Although vasodilator therapy has been shown to improve functional capacity in patients with congestive heart failure, there is no evidence that such therapy can prolong survival. Coronary artery ligation in the rat was used to produce a wide range of myocardial infarct sizes and a resultant spectrum of left ventricular dysfunction. To determine the relationship between size of myocardial infarction and long-term survival and to test the hypothesis that long-term therapy with captopril could improve survival after myocardial infarction, 302 rats were randomly assigned to either placebo or captopril therapy 14 days after coronary artery ligation. The animals were kept in a laminar flow unit and followed daily for a 1 year period or until spontaneous death. Size of myocardial infarction was determined by planimetry of serial histologic sections of the left ventricle. One year survival in placebo-treated rats decreased markedly in direct relation to increasing size of infarction (from 71 % in noninfarcted rats to only 8% in rats with large infarcts). Long-term captopril therapy prolonged the survival of rats with infarcts (p < .02). The most marked improvement in survival was noted in the animals with infarcts of moderate size. in which 1 year survival was 21 % in the placebo-treated rats and 48% in the captopril-treated rats. Thus, in this experimental preparation of myocardial infarction and left ventricular dysfunction, survival was inversely related to size of infarction. Long-term therapy with captopril, which we had previously shown to improve left ventricular function and lessen dilatation in the chronic phase of infarction, also had a pronounced effect on prolonging survival in this preparation of chronic infarction. Circulation 72, No. 2, 406-412, 1985. THE DIAGNOSIS of congestive heart failure has a grave prognosis.' 2In the Framingham Study, the 5 year mortality rate was greater than 50% for individuals newly diagnosed as having congestive heart failure.' In more recent studies, the median survival of patients with less clearly defined durations of ventricular dysfunction was often measured in months, not years.3-5 Although congestive heart failure is a syndrome that encompasses multiple etiologies, the severity of the cardiac dysfunction appears to have greater prognostic significance than does the specific cause of disease.4 The use of vasodilators, especially the angiotensin-converting enzyme inhibitors, in the treatment

Background: Advanced generation ablation technologies have been developed to achieve more effective pulmonary vein isolation (PVI) and minimize arrhythmia recurrence after atrial fibrillation (AF) ablation. Methods: We randomly assigned 346 patients with drug-refractory paroxysmal AF to contact force–guided radiofrequency ablation (CF-RF; n=115), 4-minute cryoballoon ablation (Cryo-4; n=115), or 2-minute cryoballoon ablation (Cryo-2; n=116). Follow-up was 12 months. The primary outcome was time to first documented recurrence of symptomatic or asymptomatic atrial tachyarrhythmia (AF, atrial flutter, or atrial tachycardia) between days 91 and 365 after ablation or a repeat ablation procedure at any time. Secondary end points included freedom from symptomatic arrhythmia and AF burden. All patients received an implantable loop recorder. Results: One-year freedom from atrial tachyarrhythmia defined by continuous rhythm monitoring was 53.9%, 52.2%, and 51.7% with CF-RF, Cryo-4, and Cryo-2, respectively ( P =0.87). One-year freedom from symptomatic atrial tachyarrhythmia defined by continuous rhythm monitoring was 79.1%, 78.2%, and 73.3% with CF-RF, Cryo-4, and Cryo-2, respectively ( P =0.26). Compared with the monitoring period before ablation, AF burden was reduced by a median of 99.3% (interquartile range, 67.8%–100.0%) with CF-RF, 99.9% (interquartile range, 65.3%–100.0%) with Cryo-4, and 98.4% (interquartile range, 56.2%–100.0%) with Cryo-2 ( P =0.36). Serious adverse events occurred in 3 patients (2.6%) in the CF-RF group, 6 patients (5.3%) in the Cryo-4 group, and 7 patients (6.0%) in the Cryo-2 group, with no significant difference between groups ( P =0.24). The CF-RF group had a significantly longer procedure duration but significantly shorter fluoroscopy exposure ( P <0.001 vs cryoballoon groups). Conclusions: In this multicenter, randomized, single-blinded trial, CF-RF and 2 different regimens of cryoballoon ablation resulted in no difference in 1-year efficacy, which was 53% by time to first recurrence but >98% burden reduction as assessed by continuous cardiac rhythm monitoring. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01913522.

Evidence from hemodynamic and electrophysiological measures suggests that the processing of emotionally relevant information occurs in a spatially and temporally distributed affective network. ERP studies of emotional stimulus processing frequently report differential responses to emotional stimuli starting around 120 msec. However, the involvement of structures that seem to become activated at earlier latencies (i.e., amygdala and OFC) would allow for more rapid modulations, even in distant cortical areas. Consistent with this notion, recent ERP studies investigating associative learning have provided evidence for rapid modulations in sensory areas earlier than 120 msec, but these studies either used simple and/or very few stimuli. The present study used high-density whole-head magneto-encephalography to measure brain responses to a multitude of neutral facial stimuli, which were associated with an aversive or neutral odor. Significant emotional modulations were observed at intervals of 50-80 and 130-190 msec in frontal and occipito-temporal regions, respectively. In the absence of contingency awareness and with only two learning instances, a remarkable capacity for emotional learning is observed.

The COVID-19 pandemic has led to efforts at rapid investigation and application of drugs which may improve prognosis but for which safety and efficacy are not yet established. This document attempts to provide reasonable guidance for the use of antimicrobials which have uncertain benefit but may increase risk of QT interval prolongation and ventricular proarrhythmia, notably, chloroquine, hydroxychloroquine, azithromycin, and lopinavir/ritonavir. During the pandemic, efforts to reduce spread and minimize effects on health care resources mandate minimization of unnecessary medical procedures and testing. We recommend that the risk of drug proarrhythmia be minimized by 1) discontinuing unnecessary medications that may also increase the QT interval, 2) identifying outpatients who are likely to be at low risk and do not need further testing (no history of prolonged QT interval, unexplained syncope, or family history of premature sudden cardiac R ESUM E

Emotionally significant objects and events in our environment attract attention based on their motivational relevance for survival. Such kind of emotional attention is thought to lead to affect-specific amplified processing that closely resembles effects of directed attention. Although there has been extensive research on prioritized processing of visual emotional stimuli, the spatio-temporal dynamics of motivated attention mechanisms in auditory processing are less clearly understood. We investigated modulatory effects of emotional attention at early auditory processing stages using time-sensitive whole-head magnetoencephalography. A novel associative learning procedure involving multiple conditioned stimuli (CSs) per affective category was introduced to specifically test whether affect-specific modulation can proceed in a rapid and highly differentiating fashion in humans. Auditory evoked fields (AEFs) were recorded in response to 42 different ultrashort, click-like sounds before and after affective conditioning with pleasant, unpleasant, or neutral auditory scenes. As hypothesized, emotional attention affected neural click tone processing at time intervals of the P20-50m (20 -50 ms) and the N1m (100 -130 ms), two early AEF components sensitive to directed selective attention (Woldorff et al., 1993). Distributed source localization revealed amplified processing of tones associated with aversive or pleasant compared with neutral auditory scenes at auditory sensory, frontal and parietal cortex regions. Behavioral tests did not indicate any awareness for the contingent CS-UCS (unconditioned stimulus) relationships in the participants, suggesting affective associative learning in absence of contingency awareness. Our findings imply early and highly differentiating affect-specific modulation of auditory stimulus processing supported by neural mechanisms and circuitry comparable with those reported for directed auditory attention.

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