Real-world treatment sequencing and survival in previously treated advanced renal cell carcinoma patients receiving nivolumab monotherapy: a UK retrospective cohort study.

BACKGROUND: The CheckMate 025 trial established nivolumab monotherapy as one of the standards of care in previously treated advanced or metastatic renal cell carcinoma (aRCC). However, supporting real-world data is lacking. This study investigated characteristics, treatment sequences and clinical outcomes of patients who received nivolumab monotherapy for previously treated aRCC in the UK. METHODS: This was a retrospective cohort study of aRCC patients treated with nivolumab at second line or later (2L +) at 4 UK oncology centres. Eligible patients commenced nivolumab (index date) between 01 March 2016 and 30 June 2018 (index period). Study data were extracted from medical records using an electronic case report form. Data cut-off (end of follow-up) was 31 May 2019. RESULTS: In total, 151 patients were included with median follow-up of 15.2 months. Mean age was 66.9 years, male preponderance (72.2%), and mostly Eastern Cooperative Oncology Group performance status grade 0-1 (71.5%). Amongst 112 patients with a known International Metastatic RCC Database Consortium score, distribution between favourable, intermediate, and poor risk categories was 20.5%, 53.6%, and 25.9% respectively. The majority of patients (n = 109; 72.2%) received nivolumab at 2L, and these patients had a median overall survival (OS) of 23.0 months [95% confidence interval: 17.2, not reached]. All patients who received nivolumab at 2L had received TKIs at 1L. Amongst the 42 patients (27.8%) who received nivolumab in third line or later (3L +) the median OS was 12.4 months [95% CI: 8.8, 23.2]. The most common reasons for nivolumab discontinuation were disease progression (2L: 61.2%; 3L: 68.8%) and adverse events (2L: 34.7%; 3L: 28.1%). CONCLUSION: This study provides real-world evidence on the characteristics, treatment sequences, and outcomes of aRCC patients who received 2L + nivolumab monotherapy in the UK. Nivolumab-specific survival outcomes were similar to those achieved in the CheckMate 025 trial.

Tackling the burden of the hepatitis C virus in the UK: characterizing and assessing the clinical and economic consequences.

OBJECTIVES: The hepatitis C virus (HCV) remains a significant public health issue. This study aimed to quantify the clinical and economic burden of chronic hepatitis C in the UK, stratified by disease severity, age and awareness of infection, with concurrent assessment of the impact of implementing a treatment prioritization approach. STUDY DESIGN AND METHODS: A previously published back projection, natural history and cost-effectiveness HCV model was adapted to a UK setting to estimate the disease burden of chronic hepatitis C and end-stage liver disease (ESLD) between 1980 and 2035. A published meta-regression analysis informed disease progression, and UK-specific data informed other model inputs. RESULTS: At 2015, prevalence of chronic hepatitis C is estimated to be 241,487 with 22.20%, 33.72%, 17.22%, 16.67% and 10.19% of patients in METAVIR stages F0, F1, F2, F3 and F4, respectively, but is estimated to fall to 193,999 by 2035. ESLD incidence is predicted to peak in 2031. Assuming all patients are diagnosed and treatment is prioritized in F3 and F4 using highly efficacious direct-acting antiviral (DAA) regimens, a 69.85% reduction in ESLD incidence is predicted between 2015 and 2035, and the cumulative discounted medical expenditure associated with the lifetime management of incident ESLD events is estimated to be £1,202,827,444. CONCLUSIONS: The prevalence of chronic hepatitis C is expected to fall in coming decades; however, the ongoing financial burden is expected to be high due to an increase in ESLD incidence. This study highlights the significant costs of managing ESLD that are likely to be incurred without the employment of effective treatment approaches.

Factors affecting radiation exposure in patients undergoing endoscopic treatment for urolithiasis.

Imaging techniques, such as computed tomography (CT) and fluoroscopy, are essential for the diagnosis and treatment of urolithiasis. There is increasing concern regarding the cumulative radiation dose associated with medical imaging and its adverse effects. This study aimed to assess radiation exposure in patients undergoing endoscopic management of urolithiasis and to identify factors associated with increased exposure.A retrospective analysis of all consecutive symptomatic urolithiasis cases who underwent endoscopic surgery over a two-year period at a tertiary referral center was performed. The cumulative radiation dose was recorded per stone episode, and the effective dose (ED) then calculated. Multivariable regression analysis was performed to determine the association between ED and patient, stone, and procedural characteristics.Between January 2020 and December 2021, 250 patients underwent endoscopic intervention for urolithiasis; 71% (n = 178) were male with a median age of 48 years (IQR 35-59). The median stone size was 6 mm (IQR, 5-8 mm) and the median stone volume was 110 mm3 (IQR, 60-206 mm3). Most stones were located in the distal ureter (46%, n = 114). The median ED received per stone episode was 3.99 mSv (IQR 2.9-7 mSv). On multivariable analysis, BMI, number of CT scans performed, CT protocol used, and repeat procedures strongly predicted increased radiation dose (p < 0.01).It is important for urologists to consider the cumulative radiation dosage in patients with urolithiasis. Strategies to minimize exposure, such as avoiding re-imaging, low-dose CTs, and collimation of the region of interest with judicious magnification, should be considered during treatment.

Increasing cardiac interventions among the aged.

Ireland's over 65 year population is growing. As incidence of coronary events rises with age, there is a growing population of elderly patients with cardiac disease. The changing age profile of patients treated by a tertiary hospital's Cardiology service was quantified using Hospital Inpatient Enquiry data. 53% of CCU admissions were aged > or = 65 years, with admissions aged > or = 85 years in 2008 four times greater than in 2002. Percentages of patients undergoing diagnostic coronary angiography and percutaneous coronary interventions in 1997 aged > or = 70 years were 19% and 18% respectively. By 2007, these percentages had risen to 31% and 34% respectively--greatest increases were in the very elderly age categories. The proportion of ICD recipients aged > 70 years increased from 8% in 2003 to 25% by 2008. The proportion of elderly patients receiving advanced cardiac care is increasing. This trend will continue and has clear resource implications. Outcomes of interventions in the very old need further investigation, since the 'old old' are under-represented in clinical trials.

Advances in the management of severe aortic stenosis.

BACKGROUND: Recent developments in the management of severe aortic stenosis have resulted in a paradigm shift in the way we view the condition. Patients previously denied intervention in the form of surgical aortic valve replacement (SAVR) are now candidates for transcatheter aortic valve implantation and the risk and age profiles of those undergoing SAVR are rising with the ageing population. This review article is designed to provide an overview of developments in the surgical management of severe aortic stenosis. We also discuss the expanding role of minimally invasive surgical approaches to outline the current techniques available to treat patients with severe aortic stenosis. METHODS: PubMed was searched using the terms 'severe aortic stenosis', 'surgical aortic valve replacement', 'transcatheter aortic valve replacement', 'mechanical aortic valve replacement' and 'sutureless aortic valve replacement'. Selection of articles was based on peer review, journal and relevance. Where possible articles from high-impact factor peer review journals were included. RESULTS: Minimally invasive operative approaches include mini-sternotomy and mini-thoracotomy. Sutureless aortic prostheses reduce aortic cross-clamp time and cardiopulmonary bypass time; however, long-term follow-up data are unavailable at this time. Mechanical prostheses are advised for those under 60. CONCLUSION: Multiple advances in the surgical management of aortic stenosis have occured in the past decade. An evolving spectrum of surgical and transcatheter interventions is now available depending on patient age and operative risk.

Relation of left ventricular function and prognosis in hypertrophic cardiomyopathy: an angiographic study.

Left ventricular cineangiograms performed at the time of diagnosis in 88 patients with hypertrophic cardiomyopathy were digitized to evaluate the relation of left ventricular function and prognosis in hypertrophic cardiomyopathy. Eleven patients died suddenly after a mean follow-up period of 7.5 +/- 7 years, 10 patients died of congestive heart failure or after cardiac surgery and 67 were alive after a mean follow-up period of 8.6 +/- 4 years. Measurements of left ventricular volume, ejection fraction, peak rate of ejection and filling and time to peak rate of ejection and filling were derived from curves of ventricular volume and its rate of change during the cardiac cycle. Patients who died suddenly had a lower peak rate of ventricular ejection (stroke volume-normalized peak ejection rate 5.41 +/- 0.69 versus 6.24 +/- 1.33 s-1; p = 0.006) and lower peak rate of ventricular filling (end-diastolic volume-normalized peak filling rate 4.02 +/- 0.94 versus 4.88 +/- 1.53 s-1; p = 0.02) and stroke volume-normalized peak filling rate (4.75 +/- 1.08 versus 5.82 +/- 1.70 s-1; p = 0.01) compared with survivors. Stepwise regression analysis revealed that sudden death was best predicted by the combination of increased end-diastolic volume, small end-systolic volume and low peak filling rate (predictive accuracy 32%, false negative 18% and false positive 28%). The addition of clinical features and hemodynamic measurements to the analysis improved predictive accuracy to 43% (false negative 18% and false positive 18%). Ambulatory electrocardiographic monitoring performed in 57 of the 88 patients 1 month to 17 years (median 8 years) after diagnosis revealed ventricular tachycardia in 14 (25%). Of these, 10 who survived had hyperkinetic systolic function at diagnosis, whereas the 4 who died suddenly had impaired systolic function (end-diastolic volume-normalized peak ejection rate 5.93 +/- 1.2 versus 4.01 +/- 1.2 s-1, respectively; p = 0.04). In hypertrophic cardiomyopathy, ventricular tachycardia is a sensitive but nonspecific marker of adults who are at risk of sudden death. Impaired systolic function may be an important determinant of which patients with ventricular tachycardia die suddenly. This study shows that indexes of ventricular function contribute to the identification of patients at particular risk of sudden death. However, the predictive power of the clinical features and hemodynamic and angiographic measurements that could be assessed was poor.(ABSTRACT TRUNCATED AT 400 WORDS)

Electrophysiologic testing in the upright position: improved evaluation of patients with rhythm disturbances using a tilt table.

Patients are traditionally evaluated in the supine position in the electrophysiology laboratory, although symptoms due to a cardiac rhythm disturbance are often maximal clinically during standing. The assumption of the upright position results in dependent displacement of blood, followed by prompt vasoconstriction to maintain arterial pressure. This normal response may aggravate tachyarrhythmias by increasing catecholamine levels or may precipitate vasodepressor syncope if the vasoconstrictor response is absent. The use of a tilt table during electrophysiologic testing was evaluated over a 12 month period in 104 patients having a mean age of 60 years (range 37 to 81): 59 with supraventricular tachycardia, 6 with vasovagal syncope and 39 with carotid sinus hypersensitivity. Twenty-three patients (22%) had significant abnormalities when upright that were not present when supine: eight patients with supraventricular tachycardia who had their clinical syndromes of palpitation and syncope reproduced when upright, but only minimal symptoms when supine; two patients with supraventricular tachycardia who had sustained atrioventricular reentry when upright, but only two to eight beats of tachycardia when supine; six patients with syncope and a normal cardiac evaluation before electrophysiologic testing who had their typical spells only after being placed upright during a vasovagal event and seven patients with carotid sinus hypersensitivity who had their clinical syndromes reproduced with carotid sinus massage only when upright, developing hypotension despite maintaining their heart rate with sinus rhythm or pacing (vasodepressor response). In 22% of patients, electrophysiologic testing in the upright position provided clinically important information that was not evident during standard testing in the supine position.

Cardiac histologic findings in patients with life-threatening ventricular arrhythmias of unknown origin.

Percutaneous endomyocardial biopsy (right ventricle in 10, left ventricle in 2) was performed in 12 patients, aged 9 to 57 years, with serious ventricular arrhythmias occurring in the setting of normal cardiac anatomy and mechanical function. Light microscopic examination of tissue revealed histologic abnormalities in 11 patients, including myocardial cellular hypertrophy in 7, interstitial fibrosis in 5, endocardial fibrosis in 2, myocardial degenerative changes in 1 and increased interstitial cellularity in 1. One patient had histologic evidence of acute lymphocytic myocarditis. Thus, a majority of patients with serious ventricular arrhythmias and normal cardiac anatomy had histologic abnormalities, bringing into question the concept of primary electrical heart disease or idiopathic ventricular tachycardia.

Symptomatic "isolated" carotid sinus hypersensitivity: natural history and results of treatment with anticholinergic drugs or pacemaker.

Because syncope may occur intermittently in patients with carotid sinus hypersensitivity, a knowledge of its natural history is needed as a basis for interpreting the usefulness of therapy. Fifty-six consecutive patients are described (47 men and 9 women; mean age 61 years) with carotid sinus hypersensitivity and syncope in whom 24 hour ambulatory monitoring and intracardiac electrophysiologic study revealed no other cause for the syncope. The mean duration of symptoms was 44 months (range 1 to 480) and the mean number of episodes was 4.0 (range 1 to 20). During a follow-up period of 6 to 120 months (median 40), syncope recurred in 3 of 13 patients who received no treatment, in 2 of 23 patients who received a pacemaker and in 4 of 20 patients who received anticholinergic drugs (incidences corrected for totals available at follow-up: 27, 9 and 22%, respectively). Two-thirds of the patients receiving no treatment were asymptomatic compared with all nine of the patients with syncope and a pure cardioinhibitory response to carotid sinus massage who received an atrioventricular (AV) sequential pacemaker. Although pacing was effective in abolishing syncope, its use should be reserved for recurrent episodes because of the high rate of spontaneous remission of symptoms.

Effect of amiodarone on left ventricular ejection and filling in hypertrophic cardiomyopathy as assessed by radionuclide angiography.

Left ventricular (LV) function at rest was assessed by radionuclide angiography in 30 patients with hypertrophic cardiomyopathy (HC) before and during treatment with amiodarone (600 to 800 mg for 1 week, 200 to 400 mg/day thereafter) for an initial maintenance period of 1 month in 30 patients and 6 months in 12 patients. The reproduciblity of the measurements was assessed by performing control studies within 24 hours in 13 patients and at 1 to 6 months in 6 patients, and 95% confidence limits for spontaneous change were determined. There was a significant decrease in heart rate at 1 month (from 67 +/- 9 vs 61 +/- 9 beats/min, p less than 0.004) with no further decrease at 6 months. Systemic blood pressure did not change. After amiodarone therapy, for each of the measurements of LV function except peak ejection rate, there was no mean change and the number of patients in whom the values increased and decreased by more than the 95% confidence limits were approximately equal. Peak ejection rate showed a significant decrease at 1 month, but this effect was not maintained at 6 months; 4 of 6 patients who showed a significant decrease at 1 month were reevaluated at 6 months, and in all 4 the values had returned to control levels. These findings suggest that the 95% confidence limits for spontaneous change were not wide enough and that chronic oral amiodarone therapy does not alter radionuclide indexes of LV function at rest in patients with hypertrophic cardiomyopathy.

Role of invasive electrophysiologic testing in patients with symptomatic bundle branch block.

Electrophysiologic testing was performed in 112 symptomatic patients with bundle branch block. Abnormalities included HV interval 70 ms or longer (35 patients), infra-Hisian block with atrial pacing (6 patients) and sinus node dysfunction (23 patients). Inducible ventricular tachycardia occurred in 47 patients (42%). Therapy was based on the electrophysiologic test result: group I--16 patients with no therapy (normal study results); group II--34 patients with permanent pacing alone; group III--39 patients with antiarrhythmic therapy alone; and group IV--21 patients with both antiarrhythmic therapy and permanent pacing. Cumulative 4-year survival rates were 83% in group I, 84% in group II, 63% in group III and 84% in group IV (mean follow-up 2.5 years). Recurrent syncope occurred in 19% of group I, 6% of group II, 33% of group III and 19% of group IV. In symptomatic patients with bundle branch block and normal electrophysiologic test results, prognosis is good without treatment. In patients undergoing permanent pacing based on electrophysiologic testing, survival is good and rate of symptom recurrence is low. Electrophysiologic testing identifies patients with inducible ventricular tachycardia for whom antiarrhythmic therapy is indicated but who nevertheless have a poor prognosis.

Gender differences in the management and outcome of acute myocardial infarction in unselected patients in the thrombolytic era.

This study compares the clinical features, management, and outcome in men and women from a consecutive, unselected series of patients with acute myocardial infarction (AMI) who were admitted to a university cardiac center over a 3-year period. It is a retrospective observational study of 1,059 admissions with AMI identified through the Hospital In-Patient Enquiry (HIPE) registry, validated according to Minnesota Manual criteria, and followed for a period of up to 5 years (median 36 months). Women comprised 40% of all admissions, had a higher hospital mortality (24% vs. 16%, p<0.001), and were less likely to receive thrombolysis (23% vs. 33%, p<0.01), admission to coronary care (65% vs. 77%, p<0.001), or subsequent invasive or noninvasive investigations (55% vs. 63%, p<0.01). However, women with AMI were older than men with AMI (71 vs. 65 years, p<0.001). After adjusting for age, differences that remained significant were prevalence of hypertension (odds ratio [OR] 2.12, 95% confidence intervals [CI] 1.56 to 2.88) and cigarette smoking (OR 0.47, 95% CI 0.35 to 0.65), management in coronary care (OR 0.66, 95% CI 0.49 to 0.88), and hospital mortality (OR 1.48, 95% CI 1.07 to 2.04). Excess mortality occurred predominantly in women <65 years old (18% vs. 8%, OR [multivariate] 2.35, 95% CI 1.19 to 4.56), among whom multivariate analysis demonstrated a significantly lower thrombolysis rate (OR 0.48, 95% CI 0.27 to 0.86). In this group, lack of thrombolysis independently predicted hospital mortality (OR 5.37, 95% CI 1.45 to 19.82). Female gender was not an independent predictor of mortality following AMI (OR 1.42, 95% CI 0.90 to 2.26). Thus, among unselected patients, female gender is associated with, but not an independent predictor of, reduced survival after AMI. Gender differences in mortality are greatest in younger patients, who are less likely to receive thrombolysis and in whom lack of thrombolysis is independently associated with mortality after AMI.

Results of percutaneous transluminal coronary angioplasty for unstable angina pectoris in patients 70 years of age and older.

Between November 1980 and November 1985, 54 patients ages greater than or equal to 70 years underwent percutaneous transluminal coronary angioplasty for unstable angina, defined as recent-onset (less than 1 month) angina, new onset of rest angina (greater than or equal to 2 episodes) or accelerating class III or IV angina. In these 20 men and 34 women, disease was 1-vessel in 34 (63%) and multivessel in 20 (37%). The mean (+/- standard deviation) ejection fraction was 0.62 +/- 0.12. Angioplasty was successful in 43 patients (80%). In the 11 unsuccessful cases, emergency coronary artery bypass grafting for acute occlusion was performed in 3 and elective coronary artery bypass surgery in 8. There were no deaths. Two patients (4%) sustained Q-wave myocardial infarctions. The mean duration of follow-up for the total group was 37 months (6 to 73 months). Of the 43 patients with successful dilation, 4 died, 1 had an non-Q-wave myocardial infarction and 8 had symptomatic restenosis (4 underwent successful repeat angioplasty, 1 had repeat percutaneous transluminal coronary angioplasty and then bypass surgery, 1 had repeat bypass surgery alone and 2 had medical therapy). At last follow-up, 3 patients had stable class III or IV angina and 31 patients (72%) were angina-free.

Surgical treatment of accessory atrioventricular pathways and symptomatic tachycardia in children and young adults.

Twenty-seven patients aged 21 years or younger (mean 15) with symptomatic tachycardia underwent operation for ablation of an accessory atrioventricular pathway. Six patients had associated Ebstein's malformation of the tricuspid valve. Supraventricular tachycardia had been present for a mean of 5 years. At electrophysiologic study, 4 patients were found to have 2 accessory pathways. Left ventricular free wall pathways were found in 14 patients, right ventricular free wall pathways in 10 and septal pathways in 6. Successful initial ablation of all the pathways was achieved in 26 of the 27 patients. No patient died perioperatively and none had persistent complete heart block. During a mean follow-up of 11 months, no patient had recurrence of an arrhythmia related to the accessory pathway. Thus, the surgical treatment of children and young adults with accessory atrioventricular pathways and symptomatic supraventricular tachycardia is safe and effective. For these patients, unless the tachycardia can be easily controlled with a minimal number of drugs and adverse effects, surgical ablation should be considered early in the clinical course.

Histopathologic changes in asymptomatic relatives of patients with idiopathic dilated cardiomyopathy.

Echocardiographic screening of asymptomatic relatives of patients with idiopathic dilated cardiomyopathy identifies a subset with left ventricular enlargement who are assumed to have early familial idiopathic dilated cardiomyopathy. This study shows for the first time that the myocardium in such relatives demonstrates abnormal cellularity.

Carotid sinus hypersensitivity and syncope.

The patient with a hypersensitive carotid sinus reflex and syncope may pose special challenges in evaluation and treatment. Specifically, although the finding of carotid sinus hypersensitivity may indeed indicate an exaggerated vagal tone that causes syncope, it may also be a chance association in a patient with syncope due to another cause. Careful clinical and electrophysiologic testing may be needed to distinguish these two possibilities. Furthermore, the need for drug therapy or cardiac pacing (or both) must be determined on an individual basis, depending on the relative contributions of cardioinhibitory and vasodepressor components to the patient's symptoms and also on the degree of patient limitation.

Clinical intracardiac electrophysiologic testing: technique, diagnostic indications, and therapeutic uses.

Clinical cardiac electrophysiologic testing has evolved rapidly since 1968, when the technique was first described. In an electrophysiologic study, electrode catheters are positioned within the heart to record electrical activity from the atrium, atrioventricular conduction tissue, and ventricle. Programmed stimulation is then performed, which involves pacing of the atrium or ventricle and introducing critically timed premature stimuli during sinus rhythm or paced rhythm. The use of programmed stimulation in conjunction with intracardiac recordings in electrophysiologic studies has facilitated the diagnosis of mechanisms of arrhythmias and the assessment of therapy. Electrophysiologic testing is useful in selected patients with sinus node dysfunction, conduction system disorders, supraventricular tachycardia, ventricular tachycardia, or ventricular fibrillation and in survivors of out-of-hospital cardiac arrest and patients with symptomatic but unsubstantiated rhythm disturbances. Therapeutic approaches that can be assessed by electrophysiologic testing include serial drug testing to determine the effectiveness of antiarrhythmic agents, antitachycardia pacing, the implantable defibrillator, transcatheter ablation, and electrophysiologically guided surgical procedures. In this review, we discuss the methods of electrophysiologic testing, its clinical applications in diagnosing the various cardiac rhythm disturbances, and its use in assessing various therapeutic modalities.

Refractory supraventricular tachycardia in the neonate: treatment with temporary antitachycardial pacing.

Although intracardiac antitachycardial pacing techniques are frequently used to terminate reentrant supraventricular tachycardia in adults, this approach has rarely been used in neonates. We describe two neonates, both of whom were in circulatory shock due to recurrent paroxysmal supraventricular tachycardia, who were treated with temporary antiatachycardial pacing. This approach allows repeated termination of the tachycardia at the bedside until an adequate therapeutic concentration of an effective drug regimen is achieved and obviates repeated direct-current cardioversion.

Propafenone for the treatment of refractory complex ventricular ectopic activity.

The results of therapy with propafenone were evaluated in 45 patients with complex ventricular ectopic activity that had been refractory to a mean of 3.8 antiarrhythmic drugs. The cardiac diagnoses were ischemic heart disease (in 16 patients), cardiomyopathy (in 7), mitral valve prolapse (in 7), mitral valve prolapse (in 7), idiopathic ventricular ectopic beats (in 6), valvular heart disease (in 5), and hypertension (in 4). The frequency of ventricular ectopic beats was established after therapy with antiarrhythmic agents had been discontinued. Patients then received propafenone during a dose-ranging protocol. An effective response was defined as a reduction in total ventricular ectopic beats of 80% or more. During dose ranging, therapy failed in four patients because of side effects, in eight because of a reduction in ventricular ectopic beats of less than 80%, and in three because of an aggravation of the arrhythmia. Thirty patients had a reduction in total ventricular ectopic beats of 80% or more. During a mean follow-up of 12.4 months, therapy failed in 1 patient because of sustained ventricular tachycardia and in 7 because of intolerable side effects; 22 patients continued to receive propafenone. PR and QRS intervals were significantly prolonged (P = 0.001), but the corrected QT interval and the heart rate were unchanged. The mean trough plasma level of propafenone associated with an effective response was 756 ng/ml, and that associated with intolerable side effects was 920 ng/ml. Thus, in patients with refractory complex ventricular ectopic beats, propafenone was effective and well tolerated initially in 67% of patients and during long-term administration in 49%, and toxicity was minor in most patients.

Impact of intracardiac electrophysiologic testing on the management of elderly patients with recurrent syncope or near syncope.

Seventy-five patients, 75 years of age and over, experienced recurrent syncope, with the etiology remaining unclear but presumably cardiogenic, after cardiac and neurologic examinations and noninvasive laboratory testing (including an electrocardiogram and ambulatory electrocardiographic monitoring). The mean number of previous syncopal spells was 14 (range, 1 to 64) over a mean of 36 months (range, 1 to 480 months). These patients underwent invasive electrophysiologic testing and a potential cause for syncope was identified in 68%. Abnormal findings at electrophysiologic testing included: sinus node dysfunction (55%); abnormal His-bundle conduction (39%); and ventricular tachycardia (14%), with some patients having more than one abnormality. No major complications were associated with the electrophysiologic testing. Patients were subsequently treated with permanent cardiac pacing or antiarrhythmic drugs or both, depending upon results of the electrophysiologic study. Follow-up examinations (mean of 26 months; range, 1 to 70) were possible in 90% of patients. No further syncope occurred in 84% of patients with an abnormal electrophysiologic study who received subsequent therapy to prevent the identified abnormality. Thus, in this difficult group of patients with recurrent syncope of uncertain etiology, electrophysiologic testing was safe and indicated abnormalities of conduction or rhythm in 68% of patients; treatment to correct these abnormalities prevented recurrent syncope in 84%.