Phospholamban cardiomyopathy: a Canadian perspective on a unique population.

INTRODUCTION: Phospholamban cardiomyopathy is an inherited cardiomyopathy, characterised by a defect in regulation of the sarcoplasmic reticulum Ca2+ pump, often presenting with malignant arrhythmias and progressive cardiac dysfunction occurring at a young age. METHODS: Phospholamban R14del mutation carriers and family members were identified from inherited arrhythmia clinics at 13 sites across Canada. Cardiac investigations, including electrocardiograms, Holter monitoring (premature ventricular complexes, PVCs), and imaging results were summarised. RESULTS: Fifty patients (10 families) were identified (median age 30 years, range 3-71, 46% female). Mutation carriers were more likely to be older, have low-voltage QRS, T­wave inversion, frequent PVCs, and cardiac dysfunction, compared to unaffected relatives. Increasing age, low-voltage QRS, T­wave inversion, late potentials, and frequent PVCs were predictors of cardiac dysfunction (p < 0.05 for all). Older carriers (age ≥45 years) were more likely to have disease manifestations than were their younger counterparts, with disease onset occurring at an older age in Canadian patients and their Dutch counterparts. DISCUSSION: Among Canadian patients with phospholamban cardiomyopathy, clinical manifestations resembled those of their Dutch counterparts, with increasing age a major predictor of disease manifestation. Older mutation carriers were more likely to have electrical and structural abnormalities, and may represent variable expressivity, age-dependent penetrance, or genetic heterogeneity among Canadian patients.

Evolution of a genetic diagnosis.

Understanding the relationship between genotype and phenotype has become an integral part of the diagnosis and management of patients with inherited arrhythmias and cardiomyopathies. Given the existence of background noise, the majority of genetic testing results should be incorporated into clinical decision making as probabilistic, rather than deterministic, in the diagnosis and management of inherited arrhythmias. This case report captures multiple snapshots of clinical care in the evolution of a diagnosis of a single patient, highlighting the need for repeated phenotypic and genotypic assessment for both the patient and their family.

ECG machine QTc intervals are inaccurate in hemodialysis patients.

BACKGROUND: Nephrologists need effective screening tools to identify hemodialysis patients at elevated risk for sudden cardiac death, the leading cause of death in this population. QTc intervals longer than 450 ms in males and 470 ms in females, measured by the gold standard tangent method (trueQTc), are prolonged and increase sudden cardiac death in healthy populations and patients with long QT syndrome. METHODS: We performed a retrospective ECG and chart review of hemodialysis patients. Our first objective was to determine if machine-measured QTc intervals (macQTc) could be used to identify dialysis patients with prolonged trueQTc. Our second objective was to determine at what macQTc could prolonged trueQTc be confidently diagnosed. RESULTS: macQTc differed from the trueQTc by an average of 16.54 ms, and by at least 20 ms in 46.8, 36.1, 53.6, 50.0 and 57.1% of all, short-hours daily hemodialysis, intermittent conventional hemodialysis, frequent nocturnal hemodialysis and intermittent nocturnal hemodialysis patients, respectively. The positive predictive value, negative predictive value, sensitivity and specificity of prolonged macQTc predicting prolonged trueQTc was 57.6, 92.6, 79.1 and 81.8%, respectively. Thus, macQTc is inaccurate at predicting the gold standard trueQTc in hemodialysis patients. macQTc greater than 480 ms in hemodialysis patients predicts trueQTc prolongation with a positive predictive value of 95.2%, but with a low sensitivity of 32.3%. CONCLUSION: In hemodialysis patients, ECG macQTc intervals are insufficiently sensitive or specific to predict prolonged trueQTc intervals, unless >480 ms.

Defibrillation testing at the time of ICD insertion: an analysis from the Ontario ICD Registry.

BACKGROUND: increasingly, ICD implantation is performed without defibrillation testing (DT). OBJECTIVES: To determine the current frequency of DT, the risks associated with DT, and to understand how physicians select patients to have DT. METHODS: between January 2007 and July 2008, all patients in Ontario, Canada who received an ICD were enrolled in this prospective registry. RESULTS: a total of 2,173 patients were included; 58% had new ICD implants for primary prevention, 25% for secondary prevention, and 17% had pulse generator replacement. DT was carried out at the time of ICD implantation or predischarge in 65%, 67%, and 24% of primary, secondary, and replacement cases respectively (P = <0.0001). The multivariate predictors of a decision to conduct DT included: new ICD implant (OR = 13.9, P < 0.0001), dilated cardiomyopathy (OR = 1.8, P < 0.0001), amiodarone use (OR = 1.5, P = 0.004), and LVEF > 20% (OR = 1.3, P = 0.05). A history of atrial fibrillation (OR = 0.58, P = 0.0001) or oral anticoagulant use (OR = 0.75, P = 0.03) was associated with a lower likelihood of having DT. Age, gender, NYHA class, and history of stroke or TIA did not predict DT. Perioperative complications, including death, myocardial infarction, stroke, tamponade, pneumothorax, heart failure, infection, wound hematoma, and lead dislodgement, were similar among patients with (8.7%) and without (8.3%) DT (P = 0.7) CONCLUSIONS: DT is performed in two-thirds of new ICD implants but only one-quarter of ICD replacements. Physicians favored performance of DT in patients who are at lower risk of DT-related complications and in those receiving amiodarone. DT was not associated with an increased risk of perioperative complications.

Identification of patients most likely to benefit from implantable cardioverter-defibrillator therapy: the Canadian Implantable Defibrillator Study.

BACKGROUND: Patients with resuscitated ventricular tachyarrhythmias (ventricular tachycardia/ventricular fibrillation) benefit from implantable cardioverter-defibrillators (ICDs) compared with medical therapy. We hypothesized that the patients who benefit most from an ICD are those at greatest risk of death. METHODS AND RESULTS: In the Canadian Implantable Defibrillator Study (CIDS), 659 patients with resuscitated ventricular tachyarrhythmias were randomly assigned to receive an ICD or amiodarone and were then followed for a mean of 3 years. There were 98 and 83 deaths in the amiodarone and ICD groups, respectively. We used multivariate Cox analysis to assess the impact of baseline parameters on the mortality in the amiodarone group. Reduced left ventricular ejection fraction, advanced age, and poor NYHA status identified high-risk patients (P=0.0001 to 0.0009). Quartiles of risk were constructed, and the mortality reduction associated with ICD treatment in each quartile was assessed. There was a significant interaction between risk quartile and the ICD treatment effect (P=0.011). In the highest risk quartile, there was a 50% relative risk reduction (95% CI 21% to 68%) of death in the ICD group, whereas in the 3 lower quartiles, there was no benefit. Patients who are most likely to benefit from an ICD can be identified with a simple risk score (>/=2 of the following factors: age >/=70 years, left ventricular ejection fraction /=2 risk factors. CONCLUSIONS: In CIDS, patients at highest risk of death benefited most from ICD therapy. These can be identified easily on the basis of age, poor ventricular function, and poor functional status.

Randomized assessment of syncope trial: conventional diagnostic testing versus a prolonged monitoring strategy.

BACKGROUND: Establishing a diagnosis in patients with unexplained syncope is complicated by infrequent and unpredictable events. Prolonged monitoring may be an alternative strategy to conventional testing with short-term monitoring and provocative tilt and electrophysiological testing. METHODS AND RESULTS: Sixty patients (aged 66+/-14 years, 33 male) with unexplained syncope were randomized to "conventional" testing with an external loop recorder and tilt and electrophysiological testing or to prolonged monitoring with an implantable loop recorder with 1 year of monitoring. If patients remained undiagnosed after their assigned strategy, they were offered crossover to the alternate strategy. A diagnosis was obtained in 14 of 27 patients randomized to prolonged monitoring compared with 6 of 30 patients undergoing conventional testing (52% versus 20%, P=0.012). Crossover was associated with a diagnosis in 1 of 6 patients undergoing conventional testing compared with 8 of 13 patients who completed monitoring (17% versus 62%, P=0.069). Overall, prolonged monitoring was more likely to result in a diagnosis than was conventional testing (55% versus 19%, P=0.0014). Bradycardia was detected in 14 patients undergoing monitoring compared with 3 patients undergoing conventional testing (40% versus 8%, P=0.005). CONCLUSIONS: A prolonged monitoring strategy is more likely to provide a diagnosis than conventional testing in patients with unexplained syncope. Consideration should be given to earlier implementation of a monitoring strategy.

Cryothermal ablation of the slow pathway for the elimination of atrioventricular nodal reentrant tachycardia.

BACKGROUND: We report the first successful slow pathway ablation using a novel catheter-based cryothermal technology for the elimination of atrioventricular nodal reentrant tachycardia (AVNRT). METHODS AND RESULTS: Eighteen patients with typical AVNRT underwent cryoablation. Reversible loss of slow pathway (SP) conduction during cryothermy (ice mapping) was demonstrated in 11 of 12 patients. Because of time constraints, only 2 sites were ice mapped in 1 patient. Seventeen of 18 patients had successful cryoablation of the SP. One patient had successful ice mapping of the SP, but inability to cool beyond -38 degrees C prevented successful cryoablation. A single radiofrequency lesion at this site eliminated SP conduction. No patient has had recurrent AVNRT over 4.9+/-1.7 months of follow-up. During cryoablation, accelerated junctional tachycardia was not seen and was therefore not available to guide lesion delivery. Adherence of the catheter tip during cryothermy (cryoadherence) allowed atrial pacing to test for SP conduction. Cryoablation in the anterior septum produced inadvertent transient PR prolongation consistent with loss of fast pathway conduction in 1 patient and transient (6.5 seconds) 2:1 AV block in another. On rewarming, the PR interval returned to normal, and the AV nodal effective refractory period was unchanged in both. Accelerated junctional tachycardia was seen on rewarming in both but not during cryothermy. CONCLUSIONS: Cryothermal ablation of the SP was achieved in patients with this novel technique. Successful ice mapping of both the SP and fast pathway was demonstrated. The ability to test the functionality of specific ablation sites before production of a permanent lesion may eliminate inadvertent AV block.

Progression to chronic atrial fibrillation after pacing: the Canadian Trial of Physiologic Pacing. CTOPP Investigators.

OBJECTIVES: This study examined the effect of physiologic pacing on the development of chronic atrial fibrillation (CAF) in the Canadian Trial Of Physiologic Pacing (CTOPP). BACKGROUND: The role of physiologic pacing to prevent CAF remains unclear. Small randomized studies have suggested a benefit for patients with sick sinus syndrome. No data from a large randomized trial are available. METHODS: The CTOPP randomized patients undergoing first pacemaker implant to ventricular-based or physiologic pacing (AAI or DDD). Patients who were prospectively found to have persistent atrial fibrillation (AF) lasting greater than or equal to one week were defined as having CAF. Kaplan-Meier plots for the development of CAF were compared by log-rank test. The effect of baseline variables on the benefit of physiologic pacing was evaluated by Cox proportional hazards modeling. RESULTS: Physiologic pacing reduced the development of CAF by 27.1%, from 3.84% per year to 2.8% per year (p = 0.016). Three clinical factors predicted the development of CAF: age > or =74 years (p = 0.057), sinoatrial (SA) node disease (p < 0.001) and prior AF (p < 0.001). Subgroup analysis demonstrated a trend for patients with no history of myocardial infarction or coronary disease (p = 0.09) as well as apparently normal left ventricular function (p = 0.11) to derive greatest benefit. CONCLUSIONS: Physiologic pacing reduces the annual rate of development of chronic AF in patients undergoing first pacemaker implant. Age > or =74 years, SA node disease and prior AF predicted the development of CAF. Patients with structurally normal hearts appear to derive greatest benefits.

Elevated p21 mRNA level in skeletal muscle of DMD patients and mdx mice indicates either an exhausted satellite cell pool or a higher p21 expression in dystrophin-deficient cells per se.

Abnormalities in proliferation and differentiation of the dystrophin-deficient muscle are a controversial aspect of the pathogenesis of Duchenne muscular dystrophy (DMD). Analyses of molecules involved in cell cycle modulation do not exist in this context. Cells withdrawn from the cell cycle permanently express p21. The fact that p2 1, in contrast to other cell cycle proteins, is not diminished when myotubes are reexposed to growth media, allocates this cyclin-dependent kinase inhibitor a special function. Here we report for the first time statistically increased p21 mRNA levels in dystrophin-deficient muscle tissue. Only 42% of conventional RT-PCRs from six muscle samples of human controls yielded positive results but almost all skeletal muscle biopsy samples (87%) from DMD patients (n=5). For p21 mRNA quantification in murine muscle samples we were able to use the exact real-time TaqMan PCR method due to generally higher p21 mRNA levels than in human muscles. In addition, contamination with fibroblasts can be excluded for the murine samples because they do not demonstrate fibrosis at the age of 350 days but start to lose their regenerative capacity. In accord with the results in humans, we observed p21 mRNA levels in mdx mice that were approx. four times as high as those in control mice. Elevated p21 mRNA level may indicate a shift in cell composition towards differentiated p21 expressing cells as a result of an exhausted pool of undifferentiated, non-p21-expressing satellite cells due to previous cycles of de- and regeneration. Alternatively, dystrophin-deficient cells per se may express higher p21 levels for unknown reasons. Although we cannot distinguish between these possibilities, the eventual transfec tion of a patient's own satellite cells with p21 antisense oligonucleotides may enable the dystrophic process to be influenced.

How useful is thyroid function testing in patients with recent-onset atrial fibrillation? The Canadian Registry of Atrial Fibrillation Investigators.

BACKGROUND: Patients with recent-onset atrial fibrillation often undergo routine thyroid function screening to rule out thyroid disease as a cause of atrial fibrillation. METHODS: Patients with recent (< 3 months) onset of documented atrial fibrillation or flutter were enrolled in the Canadian Registry of Atrial Fibrillation from outpatient clinics, emergency departments, and hospital wards across Canada. Seven hundred twenty-six patients underwent baseline thyroid function screening and were assessed for presence of clinical thyroid disease. Serum thyrotropin level (TSH) was measured in 707 patients (97%), and thyroxine level (T4) in 407 patients (56%). RESULTS: A TSH level less than 0.1 mU/L was present in 5 patients (0.7%). A TSH level less than normal but more than 0.1 mU/L was present in 34 patients (4.7%). No patient had definite hypothyroidism (TSH > 20 mU/L), but 56 patients (7.7%) had an elevated TSH level that was less than 20 mU/L. During 1.7 years of follow-up, only 7 patients were found to have clinical hyperthyroidism, and 11 patients (1.5%) had hypothyroidism. Logistic regression analysis showed that palpitations (odds ratio, 4.9; 95% confidence interval, 1.7-14.0) and asymptomatic presentation (odds ratio, 5.5; 95% confidence interval, 1.9-16.2) were risk factors for low TSH level, and increasing age (odds ratio, 1.32 every 10 years; 95% confidence interval, 1.01-1.66) was a risk factor for high TSH level. The positive predictive value of palpitations and asymptomatic presentation for low TSH level were 9% and 8%, respectively. CONCLUSIONS: An abnormal TSH level is common in patients with recent-onset atrial fibrillation. However, clinical thyroid disease is uncommon. Routine TSH screening of patients who have atrial fibrillation has a low yield and may be better applied to those patients at higher risk of having undiagnosed clinical thyroid disease.

The natural history of atrial fibrillation: incidence, risk factors, and prognosis in the Manitoba Follow-Up Study.

PURPOSE: Atrial fibrillation is a common arrhythmia associated with increased cardiovascular morbidity and mortality. This study was undertaken to identify the natural history of this condition, including risk factors for its development, and outcome. PATIENTS AND METHODS: The incidence of atrial fibrillation among 3,983 male air crew recruits observed continuously for 44 years was calculated based on person-years of observation. Age and 23 variables were examined to identify risk factors for atrial fibrillation. Controlling for age and 9 prognostic variables, the effect of atrial fibrillation on 8 outcomes was examined. Analysis of risk factors for atrial fibrillation and outcome after atrial fibrillation was based on a Cox proportional hazard model using time-dependent covariates. RESULTS: Of the 3,983 study members, 299 (7.5%) developed atrial fibrillation during 154,131 person-years of observation. The incidence rose with age from less than 0.5 per 1,000 person-years before age 50 to 9.7 per 1,000 person-years after age 70. Risk for atrial fibrillation was increased with myocardial infarction (relative risk [RR] 3.62), angina (RR 2.84), and ST-T wave abnormalities in the absence of ischemic heart disease (RR 2.21). The RR for atrial fibrillation was strongest at the onset of ischemic heart disease and diminished over time. The rate of atrial fibrillation was 1.42 times increased in men with a history of hypertension. Congestive heart failure, valvular heart disease, and cardiomyopathy were important but uncommon risk factors. Atrial fibrillation independently increased the risk for stroke (RR 2.07) and congestive heart failure (RR 2.98). Total mortality rate was increased 1.31 times; cardiovascular mortality including and excluding fatal stroke were also increased (RR 1.41 and 1.37, respectively). CONCLUSIONS: The incidence of atrial fibrillation in men increases with advancing age. Clinical cardiac abnormalities, particularly recent ischemic heart disease and hypertension, are strongly associated with increased risk for atrial fibrillation. Atrial fibrillation increases morbidity and mortality, but the magnitude of the increase may be less than previously reported.

Final results from a pilot study with an implantable loop recorder to determine the etiology of syncope in patients with negative noninvasive and invasive testing.

Twenty-four patients with recurrent unexplained syncope and negative tilt and electrophysiologic testing underwent implantation of the implantable loop recorder, with recurrence of syncope in 21 patients 5.1+/-4.8 months after device implantation. Eighteen of the 21 had a treatable diagnosis, with arrhythmias in 11. Treatment resulted in resolution of syncope in most patients during long-term follow-up.

Safety of slow pathway ablation in patients with atrioventricular node reentrant tachycardia and a long fast pathway effective refractory period.

Radiofrequency catheter ablation is an accepted primary therapy for atrioventricular (AV) node reentrant tachycardia (AVNRT). There is concern that slow pathway ablation in patients with a long anterograde fast pathway effective refractory period (ERP) may potentially impair subsequent node conduction. Eighteen patients (14 women; age 53 +/- 20 years) with symptomatic AVNRT, whose fast pathway ERP at baseline was > or = 500 ms, underwent slow pathway ablation. Their outcome was compared with 24 consecutive control patients (17 women; age 42 +/- 17 years) who underwent ablation for AVNRT whose fast pathway ERP at baseline was <500 ms (controls). Slow pathway ablation was successful in 16 patients (90%). One patient had inadvertent fast pathway ablation. In a second patient the slow pathway could not be ablated because of recurrent transient AV block. Ablation was successful in all patients in the control group. Transient AV block related to current application occurred in 4 patients (22%) versus 1 control (4%) (p = 0.07). After ablation, the AV node refractory period increased in patients (368 +/- 68 to 428 +/- 92 ms, p = 0.02) and in controls (282 +/- 35 to 336 +/- 55 ms, p <0.0001), but the fast pathway ERP shortened in both groups (patients: 558 +/- 63 to 428 +/- 92 ms, p = 0.003; controls: 356 +/- 53 to 336 +/- 55 ms, p = 0.05). Furthermore, the slope of the regression line relating to shortening of the fast pathway ERP to the baseline ERP was markedly steeper in patients compared with controls (1.9 vs 0.4, p <0.0001). The shortening of the fast pathway ERP was greater in patients compared with controls (122 +/- 130 vs 21 +/- 50 ms, p = 0.001). During a mean follow-up of 18 +/- 11 months, 1 patient with severe coronary artery disease died suddenly 2 years after ablation. There was no recurrence of clinical tachycardia, and none of the patients developed symptoms of bradycardia or required permanent pacing. Thus, slow pathway ablation in patients with AVNRT and a long fast pathway ERP is safe and effective.

Supraventricular tachycardia.

Supraventricular tachycardias (SVT) comprise those tachycardias that originate above the bifurcation of the bundle of His. They can be classified broadly as AV node dependent and AV node independent. The mechanism and clinical manifestation of SVTs, which is essential to their correct diagnosis, is reviewed. The therapeutic management of SVTs, including acute and chronic drug therapy and catheter ablation, is discussed also.

Recurrent syncope. Experience with an implantable loop recorder.

The cause of recurrent syncope is often difficult to determine when initial laboratory investigations are negative. Advances in implantable monitoring technology permit long-term monitoring of the electrocardiogram in patients with recurrent undiagnosed syncope. A pilot device implanted in the left pectoral region established the cardiac rhythm during syncope in all 20 of 24 patients who developed syncope during follow-up. The cause was arrhythmic in 10 and nonarrhythmic in 10. Therapy resulted in resolution of symptoms in 17 of 20 patients. The implantable loop recorder is a promising diagnostic tool for investigation of syncope.

Current role of pharmacologic therapy for patients with paroxysmal supraventricular tachycardia.

Intravenous antiarrhythmic drugs will continue to have an important role in the acute management of SVT. Long-term antiarrhythmic drug therapy is often effective in preventing or reducing frequency and severity of arrhythmic episodes. The cost, adverse effects, and inconvenience of long-term drug therapy will result in the increasing use of curative ablation for most individuals with problematic SVT.

Recurrent seizure diagnosed by the insertable loop recorder.

INTRODUCTION: The Insertable Loop Recorder (ILR) has emerged as an important new tool in the diagnostic armamentarium for patients with syncope. METHODS AND RESULTS: A case report illustrates how the ILR unexpectedly led to the diagnosis of seizure as the explanation for a man's recurrent, but infrequent episodes of sudden loss of consciousness. CONCLUSIONS: This case raises the possibility that the development of implantable recording devices which monitor physiologic parameters other than cardiac rhythm (eg. brain, nerve or muscle activity) may provide the long-term monitoring capability needed to improve the diagnostic yield for conditions, such as seizures, which occur infrequently.

Dynamic left ventricular outflow tract obstruction due to concentric left ventricular hypertrophy: effect of pacing with a short AV interval.

Dual chamber pacing with a short atrioventricular (AV) interval has emerged as a novel therapeutic approach in dynamic left ventricular outflow tract obstruction. A morbidly obese 65-year-old man with previous borderline hypertension and documented normal coronary arteries and concentric left ventricular hypertrophy who underwent uneventful elective hip replacement is reported. Eight hours postoperatively the patient developed junctional tachycardiac and hypotension. Echocardiogram revealed concentric left ventricular hypertrophy with dynamic left ventricular outflow tract obstruction and peak gradient of 262 mmHg. The patient improved with intravenous fluid replacement. The gradient fell to 112 mmHg 14 days later. Twelve days later the patient developed symptomatic sinus pauses and a dual chamber pacemaker was implanted. After testing various AV intervals, the lowest gradient of 138 mmHg was associated with an AV interval of 100 ms. One year later the gradient was 37 mmHg at the same AV interval, with a higher gradient at shorter and longer AV intervals. Dual chamber pacing with a short AV interval has been associated with improvement in hypertrophic obstructive cardiomyopathy. This case suggests the benefit of this therapy may extend to acquired forms of dynamic left ventricular outflow tract obstruction such as concentric left ventricular hypertrophy.

Recurrent unexplained syncope: diagnostic and therapeutic approach.

Patients with syncope of unknown etiology may suffer from recurrent disability. Syncopal episodes are often too infrequent and unpredictable for detection with conventional ambulatory monitoring techniques. A symptom-rhythm correlation is a frequently unattainable gold standard in many patients. Clinicians must often rely on the results of laboratory testing to make an inferential determination of the etiology of spontaneous syncope. Electrophysiological testing has a role in patients with structural heart disease and suspected ventricular arrhythmias, but is negative in 14% to 70% of patients studied and has a limited role in patients without structural heart disease. The external loop recorder is an ambulatory device worn for weeks or even months that freezes the preceding rhythm strip after an episode of spontaneous syncope. This device is useful in patients with frequent symptoms but is hampered by lack of patient compliance and technical limitations. In the absence of a diagnosis after extensive testing, an empirical trial based on index of suspicion may be warranted. This may include implantation of a pacemaker for suspected bradycardia or empirical therapy directed at a tachycardia. Finally, recent reports of an insertable loop recorder suggest a high diagnostic yield with a broad spectrum of etiologies in patients with recurrent syncope in spite of negative noninvasive and electrophysiological testing. In the future, such a device may assume a prominent role in the investigation of syncope.

Time-dependent change in fast pathway refractoriness after slow pathway ablation in atrioventricular node reentrant tachycardia. Mansfield Polaris Investigators.

OBJECTIVE: To determine the time course of change in fast pathway refractoriness after slow pathway ablation. BACKGROUND: Antegrade fast pathway refractoriness has been observed to shorten in patients undergoing slow pathway ablation for atrioventricular (AV) node reentrant tachycardia. The time course and mechanism of this observation have not been explained. METHODS: Twenty-eight patients with AV node reentrant tachycardia and dual AV node pathways undergoing slow pathway ablation had the fast pathway effective refractory period (ERP) assessed immediately before, and at 0, 15, 30 and 45 mins after slow pathway ablation (Group 1). Twenty-five additional patients with AV node reentry and dual pathways involved in a multicentre protocol evaluating the Mansfield Polaris LE catheter underwent assessment of fast pathway refractoriness before and after slow pathway ablation, and at a routine three-month follow-up electrophysiology study (Group 2). RESULTS: In Group 1, antegrade fast pathway ERP fell from 394 ms before ablation to 334 ms immediately after slow pathway ablation, increased to 348 ms within 15 mins and was 353 ms at 45 mins (ANOVA P < 0.001). Retrograde fast pathway ERP fell from 325 ms before ablation to 294 ms at 45 mins (P = 0.02). In Group 2, antegrade fast pathway ERP fell from 390 ms before ablation to 337 ms after ablation, and rose to 362 ms at three months (P = 0.01). Retrograde fast pathway ERP also fell from 347 ms to 319 ms after ablation (P = 0.01), and remained unchanged at three months. CONCLUSION: Slow pathway ablation results in an immediate and sustained change in antegrade and retrograde first pathway refractoriness. There are immediate reversible and long term nonreversible components to this phenomenon. The latter finding may be related to loss of electrotonic inhibition of the fast pathway by the slow pathway.