Long-Term Outcomes of Brugada Substrate Ablation: A Report from BRAVO (Brugada Ablation of VF Substrate Ongoing Multicenter Registry).

BACKGROUND: Treatment options for high-risk Brugada syndrome (BrS) with recurrent ventricular fibrillation (VF) are limited. Catheter ablation is increasingly performed but a large study with long-term outcome data is lacking. We report the results of the multicenter, international BRAVO (Brugada Ablation of VF Substrate Ongoing Registry) for treatment of high-risk symptomatic BrS. METHODS: We enrolled 159 patients (median age 42 years; 156 male) with BrS and spontaneous VF in BRAVO; 43 (27%) of them had BrS and early repolarization pattern. All but 5 had an implantable cardioverter-defibrillator for cardiac arrest (n=125) or syncope (n=34). A total of 140 (88%) had experienced numerous implantable cardioverter-defibrillator shocks for spontaneous VF before ablation. All patients underwent a percutaneous epicardial substrate ablation with electroanatomical mapping except for 8 who underwent open-thoracotomy ablation. RESULTS: In all patients, VF/BrS substrates were recorded in the epicardial surface of the right ventricular outflow tract; 45 (29%) patients also had an arrhythmic substrate in the inferior right ventricular epicardium and 3 in the posterior left ventricular epicardium. After a single ablation procedure, 128 of 159 (81%) patients remained free of VF recurrence; this number increased to 153 (96%) after a repeated procedure (mean 1.2±0.5 procedures; median=1), with a mean follow-up period of 48±29 months from the last ablation. VF burden and frequency of shocks decreased significantly from 1.1±2.1 per month before ablation to 0.003±0.14 per month after the last ablation (P<0.0001). The Kaplan-Meier VF-free survival beyond 5 years after the last ablation was 95%. The only variable associated with a VF-free outcome in multivariable analysis was normalization of the type 1 Brugada ECG, both with and without sodium-channel blockade, after the ablation (hazard ratio, 0.078 [95% CI, 0.008 to 0.753]; P=0.0274). There were no arrhythmic or cardiac deaths. Complications included hemopericardium in 4 (2.5%) patients. CONCLUSIONS: Ablation treatment is safe and highly effective in preventing VF recurrence in high-risk BrS. Prospective studies are needed to determine whether it can be an alternative treatment to implantable cardioverter-defibrillator implantation for selected patients with BrS. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04420078.

Device-device interaction between cardiac implantable electronic devices and continuous-flow left ventricular assist devices.

The current design of an innovative left ventricular assist device (LVAD) makes use of magnetic levitation technology, which enables the rotors of the device to be completely suspended by magnetic force, reducing friction and blood or plasma damage. However, this electromagnetic field can result in electromagnetic interference (EMI), which can interfere with proper functioning of another cardiac implantable electronic device (CIED) in its direct proximity. Approximately 80% of patients with an LVAD have a CIED, most frequently an implantable cardioverter-defibrillator (ICD). Several device-device interactions have been reported, including EMI-induced inappropriate shocks, inability to establish telemetry connection, EMI-induced premature battery depletion, undersensing by the device, and other CIED malfunctions. Unfortunately, additional procedures, including generator exchange, lead adjustment, and system extraction, are frequently required because of these interactions. In some circumstances, the additional procedure might be preventable or avoidable with appropriate solutions. In this article, we describe how EMI from the LVAD impacts the functionality of the CIED and provide possible management options, including manufacturer-specific information, for the current CIEDs (eg, transvenous and leadless pacemakers, transvenous and subcutaneous ICDs, and transvenous cardiac resynchronization therapy pacemakers and ICDs).

Intracardiac electrogram T-wave alternans/variability increases before spontaneous ventricular tachyarrhythmias in implantable cardioverter-defibrillator patients: a prospective, multi-center study.

BACKGROUND: T-wave alternans (TWA) increases before ventricular tachycardia (VT) or fibrillation (VF), suggesting that it may warn of VT/VF in implantable cardioverter-defibrillator patients. Recently, we described a method for measuring alternans and nonalternans variability (TWA/V) from electrograms (EGMs) stored in implantable cardioverter-defibrillators before VT/VF. The goal of this prospective, multicenter study was to determine whether EGM TWA/V was greater before VT/VF than at baseline. METHODS AND RESULTS: We enrolled 63 implantable cardioverter-defibrillator patients. TWA/V was computed from stored EGMs before spontaneous VT/VF and from sequential windows of 8 pairs of beats using 4 different control recordings: baseline rhythm, rapid pacing at 105 bpm, segments of ambulatory Holter EGMs matched to the time of VT/VF episodes, and EGMs before spontaneous supraventricular tachycardia. During follow-up, 28 patients had 166 episodes of VT/VF. TWA/V was greater before VT/VF (62.9 ± 3.1 µV; n = 28) than during baseline rhythm (12.8 ± 1.8 µV; P < 0.0001; n = 62), during rapid pacing (14.5 ± 2.0 µV; P < 0.0001; n = 52), before supraventricular tachycardia (27.5 ± 6.1 µV; P < 0.0001; n = 9), or during time-matched ambulatory controls (12.3 ± 3.5 µV; P < 0.0001; n = 16). By logistic regression, the odds of VT/VF increased by a factor of 2.2 for each 10-µV increment in TWA/V (P < 0.0001). CONCLUSIONS: In implantable cardioverter-defibrillator patients, EGM TWA/V is greater before spontaneous VT/VF than in control recordings. Future implantable cardioverter-defibrillators that measure EGM TWA/V continuously may warn patients and initiate pacing therapies to prevent VT/VF.

Comparison of and Frequency of Mortality, Left Ventricular Assist Device Implantation, Ventricular Arrhythmias, and Heart Transplantation in Patients With Familial Versus Nonfamilial Idiopathic Dilated Cardiomyopathy.

We postulated that familial idiopathic dilated cardiomyopathy (F-IDC) is associated with a worse prognosis than nonfamilial IDC (nonF-IDC). Patients with F-IDC had either a strong family history and/or proved genetic mutations. We studied long-term prognosis (mean follow-up: 6.1 ± 4.1 years) of 162 patients with IDC (age: 55.5 ± 17.9 years, men: 57.8%, 50% F-IDC) with an implantable cardioverter-defibrillator or cardiac resynchronization therapy. The primary end point was a composite of death, left ventricular (LV) assist device implant, or heart transplantation. The secondary end point was a ventricular arrhythmia event. There was no significant difference in the prevalence of diabetes, hypertension, New York Heart Association class, medical therapy, and years of follow-up between the F-IDC and nonF-IDC groups. Patients with F-IDC were younger than patients with nonF-IDC (49.1 ± 17.0 years vs 61.6 ± 16.5 years, p <0.001). Mean LV ejection fraction was significantly lower in F-IDC group than in the nonF-IDC group (26 ± 12% vs 31 ± 12%, p = 0.022). The primary end point was achieved in 54 patients in F-IDC group (66.7%) versus 19 in the nonF-IDC group (23.5%) (p <0.001). The Kaplan-Meier survival estimates for the composite end point and for ventricular arrhythmia were significantly lower in the F-IDC versus nonF-IDC (log-rank p ≤0.001 and 0.04, respectively). F-IDC was the only multivariable predictor of the primary composite end point (hazard ratio 3.419 [95% confidence interval 1.845 to 6.334], p <0.001). The likelihood of LV remodeling manifested by LV ejection fraction improvement (≥10%) was significantly lower in F-IDC than nonF-IDC (27.1% vs 44.8%, p = 0.042). In conclusion, F-IDC is a predictor of mortality, need for LV assist device, or heart transplantation. F-IDC is associated with significantly lower event-free survival for primary end point and ventricular arrhythmia than nonF-IDC. F-IDC has significantly lower likelihood of LV reverse remodeling than nonF-IDC.

Simulation of LV pacemaker lead in marginal vein: potential risk factors for acute dislodgement.

Although left ventricular (LV) coronary sinus lead dislodgement remains a problem, the risk factors for dislodgement have not been clearly defined. In order to identify potential risk factors for acute lead dislodgement, we conducted dynamic finite element simulations of pacemaker lead dislodgement in marginal LV vein. We considered factors such as mismatch in lead and vein diameters, velocity of myocardial motion, branch angle between the insertion vein and the coronary sinus, degree of slack, and depth of insertion. The results show that large lead-to-vein diameter mismatch, rapid myocardial motion, and superficial insertion are potential risk factors for lead dislodgement. In addition, the degree of slack presents either a positive or negative effect on dislodgement risk depending on the branch angle. The prevention of acute lead dislodgment can be enforced by inducing as much static friction force as possible at the lead-vein interface, while reducing the external force. If the latter exceeds the former, dislodgement will occur. The present findings underscore the major risk factors for lead dislodgment, which may improve implantation criterion and future lead design.

Simulation of mechanical environment in active lead fixation: effect of fixation helix size.

The risk of myocardial penetration due to active-fixation screw-in type pacing leads has been reported to increase as the helix electrodes become smaller. In order to understand the contributing factors for lead penetration, we conducted finite element analyses of acute myocardial micro-damage induced by a pacemaker lead screw-in helix electrode. We compared the propensity for myocardial micro-damage of seven lead designs including a baseline model, three modified designs with various helix wire cross-sectional diameters, and three modified designs with different helix diameters. The comparisons show that electrodes with a smaller helix wire diameter cause more severe micro-damage to the myocardium in the early stage. The damage severity, represented by the volume of failed elements, is roughly the same in the middle stage, whereas in the later stage the larger helix wire diameter generally causes more severe damage. The onset of myocardial damage is not significantly affected by the helix diameter. As the helix diameter increases, however, the extent of myocardial damage increases accordingly. The present findings identified several of the major risk factors for myocardial damage whose consideration for lead use and design might improve acute and chronic lead performance.

Subxiphoid Endoscopic Epicardial Ventricular Tachycardia Ablation.

Ventricular tachycardia refractory to traditional therapies such as medical management and endocardial catheter ablation poses a risk for sudden cardiac death and poor quality of life. We describe a patient who was successfully treated for refractory symptomatic ventricular tachycardia using hybrid endocardial and minimally invasive epicardial ablation with a subxiphoid approach.

Spinal cord stimulation improves ventricular function and reduces ventricular arrhythmias in a canine postinfarction heart failure model.

BACKGROUND: Spinal cord stimulation (SCS) reduces the incidence of ventricular tachyarrhythmias in experimental models. This study investigated the effects of long-term SCS on ventricular function in a postinfarction canine heart failure model. METHODS AND RESULTS: In stage 1, dogs underwent implantable cardioverter-defibrillator implantation and embolization of the left anterior descending artery followed by right ventricular pacing (240 ppm) for 3 weeks to produce heart failure. In stage 2, 28 surviving animals were assigned to the SCS (delivered at the T4/T5 spinal region for 2 hours 3 times a day), medicine (MED; carvedilol therapy at 12.5 mg PO BID), or control (CTRL; no therapy) group for the initial phase 1 study. In a subsequent phase 2 study, 32 stage 1 survivors were equally randomized to the SCS, MEDS (carvedilol plus ramipril 2.5 mg PO QD), SCS plus MEDS (concurrent therapy), or CTRL group. Animals were monitored for 5 weeks (phase 1) or 10 weeks (phase 2). In stage 3, all phase 1 animals underwent circumflex artery balloon occlusion for 1 hour. In the SCS group, left ventricular ejection fraction was 65+/-5% at baseline, 17+/-3% at the end of stage 1, and 47+/-7% at the end of stage 2. In the MED group, left ventricular ejection fraction was 61+/-4% at baseline, 18+/-3% at the end of stage 1, and 34+/-4% at the end of stage 2. In the CTRL group, left ventricular ejection fraction was 64+/-5% at baseline, 19+/-5% at the end of stage 1, and 28+/-3% at the end of stage 2. Left ventricular ejection fraction was significantly improved in the SCS compared with the MED and CTRL groups (P<0.001 for both). The mean number of spontaneous nonsustained ventricular tachyarrhythmias during stage 2 and the occurrence of ischemic ventricular tachyarrhythmias during stage 3 also were significantly decreased in the SCS (27+/-17 and 27%, respectively; P<0.03) and MED (58+/-42 and 33%; P<0.05) versus CTRL (88+/-52 and 76%) group. After 10 weeks in the phase 2 studies, the greatest recovery in ejection fraction was noted in the SCS (52+/-5%) and SCS+MEDS (46+/-4%) groups compared with the MEDS (38+/-2%) and CTRL (31+/-4%) groups. CONCLUSIONS: SCS significantly improved cardiac contractile function and decreased ventricular arrhythmias in canine heart failure.

Fragmented QRS and other depolarization abnormalities as a predictor of mortality and sudden cardiac death.

PURPOSE OF REVIEW: Several invasive and noninvasive tests for risk stratification of sudden cardiac death (SCD) have been studied. Tests such as microwave T wave alternans (repolarization abnormality) and signal-averaged ECG (depolarization abnormality) have high negative predictive values but low positive predictive values in patients with heart disease. The presence of a fragmented QRS (fQRS) complex on a routine 12-lead ECG is another marker of depolarization abnormality. The purpose of this review is to discuss the potential utility of tests to detect depolarization abnormalities of the heart for the risk stratification of mortality and SCD with main emphasis on fQRS. RECENT FINDINGS: fQRS is associated with increased mortality and arrhythmic events in patients with coronary artery disease. fQRS has also been defined as a marker of arrhythmogenic right ventricular cardiomyopathy and Brugada syndrome. In Brugada syndrome, the presence of fQRS predicts episodes of ventricular fibrillation during follow-up. SUMMARY: fQRS may be of value in determining the risk for SCD and guiding selection for device therapy in patients with structural heart disease and Brugada syndrome. It is possible that the predictive value of fQRS for SCD can be enhanced further by combining a marker of repolarization abnormality such as microwave T wave alternans.

Antiarrhythmic and nonantiarrhythmic drugs for sudden cardiac death prevention.

Life-threatening ventricular arrhythmias such as sustained ventricular tachycardia and ventricular fibrillation are responsible for two thirds of sudden cardiac deaths annually in the United States. Implantable cardioverter-defibrillator (ICD) therapy prevents mortality from arrhythmic death but is expensive and has some associated morbidity from proarrhythmia and mechanical malfunction. Furthermore, ICDs treat ventricular arrhythmias but do not prevent them. Antiarrhythmic drugs (AADs) can be used for acute or chronic therapy to prevent ventricular arrhythmias and sudden cardiac deaths. AADS are often used in patients with an ICD who have recurrent ICD shocks resulting from ventricular arrhythmias. Class I AADs are contraindicated in patients with structural heart disease. Other than amiodarone, all Class III drugs have either a neutral or deleterious effect on mortality. Dronedarone, a new Class III drug, may reduce mortality, but more information is needed to be sure. A class of drugs that do not qualify as an AAD can modify cardiovascular remodeling processes and have a delayed and indirect antiarrhythmic effect. These so-called "nonantiarrhythmic drugs" such as drugs acting on the renin-angiotensin-aldosterone system, fish oil, and statins can reduce the likelihood of future ventricular tachycardia/ventricular fibrillation in patients with coronary artery disease or congestive heart failure. The role of AADs for chronic therapy for primary and secondary prevention of sudden cardiac death is problematic because of proarrhythmia and adverse side effects. Because these nonantiarrhythmic drugs are well tolerated and have no proarrhythmic actions, their benefits should outweigh risks.

The initiation of the heart beat.

During a normal lifetime, the heart may beat over 2 billion times, but the mechanisms by which the heart beats are initiated remain a subject of intense investigation. Since the discovery of a pacemaker current (I(f)) in 1978, multiple studies have shown that rhythmic changes in membrane voltage (the "membrane voltage clock") underlie the mechanisms of automaticity. The I(f) is a depolarization current activated during hyperpolarization. Therefore, when the cardiac cells recover, the I(f) is activated and slowly depolarizes the cell membrane, leading to the onset of action potential. Recent studies, however, suggest that increased intracellular Ca (Ca(i)) induced by spontaneous rhythmic sarcoplasmic reticulum Ca release (the "calcium clock") is also jointly responsible for the initiation of the heart beat. Elevated Ca(i) activates another ionic current (the sodium-calcium exchanger current or I(NCX)), leading to spontaneous phase 4 depolarization. Under normal conditions, both clocks are needed to initiate the heart beat. Malfunction of the clocks is associated with sinus node dysfunction in heart failure and atrial fibrillation. More studies are needed to determine how both clocks work together to initiate heart beat under normal and disease conditions.

Skin sympathetic nerve activity as a biomarker for syncopal episodes during a tilt table test.

BACKGROUND: Autonomic imbalance is the proposed mechanism of syncope during a tilt table test (TTT). We have recently demonstrated that skin sympathetic nerve activity (SKNA) can be noninvasively recorded using electrocardiographic electrodes. OBJECTIVE: The purpose of this study was to test the hypothesis that increased SKNA activation precedes tilt-induced syncope. METHODS: We studied 50 patients with a history of neurocardiogenic syncope undergoing a TTT. The recorded signals were band-pass filtered at 500-1000 Hz to analyze nerve activity. RESULTS: The average SKNA (aSKNA) value at baseline was 1.38 ± 0.38 µV in patients without syncope and 1.42 ± 0.52 µV in patients with syncope (P = .77). On upright tilt, aSKNA was 1.34 ± 0.40 µV in patients who did not have syncope and 1.39 ± 0.43 µV in patients who had syncope (P = .65). In all 14 patients with syncope, there was a surge of SKNA before an initial increase in heart rate followed by bradycardia, hypotension, and syncope. The peak aSKNA immediately (<1 minute) before syncope was significantly higher than baseline aSKNA (2.63 ± 1.22 vs 1.39 ± 0.43 µV; P = .0005). After syncope, patients were immediately placed in the supine position and aSKNA dropped significantly to 1.26 ± 0.43 µV; (P = .0004). The heart rate variability during the TTT shows a significant increase in parasympathetic tone during syncope (low-frequency/high-frequency ratio: 7.15 vs 2.21; P = .04). CONCLUSION: Patients with syncope do not have elevated sympathetic tone at baseline or during the TTT except immediately before syncope when there is a transient surge of SKNA followed by sympathetic withdrawal along with parasympathetic surge.

Modern pacemakers: hope or hype?

In recent years, the role of implantable pacing devices has expanded beyond the arrhythmia horizon and contemporary pacemakers' attempt to meet the physiological needs of patients. Modern pacemakers' functions include various modes of dual-chamber pacing, rate-response algorithms with dual sensors for optimum physiological response, cardiac resynchronization therapy (CRT), arrhythmia-prevention algorithms, antitachycardia pacing, and hemodynamic monitoring. The automaticity features of pacemakers enable continuous or intermittent monitoring of various pacemaker parameters including battery voltage, pacing impedance, sensing levels, pacing thresholds, and daily activity log. Modern pacemakers offer "physiological pacing" algorithms that minimize ventricular pacing and reduce the incidence of atrial fibrillation significantly. Ventricular pacing in patients with intact atrioventricular (AV) conduction or intermittent advanced AV block should be minimized with a hope to reduce heart failure hospitalization and mortality. A reduction in all-cause mortality due to physiological pacing, except for the CRT, has yet to be demonstrated in a randomized trial. Overall, modern pacemakers have acceptable performances to fulfill the clinical needs and have a reasonable safety margin. Promising new technologies are currently under development and offer hope to patients who may one day derive both symptomatic and mortality benefit from these devices.

Fragmented QRS complexes on 12-lead ECG: a marker of cardiac sarcoidosis as detected by gadolinium cardiac magnetic resonance imaging.

BACKGROUND: Fragmented QRS complexes (fQRS) on a 12-lead ECG are a marker of myocardial scar in patients with coronary artery disease. Cardiac sarcoidosis is also associated with myocardial granuloma formation and scarring. We evaluated the significance of fQRS on a 12-lead ECG compared to Gadolinium-delayed enhancement images (GDE) in cardiac magnetic resonance imaging (CMR). METHOD AND RESULTS: The ECGs of patients (n = 17, mean age: 52 +/- 11 years, male: 53%) with established diagnosis of sarcoidosis who underwent a CMR for evaluation of cardiac involvement were studied. ECG abnormalities included bundle branch block, Q wave, and fQRS. fQRS, Q wave, and bundle branch block were present in 9 (53%), 1 (6%), and 4 (24%) patients, respectively. The sensitivity and specificity of fQRS for detecting abnormal GDE were 100% and 80%, respectively. Sensitivity and specificity of Q waves were 11% and 100%, respectively. CONCLUSIONS: fQRS on a 12-lead ECG in patients with suspected cardiac sarcoidosis are associated with cardiac involvement as detected by GDE on CMR.

Role of ablation therapy in ventricular arrhythmias.

Catheter ablation is an effective therapy for symptomatic ventricular arrhythmia (VA) in patients with and without structural heart disease. It is the treatment of choice to cure or reduce recurrent VA in patients who have an implantable cardioverter defibrillator and can be a life-saving procedure in patients who have electrical storm. Catheter ablation for VAs remains a challenging procedure and requires a precise understanding of cardiac electrophysiology, the arrhythmia mechanisms, and mapping techniques. Various mapping techniques such as pace mapping, activation mapping, entrainment mapping, and substrate mapping are used. These techniques complement each other in localizing the critical isthmus of a reentrant VT or the source of origin of a focal VT. Most VAs can be ablated endocardially. Epicardial ablation is needed for VAs with an epicardial circuit or a focal source.

Significance of a fragmented QRS complex versus a Q wave in patients with coronary artery disease.

BACKGROUND: Q waves on a 12-lead ECG are markers of a prior myocardial infarction (MI). However, they may regress or even disappear over time, and there is no specific ECG sign of a non-Q-wave MI. Fragmented QRS complexes (fQRSs), which include various RSR' patterns, without a typical bundle-branch block are markers of altered ventricular depolarization owing to a prior myocardial scar. We postulated that the presence of an fQRS might improve the ability to detect a prior MI compared with Q waves alone by ECG. METHODS AND RESULTS: A cohort of 479 consecutive patients (mean+/-SD age, 58.2+/-13.2 years; 283 males) who were referred for nuclear stress tests was studied. The fQRS included various morphologies of the QRS (<120 ms), which included an additional R wave (R') or notching in the nadir of the S wave, or >1 R' (fragmentation) in 2 contiguous leads, corresponding to a major coronary artery territory. The Q wave was present in 71 (14.8%) patients, an fQRS was present in 191 (34.9%) patients, and an fQRS and/or a Q wave was present in 203 (42.3%) patients. Sensitivity, specificity, and the negative predictive value for myocardial scar as detected by single photon emission computed tomography analysis were 36.3%, 99.2%, and 70.8%, respectively, for the Q wave alone; 85.6%, 89%, and 92.7%, respectively, for the fQRS; and 91.4%, 89%, and 94.2%, respectively, for the Q wave and/or fQRS. CONCLUSIONS: The fQRS on a 12-lead ECG is a marker of a prior MI, defined by regional perfusion abnormalities, which has a substantially higher sensitivity and negative predictive value compared with the Q wave.

Endocardial catheter ablation of ventricular tachycardia in patients with ventricular assist devices.

BACKGROUND: The outcomes of patients with ventricular assist devices (VADs) who undergo catheter ablation for ventricular tachycardia (VT) have not been reported. OBJECTIVE: The purpose of this study was to assess the feasibility, safety, and efficacy of endocardial VT ablation in patients with VADs. METHODS: We retrospectively reviewed three cases at our institution where endocardial catheter ablation was performed in patients with VADs and incessant VT. RESULTS: Three patients with underlying cardiomyopathies and VADs underwent VT ablation for incessant VT refractory to multiple antiarrhythmic medications. In each case, VT was either eliminated or significantly ameliorated by catheter ablation. No procedure-related complications occurred. The hemodynamic stability afforded by the VAD played an important role in facilitating ablation in two of the cases. CONCLUSION: Catheter ablation for VT in VAD patients appears to be feasible, safe, and effective based on our initial experience. Several technical issues, such as decreases in ventricular volumes that can limit maneuverability of the ablation catheter and potential entrapment of the mapping catheter in the inflow cannula, need to be considered at the time of ablation.

Fragmented QRS on a 12-lead ECG: a predictor of mortality and cardiac events in patients with coronary artery disease.

BACKGROUND: Fragmented QRS (fQRS) on a 12-lead electrocardiogram (ECG) is associated with myocardial scar in patients with coronary artery disease (CAD). OBJECTIVE: We postulated that fQRS is a predictor of cardiac events and mortality in patients who have known CAD or who are being evaluated for CAD. METHODS: The cardiac events (myocardial infarction, need for revascularization, or cardiac death) and all-cause mortality were retrospectively reviewed in 998 patients (mean age 65.5 +/- 11.9 years, male 967) who underwent nuclear stress test. The fQRS on a 12-lead ECG included various RSR' patterns (> or =1 R' prime or notching of S wave or R wave) without typical bundle branch block in 2 contiguous leads corresponding to a major coronary artery territory. RESULTS: All-cause mortality (93 [34.1%] vs 188 [25.9%]) and cardiac event rate (135 [49.5%] vs 200 [27.6%]) were higher in the fQRS group compared with the non-fQRS group during a mean follow-up of 57 +/- 23 months. A Kaplan-Meier survival analysis revealed significantly lower event-free survival for cardiac events (P <.001) and all-cause mortality (P = .02). Multivariate Cox regression analysis revealed that significant fQRS was an independent significant predictor for cardiac events but not for all-cause mortality. The Kaplan-Meier survival analysis showed no significant difference between fQRS and Q waves groups for cardiac events (P = .48) and all-cause mortality (P = .08). CONCLUSION: The fQRS is an independent predictor of cardiac events in patients with CAD. It is associated with significantly lower event-free survival for a cardiac event on long-term follow-up.