34 research outputs found
Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19
IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19.
Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19.
DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022).
INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days.
MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes.
RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively).
CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes.
TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570
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Contribution of his bundle recordings to the understanding of clinical arrhythmias
His bundle electrocardiography has enhanced our knowledge of cardiac electrophysiology. The catheter technique for recording potentials from the specialized conducting tissues is most useful in determining the site (or sites) of atrioventricular and ventriculoatrial delays and blocks. Various types of ventricular preexcitation resulting from conduction through Kent, Mahaim and James bundles are adequately identified with this method. In some cases it provides the only means of differentiation between supraventricular and ventricular arrhythmias. A secondary gain obtained from His bundle recordings is the evaluation of the electrophysiologic effects of various drugs. Information thus obtained is not only academically important but also clinically useful, since it is a significant factor in establishing the proper therapy
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Significance of His Bundle Recordings with Short H-V Intervals
The H-V interval was defined as the time elapsed between activation of His bundle and ventricular muscle. “Shortening” of this interval had a different significance in various pathologic conditions. For instance, in the presence of late ventricular extrasystoles a short H-V interval merely indicated that part of the ventricles had been depolarized by the ectopic focus before than by the impulse traversing the His bundle. This interval was also shortened in ventricular preexcitation due to a total (Kent bundle) or partial (Mahaim bundle) bypass of the normal A-V conducting system. When only the A-V node was bypassed (James bundle) the H-V interval was not short Extrasystoles arising in the posterior division of the left branch produced retrograde activation of His bundle ahead of the ventricles. Pseudoshortening of the H-V interval occurred if the His bundle was depolarized after the onset of the QRS complex in the surface electrogram but before the electrogram in the HBE leads
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Usefulness of vectorcardiography combined with his bundle recordings and cardiac pacing in evaluation of the preexcitation (Wolff-Parkinson-White) syndrome
Vectorcardiograms (Frank system) were recorded simultaneously with His bundle electrograms during atrial stimulation in 3 patients with intermittent preexcitation Wolff-Parkinson-White (WPW) syndrome. In 2 cases with classic WPW, type A, loops were obtained during (1) exclusive conduction through the normal pathway, (2) coexisting accessory bundle and normal pathway conduction, and (3) exclusive accessory pathway conduction. Combination beats (resulting from ventricular depolarization through both pathways) showed an initial delay associated with anteriorly placed QRS loops and maximal vectors. When exclusive accessory bundle conduction occurred, a rightward and anteriorly oriented terminal delay was added to the initial slowing. This terminal delay was not ascribed to right bundle branch block but to the specific pattern of activation of an impulse apparently propagating from the posterosuperior wall of the left ventricle. In fact, these vectorcardiograms were similar to those recorded from patients with ectopic impulses originating at the posterosuperior left ventricular wall. When exclusive conduction through the normal pathway was associated with right bundle branch block, the prolonged St-V interval coexisted with a loop showing only terminal conduction disturbances.
The loops seen during exclusive accessory bundle conduction in the patient with WPW, type B, had a leftward, posterior and superior orientation. The spatial delay was diffuse, although more marked toward the end of depolarization. This terminal (leftward) conduction defect was not attributed to right bundle branch block. The sequence of ventricular activation (as recorded at the body surface) was similar to that occurring during right ventricular apical pacing. Resemblance between vectorcardiograms showing exclusive accessory bundle conduction and those produced by direct stimulation of specific ventricular sites suggests, but certainly does not prove, that the electrical impulse is propagated from equivalent sites
His Bundle Electrograms in Patients with Short P-R Intervals, Narrow QRS Complexes, and Paroxysmal Tachycardias
His bundle electrograms were recorded in three patients with short P-R intervals, narrow QRS complexes, and a history of paroxysmal tachycardias. During sinus rhythm or atrial stimulation with long cycle lengths, the shortening of the P-R interval was due to a decrease in the low right atrium-His (LRA-H) interval (representing A-H conduction time). The latter was also short during retrograde (V-A) conduction. These findings support the existence of an A-V nodal bypass operation in both directions. In one patient, the LRA-H interval did not lengthen when the atrial rate was increased. Intermittent atrial pacing was performed in the two other patients. The LRA-H interval was short at long coupling intervals, but it started to increase (progressively) at a given Stimulus 1 -Stimulus 2 interval. Apparently, the refractory period of the accessory bundle was encountered so that the impulse was propagated, with various degrees of delay, through the A-V node. A James bundle need not be present in all patients with similar electrocardiograms. Abnormalities of unknown origin could cause this phenomenon. Reciprocating tachycardias were induced by stimulation of the atria in one patient. The triggering beat consistently had a long A-V conduction time. Although in this case retrograde (V-A) propagation most probably occurred through the accessory communication, the possibility of a functional intranodal dissociation of a single anatomical pathway could not be excluded
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Functional properties of the human atrioventricular and intraventricular conduction system during premature atrial stimulation
Premature atrial stimulation combined with His bundle and local ventricular electrograms was used in three patients to analyse complex AV conduction patterns resulting from variable degrees of delayed or enhanced propagation within the atria, A-V node, and ventricular specialized conducting system. The St1-St2 intervals were plotted against the corresponding responses at the low right atrium (LRA), His bundle, intitial site of ventricular depolarization (V), right ventricular apex (RVA), and posterosuperior wall of left ventricle (LV). The electrophysiological effects of a β-blocking agent, Alprenolol, were studied in two patients. This drug, at a dose of 0·2 mg/kg, increased the effective and functional refractory periods of the atria and AV node. In the presence of bifascicular blocks the effective refractory period of the ventricular specialized conducting system was also lengthened. Different grades of functional bilateral bundle branch block were detected in one case. The amount of delay in each bundle branch block could not be determined from the surface leads alone. A supernormal phase of intra-atrial conduction occurred in one patient. These studies extend the usefulness of intracardiac recordings in understanding otherwise complex electrophysiological phenomena in the human heart
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