QT Prolongation in Critically Ill Patients With SARS-CoV-2 Infection.

BACKGROUND: Several reports linked the use of repurposed drugs such as hydroxychloroquine (HCQ), azithromycin, lopinavir/ritonavir, and favipiravir with QT interval prolongation in patients with SARS-CoV2 infection. Little is known about the risk factors for QT interval prolongation in this population. We sought to describe the prevalence and identify the main risk factors associated with clinically significant corrected QT (QTc) prolongation in this population. METHODS: We conducted a retrospective analysis of critically ill patients who were admitted to our intensive care unit (ICU), had at least one electrocardiogram performed during their ICU stay, and tested positive for SARs-CoV-2. Clinically significant QTc interval prolongation was defined as QTc >500 milliseconds (ms). RESULTS: Out of the 111 critically ill patients with SARS-CoV-2 infection, QTc was significantly prolonged in 47 cases (42.3%). Patients with a clinically significant QTc prolongation had significantly higher proportions of history of cardiac diseases/surgery (22 [46.8%] vs. 10 [15.6%], P < .001), hypokalemia (10 [21.3] vs. 5 [7.8%], P = .04), and male gender (95% vs. 82.8%, P = .036) than patients with QTc ≤500 ms, respectively. A total of 46 patients (41.4%) received HCQ, 28 (25.2%) received lopinavir/ritonavir, and 5 (4.5%) received azithromycin. Multivariate logistic regression analysis showed that a history of cardiac disease was the only independent factor associated with clinically significant QTc prolongation (P = .004 for the likelihood-ratio test). CONCLUSION: The prevalence of clinically significant QTc prolongation in critically ill patients with SARS-CoV-2 infection was high and independent of drugs used. Larger prospective observational studies are warranted to elucidate independent risk factors associated with clinically significant QTc prolongation in this study population.

Direct Oral Anticoagulants in Asian Patients with Atrial Fibrillation: Consensus Recommendations by the Asian Pacific Society of Cardiology on Strategies for Thrombotic and Bleeding Risk Management.

The disease burden of AF is greater in Asia-Pacific than other areas of the world. Direct oral anticoagulants (DOACs) have emerged as effective alternatives to vitamin K antagonists (VKA) for preventing thromboembolic events in patients with AF. The Asian Pacific Society of Cardiology developed this consensus statement to guide physicians in the management of AF in Asian populations. Statements were developed by an expert consensus panel who reviewed the available data from patients in Asia-Pacific. Consensus statements were developed then put to an online vote. The resulting 17 statements provide guidance on the assessment of stroke risk of AF patients in the region, the appropriate use of DOACs in these patients, as well as the concomitant use of DOACs and antiplatelets, and the transition to DOACs from VKAs and vice versa. The periprocedural management of patients on DOAC therapy and the management of patients with bleeding while on DOACs are also discussed.

Appropriateness of the Direct Oral Anticoagulants Dosing in the Middle East Gulf Region.

ABSTRACT: Direct oral anticoagulants (DOACs) have proven efficacy to prevent cardioembolic strokes. Data are scarce about the appropriateness of DOAC dosing in the Middle East. We investigated the prevalence of inappropriate DOAC dosing in the region. A cross-sectional study was conducted at our hospital between April 2015 and February 2019 of patients receiving 1 of the 3 available DOACs. Patients with incomplete data sets, those prescribed DOACs for indications other than atrial fibrillation, on DOACs for <30 days, and dialysis patients were excluded. A total of 608 met the inclusion criteria. The mean age was 65.2 ± 13.9 years, and most were men (58.6%). The mean CHA2DS2-VASc score was 3.8 ± 2.0. There were 346 (56.9%) on apixaban, 123 (20.2%) on dabigatran, and 139 (22.9%) on rivaroxaban. The logistic regression model showed that for the 3 agents together, age, eGFR, major bleeding history, and history of prior stroke were significantly associated with the decision to inappropriately underdose (P < 0.05). Fifteen patients had an ischemic stroke after apixaban initiation (5 underdosed and 3 overdosed). Among patients with at least one follow-up encounter, major bleeding occurred in 13 patients (11.7%) with inappropriate dosing compared with 29 patients (6.0%) with appropriate dosing (P = 0.04). Ischemic stroke occurred in 11 patients (9.9%) with inappropriate dosing compared with 15 patients (3.1%) with appropriate dosing (P < 0.01). We concluded that inappropriate DOAC underdosing is common in our region, particularly with apixaban and rivaroxaban. It is associated with increased risk of stroke and bleeding. More education targeting prescribers is needed to encourage adherence to standard dosing criteria.

Usefulness of radiofrequency ablation of supraventricular tachycardia to decrease inappropriate shocks from implantable cardioverter-defibrillators.

Inappropriate implantable cardioverter-defibrillator (ICD) therapies can lead to significant adverse events and increased mortality. These therapies are often the result of supraventricular tachycardias (SVTs). The objective of this study was to evaluate the incidence of SVT leading to inappropriate shocks in a large cohort of patients with ICDs and assess the efficacy of radiofrequency ablation (RFA) in decreasing these therapies. Patients with ICDs and recurrent SVTs were identified. A cohort of patients with ICD therapies subsequently underwent electrophysiologic study and RFA. Eighty-four patients (13%) were found to have SVT leading to 122 inappropriate ICD shocks and 130 episodes of antitachycardia pacing therapies. Median time to SVT onset after ICD implantation was 269 days. Electrophysiologic studies were performed in 30 patients. Successful RFA was performed for atrial tachycardia, atrial flutter, or atrioventricular nodal reentrant tachycardia in 22 patients. Ninety-five percent of patients who underwent successful SVT ablation had no further inappropriate ICD therapies compared to 63% of patients in whom ablation was not performed during a mean follow-up of 20.7 ± 11.9 months. In conclusion, SVT is responsible for a significant number of inappropriate ICD therapies. RFA is an effective strategy to substantially decrease subsequent inappropriate ICD therapies.

The changing pattern of humoral rejection in cardiac transplant recipients.

BACKGROUND: Most humoral rejection (HR) episodes occur early after cardiac transplantation and are associated with hemodynamic compromise and poor prognosis. Late cases of HR (>6 months after transplant) have been reported. We examined the differences in clinical characteristics and outcomes in patients presenting with HR in the early (<6 months) and late transplant periods. METHODS: A retrospective chart review was performed of all cases of HR at a single large transplant center from January 1, 1995 to March 1, 2006. RESULTS: A total of 37 adult transplants had biopsy-proven HR; 13 patients had early HR and 24 patients had HR a mean of 5 yr after transplantation (range, 7 months to 17 yrs). Treatment for HR included plasmapheresis, cyclophosphamide, and rituximab. The age of the early and late humoral rejecters was similar (58+/-14 vs. 50+/-14 yrs; P=0.12). There was a trend toward more women in the early HR group (54% vs. 33%). Use of left ventricular assist devices was similar (38% vs. 33%). Early rejecters were more likely to have positive cross-matches (46% vs. 8%; P<0.01). Patients with late HR had a coexistent diagnosis of malignancy, or significant recent infection in 50% vs. 8% for early HR, suggesting an activation of a nonhuman leukocyte antigen antibody-mediated immune response to an acute illness. One-year survival after the diagnosis of HR was 78% for the both groups (P=NS). CONCLUSIONS: Humoral rejection occurs now more frequently in patients with remote transplants and is commonly associated with the presence of malignancy or infection.

Does renal function deteriorate more rapidly in diabetic cardiac transplant recipients?

BACKGROUND: Selection criteria for cardiac transplant candidates with diabetes mellitus (DM) have been liberalized resulting in increased numbers of diabetic patients receiving organs. Calcineurin inhibition results in nephrotoxicity. Whether this nephrotoxicity is accelerated in diabetic heart transplant recipients is unknown. METHODS: To investigate this question, we derived the glomerular filtration rate (GFR) at transplant and at multiple time intervals thereafter for adult heart transplants performed from January 1, 2000 to January 1, 2005. GFR was estimated using the Modification of Diet in Renal Disease Study equation (GFRMDRD) and the Cockcroft-Gault (GFRCG) formula. RESULTS: In all, 257 patients were nondiabetic and 102 patients were diabetic before and after transplant. The diabetic patients were older (57+/-8 vs. 53+/-13 years; P<0.01) and had greater body mass index (27.5+/-5.1 vs. 25.5+/-4.4 kg/m; P<0.01) than nondiabetic patients. Baseline renal function was significantly reduced in diabetic patients with higher serum creatinine (1.6+/-0.5 vs. 1.4+/-0.5 mg/dL), lower GFRCG (65+/-27 vs. 73+/-35 mL/min), and lower GFRMDRD (54+/-23 vs. 65+/-32 mL/min; all P<0.01) than nondiabetic patients. All patients were treated with cyclosporine or tacrolimus posttransplant. The change in the GFRMDRD in nondiabetic and diabetic patients was constant and comparable at 1, 2, and 3 years posttransplant. In normal subjects, GFRMDRD declined from baseline by 7+/-26, 5+/-23, and 7+/-23 mL/min(2) and in the diabetic patients was 13+/-22, 9+/-26, 10+/-22 ml/min(2) at 1, 2, and 3 years, respectively (P=NS). CONCLUSION: This data suggests that nephrotoxicity posttransplant is not accelerated in diabetic recipients.

Effects of statins beyond lipid lowering: potential for clinical benefits.

BACKGROUND: The role of statin drugs in the reduction of serum lipids has been well documented. More recently, evidence suggesting that statins may positively impact many organ systems and disease states independent of lipid reduction has emerged. The term "pleiotropic effects" has been used to refer to these properties. We reviewed the evidence exploring such potential effects. METHODS: A search of the MEDLINE database was conducted for articles published between 1985 to 2005 on the pleiotropic and the lipid-lowering independent effects of statin drugs. The search terms "statin", "HMG-CoA reductase inhibitor", "pleiotropic effects", and "inflammation" were used. English language articles were selected for inclusion along with selected cross-references. RESULTS: Numerous animal and clinical studies support the presence of a spectrum of beneficial effects for statins that are independent of their lipid-lowering properties. These effects are mediated by a variety of mechanisms and they suggest that the therapeutic role of statins may expand. CONCLUSION: Statins have shown great promise beyond their lipid-lowering effects. Ongoing and future studies will help to further clarify the potential clinical impact of these "pleiotropic effects".