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Biomedical subjects

William G Stevenson

Publications and source records attributed to William G Stevenson.

At least 19 recordsLinked to original sources
PubMed2026

Prevalence and Clinical Impact of Pathogenic Variants in Cardiomyopathy Genes Among Individuals with Cardiac Conduction Disorders.

IMPORTANCE: Cardiac conduction disorders have traditionally been regarded as a secondary manifestation of underlying structural heart diseases. However, isolated conduction disorders may precede the onset of heart failure (HF) suggesting shared mechanisms. OBJECTIVE: To evaluate the prevalence and clinical significance of pathogenic/likely pathogenic (P/LP) rare variants in cardiomyopathy genes among individuals with conduction disorders. DESIGN SETTING AND PARTICIPANTS: Biobank analysis of 192,834 participants with whole genome sequence data from Vanderbilt's BioVU and 353,092 participants from the All of Us Research Program (AoU). Participants with primary conduction disorder (left bundle branch block [LBBB], right bundle branch block [RBBB], high-grade atrioventricular block [AVB]) were identified after excluding secondary causes. EXPOSURES: P/LP variants in cardiomyopathy genes. MAIN OUTCOMES AND MEASURES: Primary outcome was P/LP carrier status by age and HF status. Secondary outcomes included incident HF and composite ventricular arrhythmias/sudden cardiac death/mortality (VA/SCD/mortality). RESULTS: Among 16,959 participants with conduction disorders in BioVU and 13,442 in AoU, 432 (2.6%) and 206 (1.5%) were P/LP carriers, respectively. Conduction disorder was independently associated with carrier status (BioVU p<0.001; AoU p=0.005). Carrier probability varied by age at conduction disorder onset and HF status. Among participants with HF at age 30 years, predicted carrier probability for LBBB was 7.5% in BioVU and 20.2% in AoU; for high-grade AVB, 7.7% and 8.5%, respectively, compared with 3.7% and 2.9% among those with HF without conduction disorder. P/LP carrier status among participants with conduction disorders was associated with increased risk of incident HF (BioVU p<0.001; AoU p<0.001) and ventricular arrhythmia/sudden death/mortality (BioVU p<0.001; AoU p<0.001). Carriers also demonstrated increased susceptibility to conduction disorder following HF diagnosis, including more than two-fold higher risk of third-degree AVB (BioVU aOR 2.48, 95% CI 1.85-3.32; AoU aOR 2.26, 95% CI 1.35-3.80). CONCLUSIONS: Adults with primary conduction disorders have an increased prevalence of P/LP variants in cardiomyopathy genes, which is most pronounced with diagnoses at early ages of adulthood. Furthermore, there is evidence of an interaction between P/LP carrier status and conduction disorder to increase HF risk and composite cardiovascular outcomes, underscoring the potential role of genetic evaluation in patients with primary conduction disorders to inform long-term outcomes.

Journal Article↗
PubMed2006

Usefulness of post-ventriculotomy signal averaged electrocardiograms in congenital heart disease.

Signal-averaged electrocardiography is a sensitive and specific technique for detecting the slow conduction electrophysiologic substrates of reentrant monomorphic ventricular tachycardia. Although well established, the method has not been used for electrophysiologic assessment after right ventriculotomy for the intracardiac repair of congenital heart disease. This 8-year prospective study provided this assessment. Recordings were obtained from 242 post-ventriculotomy patients with congenital heart disease aged 16 to 72 years (139 males, 103 females). Because ventricular volume or pressure overload can prolong the QRS duration, 40 unoperated patients with hemodynamic overload served as controls. Orthogonal X, Y, and Z body surface electrodes were used to detect ventricular late potentials by permitting the examination of portions of the electrocardiogram otherwise obscured by noise and artifacts. Positive signal-averaged electrocardiographic (SAECG) results were based on established criteria derived from 3 time-domain variables calculated by an automated algorithm. Late potentials were detected in 151 of 242 patients (62%) and were significantly higher than controls (p = 0.0001). Radiofrequency ablation of an inducible slow conduction substrate rendered 20 of 23 positive post-ventriculotomy SAECG results negative, and surgical revision of the ventriculotomy scar rendered 19 of 19 positive SAECG results negative. In conclusion, negative SAECG results connote the absence of a reentrant substrate, and therefore, the absence of risk for reentrant monomorphic ventricular tachycardia, whereas positive SAECG results connote the presence of a slow conduction substrate and the potential risk for monomorphic ventricular tachycardia.

Adolescent↗
PubMed2006

Characterization of the peri-infarct zone by contrast-enhanced cardiac magnetic resonance imaging is a powerful predictor of post-myocardial infarction mortality.

BACKGROUND: Accurate risk stratification is crucial for effective treatment planning after myocardial infarction (MI). Previous studies suggest that the peri-infarct border zone may be an important arrhythmogenic substrate. In this pilot study, we tested the hypothesis that the extent of the peri-infarct zone quantified by contrast-enhanced cardiac magnetic resonance (CMR) is an independent predictor of post-MI mortality. METHODS AND RESULTS: We studied 144 patients with documented coronary artery disease and abnormal myocardial delayed enhancement (MDE) consistent with MI. A computer-assisted, semiautomatic algorithm quantified the total infarct size and divided it into the core and peri-infarct regions based on signal-intensity thresholds (>3 SDs and 2 to 3 SDs above remote normal myocardium, respectively). The peri-infarct zone was normalized as a percentage of the total infarct size (%MDE(periphery)). After a median follow-up of 2.4 years, 29 (20%) patients died. Patients with an above-median %MDE(periphery) were at higher risk for death compared with those with a below-median %MDE(periphery) (28% versus 13%, log-rank P<0.01). Multivariable analysis showed that left ventricular systolic volume index and %MDE(periphery) were the strongest predictors of all-cause mortality (adjusted hazard ratio [HR] for %MDE(periphery), 1.45 per 10% increase; P=0.002) and cardiovascular mortality (adjusted HR, 1.51 per 10% increase; P=0.009). Similarly, after adjusting for age and left ventricular ejection fraction, %MDE(periphery) maintained strong and independent associations with all-cause mortality (adjusted HR, 1.42; P=0.005) and cardiovascular mortality (adjusted HR, 1.49; P=0.01). CONCLUSIONS: In patients with a prior MI, the extent of the peri-infarct zone characterized by CMR provides incremental prognostic value beyond left ventricular systolic volume index or ejection fraction. Infarct characteristics by CMR may prove to be a unique and valuable noninvasive predictor of post-MI mortality.

Aged↗
PubMed2006

Relation of right ventricular peak systolic pressure to major adverse events in patients undergoing cardiac resynchronization therapy.

The degree to which increased right-sided heart pressures influence outcome in cardiac resynchronization therapy (CRT) is unclear. High right ventricular (RV) pressures may contribute to septal malpositioning, thus hindering effective resynchronization. We hypothesized that patients with high RV systolic pressures before CRT implantation would have poorer outcome. We evaluated echocardiograms, electrocardiograms, and clinical records from 75 consecutive patients with CRT. RV systolic pressure was calculated from the peak tricuspid regurgitant, time-velocity profile. The primary end point was a composite of mortality, cardiac transplantation, or need for a left ventricular assist device. Events were evaluated by Kaplan-Meier curves and Cox proportional hazard ratios. Patients grouped by RV systolic pressure divided at the median of 35 mm Hg were similar except for more renal insufficiency and RV dysfunction when RV systolic pressure was >35 mm Hg. Univariate analysis identified RV systolic pressure >35 mm Hg (hazard ratio [HR] 3.32), diabetes (HR 2.45), renal insufficiency (HR 3.52), atrial fibrillation (HR 3.07), use of nonamiodarone antiarrhythmic medications (HR 2.86), atrial pacing (HR 2.57), and prolonged PR interval (HR 1.009) as associated with poorer outcome. Normal sinus rhythm at implantation (HR 0.34), baseline left bundle branch block (HR 0.44), and beta-blocker use (HR 0.47) were associated with improved outcome. In a multivariable model, high RV systolic pressure (HR 3.71, 95% confidence interval 1.31 to 10.4), renal insufficiency (HR 3.18, 95% confidence interval 1.29 to 7.86), and atrial fibrillation (HR 4.22, 95% confidence interval 1.54 to 11.6) remained significant. In conclusion, despite resynchronization, patients with high RV pressures have significantly decreased survival after adjusting for significant contributing influences.

Aged↗
PubMed2006

Refractory ventricular tachycardia secondary to cardiac sarcoid: electrophysiologic characteristics, mapping, and ablation.

BACKGROUND: Cardiac sarcoidosis is a recognized cause of ventricular tachycardia (VT) and sudden death that has not been well studied. OBJECTIVES: The purpose of this study was to describe the clinical characteristics of a consecutive series of eight patients with recurrent monomorphic VT due to cardiac sarcoidosis and to define the electrophysiologic characteristics of the VT and its electrophysiologic substrate. METHODS/RESULTS: Of 98 patents with nonischemic cardiomyopathy and VT referred for ablation over a 7-year period, sarcoid was the etiology in 8%. Mean age was 42 +/- 8 years, and all but one patient had a reduced left ventricular ejection fraction (mean 34% +/- 15%). VT was the initial manifestation of sarcoid disease in 5 of 8 cases based on retrospective analysis. All patients had not responded to therapy with multiple antiarrhythmic drugs (mean 2.5 +/- 1). Cardiac biopsy initially was negative in 3 of 7 patients, and in 2 patients the diagnosis was not made until posttransplant examination of the heart. Two patients (25%) had a previous presumptive diagnosis of arrhythmogenic right ventricular dysplasia. Electrophysiologic study revealed evidence of scar-related reentry with multiple monomorphic VTs induced (4 +/- 2 VTs per patient) with both right bundle branch block and left bundle branch block QRS configurations. Areas of low-voltage scar were present in the right ventricle in all 8 of 8 patients, in the left ventricle in 5 (63%) of 8 patients, and in the epicardium in 2 patients undergoing epicardial mapping. Ablation abolished one or more VTs in 6 (75%) of 8 patients, but other VTs remained inducible in all but one patient. Postablation, some form of sustained VT recurred in 6 of 8 patients within 6 months. However, at longer follow-up (range 6 months to 7 years), 4 of 8 patients currently are free of VT with antiarrhythmic drugs and immunosuppression. Cardiac transplantation eventually was required in 5 of 8 patients because of either recurrent VT (n = 4) or heart failure (n = 1). CONCLUSION: Sarcoid is an important diagnostic consideration in scar-related VT. Sarcoid can be misdiagnosed as idiopathic or arrhythmogenic right ventricular cardiomyopathy. Arrhythmia control can be difficult, although ablation can be helpful in some patients.

Adult↗
PubMed2006

Entrainment mapping for rapid distinction of left and right atrial tachycardias.

BACKGROUND: Distinguishing left from right atrial tachycardia is a critical step for guiding ablation. OBJECTIVES: The purpose of this study was to develop and validate a simple algorithm predicting the location of macroreentrant atrial tachycardia (AT) circuits from limited entrainment mapping in right atrium (RA) and coronary sinus (CS). METHODS: In 180 patients with organized reentrant AT, entrainment was performed at the high RA, proximal CS, and distal CS. The difference between the postpacing interval (PPI) and tachycardia cycle length (TCL) was calculated at each site. The location of the AT reentrant circuit was determined by mapping and ablation. An algorithm predicting AT regions was developed from 104 ATs in the first 90 patients (group I) and prospectively evaluated in a validation cohort of 106 ATs in the second 90 patients (group II). RESULTS: In group I, PPI-TCL difference <50 or >50 ms at the high RA distinguished RA from LA reentrant circuits. For RA tachycardias, PPI-TCL difference at the proximal CS distinguished common flutter from lateral RA circuits. For LA circuits, PPI-TCL difference at the proximal and distal CS distinguished perimitral reentry from reentry involving the right pulmonary veins and septum. In group II, an algorithm based on PPI-TCL difference >50 or <50 ms at the high RA, proximal CS, or distal CS had sensitivity of 94%, specificity of 88%, and predictive accuracy of 93% for predicting the successful ablation region. CONCLUSION: Limited entrainment from sites accessible from the RA can expeditiously suggest the AT location to guide more detailed mapping and potentially avoid unnecessary transseptal punctures in some patients.

Adult↗
PubMed2006

Predicting early mortality after implantable defibrillator implantation: a clinical risk score for optimal patient selection.

BACKGROUND: Patients with advanced heart disease are at risk from sudden death; however, benefit from implantable cardioverter defibrillators (ICDs) may be limited as a result of early mortality from other causes. The objective of this study was to develop a model to predict mortality within the first year after ICD implantation. METHODS AND RESULTS: A retrospective analysis was performed of 469 consecutive patients who underwent ICD implantation at a single tertiary-care center from 1999 to 2002. Vital status was determined from the Social Security Death Index. Patients were randomized into prediction and validation cohorts. A risk score was derived from the prediction cohort by multivariate logistic regression and applied to the validation cohort. One point was assigned for each variable in the risk score (age > 80 years, history of atrial fibrillation, creatinine > 1.8 mg/dL, New York Heart Association class III or IV). One-year mortality significantly increased with increasing risk score in both the prediction and validation cohorts. Validation cohort mortality was 3.4% for 0 points, 4.3% for 1 point, 17% for 2 points, and 33% for > or = 3 points (P for trend < .0001). A risk score > or = 2 predicted a 1-year mortality rate of 21%, whereas a risk score < 2 predicted a mortality rate of 4% at 1 year (P < .0001). CONCLUSION: A risk score using simple clinical criteria may identify patients at high risk of early mortality after ICD implantation. This may be helpful in consideration of ICD risk/benefit for individual patients. Further studies conducted in a prospective manner using these clinical criteria are warranted.

Aged↗
PubMed2006

Survival in octogenarians receiving implantable defibrillators.

BACKGROUND: Although clinical trials have expanded implantable defibrillator (ICD) indications, octogenarians have been poorly represented in these studies. Overall, survival in this subgroup is ill-defined. METHODS: Consecutive patients > or = 80 years of age at ICD implant between July 1995 and September 2003 were retrospectively analyzed. Kaplan-Meier survival analysis was performed, and mortality predictors were identified. Consecutive nonelderly patients aged 60 to 70 years (60-70 group) who received ICDs over the same period were analyzed as a reference. Mortality predictors in the > or = 80 group were compared to the 60-to-70 group. RESULTS: A total of 348 patients (age, > or = 80 years [n = 107]; age, 60-70 years [n = 241]) were included. Mean follow-up time for the entire cohort was 3.3 +/- 2.2 years. Other than the estimated glomerular filtration rate (eGFR) (58 +/- 22 vs 66 +/- 22 mL/min) in the > or = 80 group versus the 60-to-70 group, no other differences in baseline characteristics were observed. Median survival was 4.2 years after implant in the > or = 80 group versus 7 years in the 60-to-70 group (P < .01). Mortality predictors in the > or = 80 group included ejection fraction (EF) < or = 30% (hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.3-4.0) and eGFR < 60 mL/min (HR, 2.2; 95% CI, 1.3-3.7). In the 60-to-70 group, EF < or = 30% (HR, 2.7; 95% CI, 1.6-4.5), eGFR < 60 mL/min (HR, 3.4; 95% CI, 2.2-5.3), diabetes (HR, 1.8; 95% CI, 1.9-2.9), and QRS width > 120 ms (HR, 2.1; 95% CI, 1.4-3.3) predicted mortality. QRS > 120 ms and diabetes were not predictors in octogenarians (HR, 1.1 and 1.5, respectively; 95% CI, 0.7-1.9 and 0.8-2.7, respectively). Analysis of octogenarians subgrouped by EF < or = 30% and eGFR < 60 mL/min identified patients whose median survival was 6.1 years (neither predictor present; n = 28), 4.7 years (either predictor present; n = 46), and 19 months (both predictors present; n = 33) (P < .01 between groups). Survival analysis in the > or = 80-year-old cohort grouped by eGFR quartile identified groups with median survival of 5.6, 4.7, 3.5 years, and 18 months, respectively, in the highest to the lowest eGFR quartile (> 75, 61-75, 41-60, and < 41 mL/min). CONCLUSIONS: Median survival in octogenarian ICD recipients is greater than 4 years. In addition to baseline EF, eGFR is a strong predictor of mortality in elderly ICD candidates. These easily identifiable clinical variables may assist clinical decision making and help to provide appropriate post-ICD implant survival expectations in this elderly patient group.

Aged↗
PubMed2006

Epicardial catheter mapping and ablation of ventricular tachycardia.

Percutaneous entry into the pericardial space allows epicardial catheter mapping and ablation in the electrophysiology laboratory, opening a perspective on cardiac electrophysiology that previously was limited largely to the operating room. Scar-related reentry after myocardial infarction usually involves the subendocardium but in some patients can only be ablated from the epicardium. Epicardial, scar-related reentry also is an important cause of ventricular tachycardia in nonischemic cardiomyopathies. Rare supraventricular tachycardias and idiopathic ventricular tachycardia that cannot be defined from the endocardium sometimes can be ablated from the epicardium. With appropriate precautions the procedural risks are low. Epicardial catheter techniques expand the options for investigating cardiac electrophysiology and treating arrhythmias in humans and may lead to insights into transmural properties influencing repolarization and the genesis of arrhythmias.

Catheter Ablation↗
PubMed2006

Myopotentials leading to ventricular fibrillation detection after advisory defibrillator generator replacement.

We present an unusual source of oversensing following an internal cardioverter-defibrillator generator change. The early appearance of reproducible myopotentials in the defibrillator sensing channel is usually due to a technical complication at the time of device implantation. Clues such as abrupt impedance change or reproduction with mechanical stimulation can help to localize a problem. Frequently the complication requires reoperation to examine the system. What do you do when everything seems to be working fine?

Action Potentials↗
PubMed2006

Large radiofrequency ablation lesions can be created with a retractable infusion-needle catheter.

BACKGROUND: Radiofrequency (RF) catheter ablation of ventricular tachycardia is sometimes limited by inadequate lesion depth. We report the use of a novel retractable needle-tipped electrode catheter with intramyocardial (IM) saline infusion and IM RF energy delivery to create large myocardial ablation lesions. METHODS: The left ventricle was entered via the femoral artery in 6 and 11 anesthetized goats and swine (32-90 kg) with an 8-F electrode catheter with an extendable 27-gauge needle at the tip (modified for RF ablation by making the needle electrically active). The needle was advanced 5-7 mm intramyocardially and 0.9% saline was infused 1 mL/min x 60 seconds prior to, and throughout a 120-second application of RF via the active needle, with power titrated to 12 W for 9 lesions, and 30-40 W for 37 lesions, followed by a 120-second RF application using the 4-mm-tip electrode, with power titrated to achieve a 10-Omega decrease in impedance. Needle/saline lesions were compared to 18 standard 4-mm-tip control lesions (power titrated to < or =50 W, to achieve a 10-Omega impedance decrease or limited to 60 degrees Celsius) and to 17 irrigated 3.5-mm-tip lesions (power titrated to < or =50 W, temperature limited to 50 degrees Celsius, 30 mL/min infusion rate). Lesions were identified in the excised heart, fixed, serially sectioned from the endocardium, and digitally analyzed to calculate volume. RESULTS: Lesions were homogeneous and had distinct borders. Compared to 4-mm-tip and irrigated-tip lesions, high-power needle/saline lesions were significantly deeper (13 +/- 2 vs 5 +/- 1 and 8 +/- 3 mm, P < 0.001), had significantly larger volumes (1,700 +/- 750 vs 240 +/- 170 and 750 +/- 650 mm(3), P < 0.001), and had larger cross-sectional area at each millimeter depth beyond the 1 mm (P < 0.01). CONCLUSIONS: IM saline infusion and IM RF energy delivery markedly increase RF lesion size as compared to standard RF ablation and is feasible with a percutaneous catheter. This method warrants further investigation because of its potential clinical utility.

Animals↗
PubMed2005

Impact of changing activation sequence on bipolar electrogram amplitude for voltage mapping of left ventricular infarcts causing ventricular tachycardia.

INTRODUCTION: Wavefront direction is a determinant of bipolar electrogram amplitude that could influence identification of low amplitude regions indicating infarction or scar. METHODS: To assess the importance of activation sequence on electrogram amplitude 11 patients with prior infarction and ventricular tachycardia were studied. At 819 left ventricular sites bipolar electrograms were recorded during atrial pacing and ventricular pacing, followed by unipolar pacing with a stimulus of 10 mA at 2 ms. Sites with a pacing threshold > 10 mA were designated electrically unexcitable scar. RESULTS: Areas of low voltage (< or =1.5 mV) were present in all patients. Atrial paced and ventricular paced electrogram amplitudes were strongly correlated (r = 0.77; P < 0.0001). Changing the activation sequence (from atrial pacing to ventricular pacing) produced a > 50% change in electrogram amplitude at 28% of sites and a > 100% change at 10% of sites, but only 8% of sites had an electrogram amplitude classified as abnormal (< or =1.5 mV) with one activation sequence and normal (> 1.5 mV) with the other activation sequence. Electrically unexcitable scar (6% of sites) was associated with lower electrogram amplitude but could not be reliably identified based on electrogram amplitude alone for either activation sequence. CONCLUSION: Voltage maps created with bipolar recordings using these methods should be relatively robust depictions of abnormal ventricular regions despite variable catheter orientation and activation sequences that might be produced by different rhythms.

Aged↗
PubMed2005

Atrial fibrillation in heart failure: high mortality risk even if ventricular function is preserved.

BACKGROUND: The purpose of this study was to determine if patients with atrial fibrillation (AF) and heart failure (HF) have a better prognosis when systolic function is preserved as compared with those with depressed systolic function. METHODS: Data from consecutive patients presenting to the emergency department at Brigham and Women's Hospital from January 1997 to December 2002 who had a diagnosis of AF and HF and a measure of ejection fraction (EF) were reviewed. Vital status was determined from the Social Security Death Index. RESULTS: Of 478 patients (mean age 74 +/- 13 years; 47% women), EF was preserved (> 50%) in 46%. Those with preserved left ventricular (LV) function were older (76 vs 72 years, P < .0020), included more women (62 vs 35%, P < .0001), more likely to have a history of hypertension and pulmonary disease and less likely to have had a prior myocardial infarction. At 5 years, mortality was similar between the preserved and depressed EF groups (50% vs 48%, P = .74). In multivariable analysis, age > 75 years, history of cancer, cerebrovascular disease, aortic valve disease, serum creatinine > 2.0 mg/dL, and serum sodium < 130 mmol/L were associated with increased mortality. Therapy with beta-blockers and angiotensin-converting enzyme inhibitors/angiotensin receptor blocker were associated with lower mortality. CONCLUSION: Patients who present to the emergency department with AF, HF, and preserved LVEF have a similarly high mortality as compared with those with depressed LVEF. Further study is needed to assess the impact of therapies and clarify the reasons for the poor prognosis.

Aged↗