Azadeh Shohoudi

Clinical Experience With a Novel Electromyographic Approach to Preventing Phrenic Nerve Injury During Cryoballoon Ablation in Atrial Fibrillation

Background—Phrenic nerve palsy remains the most frequent complication associated with cryoballoon-based pulmonary vein (PV) isolation. We sought to characterize our experience using a novel monitoring technique for the prevention of phrenic nerve palsy. Methods and Results—Two hundred consecutive cryoballoon-based PV isolation procedures between October 2010 and October 2013 were studied. In addition to standard abdominal palpation during right phrenic nerve pacing from the superior vena cava, all patients underwent diaphragmatic electromyographic monitoring using surface electrodes. Cryoablation was terminated on any perceived reduction in diaphragmatic motion or a 30% decrease in the compound motor action potential (CMAP). During right-sided ablation, a ≥30% reduction in CMAP amplitude occurred in 49 patients (24.5%). Diaphragmatic motion decreased in 30 of 49 patients and was preceded by a 30% reduction in CMAP amplitude in all. In 82% of cases, this reduction in CMAP amplitude occurred during right superior PV isolation. The baseline CMAP amplitude was 946.5±609.2 mV and decreased by 13.8±13.8% at the end of application. This decrease was more marked in the 33 PVs with a reduction in diaphragmatic motion than in those without (40.9±15.3% versus 11.3±10.5%; P<0.001). In 3 cases, phrenic nerve palsy persisted beyond the end of the procedure, with all cases recovering within 6 months. Despite the shortened application all veins were isolated. At repeat procedure the right-sided PVs reconnected less frequently than the left-sided PVs in those with phrenic nerve palsy. Conclusions—Electromyographic phrenic nerve monitoring using the surface CMAP is reliable, easy to perform, and offers an early warning to impending phrenic nerve injury.

Electrocardiographic and electrophysiological predictors of atrioventricular block after transcatheter aortic valve replacement

BACKGROUND Electrophysiological predictors of atrioventricular (AV) block after transcatheter aortic valve replacement (TAVR) are unknown. OBJECTIVE We sought to assess the value of electrophysiology study before and after TAVR. METHODS Seventy-five consecutive pacemaker-free patients undergoing TAVR at the Montreal Heart Institute were prospectively studied. RESULTS Eleven patients (14.7%) developed AV block during the index hospitalization and 3 (4.0%) after hospital discharge over a median follow-up of 1.4 years (interquartile range 0.6-2.1 years). AV block developed in 5 of 6 patients with preprocedural right bundle branch block (83.3%), 8 of 30 patients with new-onset left bundle branch block (LBBB; 26.7%), and 1 of 7 patients with preexisting LBBB (14.3%). In multivariate analysis that considered all patients, the delta-HV interval (HV interval after TAVR minus HV interval before TAVR) was the only factor independently associated with AV block. In the subgroup of patients with new-onset LBBB, the postprocedural HV interval was strongly associated with AV block. By receiver operating characteristic analysis, a delta-HV interval of ≥13 ms predicted AV block with 100.0% sensitivity and 84.4% specificity and an HV interval of ≥65 ms predicted AV block with 83.3% sensitivity and 81.6% specificity. In multivariate analysis, the HV interval after TAVR (hazard ratio 1.073 per ms; 95% confidence interval 1.029-1.119; P = .001) was also independently associated with all-cause mortality. CONCLUSION A prolonged delta-HV interval (≥13 ms) is strongly associated with AV block after TAVR. In patients with new-onset LBBB after TAVR, a postprocedural HV interval of ≥65 ms is likewise predictive of AV block.

Blood Pressure and Atrial Fibrillation: A Combined AF-CHF and AFFIRM Analysis.

Hypertension is an established risk factor for new‐onset atrial fibrillation (AF). However, the relationship between blood pressure and recurrent AF is less well understood.

Impact of revascularization in patients with sustained ventricular arrhythmias, prior myocardial infarction, and preserved left ventricular ejection fraction.

BACKGROUND The impact of revascularization on recurrent ventricular arrhythmias (VAs) in patients with coronary artery disease and relatively preserved left ventricular ejection fraction (LVEF) is unknown. OBJECTIVE The purpose of this study was to determine the impact of revascularization on recurrent VAs or death. METHODS A cohort study was conducted on consecutive patients with prior myocardial infarction and LVEF ≥40% presenting with a first clinical sustained VA in the absence of an acute coronary syndrome. The impact of revascularization on recurrent VAs and all-cause mortality was assessed. RESULTS A total of 274 patients (mean age 66.1 ± 9.7 years, 85.4% male, mean LVEF 48.3% ± 7.2%) were included in the study. Eight-eight patients (32.1%) underwent coronary revascularization. During mean follow-up of 6.2 ± 5.1 years, 140 (51.1%) died or had recurrent sustained VAs or appropriate implantable-cardioverter defibrillator therapy. Revascularization was not associated with a significantly lower rate of recurrent VAs or death (multivariable hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.60-1.24, P = .43) regardless of whether it was complete or incomplete (HR 0.65, 95% CI 0.25-1.69, P = .37) or was performed by percutaneous or surgical means (HR 1.02, 95% CI 0.53-1.94, P = .96). An implantable-cardioverter defibrillator was associated with a significant reduction in mortality (HR 0.23, 95% CI 0.09-0.55, P = .001). CONCLUSION Patients with prior myocardial infarction and LVEF ≥40% who present with sustained VAs in the absence of an acute coronary syndrome remain at high risk for recurrent VAs and all-cause death. Coronary revascularization does not systemically mitigate this risk.

Heart rate and adverse outcomes in patients with atrial fibrillation: A combined AFFIRM and AF-CHF substudy.

BACKGROUND An elevated resting heart rate has been associated with adverse cardiovascular outcomes. Its prognostic value has not specifically been examined in patients with atrial fibrillation. OBJECTIVE The purpose of this study was to assess the relationship between resting heart rate measured in sinus rhythm and in atrial fibrillation and subsequent hospitalizations and death. METHODS An analysis of individual patient-level data from subjects enrolled in the AFFIRM and AF-CHF trials was conducted to determine the impact of resting heart rate on hospitalizations and mortality. Separate analyses were performed in atrial fibrillation and sinus rhythm. A total of 7159 baseline ECGs (4848 in atrial fibrillation, 2311 in sinus rhythm) were analyzed in 5164 patients (34.8% female, age 68.2 ± 8.3 years). RESULTS During mean follow-up of 40.8 ± 16.3 months, 1016 patients died (668 cardiovascular deaths), and 3150 required at least 1 hospitalization (2215 cardiovascular). An elevated baseline heart rate in sinus rhythm was associated with increased all-cause mortality [hazard ratio (HR) 1.24 per 10 bpm increase, 95% confidence interval (CI) 1.14-1.36, P < .0001]. In contrast, a baseline heart rate in atrial fibrillation was not associated with mortality. However, compared to heart rates 90-114 bpm in atrial fibrillation, a heart rate >114 bpm was independently associated with all-cause (HR 1.18, 95% CI 1.06-1.31, P = .0018) and cardiovascular (HR 1.25, 95% CI 1.10-1.42, P = .0005) hospitalizations. CONCLUSION In patients with a history of atrial fibrillation, an elevated baseline heart rate in sinus rhythm is independently associated with mortality. In contrast, the baseline heart rate in atrial fibrillation is not associated with mortality but predicts hospitalizations.

Characteristics of premature ventricular contractions in healthy children and their impact on left ventricular function

BACKGROUND There are few data regarding the characteristics of premature ventricular contractions (PVCs) in healthy children and their impact on left ventricular (LV) function. OBJECTIVE The purpose of this study was to assess the prevalence of LV systolic dysfunction in children with frequent PVCs (≥10%) and determine whether it is associated with PVC characteristics (e.g., proportion, coupling interval, width, and/or morphology). METHODS We conducted a single-center cohort study of children with structurally normal hearts and PVC burden ≥10% by 24-hour Holter monitoring performed between 2008 and 2012. Clinical, arrhythmic, and echocardiographic data were reviewed at baseline and during follow-up. RESULTS A total of 47 children (22 female [47%], mean age 8.2 ± 6.5 years) had a mean PVC burden of 20.9 ± 11.9% at baseline. The PVC coupling interval averaged 430 ± 110 ms, with a PVC width of 118 ± 27 ms. PVCs were monomorphic in 44 patients (94%). Although no patient had severe cardiomyopathy, 7 (15%) had reduced shortening fraction (Z-score <-2). A strong association was observed between PVC coupling interval and LV shortening fraction Z-score <-2.0 (area under the curve 0.95 ± 0.03, P <.001). A cutoff value <365 ms yielded the greatest discriminatory ability (Youden J-statistic 0.72, sensitivity 85.7%, specificity 86.5%). PVC proportion, width, and morphology were not significantly associated with LV shortening fraction. During 4.0 ± 2.8 years of follow-up, the PVC burden decreased from a median of 18% to 1.5% (P<.001). CONCLUSION PVCs in children with structurally normal hearts are associated with a relatively benign course, with spontaneous resolution in most children. Mild LV systolic dysfunction, observed in 15%, is strongly correlated with a shorter coupling interval (<365 ms).

Late Onset Postcapillary Pulmonary Hypertension in Patients With Transposition of the Great Arteries and Mustard or Senning Baffles

Background There is a paucity of data regarding late‐onset pulmonary hypertension (PH) in patients with transposition of the great arteries and atrial switch surgery. Methods and Results A retrospective cohort study was conducted on 140 adults with transposition of the great arteries and atrial switch surgery, age 37.3±7.8, 37.1% female, in order to assess the prevalence and characteristics of late‐onset PH and explore associated factors. Patients were followed for a median of 32.3 years after atrial switch surgery and 10.0 years after their first referral visit. PH was detected in 18 of 33 (54.5%) patients who had invasive hemodynamic studies. Average age at diagnosis of PH was 33.9±8.1 years. PH was postcapillary in all, with a mean pulmonary artery pressure of 36±12 mm Hg and mean pulmonary capillary wedge pressure of 28±8 mm Hg. PH was diagnosed in 13 of 17 (76.5%) patients who had cardiac catheterization for heart failure or decreased exercise tolerance. In multivariable analyses, systemic hypertension (odds ratio 9.4, 95% confidence interval 2.2‐39.4, P=0.002) and heart failure or New York Heart Association class III or IV symptoms (odds ratio 49.8, 95% confidence interval 8.6‐289.0, P<0.001) were independently associated with PH. Patients with PH were more likely to develop cardiovascular comorbidities including atrial (P=0.001) and ventricular (P=0.008) arrhythmias, require hospitalizations for heart failure (P<0.001), and undergo tricuspid valve surgery (P<0.001). Mortality was significantly higher in patients with PH (hazard ratio 9.4, 95% confidence interval 2.1‐43.0], P<0.001). Conclusions Late‐onset postcapillary PH is highly prevalent in adults with transposition of the great arteries and atrial switch surgery and is associated with an adverse prognosis.

ECG Features Associated With Adverse Cardiovascular Outcomes in Patients With Atrial Fibrillation: A Combined AFFIRM and AF-CHF Analysis.

The association between standard parameters from a simple 12‐lead ECG (i.e., QRS duration and PR, JT, and QT intervals) and adverse cardiovascular outcomes (cardiovascular mortality, all‐cause mortality, arrhythmic mortality, and hospitalizations) in patients with a history of atrial fibrillation (AF) has not been previously studied.

Use of digoxin in atrial fibrillation: One step further in the mortality controversy from the AFFIRM study

Whether there is a causal association between digoxin and mortality among patients with atrial fibrillation (AF), with or without congestive heart failure (HF), has been controversial; in particular, two prior analyses of data from the Atrial Fibrillation Follow‐up Investigation of Rhythm Management (AFFIRM) trial have yielded conflicting results. We sought to investigate how digoxin impacts mortality, in the full AFFIRM cohort and for various subgroups, by applying marginal structural modeling (MSM) to AFFIRM data.

Bayesian adaptive trials for rare cardiovascular conditions

Escalating costs of cardiovascular trials are limiting medical innovations, prompting the development of more efficient and flexible study designs. The Bayesian paradigm offers a framework conducive to adaptive trial methodologies and is well suited for the study of small populations. Bayesian adaptive trials provide a statistical structure for combining prior information with accumulating data to compute probabilities of unknown quantities of interest. Adaptive design features are useful in modifying randomization schemes, adjusting sample sizes and providing continuous surveillance to guide decisions on dropping study arms or premature trial interruption. Advantages include greater efficiency, minimization of risks, inclusion of knowledge as it is generated, cost savings and more intuitive interpretability. Extensive high-level computations are facilitated by an expanding armamentarium of available tools.