Comparison of Severe Maternal Morbidities Associated With Delivery During Periods of Circulation of Specific SARS-CoV-2 Variants.

Importance: Infection with SARS-CoV-2, which causes COVID-19, is associated with adverse maternal outcomes. While it is known that severity of COVID-19 varies by viral strain, the extent to which this variation is reflected in adverse maternal outcomes, including nonpulmonary maternal outcomes, is not well characterized. Objective: To evaluate the associations of SARS-CoV-2 infection with severe maternal morbidities (SMM) in pregnant patients delivering during 4 pandemic periods characterized by predominant viral strains. Design, Setting, and Participants: This retrospective cohort study included patients delivering in a multicenter, geographically diverse US health system between March 2020 and January 2022. Individuals with SARS-CoV-2 infection were propensity-matched with as many as 4 individuals without evidence of infection based on demographic and clinical variables during 4 time periods based on the dominant strain of SARS-CoV-2: March to December 2020 (wild type); January to June 2021 (Alpha [B.1.1.7]); July to November 2021 (Delta [B.1.617.2]); and December 2021 to January 2022 (Omicron [B.1.1.529]). Data were analyzed from October 2021 to June 2022. Exposures: Positive SARS-CoV-2 nucleic acid amplification test result during the delivery encounter. Main Outcomes and Measures: The primary outcome was any SMM event, as defined by the US Centers for Disease Control and Prevention, during hospitalization for delivery. Secondary outcomes were number of SMM, respiratory SMM, nonrespiratory SMM, and nontransfusion SMM events. Results: Over all time periods, there were 3129 patients with SARS-CoV-2, with a median (IQR) age of 29.1 (24.6-33.2) years. They were propensity matched with a total of 12 504 patients without SARS-CoV-2, with a median (IQR) age of 29.2 (24.7-33.2) years. Patients with SARS-CoV-2 infection had significantly higher rates of SMM events than those without in all time periods, except during Omicron. While the risk of any SMM associated with SARS-CoV-2 infection was increased for the wild-type strain (odds ratio [OR], 2.74 [95% CI, 1.85-4.03]) and Alpha variant (OR, 2.57 [95% CI, 1.69-4.01]), the risk during the Delta period was higher (OR, 7.69 [95% CI, 5.19-11.54]; P for trend < .001). The findings were similar for respiratory complications, nonrespiratory complications, and nontransfusion outcomes. For example, the risk of nonrespiratory SMM events for patients with vs without SARS-CoV-2 infection were similar for the wild-type strain (OR, 2.16 [95% CI, 1.40-3.27]) and Alpha variant (OR, 1.96 [95% CI, 1.20-3.12]), highest for the Delta variant (OR, 4.65 [95% CI, 2.97-7.29]), and not significantly higher in the Omicron period (OR, 1.21 [95% CI, 0.67-2.08]; P for trend < .001). Conclusions and Relevance: This cohort study found that the SARS-CoV-2 Delta variant was associated with higher rates of SMM events compared with other strains. Given the potential of new strains, these findings underscore the importance of preventive measures.

Treatment of Atrial Fibrillation.

IMPORTANCE: Atrial fibrillation is a common arrhythmia that affects more than 2.5 million people in the United States and causes substantial morbidity and mortality, especially regarding the increased risk of stroke. OBJECTIVE: To summarize atrial fibrillation treatment exclusive of stroke prevention. EVIDENCE REVIEW: An Ovid MEDLINE comprehensive literature search was performed on atrial fibrillation therapy excluding anticoagulation and emphasizing studies published within the last 5 years through April 2015 (N = 5044 references). The 2014 atrial fibrillation guideline from the American Heart Association, the American College of Cardiology, and the Heart Rhythm Society also was reviewed. FINDINGS: Reversible causes of atrial fibrillation should be identified. Risk factor modification, including weight loss and treatment of hypertension, diabetes, and obstructive sleep apnea can reduce atrial fibrillation episodes. Appropriate anticoagulation is necessary for patients at substantial stroke risk regardless of rate or rhythm treatment strategy. Sinus rhythm is often needed to control symptoms; however, an alternative strategy for atrial fibrillation is appropriate rate control. Rate control is safe in older patients (those who are about age ≥65 years) followed up for a few years, but no such safety data exist for patients younger than 60 years or for those followed up for longer periods. Thus, selection of therapy is individualized, taking into account present and future medical problems for the patient. Choice of an antiarrhythmic drug is based on safety first vs efficacy. Catheter ablation is an effective nonpharmacological alternative that is often, but not always, the second-line treatment. Reduction of the frequency and duration of atrial fibrillation episodes that result in a significant improvement in quality of life is a good marker of drug treatment success and complete elimination of atrial fibrillation is not required in many patients. Rate control is usually achieved with a ß-blocker or non-dihydropyridine calcium channel blockers. It is important to assess adequate rate control during both rest and activity. If the ventricular rate goes uncontrolled for a prolonged period, tachycardia-mediated cardiomyopathy can occur. CONCLUSIONS AND RELEVANCE: Therapy for atrial fibrillation includes prevention and modification of inciting causes and appropriate anticoagulation. Rate control is necessary for all patients. Maintenance of sinus rhythm with drugs or catheter ablation should be considered based on the individual needs of each patient.

Electrocardiographic features and prevalence of bilateral bundle-branch delay.

BACKGROUND: Definitive diagnosis of bilateral bundle-branch delay/block may be made when catheter-induced right bundle-branch block (RBBB) develops in patients with baseline left bundle-branch (LBB) block. We hypothesized that a RBBB pattern with absent S waves in leads I and aVL will identify bilateral bundle-branch delay/block. METHODS AND RESULTS: Fifty patients developing transient RBBB pattern in lead V1 during right heart catheterization were studied. Patients were grouped according to whether the baseline ECG demonstrated a normal QRS, left fascicular blocks, or LBB block pattern. The RBBB morphologies in each group were compared. The prevalence of bilateral bundle-branch delay/block pattern was examined in our hospital ECG database. All patients with baseline normal QRS complexes (n=30) or left fascicular blocks (4 anterior, 5 posterior) developed a typical RBBB pattern. Among the 11 patients with a baseline LBB block pattern, 7 developed an atypical RBBB pattern with absent S waves in leads I and aVL and the remaining 4 demonstrated a typical RBBB. The absence of S waves in leads I and aVL during RBBB was 100% specific and 64% sensitive for the presence of pre-existing LBB block. Among the consecutive 2253 hospitalized patients with RBBB, 34 (1.5%) had the bilateral bundle-branch delay/block pattern. CONCLUSIONS: An ECG pattern of RBBB in lead V1 with absent S wave in leads I and aVL indicates concomitant LBB delay. Pure RBBB and bifascicular blocks are associated with S waves in leads I and aVL.

The disconnect between the guidelines, the appropriate use criteria, and reimbursement coverage decisions: the ultimate dilemma.

Recently, the American College of Cardiology Foundation in collaboration with the Heart Rhythm Society published appropriate use criteria (AUC) for implantable cardioverter-defibrillators and cardiac resynchronization therapy. These criteria were developed to critically review clinical situations that may warrant implantation of an implantable cardioverter-defibrillator or cardiac resynchronization therapy device, and were based on a synthesis of practice guidelines and practical experience from a diverse group of clinicians. When the AUC was drafted, the writing committee recognized that some of the scenarios that were deemed "appropriate" or "may be appropriate" were discordant with the clinical requirements of many payers, including the Medicare National Coverage Determination (NCD). To charge Medicare for a procedure that is not covered by the NCD may be construed as fraud. Discordance between the guidelines, the AUC, and the NCD places clinicians in the difficult dilemma of trying to do the "right thing" for their patients, while recognizing that the "right thing" may not be covered by the payer or insurer. This commentary addresses these issues. Options for reconciling this disconnect are discussed, and recommendations to help clinicians provide the best care for their patients are offered.

Association between left ventricular ejection fraction post-cardiac resynchronization treatment and subsequent implantable cardioverter defibrillator therapy for sustained ventricular tachyarrhythmias.

BACKGROUND: Although cardiac resynchronization therapy (CRT) can improve left ventricular ejection fraction (LVEF), it is not known whether a specific level of improvement will predict future implantable cardioverter defibrillator (ICD) therapy. METHODS AND RESULTS: CRT-defibrillator (CRT-D) was implanted in 423 patients at 1 institution between October 2, 2001 and January 19, 2007. A retrospective analysis was performed to evaluate the relationship between post-CRT-D LVEF and ICD therapy for ventricular tachyarrhythmias. A landmark population of 270 patients, with post-CRT-D LVEF measured and no ICD therapy within 1 year of device implantation, was followed for subsequent outcomes. Of these, 22 patients (8.2%) had subsequent appropriate ICD therapy over a median follow-up of 1.5 years. The estimated 2-year risk of appropriate ICD therapy is 3.0% (95% confidence interval [95% CI], 0%-6.3%), 2.1% (95% CI, 0%-5.0%), and 1.5% (95% CI, 0%-3.9%) for post-CRT-D LVEF of 45%, 50%, and 55%, respectively. In patients with a primary prevention indication for CRT-D, the estimated 2-year risk is 3.3% (95% CI, 0%-7.3%), 2.5% (95% CI, 0%-6.1%), and 1.9% (95% CI, 0%-5.1%) for post-CRT-D LVEF of 45%, 50%, and 55%, respectively. CONCLUSIONS: When a CRT responder demonstrates near normalization in LVEF to ≥45%, the incidence of ICD therapy for ventricular arrhythmias becomes low. Future studies are needed to determine whether an ICD is still needed in some of these patients at the time of generator replacement.

Ventricular arrhythmias in the absence of structural heart disease.

Ventricular arrhythmia (VA) in structurally normal hearts can be broadly considered under non-life-threatening monomorphic and life-threatening polymorphic rhythms. Monomorphic VA is classified on the basis of site of origin in the heart, and the most common areas are the ventricular outflow tracts and left ventricular fascicles. The morphology of the QRS complexes on electrocardiogram is an excellent tool to identify the site of origin of the rhythm. Although these arrhythmias are common and generally carry an excellent prognosis, rare sudden death events have been reported. Very frequent ventricular ectopy may also result in a cardiomyopathy in a minority of patients. Suppression of VA may be achieved using calcium-channel blockers, beta-adrenergic blockers, and class I or III antiarrhythmic drugs. Radiofrequency ablation has emerged as an excellent option to eliminate these arrhythmias, although certain foci including aortic cusps and epicardium may be technically challenging. Polymorphic ventricular tachycardia (VT) is rare and generally occurs in patients with genetic ion channel disorders including long QT syndrome, Brugada syndrome, catecholaminergic polymorphic VT, and short QT syndrome. Unlike monomorphic VT, these arrhythmic syndromes are associated with sudden death. While the cardiac gross morphology is normal, suggesting a structurally normal heart, abnormalities exist at the molecular level and predispose them to arrhythmias. Another fascinating area, idiopathic ventricular fibrillation and early repolarization syndrome, are undergoing research for a genetic basis.

Pacing threshold testing induced ventricular fibrillation following acute rate control of atrial fibrillation.

BACKGROUND: A properly placed stimulus on the T-wave during ventricular repolarization can result in ventricular fibrillation (VF). Initiation of VF with pacing on T-wave is a rare event with a few reported cases in the literature. We present a unique case of induced VF attributed to a pacing stimulus on T-wave during ventricular pacing threshold testing of a permanent pacemaker. CASE REPORT: A 64-year-old woman with persistent atrial fibrillation (AF) and a permanent pacemaker for tachycardia-bradycardia syndrome presented with symptomatic AF with rapid ventricular response. Acute rate control was achieved with intravenous diltiazem. During ventricular pacing threshold testing, noncapture occurred followed by a pacing spike on T-wave initiating VF. Cardiopulmonary resuscitation and defibrillation converted the rhythm to rate-controlled AF. An acute prolongation of the QT was noted and normalized within 12 hours. No antiarrhythmic medications were used. Postevent laboratory values were within normal limits. She was free of ischemia and an echocardiogram revealed normal left ventricular function. She recovered from the event and was discharged with rate-controlled AF. No further pacing-induced arrhythmias have occurred during follow-up pacemaker interrogation and 12-lead electrocardiograms continued to show normal QT intervals. CONCLUSION: Pacemaker-induced VF is an extraordinarily rare complication of cardiac pacing. Alterations in ventricular repolarization with rapid slowing of the heart rate demonstrated by acute prolongation of QT intervals may play a role. This report should alert physicians to the possibility of QT prolongation and an increased risk of ventricular arrhythmias following acute rate control of AF.

Implantable Cardioverter Defibrillator Therapy for Primary Prevention of Sudden Cardiac Death-An Argument for Guideline Adherence.

Sudden cardiac death is the leading cause of death among adults in the United States. Multiple randomized controlled trials have provided clear-cut data on appropriate subgroups of patients whose survival has improved through primary prevention therapy with an implantable cardioverter defibrillator. Current guidelines specify a class I indication in patients with reduced left ventricular ejection fractions with both ischemic and nonischemic cardiomyopathy under various conditions. Cardiac resynchronization therapy has also been demonstrated to reduce mortality in selected patient subgroups and should be combined with an implantable cardioverter defibrillator in appropriate patients. Adherence to these guidelines should result in a reduction in sudden-death mortality.

Differentiating junctional tachycardia and atrioventricular node re-entry tachycardia based on response to atrial extrastimulus pacing.

OBJECTIVES: The purpose of this study was to differentiate non-re-entrant junctional tachycardia (JT) and typical atrioventricular node re-entry tachycardia (AVNRT). BACKGROUND: JT may mimic AVNRT. Ablation of JT is associated with a lower success rate and a higher incidence of heart block. Electrophysiologic differentiation of these tachycardias is often difficult. METHODS: We hypothesized that JT can be distinguished from AVNRT based on specific responses to premature atrial complexes (PACs) delivered at different phases of the tachycardia cycle: when a PAC is timed to His refractoriness, any perturbation of the subsequent His indicates that anterograde slow pathway conduction is involved and confirms a diagnosis of AVNRT. A PAC that advances the His potential immediately after it without terminating tachycardia indicates that retrograde fast pathway is not essential for the circuit and confirms a diagnosis of JT. This protocol was tested in 39 patients with 44 tachycardias suggesting either JT or AVNRT based on a short ventriculo-atrial interval and apparent AV node dependence. Tachycardias were divided into 3 groups: clinically obvious AVNRT, clinically obvious JT, and clinically indeterminate rhythm. RESULTS: In the 26 cases of clinically obvious AVNRT, the sensitivity and specificity of the test were 61% and 100%, respectively. In the 9 cases of clinically obvious JT, the sensitivity and specificity were 100% and 100%, respectively. In the 9 cases of clinically indeterminate rhythm, the technique indicated AVNRT in 1 patient and JT in 7 patients, and the test was indeterminate in 1 patient. CONCLUSIONS: The response to PACs during tachycardia can distinguish JT and AVNRT with 100% specificity in adult patients.

Complications associated with generator replacement in response to device advisories.

INTRODUCTION: Device recalls create problems for patients and physicians, for the risks associated with replacement may be greater than the device failure rate. In 2005, Medtronic, Guidant, and St. Jude had implantable cardioverter defibrillator (ICD) recalls on several of their devices. There were no national standards to guide physicians on the management of such patients. We report the reasons for and outcomes of ICD and pacemaker generator changes from our practice resulting from these advisories. METHODS AND RESULTS: After an advisory was issued, the patients with an affected device were contacted, evaluated in the office by one of the electrophysiologists in our group, and a management plan was determined. Two hundred and twenty-two of 1,039 (Medtronic 273, Guidant 766) (21.4%) patients with advisory devices underwent device replacement. Nine minor complications occurred: hematoma managed conservatively (n = 6); local discomfort (n = 1); and incisional infections treated successfully with oral antibiotics (n = 2). Major complications occurred in nine patients (4.1%). Four atrial leads were damaged, two of which were repaired, one during the same procedure and the other at a later date. One patient required a reoperation to tighten a loose ventricular lead set screw. Hematoma requiring evacuation occurred in one patient, and pocket revision was necessary in two patients secondary to severe discomfort due to the positioning of the device in the pocket. One patient had a cerebrovascular accident preoperatively. There were no perioperative deaths or infections requiring system removal. CONCLUSION: Even with experienced operators complications can occur when replacing generators for a device recall. Careful risk assessment for each individual patient should be performed and efforts made to minimize generator changes.

Mechanism of induction of atrioventricular node reentry by simultaneous anterograde conduction over the fast and slow pathways.

INTRODUCTION: AV node reentry (AVNRT) is typically induced with anterograde (Ant) block over the fast pathway (FP) and conduction over the slow pathway (SP), with subsequent retrograde (Ret) conduction over the FP. Rarely, a premature atrial complex (PAC) conducts simultaneously over the FP and SP to induce AVNRT (2 for 1). This study investigates the mechanism of 2 for 1 induction. METHODS AND RESULTS: Of 192 consecutive patients (pts) undergoing posteroseptal radiofrequency ablation to treat AVNRT, 4 pts (2%) had 2 for 1 AVNRT induction. All needed isoproterenol for AVNRT initiation, and Ant conduction was over the SP during AVNRT. Controls (n = 15) were randomly selected from the remaining 188 pts and required isoproterenol to induce AVNRT with Ant block over the FP. For 2 for 1 versus control, respectively, there was no difference in mean age (55 vs. 46 yr), AVNRT cycle length (420 vs. 320 ms), or the Ant effective refractory period of the FP (320 vs. 344 ms). Of note, the PAC that induced AVNRT had a significantly longer AH interval over the SP in pts with 2 for 1 versus control (470 vs. 320 ms, P = 0.016), even though the A1A2 interval for induction was longer for 2 for 1 (315 vs. 260 ms, P = 0.003). Ret conduction over the SP was relatively poor in the 2 for 1 group as evidenced by 4/4 pts with induction of AVNRT during incremental ventricular pacing versus only 1/15 control pts (P < 0.001). CONCLUSION: The unique induction of AVNRT by a PAC with simultaneous conduction over the FP and SP is best explained by minimal to no retrograde invasion of the SP from the anterogradely conducted fast pathway impulse, and consistent with this observation is the initiation of slow/fast AVN reentry during incremental RV pacing.

Termination of paroxysmal supraventricular tachycardia by tecadenoson (CVT-510), a novel A1-adenosine receptor agonist.

OBJECTIVES: The aim of this study was to evaluate tecadenoson safety and efficacy during conversion of paroxysmal supraventricular tachycardia (PSVT) to sinus rhythm. BACKGROUND: Tecadenoson (CVT-510), a novel adenosine receptor (Ado R) agonist, selectively activates the A1 Ado R and prolongs atrioventricular (AV) nodal conduction at doses lower than those required to cause A2 Ado R-mediated coronary and peripheral vasodilation. Unlike adenosine, which non-selectively activates all four Ado R subtypes and produces unwanted effects, tecadenoson appears to terminate AV node-dependent supraventricular tachycardias without hypotension and bronchoconstriction. METHODS: In this open-label, multicenter, dose escalation study, tecadenoson was administered to 37 patients (AV node re-entrant tachycardia, n = 29; AV re-entrant tachycardia, n = 8) with inducible PSVT sustained for > or =1 min during an electrophysiology study. Seven regimens (0.3 to 15 microg/kg) of up to two identical tecadenoson intravenous bolus doses were administered. RESULTS: After the first or second bolus, PSVT converted to sustained sinus rhythm for > or =5 min in 86.5% (32/37) of the patients, with 91% (29/32) of the conversions occurring after the first bolus (most within 30 s), coincident with anterograde conduction block in the AV node. No effects on sinus cycle length (SCL) or systolic blood pressure were observed. The atrial-His (AH), but not the His-ventricular (HV) interval was prolonged up to 5 min after the final tecadenoson bolus, returning to baseline by 10 min. Tecadenoson was generally well tolerated. CONCLUSIONS: In this study, tecadenoson rapidly terminated sustained PSVT by depressing AV nodal conduction without causing hypotension. After sinus rhythm restoration, there was minimal AH interval prolongation without HV interval or SCL prolongation.