Language prediction mechanisms in human auditory cortex.

Spoken language, both perception and production, is thought to be facilitated by an ensemble of predictive mechanisms. We obtain intracranial recordings in 37 patients using depth probes implanted along the anteroposterior extent of the supratemporal plane during rhythm listening, speech perception, and speech production. These reveal two predictive mechanisms in early auditory cortex with distinct anatomical and functional characteristics. The first, localized to bilateral Heschl's gyri and indexed by low-frequency phase, predicts the timing of acoustic events. The second, localized to planum temporale only in language-dominant cortex and indexed by high-gamma power, shows a transient response to acoustic stimuli that is uniquely suppressed during speech production. Chronometric stimulation of Heschl's gyrus selectively disrupts speech perception, while stimulation of planum temporale selectively disrupts speech production. This work illuminates the fundamental acoustic infrastructure-both architecture and function-for spoken language, grounding cognitive models of speech perception and production in human neurobiology.

Atrial support pacing in heart failure: results from the multicenter PEGASUS CRT trial.

INTRODUCTION: Cardiac resynchronization therapy (CRT) efficacy trials to date used atrial-synchronous biventricular pacing wherein there is no or minimal atrial pacing. However, bradycardia and chronotropic incompetence are common in this patient population. This trial was designed to evaluate the effect of atrial support pacing among heart failure patients receiving a CRT defibrillator. METHODS AND RESULTS: PEGASUS CRT was a multicenter, 3-arm, randomized study. At 6 weeks, patients were randomized to DDD mode at a lower rate of 40 bpm (DDD-40; control arm), or one of the following 2 treatment arms: DDD-70, or DDDR-40. The primary endpoint was a clinical composite endpoint that included all-cause mortality, heart failure events, NYHA functional class, and patient global self-assessment. Subjects were classified as improved, unchanged, or worsened at 12 months. There were 1,433 patients randomized, of whom 66% were male, mean age was 67 ± 11 years, and mean left ventricular ejection fraction was 23 ± 7%. The average follow-up time was 10.5 ± 3.5 months and 1,309 patients contributed to the primary endpoint. No significant differences were observed in the composite endpoint between either of the 2 treatment arms compared to the control arm (P>0.05 for both comparisons). Additionally, there were no differences among the groups in mortality or heart failure events. CONCLUSION: In advanced heart failure patients treated with CRT, atrial support pacing did not improve clinical outcomes compared to atrial tracking. However, atrial pacing did not adversely affect mortality or heart failure events.

Postoperative atrial fibrillation and mortality after coronary artery bypass surgery.

OBJECTIVES: We sought to determine if the occurrence of postoperative atrial fibrillation (AF) affects early or late mortality following coronary artery bypass surgery (CABG). BACKGROUND: Atrial fibrillation is the most common arrhythmia seen following CABG. METHODS: The Texas Heart Institute Cardiovascular Research Database was used to identify all patients that developed AF after isolated initial CABG from January 1993 to December 1999 (n = 994). This population was compared with patients who underwent CABG during the same period but did not develop AF (n = 5,481). In-hospital end points were adjusted using logistic regression models to account for baseline differences. Long-term survival was evaluated using a retrospective cohort design, where Cox proportional hazards methods were used to adjust for baseline differences, and with case-matched populations (n = 390, 195 per arm). RESULTS: Atrial fibrillation was diagnosed in 16% of the population. Postoperative AF was associated with greater in-hospital mortality (odds ratio [OR] 1.7, p = 0.0001), more strokes (OR 2.02, p = 0.001), prolonged hospital stays (14 vs. 10 days, p < 0.0001), and a reduced incidence of myocardial infarction (OR 0.62, p = 0.01). At four to five years, survival was worse in patients who developed postoperative AF (74% vs. 87%, p < 0.0001 in the retrospective cohort; 80% vs. 93%, p = 0.003 in the case-matched population). On multivariate analysis, postoperative AF was an independent predictor of long-term mortality (adjusted OR 1.5, p < 0.001 in the retrospective cohort; OR 3.4, p = 0.0018 in the case-matched population). CONCLUSIONS: The occurrence of AF following CABG identifies a subset of patients who have a reduced survival probability following CABG. The impact of various strategies, such as antiarrhythmics and warfarin, aimed at reducing AF and its complications deserves further study.

Inappropriate shock delivery and biventricular pacing cardiac defibrillators.

In the United States, physicians adapt currently available defibrillators to accommodate leads for biventricular pacing in those congestive heart failure patients who might benefit from cardiac resynchronization and who are additionally at risk for sudden cardiac death. The adaptation of the lead system of available defibrillators to also allow them to function as biventricular pacemakers presents occasions in which inappropriate shocks are delivered due to double counting of the right and left ventricular depolarizations by the implantable cardiac defibrillator. We reviewed a series of inappropriate shock deliveries that occurred after the implantation of biventricular pacing cardiac defibrillators at our institution; all of these shocks were related to ventricular double counting. Each had different underlying causes and management strategies. Complications such as these emphasize the importance of attentiveness to ventricular channel electrograms and to device sensing with the use of biventricular pacing cardiac defibrillators. In addition, a thorough working knowledge of pacemaker and defibrillator operation is essential for the prediction and correction of inappropriate therapies.

Magnetic resonance imaging of myocardial fibrosis in hypertrophic cardiomyopathy.

Myocardial fibrosis can occur in patients who have hypertrophic cardiomyopathy in the absence of epicardial coronary disease. In such patients, myocardial fibrosis has been linked to a poorer prognosis than in those without fibrosis. Gadolinium-DTPA delayed-enhancement magnetic resonance imaging (de-MRI) accurately identifies regions of myocardial fibrosis. We used de-MRI to screen for myocardial fibrosis in 8 patients with nonobstructive hypertrophic cardiomyopathy that had been diagnosed by 2-dimensional echocardiography. After localization of the heart and acquisition of electrocardiographically gated cine images, gadolinium-DTPA (0.2 mmol/kg) was administered to the patient. Fifteen minutes later, de-MRI images were obtained using a T1-weighted, inversion-recovery fast, low-angle shot sequence. Images were gated to end-diastole and obtained during a single breath-hold. The inversion time was modified iteratively to obtain maximal nulling of the signal from the ventricular myocardium. Regions of myocardium with abnormally high signals (>300% of remote normal myocardium) were designated as fibrotic. Eight patients with hypertrophic cardiomyopathy underwent de-MRI. The mean age was 52 years, the mean left ventricular mass was 201 grams, and the mean ejection fraction was 0.68. In the 6 patients with recent clinical deterioration, de-MRI showed clearly delineated areas of myocardial fibrosis; no such areas were seen in the 2 asymptomatic patients. We conclude that patients with symptomatic hypertrophic cardiomyopathy display regions of abnormal signal intensity on de-MRI that likely represent fibrosis. This technique may provide useful information in the evaluation of such patients and warrants further study.

Rapid ventricular tachycardias associated with cilostazol use.

A 92-year-old woman with normal systolic function had recently begun using the newly approved phosphodiesterase III inhibitor cilostazol when she was admitted with lower-extremity pain. Cilostazol is indicated for patients with intermittent claudication and contraindicated for patients with congestive heart failure. Two days after admission, the patient developed ventricular tachycardia. Cilostazol was discontinued, and shortly thereafter the ventricular tachycardia subsided. In this case, cilostazol was apparently an important predisposing factor for ventricular tachycardia.

Coronary artery bypass surgery versus coronary stenting: risk-adjusted survival rates in 5,619 patients.

We used the Texas Heart Institute Cardiovascular Research Database to retrospectively identify patients who had undergone their 1st revascularization procedure with coronary artery bypass surgery (CABG; n=2,826) or coronary stenting (n=2,793) between January 1995 and December 1999. Patients were classified into 8 anatomic groups according to the number of diseased vessels and presence or absence of proximal left anterior descending coronary artery disease. Mortality rates were adjusted with proportional hazards methods to correct for baseline differences in severity of disease and comorbidity. We found that in-hospital mortality was significantly greater in patients undergoing CABG than in those undergoing stenting (3.6% vs 0.75%; adjusted OR 8.4; P < 0.0001). At a mean 2.5-year follow-up, risk-adjusted survival was equivalent (CABG 91%, stenting 95%; adjusted OR 1.26; P = 0.06). When subgroups matched for severity of disease were compared, no differences in risk-adjusted survival were seen. A survival advantage of stenting was noted in 3 categories of patients: those >65 years of age (OR 1.33, P = 0.049), those with non-insulin-requiring diabetes (OR 2.06, P = 0.002), and those with any noncoronary vascular disease (OR 1.59, P = 0.009). In this nonrandomized observational study, CABG had a higher periprocedural mortality rate than did percutaneous stenting. At 2.5 years, however, the survival advantage of stenting was no longer evident. These data suggest that there is no intermediate-term survival advantage of CABG over stenting in patients who have multivessel disease with lesions that can be treated percutaneously.

Heart rate variability and cardiovascular mortality.

The autonomic nervous system plays a major role in affecting the cardiac milieu and promoting malignant ventricular activity. The measurement of heart rate variability (HRV) is a noninvasive tool for assessing the status of the autonomic nervous system. A depressed HRV among post-myocardial infarction patients is a well-established risk factor for arrhythmic death. A reduced HRV has also been used to identify diabetic patients with autonomic neuropathy. This paper presents recent developments in the use of HRV, focusing on further refinement and validation of the use of both linear and nonlinear dynamics for sudden death prognostication, evaluation of the effect of specific pharmacologic agents on HRV, and assessment of HRV in health and in specific disease states that have been associated with an increased mortality risk.

Coding criteria of bladder cancer: effects on estimating survival.

The aim of this study is to evaluate the consistency between routine methods for coding urinary bladder tumours in eight Italian cancer registries and the European Network of cancer registries (ENCR) criteria. Furthermore, it aims to evaluating the impact of the discordance on survival data. Eight cancer registries took part in the study: Ferrara, Florence, Macerata, Ragusa, Romagna, Sassari, Turin and Varese. The first 100 cases of neoplasm of the urinary bladder incident in the years 1993-1994 were identified from the files of each registry. The original pathology reports were made available. A working group considered eligible to the study 699 cases of microscopically confirmed transitional carcinoma (ICD-O morphology code 812-813). Using the ENCR criteria, each of these was classified according to morphology code (8120 vs. 8130) and behaviour (1/ uncertain, /2 non-invasive, 3/ invasive). Information of tumour behaviour was classified as follows: (i) present, when expressly stated in the original report, (ii) deducible, when not expressly stated but suggested by the pathologist's description, and (iii) absent, when impossible to determine on the basis of the original pathology report. The working group classification of tumour behaviour and the classification of the registry of origin were compared. There was a full concordance in the case of complete agreement on the morphology code, and partial concordance when only the invasive or non-invasive behaviour code was agreed upon. As much as 92.5% cases were microscopically confirmed. Tumour behaviour was expressly stated in the original report of 69.2% cases, not stated but suggested by the pathologist's description in 21.2% cases, and impossible to determine in 9.6%. Agreement between the panel and the registry of origin was complete in 71.2% cases and partial in 12.3% while there was a complete discordance in 16.5% cases. The panel interpreted as non-invasive 111 cases coded as invasive by the registry of origin. Conversely, it was estimated that 24% cases included in incidence data were non-invasive. This article discusses the impact of misclassification on survival data.