Mar, Philip L.

Introduction: Incident cardiac arrhythmias are common in hospitalized COVID-19 patients, but the impact of a second incident cardiac arrhythmia during hospitalization on clinical outcomes remain unclear. Hypothesis: The aim of this study was to assess the frequency and prognostic implications of a second incident arrhythmia in hospitalized COVID-19 patients over the pandemic course till vaccine availability. Methods: The multicenter COVID-RHYTHM Registry enrolled hospitalized COVID-19 patients from 3/8/2020 to 1/24/2021. Cardiac arrhythmia included documented atrial fibrillation (AF), atrial flutter (AFL), ventricular tachycardia (VT), severe sinus bradycardia (<40 bpm) or AV block. Outcomes were compared between patients with single vs. more than one incident arrhythmias adjusting for baseline variables. Results: Of 6299 hospitalized COVID-19 patients, 4398 had an had an incident cardiac arrhythmia during hospitalization, of which 822 (19%) had a second incident arrhythmia. Those with >1 incident arrhythmia had a higher baseline prevalence of heart failure, chronic kidney disease, coronary artery disease and sleep apnea (Table). Those with >1 incident arrhythmia had higher in-hospital mortality, need for ICU admission and need for rehab upon discharge. Length of stay was similar between the groups. Conclusions: In hospitalized COVID-19 patients with incident cardiac arrhythmias, a second incident arrhythmia during hospitalization was seen in 19%. Having >1 incident arrhythmia was associated with increased need for ICU admission and reduced survival.

Introduction: Cardiac arrhythmias are common in continuous flow left ventricular assist device (LVAD) recipients. The impact of axial vs. intrapericardial centrifugal LVAD pumps on arrhythmia incidence and associated clinical outcomes is unclear. Hypothesis: This multicenter study evaluated the impact of LVAD type (axial vs. centrifugal) on incidence of atrial and ventricular arrhythmias, ICD shocks and mortality in LVAD patients. Methods: Analysis was done on 536 patients who underwent LVAD implantation at 5 US centers from 2008 to 2016. The groups were divided based on their LVAD type (axial - HeartMate II [HMII, n=433] vs. centrifugal - HeartWare (HW, n=103). Baseline characteristics as well as incidence of post-LVAD atrial arrhythmias (PL-AA), ventricular arrhythmias (PL-VA) and ICD shocks were analyzed in these groups. Multivariable Cox Regression analysis was used to identify predictors of survival. Results: Of 536 patients, 433 had HMII axial LVAD and 103 had HW centrifugal VAD implant. At baseline, HMII group had more males, higher proportion of CRT-D and higher prevalence of AA (Table 1A). Left ventricular dimensions were similar between groups. During a median follow-up of 537 days of LVAD support, incidence of PL-VA and ICD shocks were significantly higher in the HM2 group compared to HW group whereas incidence of PL-AA was not significantly different (Table 1A). In multivariable Cox Regression analysis, LVAD indication was the only variable that predicted survival (Table 1B). Type of LVAD (axial vs. centrifugal) was not associated with survival (HMII vs. HW - HR 1.04, P=0.48). Conclusions: In this multi-center continuous flow LVAD cohort, axial HM2 VAD patients had a higher incidence of PL-VA and ICD shocks. Type of LVAD (axial vs. centrifugal) was not associated with survival.

Oral anticoagulants (OACs) are medications commonly used in patients with atrial fibrillation and other cardiovascular conditions. Both warfarin and direct oral anticoagulants are susceptible to drug-drug interactions (DDIs). DDIs are an important cause of adverse drug reactions and exact a large toll on the health care system. DDI for warfarin mainly involve moderate to strong inhibitors/inducers of cytochrome P450 (CYP) 2C9, which is responsible for the elimination of the more potent S-isomer of warfarin. However, inhibitor/inducers of CYP3A4 and CYP1A2 may also cause DDI with warfarin. Recognition of these precipitating agents along with increased frequency of monitoring when these agents are initiated or discontinued will minimize the impact of warfarin DDI. Direct oral anticoagulants are mainly affected by medications strongly affecting the permeability glycoprotein (P-gp), and to a lesser extent, strong CYP3A4 inhibitors/inducers. Dabigatran and edoxaban are affected by P-gp modulation. Strong inducers of CYP3A4 or P-gp should be avoided in all patients taking direct oral anticoagulant unless previously proven to be otherwise safe. Simultaneous strong CYP3A4 and P-gp inhibitors should be avoided in patients taking apixaban and rivaroxaban. Concomitant antiplatelet/anticoagulant use confers additive risk for bleeding, but their combination is unavoidable in many cases. Minimizing duration of concomitant anticoagulant/antiplatelet therapy as indicated by evidence-based clinical guidelines is the best way to reduce the risk of bleeding.

Antiarrhythmic drugs (AAD) play an important role in the management of arrhythmias. Drug interactions involving AAD are common in clinical practice. As AADs have a narrow therapeutic window, both pharmacokinetic as well as pharmacodynamic interactions involving AAD can result in serious adverse drug reactions ranging from arrhythmia recurrence, failure of device-based therapy, and heart failure, to death. Pharmacokinetic drug interactions frequently involve the inhibition of key metabolic pathways, resulting in accumulation of a substrate drug. Additionally, over the past 2 decades, the P-gp (permeability glycoprotein) has been increasingly cited as a significant source of drug interactions. Pharmacodynamic drug interactions involving AADs commonly involve additive QT prolongation. Amiodarone, quinidine, and dofetilide are AADs with numerous and clinically significant drug interactions. Recent studies have also demonstrated increased morbidity and mortality with the use of digoxin and other AAD which interact with P-gp. QT prolongation is an important pharmacodynamic interaction involving mainly Vaughan-Williams class III AAD as many commonly used drug classes, such as macrolide antibiotics, fluoroquinolone antibiotics, antipsychotics, and antiemetics prolong the QT interval. Whenever possible, serious drug-drug interactions involving AAD should be avoided. If unavoidable, patients will require closer monitoring and the concomitant use of interacting agents should be minimized. Increasing awareness of drug interactions among clinicians will significantly improve patient safety for patients with arrhythmias.