Risks of adverse events in patients with orthostatic intolerance undergoing surgery with general anesthesia.

INTRODUCTION: Orthostatic intolerance (OI) is a group of disorders characterized by symptoms that occur upon standing and resolve with recumbence. Although well established but not widely recognized, these diagnoses may create uncertainty for clinicians dealing with a patient affected by OI and requiring a surgical procedure. OBJECTIVES: To determine the rate of intra- and postoperative major adverse events in patients with OI undergoing surgery with general anesthesia. METHODS: The study was a retrospective study of patients with orthostatic intolerance who underwent surgery requiring general anesthesia from 1 January 2000 to 31 December 2018. RESULTS: A total 171 patients with OI underwent 190 surgeries. In patients with POTS and orthostatic-induced VVS, there were no major significant adverse events. There was one episode of AVNRT in a patient with POTS and one episode of bradycardia secondary to vasovagal reflex in a patient with orthostatic-induced VVS. Moreover, there were 13 (6.8%) episodes of postoperative hypotension. However, the majority of these episodes were related to bleeding, volume depletion or sepsis. All cases of hypotension responded well to appropriate therapy. In patients with OH, the rate of postoperative major adverse cardiac events was 4.7%, and the 30-day mortality rate was 6.1%. This is not significantly different from the calculated risk for patients without OH. There were no myocardial infarctions or deaths at 30 days in patients with POTS or orthostatic-induced VVS. CONCLUSION: Patients with OI may not experience higher rates of perioperative complications compared with patients without OI syndromes.

A new direction for anticoagulants: inhibiting fibrin assembly with PEGylated fibrin knob mimics.

Current anticoagulants target coagulation factors upstream from fibrin assembly and polymerization (i.e., formation of fibrin clot). While effective, this approach requires constant patient monitoring since pharmacokinetics and pharmacodynamics vary from patient to patient. To address these limitations, we developed an alternative anticoagulant that effectively inhibits fibrin polymerization. Specifically, we investigated PEGylated fibrin knob "A" peptides, evaluating the effect of both polyethylene glycol (PEG) chain length (0, 2, 5, and 10-30 kDa) and knob peptide sequence (GPRPAAC, GPRPFPAC, and GPRPPERC) on inhibiting fibrin polymerization (i.e., clot formation). Thrombin-initiated clotting assays with purified fibrinogen were performed to compare clot formation with each peptide-PEG conjugate. Results indicated a biphasic effect of PEG chain length, whereby, active-PEG conjugates demonstrated increasingly enhanced inhibition of fibrin polymerization from 0 to 5 kDa PEG. However, the anticoagulant activity diminished to control levels for PEG chains above 5 kDa. Ultimately, we observed a 10-fold enhancement of anticoagulant activity with active peptides PEGylated with 5 kDa PEG compared to non-PEGylated knob peptides. The sequence of the active peptide significantly influenced the anticoagulant properties only at the highest 1:100 molar ratio where GPRPFPAC-5 kDa PEG and GPRPPERC-5 kDa PEG demonstrated significantly lower percent clottable protein than GPRPAAC-5 kDa PEG. Moreover, human plasma treated with the active 5 kDa PEG conjugate exhibited delayed prothrombin time to within the therapeutic range specified for oral anticoagulants. Collectively, this study demonstrated the utility of PEGylated fibrin knob peptides as potential anticoagulant therapeutics. Biotechnol. Bioeng. 2011;108: 2424-2433. © 2011 Wiley Periodicals, Inc.

Dataset for amiodarone adverse events compared to placebo using data from randomized controlled trials.

The dataset presented here provides a detailed description of the adverse events of amiodarone versus placebo using data from 43 randomized controlled trials. Two authors (M.M., M.R.) independently extracted the data. The dataset also includes baseline patient characteristics, amiodarone loading and maintenance doses, as well as forest plots describing the relative risk (RR) of developing an adverse event related to the pulmonary, thyroid, hepatic, cardiac, skin, gastrointestinal, neurological, and ocular systems. The Mantel-Haenszel random effects model was used to determine the relative risk of adverse events of amiodarone compared to placebo. This dataset is complementary to our article "Meta-analysis Comparing the Relative Risk of Adverse Events for Amiodarone Versus Placebo", which was published in the American Journal of Cardiology [1]. The data can be used to assess certain adverse events and their relation to amiodarone loading and/or maintenance dose.

Meta-Analysis Comparing the Relative Risk of Adverse Events for Amiodarone Versus Placebo.

Amiodarone has been associated with adverse events that may restrict its use. We performed a meta-analysis of placebo-controlled trials to assess the relative risk of adverse events of amiodarone compared with placebo. In total, 43 randomized trials were included. A total of 11,395 patients were included (5,792 patients randomized to amiodarone and 5,603 patients randomized to placebo). The incident rate of adverse events per 10,000 person-years was higher in the amiodarone group compared with placebo for pulmonary (129 vs 74; relative risk (RR) 1.77, p = 0.002), thyroid (201 vs 42; RR 4.44, p <0.001), hepatic (54 vs 25; RR 2.27, p = 0.01), cardiac (771 vs 450; RR 1.94, p <0.001), neurological (140 vs 76; RR 1.93, p <0.001), and skin (81 vs 23; RR 1.99, p = 0.04) adverse events. Low-dose amiodarone was not associated with statistically significant increase in pulmonary adverse events but was still associated with thyroid and liver adverse events. In conclusion, the likelihood of experiencing adverse events related to amiodarone was higher than that of placebo. The overall rate of adverse events however, was low, and severe adverse events were rare.

A Meta-Regression Analysis of Atrial Fibrillation Ablation in Patients with Systolic Heart Failure.

BACKGROUND: Meta-analyses of randomized controlled trials comparing atrial fibrillation (AF) ablation to medical therapy in patients with heart failure (HF) reported improvement in left ventricular ejection fraction (LVEF), quality of life using the Minnesota Living with HF Questionnaire (MLWHFQ), and 6-minute walk test (6MWT). Nonetheless, there was significant heterogeneity not accounted for suggesting that not all HF patients derive the same effect from AF ablation. OBJECTIVES: To evaluate if baseline LVEF or the etiology of the cardiomyopathy would moderate the efficacy of AF ablation. METHODS: We performed random effects meta-regression using the mean baseline LVEF and total percentage of patients with non-ischemic cardiomyopathy (NICMP) in the placebo arms as moderator variables. RESULTS: Six trials with a total of 687 patients were included. The baseline LVEF in the control arm of trials ranged from 25% - 42.9%, and the percentage of patients with NICMP within each trial varied from 35% to 100%. When baseline LVEF was used as the moderator variable, no significant change in heterogeneity was observed for any of the outcomes of interest (R2 0.00 - 0.02). However, when controlling for NICMP, heterogeneity dropped substantially for the outcomes of LVEF (I2 44.7%, R2 0.91), and MLWHFQ (I2 0.00%, R2 1.00) but not 6MWT (I2 67.4%, R2 0.00). This indicates that improvement in LVEF and MLWHFQ was greater in the AF ablation group when more patients with NICMP were included in the trials. CONCLUSIONS: In patients with systolic HF, AF ablation may be more beneficial in patients with NICMP.

Meta-Analysis of Atrial Fibrillation Ablation in Patients with Systolic Heart Failure.

Atrial fibrillation (AF) and heart failure (HF) are two common conditions that often coexist and predispose each to one another. AF increases hospitalization rates and overall mortality in patients with HF. The current available therapeutic options for AF in patients with HF are diverse and guidelines do not provide a clear consensus regarding the best management approach. To determine if catheter ablation for AF is superior to medical therapy alone in patients with coexisting HF, we conducted this systematic review and meta-analysis. The primary outcomes evaluated are left ventricular ejection fraction (LVEF), Minnesota Living with Heart Failure Questionnaire (MLWHFQ) scores, 6-minute walk test (6MWT) distance, heart failure hospitalizations, and mortality. The results are presented as a mean difference for continuous outcome measures and odds ratios for dichotomous outcomes (using Mantel-Haenszel random effects model). 7 full texts met inclusion criteria, including 856 patients. AF catheter ablation was associated with a significant increase in LVEF (mean difference 6.8%; 95% CI: 3.5 - 10.1; P<0.001) and 6MWT (mean difference 29.3; 95% CI: 11.8 - 46.8; P = 0.001), and improvement in MLWHFQ (mean difference -12.1; 95% CI: -20.9 - -3.3; P = 0.007). The risk of all-cause mortality was significantly lower in the AF ablation arm (OR 0.49; 95% CI: 0.31 - 0.77; P = 0.002). In conclusion, atrial fibrillation ablation in patients with systolic heart failure is associated with significant improvement in LVEF, quality of life, 6MWT, and overall mortality.