perfused ventricular muscle preparations, different mechanisms may be operative in ischemic and reperfusion arrhythmias and Ca2+ may play an important role in the development of arrhythmias during the reperfusion phase of ischemia/reperfusion sequences.

Percutaneous transluminal balloon valvuloplasty of adult aortic stenosis: report of 92 cases.

Percutaneous transluminal balloon valvuloplasty was attempted in 92 adult patients with severe calcific aortic stenosis. The mean age was 75 +/- 11 years (range 38 to 91) and 35 patients were more than 80 years old. Most of the patients were severely disabled; 66 were in New York Heart Association functional class III or IV, 27 had syncopal attacks and 21 had severe angina pectoris. Because of unacceptably high surgical risk or contraindication to thoracic surgery, 42 patients could not be considered for valve replacement. Other patients either were in a category of high operative risk or refused the surgical intervention. Valvuloplasty was performed by way of the femoral route (82 patients) or the brachial route (10 patients). Catheters of size 15, 18 and 20 mm were successively placed across the aortic valve and three inflations were usually done with each of them, lasting 80 seconds on average, until a decrease in peak to peak systolic pressure gradient to 40 mm Hg or less was attained, a result considered satisfactory. The inflated balloons were not totally occlusive in most cases and clinical tolerance of inflation was good. Valvuloplasty resulted in a reduction of mean systolic gradient from 75 +/- 26 to 30 +/- 13 mm Hg (p less than 0.001); the final gradient was less than 40 mm Hg in 78 patients. Mean calculated aortic valve area increased from 0.49 +/- 0.17 to 0.93 +/- 0.36 cm2 (p less than 0.001). Immediately after the procedure, ejection fraction increased from 48 +/- 16 to 51 +/- 16% (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Dobutamine stress echocardiography in orthotopic heart transplant recipients. VACOMED Research Group.

OBJECTIVES: This study sought to determine whether dobutamine stress echocardiography could accurately identify coronary artery disease after heart transplantation. BACKGROUND: After heart transplantation, coronary artery disease is related to either diffuse concentric intimal thickening or focal stenosis and may be underdiagnosed by coronary angiography. METHODS: We enrolled 41 patients, a mean (+/- SD) of 40 +/- 20 months after heart transplantation, at the time of their routine control coronary angiogram. Three patients were excluded because of poor echogenicity on the angiogram and one because of ventricular premature beats. Standard echocardiographic views were acquired at baseline and at incremental dobutamine infusion levels (from 5 to a maximal dose of 40 micrograms/kg body weight per min at 3-min intervals). Regional wall motion score was calculated from a 16-segment model, and each segment was graded from 1 (normal) to 4 (dyskinesia). Coronary angiography was performed 24 h after dobutamine stress echocardiography, and angiograms were analyzed in blinded manner. RESULTS: Twenty-three (62%) of 37 patients had normal coronary angiographic findings. Dobutamine stress echocardiography showed abnormalities in only 2 of 23 patients. Fourteen patients (38%) had abnormal angiographic findings, seven of whom had stenoses > 50%. Dobutamine stress echocardiography correctly identified the corresponding hypoperfused segments in these seven patients. More of interest were the other seven patients, of whom three had angiographic nonsignificant stenoses (< 50%), and four had minor diffuse coronary irregularities. Dobutamine stress echocardiography showed hypokinesia in five of these seven patients despite nonsignificant lesions at coronary angiography. The respective overall sensitivity and specificity of dobutamine stress echocardiography were 86% and 91%. At follow-up, 2 of the 37 patients had an acute myocardial infarction. Both had abnormal findings on dobutamine stress echocardiography: One had normal coronary angiographic results, and one had significant coronary lesions. CONCLUSIONS: Dobutamine stress echocardiography is a useful technique for the diagnosis of coronary artery disease after heart transplantation. These preliminary results indicate that dobutamine stress echocardiography may have a predictive value for further ischemic events in heart transplant recipients.

[Arrhythmia and sport]. / Arythmies du sportif.

Sports arrhythmia has gained wide attention with the mediatization of the death of famous sports stars. Sport strongly modifies the structure of the heart with the development of left ventricular hypertrophy which may be difficult to differentiate from that due to doping. Intense training modifies also the resting electrocardiogram with appearance of signs of left ventricular hypertrophy whereas resting sinus bradycardia and atrioventricular conduction disturbances usually reverts upon exertion. Accordingly, arrhythmia may develop ranging from extrasystoles to atrial fibrillation and even sudden death. Recent data suggest that if benign arrhythmia may be the result of the sole intense training and are reversible, malignant ventricular arrhythmia and sudden death mostly occur in unknown structural heart disease. Hypertrophic cardiomyopathy is amongst the most frequent post mortem diagnosis in this situation. Doping is now present in many sports and further threatens the athlete in the safe practice of sport.

[The use of transesophageal echocardiography to guide the trans-septal puncture. Practical guide, tips and tricks]. / Échocardiographie transœsophagienne pour guider la ponction transseptale. Guide pratique, astuces, particularités, pièges.

Transesophageal echocardiography is very useful to guide transseptal puncture for left atrial ablation procedures. This paper is a practical guide for the ultrasonographer who seeks to meet the expectations of the electrophysiologist, but also for young EP's in order to improve their understanding of the echocardiographical views and to ameliorate the communication between the two specialists. The tips and tricks of all the steps of the exam are presented.

Electrophysiologic basis of catheter ablation in atrial flutter.

A reentrant mechanism is believed to be responsible for atrial flutter. The recent development of the entrainment criteria further supports this theory, and there is a general consensus that circus movement is the underlying abnormality that supports this arrhythmia. In most clinical studies, abnormal fragmented (or double spike) electrograms, suggesting the presence of areas of localized slowing of conduction or block, have been reported. They are almost always recorded in the lower and posterior portion of the right interatrial septum, but also frequently in the high lateral portion of the right atrium. The determination of their involvement in the reentry pathway is important for designing curative procedures such as surgery or ablation. The low atrial septal area surrounding the mouth of the coronary sinus was suspected as being the critical area of slow conduction in atrial flutter. Rapid pacing at that site can yield a surface electrocardiographic pattern similar to the clinically occurring arrhythmias. Additionally, the flutter circuit can be accelerated during atrial pacing at fixed and slightly faster rates than the intrinsic tachycardia rate--the so-called entrainment phenomenon. When entrainment criteria are fulfilled, tachycardia termination being by definition ruled out, any concomitant recorded local type II block identifies an area that must be outside the circuit. Such local block may be recorded either spontaneously or during entrainment and therefore helps in identifying atrial slow conduction areas that do not belong to the reentrant path. This approach was applied to identify the optimal ablation site in 8 patients with long-standing drug resistant atrial flutter. In 7 of 8 patients, we were able to identify a fragmented potential in the low posteroseptal area during sustained atrial flutter.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of effectiveness of an 8-mm versus a 4-mm tip electrode catheter for radiofrequency ablation of typical atrial flutter.

An 8-mm catheter does not appear superior to 4-mm tip electrode for atrial flutter ablation. The potential advantage of allowing higher energy delivery on a larger surface is compensated by the lack of consistent contact with the endocardial surface.

Dynamics of, and alternating Wenckebach periods during, 4:1 and 6:1 atrioventricular block.

In summary, the irregular dynamics of progression of 4:1 AV block in atrial flutter, presumably different from those observed in similar degrees of rate-dependent block, most likely reflected the complex electrophysiologic mechanisms operating during the highest degrees of AV nodal block. Occurrence of previously undescribed arrhythmias, namely Wenckebach periods during 4:1 and 6:1 block, tends to support the multilevel block hypothesis.

How smart should pacemakers Be?

The concept of the "smart" pacemaker has been continuously changing during 40 years of progress in technology. When we talk today about smart pacemakers, it means optimal treatment, diagnosis, and follow-up for patients fitting the current indications for pacemakers. So what is smart today becomes accepted as "state of the art" tomorrow. Originally, implantable pacemakers were developed to save lives from prolonged episodes of bradycardia and/or complete heart block. Now, in addition, they improve quality of life via numerous different functions acting under specific conditions, thanks to the introduction of microprocessors. The devices have become smaller, with the miniaturization of the electrical components, without compromising longevity. Nevertheless, there are still some unmatched objectives for these devices, for example, the optimization of cardiac output and the management of atrial arrhythmias in dual-chamber devices. Furthermore, indications continue to evolve, which in turn require new, additional functions. These functions are often very complex, necessitating computerized programming to simplify application. In addition, the follow-up of these devices is time-consuming, as appropriate system performance has to be regularly monitored. A great many of these functions could be automatically performed and documented, thus enabling physicians and paramedical staff to avoid losing time with routine control procedures. In addition, modern pacemakers offer extensive diagnostic functions to help diagnose patient symptoms and pacemaker system problems. Different types of data are available, and their presentation differs from one company to the other. This huge amount of data can only be managed with automatic diagnostic functions. Thus, the smart pacemaker of the near future should offer high flexibility to permit easy programming of available therapies and follow-up, and extensive, easily comprehensible diagnostic functions.

Randomized comparison of two targets in typical atrial flutter ablation.

Typical atrial flutter ablation has become anatomically guided to 2 separate sites within the isthmus at the inferior right atrium: (1) between the inferior vena cava and the tricuspid annulus (anterior side of the isthmus [A]), (2) between the eustachian crest, the coronary sinus ostium and tricuspid annulus (posterior side of the isthmus [P]). We prospectively compared ablation results at these sites in 72 consecutive patients. Patients were randomized in group P or A according to the initial target site. If ablation failed at 1 site after 15 radiofrequency (RF) pulses, the other side of the isthmus was targeted. Before 15 RF pulses, complete bidirectional isthmus block was achieved in 30 of 36 group A patients and in 25 of 36 group P patients, with similar mean RF pulses number, procedure time, and fluoroscopy time. After shifting to the other target, success was finally obtained at P in 2 of 6 group A patients, and at A in 8 of 11 group P patients before a maximum of 30 RF pulses. Among successful patients, number of RF pulses, procedure time, and fluoroscopy time were significantly lower in group A (7.2 +/- 5.4 vs 11.0 +/- 8.1 pulses, p = 0.03; 131 +/- 44 vs 163 +/- 66 minutes, p = 0.03; 31 +/- 19 vs 46 +/- 24 minutes, p = 0.01, respectively). Impairment of atrioventricular (AV) nodal conduction occurred in 5 patients only during ablation at P. AV block was transient in 4 patients and permanent in 1. Although atrial flutter ablation is equally effective at P and A, success seems easier to obtain when A is first targeted. Ablation at P is associated with a significant risk of AV block.

Concealment of manifest, and exposure of concealed, ventricular parasystole produced by isoproterenol.

Few studies have dealt with the effects of isoproterenol on ventricular parasystole. Intravenous isoproterenol (2 to 4 micrograms/min) was administered to 11 nonmedicated patients with ventricular parasystole. At the onset of the drip infusion, 8 patients had continuous parasystole, 2 had intermittent parasystole, and 1 patient (in whom intermittent parasystole was documented 2 to 5 days earlier) showed no manifest parasystolic activity. In all patients, whose control parasystolic cycle length varied between 960 and 2,530 ms, isoproterenol caused a decrease of the parasystolic cycle lengths ranging from 12 to 36%. Therefore, isoproterenol produced a consistent increase of the parasystolic rate. In 4 patients, parasystolic activity ceased to be manifest when the concomitantly enhanced (by isoproterenol) sinus cycle lengths became shorter than 430 ms. This phenomenon reflected a tachycardia-dependent parasystolic concealment, presumably as a result of interference in the parasystolic-ventricular junction. In every case, the arrhythmia reappeared at its initial rate upon stopping the drip infusion. In no patient did parasystolic ventricular tachycardia develop. In the patient without manifest parasystolic beats, isoproterenol unmasked the intermittent parasystole that previously had been intrinsically manifest. The latter effect reflected a true exposure, or unmasking of a latent, rate-independent concealed, parasystolic focus.(ABSTRACT TRUNCATED AT 250 WORDS)