Biomedical subjects
Publications and source records attributed to Francis E Marchlinski.
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INTRODUCTION: Radiofrequency catheter ablation can effectively treat patients with refractory atrial fibrillation (AF). Very late AF recurrence (> or = 12 months post-ablation) is uncommon and may represent a unique patient cohort. METHODS AND RESULTS: A nested case-control study was performed in the cohort who underwent AF ablation at the University of Pennsylvania to characterize patients who develop very late AF recurrence after ablation. The procedure consisted of isolation of pulmonary veins (PVs) demonstrating triggers and elimination of non-PV triggers initiating AF. Twenty-seven (7.9%) patients with very late recurrence were compared to 219 patients without recurrence and > or = 12 months of follow-up. The mean age was 54.6 +/- 11.3 years and 79% were men. Very late recurrence patients more likely weighed >200 lbs (70% vs 55%, P = 0.01); during initial ablation had fewer PVs isolated (2.8 +/- 1.1 vs 3.3 +/- 1.0, P = 0.03); and were less likely to have right inferior PV isolation (37% vs 61%, P = 0.02), less likely to have isolation of all PVs (30% vs 56%, P = 0.01), and more likely to have non-PV triggers (30% vs 11% OR 3.4(95% CI, 1.3-8.7), P = 0.01). PV reconnectivity and new triggers were found in the majority of patients with very late recurrence of AF who underwent repeat ablation. CONCLUSION: Very late recurrence of AF more likely occurred in patients >200 lbs who demonstrated non-PV triggers and did not undergo right inferior PV isolation. The majority of patients undergoing repeat ablation for very late recurrence demonstrated PV reconnectivity and new non-PV and PV triggers not observed during the initial ablation.
BACKGROUND: Evaluation of ventricular rate control in atrial fibrillation (AF) can be difficult, and the presence of an AF-induced ventricular cardiomyopathy due to intermittent poor rate control or other causes may be underestimated. The outcome with AF ablation in patients with a decreased left ventricular ejection fraction (LVEF) may provide insight into this important clinical issue. OBJECTIVE: To determine the effect of pulmonary vein isolation on LVEF in patients with AF and decreased LVEF (< or = 50%). METHODS: Ablation consisted of proximal isolation of arrhythmogenic pulmonary veins (PVs) and elimination of non-PV triggers. LVEF was determined within 24 hours after ablation and again at up to 6 months follow-up. Transtelephonic monitoring was performed routinely for 2-3 weeks prior to ablation, at 6 weeks, and 6 months post and with symptoms following ablation. AF control was defined as freedom from AF or marked (>90%) reduction in AF burden on or off previously ineffective antiarrhythmic medication. RESULTS: AF ablation was performed in 366 patients and 67 (18%) patients had decreased LV function with a mean LVEF of 42 +/- 9%. An average of 3.4 +/- 0.9 PVs were isolated. AF control in the depressed LVEF group compared favorably with the normal EF group (86% vs. 87% P = NS), although more redo procedures were required (1.6 +/- 0.8 vs 1.3 +/- 0.6 procedures; P < or = 0.05). Only 15 of 67 patients (22%) with decreased LVEF had shown tachycardia (>100 bpm) on repeated preablation ECG recordings during AF. In the decreased LVEF group, the LVEF increased from 42 +/- 9% to 56 +/- 8% (P < 0.001) after ablation. CONCLUSIONS: Patients with AF and decreased LVEF undergoing AF ablation have similar success to patients with normal LVEF and have improvement in LVEF after ablation. These results suggest the presence of a reversible AF-induced ventricular cardiomyopathy in many patients with AF and depressed LV function. The presence of under-recognized and reversible cardiomyopathy even when tachycardia is not persistent is important to recognize.
BACKGROUND: Catheter ablation procedures for treating atrial fibrillation (AF) have dramatically increased since triggers of AF were first described in 1998. OBJECTIVE: We explored changes in patient characteristics in patients referred for catheter ablation of AF over a seven-year period from 1999 through 2005. METHODS: Patient characteristics were examined for all patients undergoing AF ablation from 1999 through 2005 at the University of Pennsylvania Health System (UPHS). The gender of patients undergoing ablation was also compared with outpatients seen at UPHS with a primary diagnosis of AF. RESULTS: From 1999 to 2005 the number of patients undergoing ablation has increased steadily, from 29 patients in 1999 to 265 patients in 2005 (P < 0.01). Patients have become older (47 to 56 years; P < 0.01), with more persistent or permanent AF (17% to 45%; P < 0.01), larger left atrial size (4.0 to 4.4 cm; P < 0.01), and fewer antiarrhythmic drugs used prior to ablation (3.9 to 2.0 drugs; P < 0.01). Patients undergoing ablation have been predominantly male, with a significantly higher male prevalence than patients seen in the UPHS outpatient primary care clinic with AF (77% vs 59% male; P < 0.001). CONCLUSIONS: Patients undergoing AF ablation from 1999 to 2005 are older, with larger left atrial size, more persistent/permanent AF, and fewer prior antiarrhythmic agents used. Compared with the gender-specific rates of AF in the population, the majority of patients referred for ablation are men, suggesting a referral bias against this invasive procedure for women. These findings are important for interpreting the outcome of ablation in the current era, and for designing prospective randomized trials.
OBJECTIVE: To compare safety and efficacy of 8-mm versus cooled tip catheter in achieving electrical isolation (EI) of pulmonary veins (PV) for long-term control of atrial fibrillation (AF). BACKGROUND: There is paucity of studies comparing safety/efficacy of 8-mm and cooled tip catheters in patients undergoing AF ablation. METHODS AND RESULTS: This was a randomized and patient-blinded study. Subjects were followed by clinic visits (at 6 weeks and 6 months) and transtelephonic monitoring (3-week duration) done around each visit. Primary endpoints were: (1) long-term AF control (complete freedom and/or >90% reduction in AF burden on or off antiarrhythmic drugs at 6 months after a single ablation), and (2) occurrence of serious adverse events (cardiac tamponade, stroke, LA-esophageal fistula, and/or death). Eighty-two patients (age 56 +/- 9 years, 60 males, paroxysmal AF = 59) were randomized (42 patients to 8-mm tip and 40 patients to cooled tip). EI of PVs was achieved in shorter time by the 8-mm tip as compared with cooled tip catheter (40 +/- 23 minutes vs 50 +/- 30 minutes; P < 0.05) but long-term AF control was not different between the two (32 patients [78%] vs 28 patients [70%], respectively; P = NS). One serious adverse event occurred in each group (LA-esophageal fistula and stroke, respectively) and no significant PV stenosis was observed in either. CONCLUSION: EI of PVs using either 8-mm or cooled tip catheter results in long-term AF control in the majority after a single ablation procedure, with comparable efficacy and safety.
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BACKGROUND: Although the most common sites of atrial ectopy that trigger atrial fibrillation (AF) are in or around the pulmonary veins (PVs), atrioventricular nodal reentrant tachycardia (AVNRT) can also cause or coexist with AF. We sought to characterize patients with AF and AVNRT and assess clinical outcomes after ablation. METHODS AND RESULTS: To determine the prevalence of concomitant AVNRT and AF, 629 consecutive patients referred for catheter ablation between November 1998 and March 2005 were studied. Electrophysiological studies with programmed stimulation during isoproterenol infusion identified atrial ectopy that initiated AF and the presence of inducible AVNRT. AF ablation consisted of proximal isolation of PVs and elimination of any non-PV trigger of AF, including AVNRT. There were 27 patients (4.3%) who had inducible AVNRT at the time of AF ablation. Of these, 13 underwent AVNRT ablation without PV isolation. Compared with the rest of the cohort, patients with AVNRT and AF were younger at the time of symptom onset (age 36.8+/-13.8 versus 48.2+/-11.7 years; P<0.01). Freedom from AF with or without previously ineffective antiarrhythmic medication was similar in both groups (96.3% versus 90.7%; mean follow-up 21.4+/-9.4 months); however, patients with AVNRT targeted for ablation were more likely to be AF free while not taking any antiarrhythmic medication after a single procedure during the follow-up period (87.5% versus 54.7%; P<0.01) and had fewer complications (0% versus 2.5%; P=0.30). Twelve of the 13 patients who underwent slow-pathway ablation without left atrial ablation remained AF free without the need for antiarrhythmic medication after a single procedure. CONCLUSIONS: AVNRT is an uncommon AF trigger seen more frequently in younger patients. Ablation of AVNRT in patients with AF was associated with improved outcomes compared with those with other triggers of AF.
BACKGROUND: Usefulness of 12-lead ECG for predicting an epicardial origin for ventricular tachycardia (VT) arising from the right ventricle (RV) has not been assessed. An epicardial approach is sometimes warranted to eliminate RV VT. OBJECTIVES: The purpose of this study was investigate the hypothesis that specific ECG features identify an epicardial origin for RV VT. METHODS: To mimic an endocardial or epicardial origin, we paced representative sites in 13 patients undergoing RV endocardial/epicardial mapping (134/180 pace map sites). RESULTS: QRS duration from epicardial vs endocardial sites was not different (183 +/- 27 ms vs 185 +/- 28 ms, P = .3). Reported cut-off values for identifying epicardial left ventricular origin, pseudo-delta wave (> or =34 ms), intrinsicoid deflection time (> or =85 ms), and RS complex (> or =121 ms) did not apply to the RV. A Q wave in lead II, III, or aVF was more likely noted from inferior epicardial vs endocardial sites (53/73 vs 16/43, P <.01). A Q wave in lead I was more frequently present from epicardial vs endocardial anterior RV sites (30/82 vs 5/52, P <.001). QS in lead V(2) was noted from anatomically matched epicardial anterior RV sites (22/33 vs 13/33, P <.05). In the RV outflow tract, no ECG feature distinguishing epicardial/endocardial origin reached statistical significance. CONCLUSION: A Q wave or QS in leads that best reflect local activation suggest an epicardial origin for RV depolarization and may help in identifying a probable epicardial site of origin for RV VT. QRS duration and reported criteria for epicardial origin of VT in the left ventricle do not identify a probable epicardial origin in the RV.
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BACKGROUND: The biventricular implantable cardioverter-defibrillator (ICD) is an important therapy for select patients with severe heart failure. Given reported risk factors for elevated defibrillation thresholds (DFTs), patients undergoing biventricular ICD placement would be suspected of having a higher incidence of elevated DFT. OBJECTIVES: The purpose of this study was to examine the clinical predictors and mortality risk of elevated DFTs in patients receiving a biventricular ICD. METHODS: Characteristics of patients undergoing biventricular ICD placement with an elevated DFT were compared to those without an elevated DFT. RESULTS: An elevated DFT was found in 14 (12%) of 121 patients. Mean QRS duration was 210 +/- 50 ms in the elevated DFT group and 171 +/- 36 ms in the normal DFT group (P = .01). Patients with a QRS duration >or=200 ms were more likely to have an elevated DFT than those with a duration <200 ms (odds ratio 13.4, 95% confidence interval 3.1-66.7, P <.01). No other clinical characteristics were associated with an elevated DFT. More than 90% of patients with an elevated DFT achieved an adequate safety margin through system modification or manipulation of their drug regimen. An elevated DFT did not have an impact on 2-year mortality. CONCLUSION: Patients with a biventricular ICD had a 12% incidence of elevated DFT in our sequential patient cohort. QRS duration prior to biventricular ICD placement is the most powerful predictor of patients at risk for an elevated DFT. An elevated DFT does not have an impact on mortality, perhaps because of successful implementation of system modifications to ensure an adequate defibrillation safety margin.
BACKGROUND: Part of the esophagus is contiguous to the posterior wall (PW) of the left atrium (LA). Esophageal injury has occurred during LA ablation for atrial fibrillation (AF). The ability to identify the esophagus and monitor LAPW lesions with intracardiac echocardiography (ICE) has not been documented. METHODS: We report an index case of atrioesphageal fistula as a complication of transcatheter ablation of AF. After the index case, we retrospectively reviewed morphologic changes with radiofrequency (RF) delivered at LAPW during pulmonary vein (PV) electrical isolation using an 8-mm tip electrode (up to 70 W at a maximum of 50-52 degrees C for 60 seconds) or Chilli catheter (up to 50 W at a maximum of 40 degrees C for 60 seconds). ICE did not influence lesion application. After the index case, RF power was reduced at areas adjacent to the esophagus (8 mm/30-50 W at 50 degrees C or Chilli/40 W at a maximum of 38 degrees C). Duration of RF, 10-30 seconds, was titrated based on accelerated bubble formation or early echogenic lesion formation. RESULTS: The longitudinal extent of the contiguous LAPW-esophageal wall (length 18-59 mm) was identified in all 152 patients (ages 56 +/- 10 years, 117 men). Preablation LAPW (2.8 +/- 0.7 mm) and contiguous anterior esophageal wall (3.0 +/- 0.8 mm) thickness were noted. A total of 6 +/- 4.9 lesions/patient were delivered to the LAPW contiguous to the esophagus. Echogenic LAPW thickness increased to 7.5 +/- 2.1 mm (vs. 2.8 +/- 0.5 mm preablation) before the index case (n = 70 patients) and 4.7 +/- 1.6 mm (vs. 2.9 +/- 0.6 mm) after the index case (n = 67), with power reduction and titration of duration of energy delivery RF (P <.01) and PV isolation in all. CONCLUSIONS: The LAPW-esophageal region can be identified and monitored with ICE imaging during ablation procedures. RF lesions to the LAPW in PV isolation can produce dramatic morphologic changes immediately adjacent to the anterior esophageal wall. A reduction in power amount and duration as described coupled with online lesion monitoring to further titrate duration (<30 seconds) of power delivery decreases the depth of lesion formation and limits the risk of esophageal involvement.
Cardiac tamponade as a late complication of device placement is exceedingly rare, with only several case reports previously published. We sought to characterize our institution's experience with cardiac tamponade occurring >30 days after permanent pacemaker or implantable cardioverter-defibrillator placement. From January 2000 to June 2003, 2,535 patients received an implantable cardiac device at our institution. Four patients (0.17%) presented with cardiac tamponade>30 days after the procedure. A fifth patient who had undergone implantation at another institution but was referred to our group with tamponade was also included in the analysis. The baseline characteristics varied widely with respect to age, gender, device type, and anticoagulation status. Lead parameters were altered in 2 of 5 patients. Two patients were treated with pericardiocentesis, 1 patient had pericardiocentesis followed by lead extraction, and 2 patients required cardiac surgical intervention. Pericardial fluid culture and cytologic findings were negative in all patients. All patients had normal recovery and were well at a mean follow-up of 31 months. In conclusion, cardiac tamponade is a rare, but serious late complication of permanent pacemaker and implantable cardioverter-defibrillator placement. The patient characteristics and mode of presentation vary widely. Once tamponade is recognized and treated, these patients appear well at long-term follow-up, with no other device-related problems. A role for lead manipulation does not appear to exist in the standard treatment of these patients.
BACKGROUND: Pulmonary vein electrical isolation (PVI) is an effective treatment for atrial fibrillation (AF). However, recurrence of pulmonary vein (PV) conduction after ablation may limit long-term success. OBJECTIVE: We sought to determine the clinical predictors of acute PV reconnection during PVI and assess the long-term clinical outcomes associated with this phenomenon. METHODS: We studied all patients with AF referred for PVI between November 2000 and August 2004. Over the course of the study period, PVI of arrhythmogenic PVs was performed segmentally using a 4-mm tip (52 degrees , 40 W, up to 90 seconds) or 8-mm tip catheter (50 degrees , 70 W, up to 60 seconds). PVI was defined as entry and exit block using a multipolar Lasso catheter. All veins were resampled to confirm isolation after 20-60 minutes. AF control was defined as no AF on or off a previously ineffective antiarrhythmic drug. Follow-up data included transtelephonic monitoring and clinical data collection from patient interviews. RESULTS: There were 424 patients who underwent isolation of 1,347 PVs during the study period. Acute reconnection of at least one PV occurred in 211 (50%) of the 424 patients and 326 (24%) of 1,347 of the PVs targeted. The left superior PV was most likely to acutely recover conduction compared with the other veins (left superior 31%, right superior 26%, right inferior 22%, left inferior 24%; P = .03). Patients with acute reconnection were more likely to be older, have a larger left atrium, have a history of hypertension or obstructive sleep apnea, and demonstrate persistent AF. After a single procedure, AF control was achieved in 153 (70%) of the 213 patients who demonstrated acute PV reconnection compared with 148 (73%) of 211 patients without acute PV reconnection observed (P = .52). CONCLUSIONS: Acute return of PV conduction is common after successful PVI and is more likely to occur in older patients with nonparoxysmal AF, hypertension, a large left atrium, and sleep apnea. There was no significant difference in acute PV reconnection between the 4-mm and 8-mm tip RF catheter despite differences in power and duration of energy delivery. Furthermore, there was no effect of PV reconnection on long-term AF control after repeated disconnection was performed.
BACKGROUND: We previously demonstrated the existence of a left-to-right atrial dominant frequency gradient during paroxysmal but not persistent atrial fibrillation (AF) in humans. One possible mechanism of the left-to-right dominant frequency gradient involves the role of the pulmonary veins (PVs) in AF maintenance. OBJECTIVES: The purpose of this study was to examine the effect of PV isolation on the dominant frequency gradient and outcome after PV isolation. METHODS: Patients with either paroxysmal or persistent AF were studied. Recordings were made from catheters in the coronary sinus (CS), posterior right atrium (RA), and posterior left atrium (LA) during AF before and after PV isolation. Mean left-to-right dominant frequency gradient was measured before and after segmental PV isolation. Patients were followed for AF recurrence after PV isolation. RESULTS: Twenty-seven patients with paroxysmal (n = 15) or persistent (n = 12) AF were studied. In the paroxysmal group, baseline dominant frequency was greatest in the posterior LA with a significant left-to-right atrial dominant frequency gradient (posterior LA = 6.2 +/- 0.9 Hz, CS = 5.8 +/- 0.8 Hz, posterior RA = 5.4 +/- 0.9 Hz; P <.001). After PV isolation, there was no regional difference in dominant frequency (5.9 +/- 0.7 Hz vs 5.7 +/- 0.6 Hz vs 5.7 +/- 0.7 Hz, respectively; P = NS). In the persistent AF group, there was no overall difference in dominant frequency among sites before or after PV isolation (P = NS); however, patients with long-term freedom from AF after PV isolation had a higher left-to-right dominant frequency gradient compared with patients with recurrent AF (0.4 vs 0.1 Hz; P <.05). CONCLUSION: PV isolation results in a loss in the left-to-right dominant frequency gradient in patients with paroxysmal AF. This finding supports the critical role of PVs in the maintenance of ongoing paroxysmal AF. Patients with persistent AF and a baseline left-to-right dominant frequency gradient have a better success rate with PV isolation alone compared with patients without a dominant frequency gradient.
Clinical events committees (CECs) are the current standard for endpoint adjudication in clinical trials. However, little data exist with which to compare CEC and site investigator determinations or to evaluate internal agreement among CEC members. Using data from the Mode Selection Trial in Sinus Node Dysfunction (MOST), we analyzed classifications of death in order to compare internal agreement among CEC physician reviewers and agreement between the CEC and site investigators. Death was classified at 2 levels: by major cause (cardiac, noncardiac, or unknown) and by minor subclassification of the major classifications. Reviewer agreement was tabulated at the major and minor levels, and standard and weighted kappa statistics were calculated. Disagreement at both levels was also determined. Individual decision-making was tabulated in terms of frequency in classifying death as unknown. All 404 deaths were classified by the CEC. Site investigators determined major classifications in 382 cases and minor classification in 379 cases. The CEC and the site investigators disagreed in classifying 41 cases (10.7%) at the major level and 117 (30.9%) at the minor level. CEC reviewers disagreed internally at the major level in 64 cases (15.8%), at the minor level in 63 cases (15.6%), and at any level in 127 cases (31.4%) (kappa = 0.60, 95% confidence interval (CI) [0.55, 0.66]; weighted kappa = 0.66, 95% CI [0.62, 0.75]). In resolving internal disagreements, the full CEC agreed with 1 of 2 CEC reviewers in 85.9% of cases. Disagreements occurred between site investigators and CEC reviewers in classifying deaths. Endpoint determination and decision-making varied among individual CEC reviewers, but second-tier reviews by the full CEC resolved all disagreements. These findings support continued use of CECs for endpoint adjudication in clinical trials.
BACKGROUND: Detailed anatomic characterization of endocardial substrate of ventricular tachycardia (VT) is limited. OBJECTIVES: The purpose of this study was to determine the endocardial dimensions and local electrogram voltage characteristics of the reentrant circuit. VT-related conducting channels corresponding to zones of slow conduction may be identified. METHODS: Electroanatomic mapping was performed in 26 patients with uniform VT. Entrainment mapping was performed in 53 VTs, of which 19 entrance, 37 isthmus, 48 exit, and 32 outer loop sites were identified. The color display of voltage maps was adjusted to identify conducting channels associated with VT circuits. A conducting channel was defined as a path of multiple orthodromically activated sites within the VT circuit that demonstrated an electrogram amplitude higher than that of surrounding areas as evidenced by voltage color differences. RESULTS: Forty-seven (84%) of 56 entrance or isthmus sites were located within dense scar (<0.5 mV). Nearly all exits (92%) were located in abnormal endocardium (<1.5 mV), with more than half (54%) located in the border zone (0.5-1.5 mV). VT-related conducting channels was identified in 18 of 32 VTs with detailed mapping (average length 32 +/- 22 mm). The voltage threshold in the conducting channels ranges from 0.1 to 0.7 mV (mean 0.33 +/- 0.15 mV). CONCLUSION: (1) Most entrance and isthmus sites of hemodynamically stable VT are located in dense scar, whereas exits are located in the border zone. (2) VT-related conducting channels may be identified by careful voltage threshold adjustment. These findings have important implications regarding strategies for substrate-based VT ablation.
BACKGROUND: Atrial fibrillation (AF) ablation procedures typically involve isolation of all pulmonary veins (PVs) in addition to adjunctive linear lesions, yet the need for such an extensive ablation strategy in all patients is unclear. OBJECTIVES: The purpose of this study was to identify a subgroup of patients undergoing AF ablation with good clinical success after limited PV isolation. METHODS: Patients (N = 450) underwent trigger-guided segmental isolation of only arrhythmogenic PVs. We compared clinical characteristics of patients who required isolation of only one or two PVs to those in whom AF ablation required isolating > or = 3 PVs. RESULTS: For the group of patients undergoing isolation of < or = 2 PVs, AF freedom without antiarrhythmic drug use was achieved in 56 (58%) of 97 patients, and AF control was achieved in 66 (68%) of 97 patients after a single procedure. After additional procedures, 77 (79%) of 97 patients achieved complete AF freedom without antiarrhythmic drugs, and 82 (85%) of 97 patients achieved AF control. Younger age (odds ratio [OR] 1.05; confidence interval [CI] 1.01,1.09) and lack of persistent AF (OR 3.27; CI 1.0, 10.7) were each independent predictors of freedom from AF. In patients younger than 50 years with paroxysmal AF undergoing isolation of < or = 2 PVs (n = 44), AF freedom without antiarrhythmic drugs was achieved in 32 (73%) of 44 after a single ablation procedure. CONCLUSION: Targeted PV isolation has a good long-term (18-month) success rate in patients younger than 50 years with paroxysmal AF and < or = 2 PVs triggering AF.