A descriptive study of the self-perceived needs of carers for dependants with a range of long-term problems

This report describes an unusual arrhythmia due to partial damage of an accessory pathway by radiofrequency energy delivered during a catheter ablation procedure. The following phenomena were observed after the first radiofrequency current application: a) manifest anterograde conduction over the Kent bundle was abolished, so that preexcitation disappeared; b) concealed anterograde conduction over the accessory pathway was interrupted, resulting in initiation of orthodromic re-entrant tachycardia by any sinus impulse; c) retrograde conduction through the accessory pathway was impaired, but still present, and a pattern of longitudinal dissociation manifested; this was suggested by alternation of the R-P intervals, that during orthodromic tachycardia were alternatively long and short. Following a second radiofrequency application, the R-P interval during orthodromic tachycardia became markedly prolonged (0.36 sec), to the extent that the pattern mimicked a form of atrial or sinus tachycardia. Retrograde accessory pathway conduction was totally interrupted following a third radiofrequency energy application.     

Benzo(a)pyrene-albumin adducts in humans exposed to polycyclic aromatic hydrocarbons in an industrial area of Poland

Antiarrhythmic drugs administered intravenously run the risk of producing a hemodynamic collapse even when used by expert and well trained hands. The arrhythmias in the focal point of a preexcitation syndrome constitute a very special situation in which extreme caution must be used when using intravenous drugs, because the conduction through accessory channels can vary, depending on multiple factors. We describe a case of a patient with an accessory atrioventricular pathway and orthodromic tachycardia who developed cardiac arrest by wide QRS tachycardia after receiving intravenous amiodarone.     

Atrial fibrillation in Wolff-Parkinson-White syndrome. Development and therapy

In patients with Wolff-Parkinson-White syndrome the accessory pathway may participate in various tachyarrhythmias thereby influencing symptoms and prognosis. Atrial fibrillation occurs in 10 to 32% of patients and may have life-threatening consequences by precipitating ventricular fibrillation in patients with rapid conduction due to an accessory pathway with short anterograde refractory period (< 250 ms). Pathogenesis of atrial fibrillation in the WPW syndrome and therapeutic options are reviewed in this presentation. Spontaneous degeneration of atrioventricular reentrant tachycardia has been reported to represent the most frequent mode of initiation of atrial fibrillation during electrophysiologic study (up to 64% of episodes). Hemodynamic changes during tachycardia may lead to increased sympathetic tone, hypoxemia or increased tension of the atrial wall, thus, triggering atrial fibrillation. Induction of reentrant tachycardia during electrophysiologic study also has shown to be strongly correlated to its clinical prevalence and is inducible in up to 77% of patients with atrial fibrillation. The pathogenesis and high incidence of atrial fibrillation in patients with WPW syndrome is related to presence and functional properties of the accessory pathway. After surgical excision or catheter ablation more than 90% of patients are free of this arrhythmia. Anterograde conduction properties of the pathway appear to be more important than retrograde properties. High incidence of atrial fibrillation is related to short anterograde refractory periods, and of note, this arrhythmia is rare (3%) in patients with concealed pathways. With intracardiac recordings, Jackman et al. could demonstrate atrial fibrillation due to micro-reentry originating in accessory pathway networks.(ABSTRACT TRUNCATED AT 250 WORDS)     

Multiple accessory pathways in patients with the pre-excitation syndrome

We have studied 135 patients with the pre-excitation syndrome and have demonstrated evidence of multiple accessory pathways in 20 patients. Five patients had two distinct accessory atrioventricular (A-V) connections, associated with enhanced A-V node conduction in one patient. Twelve patients had a single accessory A-V connection associated with enhanced A-V conduction. In one of these there was an additional fasciculo-ventricular connection. One patient had an accessory A-V connection associated with a nodoventricular bundle. Two patients had fasciculo-ventricular connections combined with enhanced A-V conduction. The latter two patients had electrocardiograms suggestive of a complete accessory A-V connection. Patients with enhanced A-V conduction had shorter cycle lengths during reciprocating tachycardia, primarily because of a short A-H during the dysrhythmia, than those without such conduction. In addition, patients with enhanced A-V conduction demonstrated more rapid conduction from atrium to His bundle during induced atrial fibrillation and two developed life-threatening ventricular responses during atrial fibrillation. A nodo-ventricular pathway was documented to participate in reciprocating tachycardia in one patient. Surgery was undertaken in 13 patients. In 11, the intraoperative mapping studies confirmed the preoperative predictions. In two patients, the presence of a second accessory A-V connection was documented after ablation of one.     

Atypical form of the fourth criterion for transient entrainment

The typical fourth criterion for transient entrainment is defined when both a sudden shortening in conduction interval to and a distinct change in electrogram morphology at a bipolar recording site are demonstrated while performing overdrive pacing of a reentrant tachycardia from a single pacing site at two different constant rates. The purpose of this article was to test the hypothesis that if an intracardiac recording site showing both orthodromic and antidromic capture with entrainment pacing is located suitably distant from the circuit, sudden shortening in conduction interval to that site may occur without any significant change in the bipolar electrogram morphology (i.e., atypical form of the fourth criterion). Atrial overdrive pacing of orthodromic tachycardia was performed in 20 patients with either left anterior (12 patients) or left posterior (8 patients) accessory pathways. We investigated the effects of overdrive pacing from the proximal or distal coronary sinus, specifically effects on the electrogram interval and the electrogram morphology at the right atrial appendage. Overdrive pacing of orthodromic tachycardia from the proximal coronary sinus was performed in 10 of the 12 patients with left anterior accessory pathways; those 10 patients demonstrated the first entrainment criterion at the right atrial appendage site. Overdrive pacing of orthodromic tachycardia at still shorter cycle lengths demonstrated a sudden shortening in conduction interval to the right atrial appendage site. Despite shortening in conduction interval the morphology of the right atrial appendage electrogram was completely or almost identical to that during orthodromic tachycardia, indicating an atypical form of the fourth criterion. This criterion was not demonstrated in patients with left posterior accessory pathways. Thus, atypical fourth entrainment criterion was demonstrated during overdrive pacing of orthodromic tachycardia from the proximal coronary sinus only in patients with left anterior accessory pathways. Demonstration of atypical fourth criterion seems largely dependent on the location of the accessory pathway, the pacing, and the recording sites.     

The phospholipids in Enterocytozoon bieneusi: an electron spectroscopic imaging study

A case of a 38 year old male with WPW syndrome and frequently recurrent antidromic atrio-ventricular sustained tachycardias is presented. In his ecg recordings delta wave depolarizations indicated right free wall accessory pathway. This was proved during electrophysiologic study. The effective refractory period of this pathway was short in both directions-below 200 ms. There was a wide zone of sustained antidromic tachycardia 236-247/min induction. Intravenous injection of flecainide terminated antidromic tachycardia but a wide zone of sustained orthodromic tachycardia 150/min induction appeared. Dissection of the right free wall accessory pathway was performed using Sealy technique (Cox modification). During the intraoperation electrophysiologic study an orthodromic tachycardia with retrograde conduction through an antero-septal accessory pathway was induced. After dissection of that second pathway abnormal atrioventricular conduction was abolished. The patients has been free from episodes of tachycardia during one year follow-up period.     

Clinical course of persistent junctional reciprocating tachycardia

OBJECTIVE: The purpose of this study is to review the clinical course of persistent junctional reciprocating tachycardia (PJRT) in 21 patients spanning a wide age range to examine the electrophysiologic characteristics of the conduction system in these patients with PJRT, particularly in regards to its incessant nature and to evaluate the long-term response to radiofrequency ablation. BACKGROUND: Persistent junctional reciprocating tachycardia is uncommon, occurring in 1% of patients with supraventricular tachycardia. Its presentation, course and treatment are incompletely characterized. METHODS: The clinical, electrocardiographic, electrophysiologic and echocardiographic data of 21 patients with PJRT were reviewed. RESULTS: In 9 of these 21 patients, the mean tachycardia cycle length increased significantly (p < 0.0001) as the patients grew, from a mean tachycardia cycle length of 308+/-64 ms in the patients less than 2 years, 414+/-57 ms in the patients between 2 years and 5 years, to 445+/-57 ms in the patients greater than 5 years, primarily due to slowing of retrograde conduction in the accessory pathway. Persistent junctional reciprocating tachycardia was associated with impaired ventricular function in 11, improving spontaneously in 4 and, after successful ablation of the accessory pathway, in 7. All patients except one were uncontrolled on one or more medications. Ablation of the accessory pathway was successful in 19 of 21 patients. CONCLUSIONS: We conclude that PJRT is characterized by an onset in early childhood and by an age-related prolongation of the tachycardia cycle length mediated primarily through conduction delay in the concealed, retrogradely conducting accessory pathway. Ablation of the accessory pathway provides definitive treatment for PJRT.     

New diagnostic finding to assess para-Hisian pacing observed in a patient with a permanent form of junctional reciprocating tachycardia

Para-Hisian pacing, a useful method to differentiate conduction over an accessory pathway from conduction over the AV node, is assessed essentially by comparing the timing of local atrial electrograms between His-bundle captured beats and His-bundle noncaptured beats. We describe the case of a patient with a permanent form of junctional reciprocating tachycardia, in whom an atrial double potential was recorded only during the tachycardia at the right posterior septum. During para-Hisian pacing, a morphologic change in the atrial electrogram at the posterior septum was also identified, as well as a change in the retrograde atrial sequence. Since the morphologic change of atrial electrograms during para-Hisian pacing cannot be demonstrated in a patient without an accessory pathway, this new finding could be considered a new additional diagnostic criterion suggesting the presence of an accessory pathway.     

Ventriculo-atrial conduction time during reciprocating tachycardia with intermittent bundle-branch block in Wolff-Parkinson-White syndrome

Records from patients with the Wolff-Parkinson-White syndrome were reviewed with particular emphasis on the occurrence of bundle-branch block aberration during reciprocating tachycardia and the significance of this observation with respect to accessory pathway location. Increase by greater than 25 ms in the ventriculoatrial interval during reciprocating tachycardia with bundle-branch block, when compared to reciprocating tachycardia with normal intraventricular conduction, occurred only with right or left free wall accessory pathways. No patient with a septal accessory pathway proven by epicardial mapping showed a ventriculoatrial interval prolongation greater than 20 ms during bundle-branch block aberration. Measurement of ventriculo-atrial interval during bundle-branch block abe-ration also helped to diagnose accessory pathways AH and HV intervals as well as ventriculo-atrial times, may give midleading information. In one patient increase in cycle length during left bundle-branch block was the result of prolonged HV interval rather than prolonged ventriculo-atrial interval. In another patient cycle length remained the same during bundle-branch block while the ventriculo-atrial interval increased by an increment identical to the decrease in AH interval.     

Radiofrequency catheter ablation of an incessant supraventricular tachycardia initiated by a Hisian parasystole

The coexistence of a parasystolic focus, tachycardia dependent right bundle branch aberrancy, and an AV accessory pathway is reported here. This condition was present in a 40-year-old man, which led to an incessant AV reciprocating tachycardia. Further electrophysiological study revealed that the parasystolic focus was located somewhere in the His bundle; endocardial mapping disclosed a right posterior accessory pathway. Radiofrequency current was delivered at the atrial level of the right posterolateral AV groove and successfully ablated the accessory pathway, leading to a dramatic improvement in cardiac function. In conclusion, the recognition of the electrophysiological mechanism of incessant supraventricular tachycardia was of crucial importance for the therapy decision. A definitive intervention using radiofrequency catheter ablation should be considered early and not postponed in patients with tachycardia-induced cardiomyopathy.     

High frequency current ablation of supraventricular tachyarrhythmias in congenital heart defects

Supraventricular tachycardia is a frequent cause of disease in patients with congenital heart defects and has a potentially high impact on quality of life, morbidity and mortality of this patient cohort. Conventional treatment often fails to avoid recurrences of tachycardia in a long-term perspective. Potential side effects of antiarrhythmic drugs include aggravation of heart disease related disturbances of impulse generation and conduction properties or negative inotropic effects on haemodynamically impaired ventricular chambers. For these reasons, interventional electrophysiology is increasingly used for the treatment of supraventricular tachycardias in patients with congenital heart disease. Until March 1998 a total of 83 patients with congenital heart defects underwent an attempt for radiofrequency current treatment of supraventricular tachycardias. Among these were 36 children with an age of 5 months to 15 years (8.2 +/- 4.6 years) and 4.7 grown ups with an age of 17 to 76 years (39.3 +/- 14.3 years). In a natural course or preoperative status of the congenital heart disease were 35 patients, while palliative or corrective surgery was performed in 48 patients. Supraventricular tachycardia was based on a total of 63 congenital arrhythmogenic substrates, among them were 53 accessory pathways, 4 Mahaim fibres, 5 functionally dissociated AV-nodes and an anatomically doubled specific conduction system including 2 distinct AV-nodes in one case. In the remaining patients with tachycardia based on acquired arrhythmogenic substrates there were 45 incisional atrial reentrant tachycardias, 15 atrial flutters of the common type and 6 ectopic atrial tachycardias. In a total of 105 sessions 78 of the 83 patients were successfully treated with the use of radiofrequency current ablation. There were no significant procedure related complications. Radiofrequency current ablation can be carried out safely and successfully for the treatment of supraventricular tachycardia in young and adult patients with congenital heart disease. As such therapeutic strategy meets the specific requirements of this patient cohort, early consideration for this therapy is recommended.     

Cardiac anatomy and diastolic filling in professional road cyclists

The electrophysiologic effects of intravenous verapamil (0.15 mg/kg) and oral sustained-release verapamil (verapamil-SR) (240 mg once daily for 7 days) were studied in 17 patients with paroxysmal supraventricular tachycardia (SVT). Ten patients had atrioventricular (AV) nodal reentrant tachycardia and 7 had AV reciprocating tachycardia involving an accessory AV pathway. Both preparations significantly prolonged anterograde effective refractory period of the AV node and depressed the retrograde AV nodal conduction system. The sinus cycle length, and atrial and ventricular effective refractory periods were prolonged after oral verapamil-SR. Furthermore, oral verapamil-SR depressed retrograde accessory pathway conduction which was not interfered with by intravenous verapamil. Intravenous verapamil and oral verapamil-SR prevented induction of sustained SVT in 12 of 17 (71%) and 10 of 17 (59%) patients, respectively. Follow-up study with oral verapamil-SR 240 mg once daily in 15 patients for 19 +/- 6 months revealed that among the 8 patients without induction of sustained SVT, 7 have been free of symptomatic arrhythmia; only 1 patient had occasional SVT attacks. For the 7 patients with induction of sustained SVT, 3 patients failed to respond to oral verapamil-SR, 1 patient became symptom free, and the remaining 3 patients had less frequent SVT attacks. Thus, immediate intravenous verapamil testing predicts the electrophysiologic results of oral verapamil-SR therapy, and oral verapamil-SR once daily may be used for long-term prophylaxis of SVT with better patient compliance.     

A case of AV reentrant tachycardia due to a concealed accessory pathway with retrograde conduction manifested by isoproterenol

Retrograde conduction of the concealed accessory pathway (AP) is a prerequisite for the induction of atrioventricular reentrant tachycardia (AVRT). In patients with AVRT due to a concealed AP, the absence of retrograde conduction of the AP in the baseline state has rarely been reported. We report a case of AVRT due to a concealed left lateral AP, in which the retrograde conduction was absent in the baseline state and manifested by isoproterenol infusion. A 61-year-old man had suffered from intermittent palpitation for 17 years. A narrow QRS complex tachycardia with a retrograde P wave in the ST segment was recorded in 24-h Holter monitoring. An electrophysiologic study was performed while he was in a nonsedated state. No ventriculoatrial conduction over either the normal atrioventricular conduction system or the AP was demonstrated in the baseline state. Isoproterenol was infused at a rate of 1.0 microg/min. Retrograde conduction over the AP became manifest and AVRT was induced. The AP was ablated with radiofrequency energy at the left free wall. After ablation of the AP, no tachycardia was induced. To the authors'best knowledge, only 1 other similar case has been reported in the literature.     

Electrophysiological mechanisms and determinants of vagal maneuvers for termination of paroxysmal supraventricular tachycardia

BACKGROUND: The vagal maneuvers used for termination of paroxysmal supraventricular reentrant tachycardia (PSVT) appear to involve more complex mechanisms than we have known, and further study should be done to explore the possible mechanisms. METHODS AND RESULTS: In this study, 133 patients with PSVT and 30 age- and sex-matched control subjects were included. We assessed the effects of different vagal maneuvers on termination of PSVT and compared baroreflex sensitivity and beta-adrenergic sensitivity between the patients with PSVT and control subjects. Out of 85 patients with atrioventricular reciprocating tachycardia (AVRT), vagal maneuvers terminated in 45 (53%). Of these, 28 (33%) terminated in the antegrade limb and 17 (20%) terminated in the retrograde limb. Out of 48 patients with atrioventricular nodal reentrant tachycardia (AVNRT), vagal maneuvers terminated the tachycardia in the antegrade slow pathway (14%) or in the retrograde fast pathway (19%). Baroreflex sensitivity was poorer but isoproterenol sensitivity test better in patients with AVNRT. Poorer antegrade atrioventricular node conduction properties and better vagal response determined successful antegrade termination of AVRT by vagal maneuvers. Poorer retrograde accessory pathway conduction property but better vagal response determined successful retrograde termination of AVRT. Better sympathetic and vagal response associated with poorer retrograde atrioventricular node conduction determined retrograde termination of AVNRT by the Valsalva maneuver. CONCLUSIONS: Both the vagal response and conduction properties of the reentrant circuit determine the tachycardia termination by vagal maneuvers. Improved understanding of the interaction of autonomic and electrophysiological mechanisms in maintaining or terminating PSVT may provide important insight into the pathophysiology of these two tachycardias.     

Dissimilar atrial rhythms in a patient with the Wolff-Parkinson-White syndrome

In this report, we present the findings in a patient who had paroxysmal supraventricular tachycardia and atrial flutter associated with the Wolff-Parkinson-White syndrome. During atrial flutter, localized atrial fibrillation was recorded in the coronary sinus (dissimilar atrial rhythms), near the accessory pathway; and during 90 minutes of observation, ventricular activation occurred solely over the normal pathway. We postulate that localized atrial fibrillation repetitively invaded the accessory pathway and rendered it refractory to conduction by flutter impulses.     

Differential effect of adenosine on anterograde and retrograde fast pathway conduction in patients with atrioventricular nodal reentrant tachycardia

INTRODUCTION: Several studies have shown that the fast pathway is more responsive to adenosine than the slow pathway in patients with AV nodal reentrant tachycardia. Little information is available regarding the effect of adenosine on anterograde and retrograde fast pathway conduction. METHODS AND RESULTS: The effects of adenosine on anterograde and retrograde fast pathway conduction were evaluated in 116 patients (mean age 47 +/- 16 years) with typical AV nodal reentrant tachycardia. Each patient received 12 mg of adenosine during ventricular pacing at a cycle length 20 msec longer than the fast pathway VA block cycle length and during sinus rhythm or atrial pacing at 20 msec longer than the fast pathway AV block cycle length. Anterograde block occurred in 98% of patients compared with retrograde fast pathway block in 62% of patients (P < 0.001). Unresponsiveness of the retrograde fast pathway to adenosine was associated with a shorter AV block cycle length (374 +/- 78 vs 333 +/- 74 msec, P < 0.01), a shorter VA block cycle length (383 +/- 121 vs 307 +/- 49 msec, P < 0.001), and a shorter VA interval during tachycardia (53 +/- 23 vs 41 +/- 17 msec, P < 0.01). CONCLUSION: Although anterograde fast pathway conduction is almost always blocked by 12 mg of adenosine, retrograde fast pathway conduction is not blocked by adenosine in 38% of patients with typical AV nodal reentrant tachycardia. This indicates that the anterograde and retrograde fast pathways may be anatomically and/or functionally distinct. Unresponsiveness of VA conduction to adenosine is not a reliable indicator of an accessory pathway.     

Radiofrequency catheter ablation of accessory atrioventricular pathways in children and young adults

OBJECTIVE: To assess the efficacy of radiofrequency ablation for reentrant tachyarrhythmias in children and young adults. SETTING: A tertiary cardiac referral centre. PATIENTS AND INTERVENTIONS: Over a 16 month period 22 patients aged less than 20 years (median age 16.5 years) underwent 26 radiofrequency ablation procedures for atrioventricular reentry tachycardia through an accessory pathway. The results of radiofrequency ablation were compared with those in a group of 16 patients (median age 14 years) who had had surgical ablation for atrioventricular reentry tachycardia over a preceding six year period. RESULTS: Ablation of an accessory atrioventricular pathway was accomplished for 18 (76%) of 25 pathways in 16 (73%) of 22 patients. There were no procedure-related complications. Surgery was eventually curative in 15/16 patients (94%). However, three patients required a second open heart surgical procedure because tachyarrhythmia recurred. There were no surgical deaths. Failures for radiofrequency ablation were related to accessory pathway location, and were greater for right free wall and posteroseptal pathways (success rate of 50% and 57% respectively). Recurrence after surgery was also associated with pathways in these locations. CONCLUSIONS: Transcatheter radiofrequency current ablation was safe and achieved a cure with less patient morbidity and improved cost efficiency. It is an attractive alternative to long-term drug therapy or surgery in older children and adolescents. A higher success rate may be expected with increased experience.     

Comparison of electrical and radiofrequency ablation of the AV junction in patients with refractory supraventricular tachycardia

The radiofrequency ablation (RFA) is advantageous due to gradual destruction of tissue which enables not only an interruption of conduction, but also its modification-retardation of conduction. This state is in most cases sufficient for the control of tachycardia. It is necessary to be aware that radiofrequency ablation does not coincide with barrotrauma, uncontrollable increase of temperature of electrodes and the requirement of general anaesthesis. This technique enables the RF ablation therapy: 1. ectopic atrial tachycardia, 2. intraatrial tachycardia, 3. atrial flutter of type Z by ablation of the lower posterolateral area. (Tab. 1, Fig. 5, Ref. 9.)     

Radiofrequency ablation of accessory pathways in pre-excitation syndrome

Various parameters relating to the radio-frequency ablation of accessory pathways were studied in 53 patients (27 males, 26 females: mean age 38.5 [14-64] years) with a history of paroxysmal tachycardia (over 1 month to 50 years), shown to be caused by an accessory pathway (Wolff-Parkinson-White syndrome). In all patients the following values were obtained: (1) number of procedures necessary to achieve permanent blockage of the accessory pathway (1-4); (2) duration of each procedure (45-420 min); (3) duration of fluoroscopy (5-102 min); (4) number of necessary radio-frequency applications (1-48); and (5) cumulative energy per procedure. To ablate left-lateral pathways (n = 10) required fewer procedures, shorter duration per procedure, shorter fluoroscopy time, fewer current applications and less total energy than coagulation of right-sided pathways (n = 10). Those various parameters were greatest for ablation of septal and para-septal pathways (n = 9). Pathways which conducted only retrogradely (n = 15) were more difficult to ablate than those with anterograde conduction (n = 38). There were two complications. In one case a tension pneumothorax occurred after faulty puncture of the subclavian vein; in the other, the left ventricle was perforated causing an acute tamponade which required pericardiocentesis with subsequent suture closure of the perforation. It is concluded that, in principle, all accessory pathways, regardless of their conduction potential and site, can be ablated by a radio-frequency current.     

Can bilharziasis be considered a health priority in western Africa, justifying control programs of large scope?

INTRODUCTION: The aim of the study was the evaluation of the usefulness of transesophageal atrial pacing in predicting chronic oral treatment efficacy of symptomatic reciprocating supraventricular tachycardia in infants and in avoiding the risk of very dangerous recurrences at home. METHODS: We studied 13 infants (11 males, 2 females, mean age 43 +/- 31 days) with symptomatic reciprocating supraventricular tachycardia and no structural heart disease. All patients had chronic oral therapy, using the drug effective in acute i.v. somministration. Each patient was discharged when supraventricular tachycardia was not inducible with transesophageal atrial pacing after 5 half-lives of the drug used in chronic oral treatment. All patients, every 6 months, were retested with transesophageal atrial pacing alternatively during chronic oral therapy and after complete wash out. Oral therapy was stopped in each patient when supraventricular tachycardia was not inducible after the wash out. RESULTS: The number of oral treatments tested for each patient were 2 +/- 1 (range 1-5). The number of transesophageal studies performed for each patient were 4 +/- 2 (range 3-7). No patient had symptomatic episodes of supraventricular tachycardia or needed to change therapy during the follow-up. The oral treatment was stopped after the twelfth month of life in 8 patients and after the twenty-fourth in 2 others without recurrences. CONCLUSION: Transesophageal atrial pacing seems to be useful in predicting accurately and rapidly the oral treatment efficacy of supraventricular tachycardia in infants. Our protocol seems to be effective to avoid dangerous recurrences of tachycardia and to decide when we can stop therapy without risk.