Use of Therapeutic Drug Monitoring in Amiodarone Treatment: A Systematic Review of Recent Literature.

BACKGROUND: Amiodarone is a class III antiarrhythmic drug used to prevent supraventricular and ventricular tachyarrhythmias. It has substantial toxicity; however, the use of therapeutic drug monitoring (TDM) seems unclear in the absence of a therapeutic range or an association between amiodarone blood concentration and effect. In this review, the authors examined the reported amiodarone blood concentration measurements in the last 10 years and subsequently noted the frequency by which TDM was used to optimize therapy. METHODS: In March 2022, the Embase and MEDLINE databases were searched for articles published in English in the previous 10 years using the keywords "amiodarone," "therapeutic drug monitoring," or "serum/plasma/blood". RESULTS: This study included 19 of the 478 articles identified. TDM has not been studied in conjunction with regular amiodarone maintenance therapy. One study used TDM during the initial treatment phase but the amiodarone dose was not changed. In 3 other case reports, TDM was used to guide amiodarone treatment through drug-drug interactions, and plasma levels of the active metabolite mono-N-desethyl-amiodarone (MDEA) verified 2 amiodarone toxicities. CONCLUSIONS: Because the antiarrhythmic effect of amiodarone is not correlated with blood concentrations and is easily detectable by electrocardiogram, the routine use of TDM in maintenance therapy is controversial, as evidenced by a scarcity of published literature in the recent decade. Furthermore, amiodarone toxicity is evident with normal/low amiodarone or MDEA levels; hence, TDM of amiodarone provides no therapeutic benefit to patients.

Peripheral Endothelial Function and Coronary Flow Velocity Reserve Are Not Associated in Women with Angina and No Obstructive Coronary Artery Disease: The iPOWER Study.

PURPOSE: We investigated whether impaired flow-mediated dilation (FMD) and plasma biomarkers reflecting endothelial dysfunction are associated with coronary microvascular dysfunction (CMD) in women with angina and no obstructive coronary artery disease (CAD). METHODS: Patients (n = 194) were randomly selected women with angina pectoris and no obstructive CAD (<50% stenosis). A reference population of asymptomatic women without CAD (n = 25) was included. We measured FMD in the brachial artery by high-resolution ultrasound. Coronary flow velocity reserve (CFVR) was assessed by transthoracic Doppler flow echocardiography (TTDE) of the left anterior descending artery during rest and high-dose dipyridamole infusion. CMD was defined as CFVR <2. RESULTS: FMD and CFVR were measured in 128 patients and 21 controls. Mean (SD) age was 64.5 (8.9) years, mean CFVR was 2.3 (2.0-2.7), and mean FMD was 8.4% (4.8%) in angina patients. Angina patients had a higher risk factor burden compared with the reference population. Measures of peripheral endothelial dysfunction and endothelial plasma biomarkers did not differ according to angina or CFVR. CFVR and FMD did not correlate (Spearman ρ = -0.07, p = 0.45). CONCLUSIONS: FMD and biomarkers of endothelial dysfunction did not identify individuals with CMD assessed as impaired CFVR by TTDE in women with angina and no obstructive CAD.

Graduated elastic compression stockings in the prevention of post-thrombotic syndrome: A systematic review and meta-analysis.

BACKGROUND: The effect of graduated elastic compression stockings (ECS) in the prevention of post-thrombotic syndrome (PTS) has been questioned since a large randomized trial found no prophylactic effect of ECS. OBJECTIVE: To assess the effect of the wearing time of ECS on the incidence of post-thrombotic syndrome (PTS) after proximal deep venous thrombosis, we performed a meta-analysis of the incidence of PTS across randomized and observational studies. METHOD: PubMed, Embase and Cochrane databases were searched until 12 June 2023 for studies on the effect of ECS on PTS. References of eligible studies were also screened in order to identify other potential studies that might have been missed during the search. RESULTS: Four studies comprising a total of 1467 patients met our inclusion criteria for early initiation and consistent use of ECS in patients with acute proximal DVT. ECS significantly reduced the incidence of mild-moderate PTS (OR: 0.48; 95% CI: 0.36-0.63) as well as severe PTS (OR: 0.44; 95% CI: 0.28-0.58).

Endothelial function is unaffected by changing between carvedilol and metoprolol in patients with heart failure--a randomized study.

BACKGROUND: Carvedilol has been shown to be superior to metoprolol tartrate to improve clinical outcomes in patients with heart failure (HF), yet the mechanisms responsible for these differences remain unclear. We examined if there were differences in endothelial function, insulin stimulated endothelial function, 24 hour ambulatory blood pressure and heart rate during treatment with carvedilol, metoprolol tartrate and metoprolol succinate in patients with HF. METHODS: Twenty-seven patients with mild HF, all initially treated with carvedilol, were randomized to a two-month treatment with carvedilol, metoprolol tartrate or metoprolol succinate. Venous occlusion plethysmography, 24-hour blood pressure and heart rate measurements were done before and after a two-month treatment period. RESULTS: Endothelium-dependent vasodilatation was not affected by changing from carvedilol to either metoprolol tartrate or metoprolol succinate. The relative forearm blood flow at the highest dose of serotonin was 2.42 ± 0.33 in the carvedilol group at baseline and 2.14 ± 0.24 after two months continuation of carvedilol (P = 0.34); 2.57 ± 0.33 before metoprolol tartrate treatment and 2.42 ± 0.55 after treatment (p = 0.74) and in the metoprolol succinate group 1.82 ± 0.29 and 2.10 ± 0.37 before and after treatment, respectively (p = 0.27). Diurnal blood pressures as well as heart rate were also unchanged by changing from carvedilol to metoprolol tartrate or metoprolol succinate. CONCLUSION: Endothelial function remained unchanged when switching the beta blocker treatment from carvedilol to either metoprolol tartrate or metoprolol succinate in this study, where blood pressure and heart rate also remained unchanged in patients with mild HF. TRIAL REGISTRATION: Current Controlled Trials NCT00497003.

[Perioperative heparin bridging is rarely indicated].

Numerous studies have shown that perioperative heparin bridging in patients treated with a vitamin K antagonist leads to an increased incidence of bleeding and so far, there is no evidence that it leads to a significant reduction in postoperative thromboembolism as summarised in this review. Prophylactic dosage of heparin is recommended after major surgery. Heparin bridging is not relevant in patients receiving a direct oral anticoagulant due to the rapid onset and offset of action of DOACs.

The effect of chronic heart failure and type 2 diabetes on insulin-stimulated endothelial function is similar and additive.

AIM: Chronic heart failure is associated with endothelial dysfunction and insulin resistance. The aim of this investigation was to study insulin-stimulated endothelial function and glucose uptake in skeletal muscles in patients with heart failure in comparison to patients with type 2 diabetes. METHODS: Twenty-three patients with systolic heart failure and no history of diabetes, seven patients with both systolic heart failure and type 2 diabetes, 19 patients with type 2 diabetes, and ten healthy controls were included in the study. Endothelial function was studied by venous occlusion plethysmography. Insulin-stimulated endothelial function was assessed after intra-arterial infusion of insulin followed by co-infusion with serotonin in three different dosages. Forearm glucose uptake was measured during the insulin infusion. RESULTS: Patients with systolic heart failure had impaired insulin-stimulated endothelial function. The percentage increase in blood flow during co-infusion with insulin and serotonin dose response study was 24.74% ± 6.16%, 23.50% ± 8.32%, and 22.29% ± 10.77% at the three doses respectively, compared to the healthy control group 45.96% ± 11.56%, 67.40% ± 18.11% and 84.57% ± 25.73% (P = 0.01). Insulin-stimulated endothelial function was similar in heart failure patients and patients with type 2 diabetes, while it was further deteriorated in patients suffering from both heart failure and diabetes with a percentage increase in blood flow of 19.15% ± 7.81%, -2.35% ± 11.76%, and 5.82% ± 17.70% at the three doses of serotonin, respectively. Forearm glucose uptake was impaired in patients with heart failure compared to healthy controls (P = 0.03) and tended to be further impaired by co-existence of diabetes (P = 0.08). CONCLUSION: Systolic heart failure and type 2 diabetes result in similar vascular insulin resistance and reduced muscular insulin-stimulated glucose uptake. The effects of systolic heart failure and type 2 diabetes appear to be additive.