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Biomedical subjects

Mark E Josephson

Publications and source records attributed to Mark E Josephson.

At least 37 records · Page 2Linked to original sources

Prognostic utility of comparative methods for assessment of ST-segment resolution after primary angioplasty for acute myocardial infarction: the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) trial.

OBJECTIVE: This study was done to assess and compare the prognostic significance of multiple methods for measuring ST-segment elevation resolution (STR) following primary percutaneous coronary intervention (PCI). BACKGROUND: Resolution of ST-segment elevation (STE) is a powerful predictor of both infarct-related artery patency and mortality in acute myocardial infarction (AMI). Recent thrombolytic studies have suggested that simple measures of STR may be as powerful as more complex algorithms. The optimal method of assessing STR following primary PCI has not been studied. METHODS: We analyzed 700 patients with technically adequate baseline and post-PCI electrocardiograms from the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) trial. Five methods were used to assess STR: 1) summed %STR across multiple leads (SigmaSTR); 2) %STR in the single lead with maximum baseline STE (MaxSTR); 3) absolute maximum STE before the procedure; 4) absolute maximum STE after intervention (MaxSTPost); and 5) a categorical variable based upon MaxSTPost (High Risk). RESULTS: At 30 days, SigmaSTR, MaxSTR, and MaxSTPost all correlated strongly with mortality (p = 0.004, p = 0.005, and p < 0.0001, respectively) and the combined end point of mortality or reinfarction (p = 0.001, p = 0.001, and p < 0.0001). At one year, SigmaSTR and MaxSTPost correlated with mortality (p = 0.04, p = 0.0001), reinfarction (p = 0.02, p = 0.0015), and the combined end point (p = 0.02, p < 0.0001). By multivariate analysis, only the simpler measures of MaxSTPost and High Risk categorization independently predicted all outcomes at both time points. CONCLUSIONS: The STR following primary PCI in AMI correlates strongly with mortality and reinfarction, independent of target vessel patency. The simple measure of the maximal residual degree of STE after primary PCI is a strong independent predictor of both survival and freedom from reinfarction at 30 days and 1 year.

Aged↗

Electrocardiographic predictors of arrhythmic death and total mortality in the multicenter unsustained tachycardia trial.

BACKGROUND: Stratifiers of sudden and total mortality risk are needed to optimally target preventive therapies in patients with coronary artery disease and impaired ventricular function. We assessed the prognostic significance of ECG markers of conduction abnormalities and left ventricular hypertrophy in the Multicenter Unsustained Tachycardia Trial (MUSTT). METHODS AND RESULTS: We analyzed the ECGs of 1638 patients from MUSTT who did not receive antiarrhythmic therapy (antiarrhythmic medication or implantable cardioverter-defibrillator). After adjustment for other significant factors, left bundle-branch block and intraventricular conduction delay were associated with a 50% increase in the risk of both arrhythmic and total mortality. Right bundle-branch block was not associated with arrhythmic or total mortality. Left ventricular hypertrophy was the only ECG predictor of arrhythmic (hazard ratio, 1.35; 95% CI, 1.08 to 1.69) but not total mortality. CONCLUSIONS: In patients with coronary artery disease, depressed left ventricular function, and nonsustained ventricular tachycardia, QRS prolongation resulting from left bundle-branch block or intraventricular conduction delay but not right bundle-branch block provided prognostic information about the risk of arrhythmic and total mortality independently of electrophysiological evaluation and ejection fraction. Left ventricular hypertrophy was associated with increased arrhythmic but not total mortality.

Aged↗

Two levels of block within a pulmonary vein.

We present a 37-year-old woman with drug refractory atrial fibrillation referred for a pulmonary vein (PV) isolation procedure who manifested a tachycardia with 2:1 intra-PV block within a dissociated PV. During ablation in the right superior PV, the surface rhythm became normal sinus, with persistent atrial fibrillation within the PV. Shortly thereafter, an atrial tachycardia with a cycle length of 190 ms and 2:1 distal to proximal exit block was observed within the isolated PV. Conduction block within a PV electrically isolated from the left atrium is a newly observed phenomenon that may have implications to the electrophysiologic properties of the PV muscular sleeves.

Adult↗

Early recurrence of arrhythmia in patients taking amiodarone or class 1C agents for treatment of atrial fibrillation or atrial flutter.

Amiodarone use for the prevention of recurrent atrial fibrillation or atrial flutter requires drug loading over a period of several days to weeks, whereas class 1C agents do not. Three hundred thirty-nine patients were evaluated during drug loading with amiodarone or class 1C agents, and it was found that recurrent arrhythmia was common, usually not persistent, and frequently asymptomatic. Recurrent arrhythmia was not more common with amiodarone.

Age Factors↗

Catheter ablation of ventricular epicardial tissue: a comparison of standard and cooled-tip radiofrequency energy.

BACKGROUND: Transthoracic epicardial catheter ablation is an emerging catheter ablation strategy being used clinically at increasing frequency. However, the efficacy of standard RF ablation on the epicardial surface of the heart is hindered by (1) the lack of convective cooling of the ablation electrode and (2) the varying presence of epicardial adipose tissue interposed between the ablation electrode and the target site. This experimental animal study examines the biophysical characteristics of radiofrequency (RF) ablation lesions generated by either standard or cooled-tip ablation of the ventricular epicardium. METHODS AND RESULTS: Nonsurgical subxyphoid pericardial access was achieved in 10 normal goats and 7 pigs with healed myocardial infarctions. A 4-mm cooled-tip RF ablation catheter (continuous 0.9% saline circulation at 0.6 mL/s; goal temperature, 40 degrees C; 60 seconds) was used to deliver epicardial ventricular lesions: 47 in normal tissue and 22 in infarcted tissue. Standard RF ablation lesions (n=33) using a 4-mm top catheter (goal temperature, 70 degrees C; 60 seconds) were also placed on normal epicardial tissue. Lesions created with standard and cooled-tip RF ablation were 3.7+/-1.3 mm (25+/-16.8 W) and 6.7+/-1.7 mm (44.8+/-6.8 W) in depth, respectively. On scar tissue, lesions made with the cooled-tip catheter measured 14.6+/-2.7 mm in length, 11.8+/-2.9 mm in width, and 5.6+/-1.2 mm in depth (35.6+/-7.1 W). In areas covered by epicardial fat (3.1+/-1.2 mm thick), standard RF energy did not generate any appreciable lesions, but cooled-tip RF lesions were 4.1+/-2 mm in depth (45+/-4.4 W). CONCLUSIONS: Cooled-tip RF ablation can generate epicardial lesions more effectively than standard RF ablation and appears to be of particular benefit in ablating areas with overlying epicardial fat.

Adipose Tissue↗

Standard right atrial ablation is effective for atrioventricular nodal reentry with earliest activation in the coronary sinus.

INTRODUCTION: Reports suggest that coronary sinus (CS) or left atrial ablations may be necessary for treatment of AV nodal reentrant tachycardia (AVNRT) with earliest retrograde atrial activation in the CS. We assessed the efficacy of standard right atrial catheter ablation approaches in these tachycardias and determined the incidence of earliest activation in the CS in AVNRT. METHODS AND RESULTS: We retrospectively evaluated intracardiac recordings from 225 consecutive patients who underwent electrophysiologic studies and radiofrequency (RF) ablation for AVNRT in two institutions. Atrial activation during AVNRT was evaluated using multiple catheters according to standard protocol used in our laboratories. RF ablations in the triangle of Koch were performed in all patients. Eighteen of 225 patients (8%) had earliest activation in one of the CS poles. The demographics and AVNRT characteristics of these 18 patients were similar to those of the other 207 patients who did not have CS as earliest activation site and included both typical and atypical AVNRT. Following RF ablation, none of the 18 patients had inducible AVNRT. CONCLUSION: Successful RF ablation can be performed at standard sites in the triangle of Koch regardless of earliest site of atrial activation. The incidence of CS as earliest retrograde atrial activation site in AVNRT is 8%.

Adult↗

Assessment of left atrial volume by contrast enhanced magnetic resonance angiography.

Left atrial (LA) volume is associated with cardiovascular morbidity, particularly atrial fibrillation. Contrast-enhanced magnetic resonance angiography (CE-MRA) visualizes the LA, but the validity of LA volume measurements using this technique has not been evaluated. We performed CE-MRA and cine magnetic resonance (MR) in 18 consecutive patients referred for CE-MRA prior to atrial fibrillation ablation. The CE-MRA LA volumes were compared to cine MR LA volumes at the maximal LA size and at LA end-diastole using linear regression and limits of agreement analysis. The mean cine MR LA volume was 118 +/- 39 mL at maximal LA size and 91 +/- 38 mL at LA end-diastole. Left atrial volume determined by CE-MRA was 93 +/- 38 mL. Although the CE-MRA LA volume had a strong correlation with the maximal cine MR LA volume (R2 = 0.86, p < 0.001), the 95% limits of agreement were relatively wide (-54 to 3 mL). The cine MR LA end-diastolic and CE-MRA LA volumes were more closely correlated (R2 = 0.98, p < 0.001) with narrow 95% limits of agreement (-8 to 11 mL). The CE-MRA LA volumes correspond most closely to LA end-diastolic cine MR LA volumes and may be a useful measure of LA size.

Cardiac Volume↗

A method for the determination of proximal pulmonary vein size using contrast-enhanced magnetic resonance angiography.

OBJECTIVES: We sought to develop a reproducible method for characterizing the anatomy of the proximal pulmonary veins. BACKGROUND: Contrast-enhanced three-dimensional magnetic resonance angiography (CE-MRA) is a commonly requested test before and after radiofrequency ablation for the treatment of atrial fibrillation. While CE-MRA readily visualizes the pulmonary veins, there is no standardized method for determining their size and cross-sectional anatomy. METHODS: Data for 24 consecutive patients referred for pulmonary vein CE-MRA before an elective ablation procedure for the treatment of atrial fibrillation were analyzed. Detailed measurements of the pulmonary vein diameter, circumference, and cross-sectional area were obtained at three locations: the juncture of the pulmonary vein with the left atrium (LA) (position 1J), the narrowest segment within 5 mm of the juncture (position 2(5mm)), and at the location in the sagittal plane at which the pulmonary veins separate from the LA and from each other (position 3Sag). Intraobserver and interobserver variabilities were also determined for each method. RESULTS: The left lower pulmonary vein was significantly smaller than the other pulmonary veins at positions 1J and 2(5mm) (p<0.05). The right upper pulmonary vein was significantly larger than the other pulmonary vein at position 3Sag (p<0.05). At positions 1J and 2(5mm), the diameter had a low correlation with the circumference and cross-sectional area. At position 3Sag, the major and minor axis dimensions had a very high correlation with the circumference and cross-sectional area. The intraobserver and interobserver variabilities were substantially lower (better) for position 3Sag. CONCLUSIONS: Pulmonary vein diameter measurements are highly variable and do not reflect true anatomic variation in cross-sectional anatomy. A sagittal method of determining pulmonary vein size was highly reproducible and may therefore be advantageous for use in patients likely to need serial examinations.

Adult↗

Relationship of baseline electrocardiographic characteristics with the response to cardiac resynchronization therapy for heart failure.

Prospective identification of patients most and least likely to respond to cardiac resynchronization therapy (CRT) for congestive heart failure (CHF) will allow clinicians to target this intervention most efficiently. The authors hypothesized that ECG variables including RBBB and indicators of RV dysfunction and extensive prior myocardial infarction would correlate with diminished response to CRT. This study analyzed preimplantation ECGs in 110 patients with ICD indications and CHF due to left ventricular systolic dysfunction randomized to active biventricular pacing in the MIRACLE ICD trial. Clinical and ECG variables on the outcome of change in peak oxygen consumption from baseline to 6 months (Delta-VO2 ) were evaluated. For this cohort, average peak VO2 improved from 13.4 to 14.3 mL/kg per minute. Among clinical variables, the strongest predictors of increasing Delta-VO2 were reduced exercise time and peak VO2 at baseline. A dominant R wave in lead a VR, RBBB, and evidence of prior anterior infarction were each associated with significantly smaller average improvements in Delta-VO2 than their absence in univariate analysis. Alternative ECG criteria, including QRS duration, had no relationship with the outcome. In a multivariate model, only baseline VO2 (beta=-0.3, P=0.001) and ECG evidence of prior anterior infarction (beta=-1.3, P=0.03) were associated with the outcome. ECG markers of anterior infarction and RV dilation may help identify CHF patients unlikely to benefit from biventricular pacing. Further assessment is needed of these and other predictors of therapeutic response to CRT.

Aged↗

Impact of a practice guideline for patients with atrial fibrillation on medical resource utilization and costs.

Health care resource utilization is high for patients presenting with acute atrial fibrillation (AF). The potential for treatment algorithms to safely reduce resource consumption in this setting has not been prospectively evaluated. We designed and implemented a practice guideline for the management of patients presenting to the emergency department (ED) with the primary diagnosis of AF, with emphasis on appropriate cardioversion, use of oral rate-controlling medications, and expedited referral to an outpatient AF clinic. We prospectively collected clinical and resource utilization data on all such patients for 14 months before and after institution of the guideline. Institution of the guideline was associated with a decreased rate of hospital admission (from 74% to 38%), with no differences in ED return visits or hospital readmission within 30 days. No strokes or deaths were observed. This large decrease in resource utilization during the intervention phase of the study translated to an average decrease in 30-day total direct health care costs of approximately $1,400 US dollars per patient. Our clinical and cost outcomes were minimally affected after statistical adjustment for baseline differences between study groups. We conclude that the implementation of our practice guideline was feasible, safe, and effective. Widespread adoption of such practices may have large financial implications for the health care system.

Aged↗

Safety and feasibility of a clinical pathway for the outpatient initiation of antiarrhythmic medications in patients with atrial fibrillation or atrial flutter.

We sought to establish the safety and feasibility of a clinical pathway for the outpatient initiation of antiarrhythmic medications (AAMs) for the maintenance of sinus rhythm in patients with atrial fibrillation (AF) or atrial flutter (AFl). AAMs are frequently utilized to maintain sinus rhythm in patients with AF or AFl. Although they are often initiated in an outpatient setting, there is little prospective evidence for the safety of this approach. Patients with a history of AF or AFl were prospectively monitored with an event recorder during 409 AAM initiation trials. All AAMs were initiated in sinus rhythm. Patients transmitted a recording (30 seconds) once daily for 10 consecutive days. Amiodarone was used for 212 patients (51.8%), 127 (31.1%) received a type 1C AAM, 37 (9.0%) received sotalol, and 33 (8.1%) received a type 1A AAM. Adverse events occurred in 17 patients (3 died, 3 had bradycardia that required permanent pacemaker implantation, and 11 had bradycardia requiring a decrease in the dose of antiarrhythmic or rate-controlling medication). Most events were due to bradycardia in patients who received amiodarone. There was a significant association between amiodarone-associated bradycardia and women. The only event that occurred during the first 48 hours was an episode of bradycardia in a patient who received amiodarone and was managed as an outpatient. The outpatient initiation of AAMs for patients with a history of AF or AFl while in sinus rhythm is associated with significant risk. Most adverse events occurred beyond the usual time period for in-hospital monitoring of the initiation of AAMs.

Adult↗

Combined epicardial and endocardial electroanatomic mapping in a porcine model of healed myocardial infarction.

BACKGROUND: Substrate mapping of post-myocardial infarction ventricular tachycardia involves electroanatomic delineation of scarred tissue on the basis of electrogram characteristics during sinus rhythm. A percutaneous transthoracic technique was recently described that allows catheter mapping of the epicardial surface of the heart. This study sought to determine whether the epicardial extent of a myocardial infarct could be defined during sinus rhythm. METHODS AND RESULTS: In a porcine model of healed anterior wall myocardial infarction (n=13 animals), detailed in vivo left ventricular endocardial and ventricular epicardial electroanatomic mapping was performed. Catheter access to the pericardial space was achieved by subxyphoid puncture under fluoroscopic guidance. Bipolar electrogram amplitude and duration characteristics of normal tissue were established on the basis of in vivo epicardial mapping data in 8 additional normal animals. With the use of these criteria, radiofrequency lesions (4 to 11 per animal) were placed along the endocardial and epicardial scar borders as defined by the electroanatomic map. The area of epicardial scar defined by abnormal bipolar voltage correlated well with the dimensions measured on pathological examination. The size and location also correlated well with the scar dimensions defined by electrogram duration criteria. Late potentials were noted in the border zones of both surfaces of the scar. During pathological examination, the radiofrequency lesions were situated at the borders of the epicardial scar. CONCLUSIONS: A 3-dimensional construct of the infarcted myocardium can be rendered by combined epicardial and endocardial electroanatomic mapping. This experimental protocol is propaedeutic to future clinical studies incorporating endocardial and epicardial substrate mapping into catheter ablation strategies to treat post-myocardial infarction ventricular tachycardia.

Animals↗