Comparison of Outcomes with Midodrine and Fludrocortisone for Objective Recurrence in Treating Syncope (COMFORTS trial): Rationale and design for a multi-center randomized controlled trial.

BACKGROUND: The cornerstone of the treatment of vasovagal syncope (VVS) is lifestyle modifications; however, some patients incur life-disturbing attacks despite compliance with these treatments which underscores the importance of pharmacological interventions. METHODS: In this open-label multi-center randomized controlled trial, we are going to randomize 1375 patients with VVS who had ≥2 syncopal episodes in the last year into three parallel arms with a 2:2:1 ratio to receive midodrine, fludrocortisone, or no medication. All patients will be recommended to drink 2 to 3 liters of fluids per day, consume 10 grams of NaCl per day, and practice counter-pressure maneuvers. In medication arms, patients will start on 5 mg of midodrine TDS or 0.05 mg of fludrocortisone BD. After one week the dosage will be up-titrated to midodrine 30 mg/day and fludrocortisone 0.2 mg/day. Patient tolerance will be the principal guide to dosage adjustments. We will follow-up the patients on 3, 6, 9, and 12 months after randomization. The primary outcome is the time to first syncopal episode. Secondary outcomes include the recurrence rate of VVS, time interval between first and second episodes, changes in quality of life (QoL), and major and minor adverse drug reactions. QoL will be examined by the 36-Item Short Form Survey questionnaire at enrollment and 12 months after randomization. CONCLUSION: The COMFORTS trial is the first study that aims to make a head-to-head comparison between midodrine and fludrocortisone, against a background of lifestyle modifications for preventing recurrences of VVS and improving QoL in patients with VVS.

Comparison of characteristics and outcomes of percutaneous coronary intervention in military and non-military men.

OBJECTIVES: Living in a military environment, as a unique job and lifestyle, may affect the physical and mental status of military personnel. Coronary artery disease (CAD) status and outcomes of percutaneous coronary intervention (PCI) in military personnel as a unique part of each society are less investigated. METHOD: In a registry-based study, data of 338 military men and 1954 non-military men who underwent successful PCI from March 2012 to March 2013 were analysed. The primary endpoint was major adverse cardiac events (MACE) after hospital discharge during 1-year follow-up. RESULTS: Military men were significantly younger and had a higher frequency of hypertension, familial history of CAD and cigarette smoking. Other risk factors were more prevalent in non-military men. PCI for ST-segment elevation myocardial infarction and lower left ventricular ejection fraction were also more prevalent in soldiers. After mean follow-up duration of 12.3 months, MACE that was defined as the composite endpoint of all-cause mortality, non-fatal myocardial infarction or target vessel revascularisation was similar in both groups (HR=1.01 (95% CI 0.88 to 1.16); p=0.872). By adjustment for confounding factors, results were unchanged. CONCLUSIONS: Although there are a number of differences in basic and procedural characteristics between military and non-military men who underwent PCI, 1-year clinical outcomes of this procedure are not different in these patient groups.

The significant coronary tortuosity and atherosclerotic coronary artery disease; What is the relation?

Introduction: Although coronary tortuosity is relatively common in coronary angiograms, there is much debate over the significance of this anatomical variation. So in this study the relation between significant coronary tortuosity (SCT) and coronary artery disease (CAD) was examined. Methods: The cross-sectional study included 737 patients (57% male) who were admitted to the hospital for a coronary angiography, based on their symptoms or non-invasive imaging. Coronary arteries defined as SCT are in the presence of either ≥3 consecutive curvatures of 90◦ to 180◦ or ≥2 consecutive curvatures of ≥180◦ measured at the end-diastole, in a major epicardial coronary artery ≥2 mm in diameter. Results: 29.17% of the patients had SCT of which females (64.7% vs. 34.1%, P < 0.001) and higher aged persons (62.9±8.4 vs. 57.8±10.7 years ± SD; P < 0.001) were significantly associated with SCT compared to non-SCT. Left anterior descending artery (LAD), left circumflex artery (LCX) and right coronary artery (RCA) with SCT in comparison to non-SCT, had lesser probability of CAD with stenosis severity of ≥50% (34.5% vs. 46.1%; P = 0.019 and 17.7% vs. 31.1%; P = 0.001 and 27.9% vs. 43.5%; P = 0.013 respectively) and also had significant lower Gensini scores (4.1±5.3 vs. 8.4±11.9; P = 0.011; 2.1±3.4 vs. 5.2±9.5; P = 0.01 and 1.2±1.9 vs. 5.03±8.9; P < 0.001 respectively) but higher TIMI frame count (15.7±5.3 vs. 11.9±4.6; P < 0.001 and 17.1±4.4 vs. 12.7±4.4; P < 0.001 and 15.2±3.9 vs. 11.6±4.8; P < 0.001 respectively). Conclusion: SCT is negatively correlated with CAD and there is a significant association between SCT and reduced coronary flow rate.

Salivary B-type natriuretic peptide: a new method for heart failure diagnosis and follow-up.

BACKGROUND: Frequent hospital admissions and reduced quality of life are the main complications of heart failure (HF). Plasma B-type natriuretic peptide (BNP) levels have been considered as a cost-effective method of screening for left ventricular dys-function. Studies regarding BNP-guided therapy revealed reduction in death or hospital stay for HF. AIM: As saliva has fewer limitations than blood in regard to sampling, the aim of the present study was to test if salivary BNP concentration might be a new biomarker in patients with chronic HF. METHODS: This pilot study involved 35 admitted patients with decompensated HF diagnosis and 35 HF patients who had come for a check-up at the Department of Cardiology. The control group consisted of 25 people with no history of cardiac events. Saliva and plasma samples of all the participants were collected. RESULTS: Mean plasma NT-proBNP was found at higher levels in admitted HF patients compared to outpatient HF (9.37 vs. 6.62 pg/mL, p < 0.001) and control groups (9.37 vs. 4.69 pg/mL, p < 0.001). Also, mean salivary BNP levels were higher in admitted patients with HF (6.50 ng/L, p < 0.001); and outpatient HF group (5.87 ng/L, p = 0.02) compared to the control group (5.64 ng/L). CONCLUSIONS: Our study demonstrated that BNP could be detected in saliva and that the level is higher in HF patients, especially symptomatic ones. This means that salivary BNP may be useful in the diagnosis and follow-up for patients with HF, especially in emergency settings.

Effects of Pioglitazone on Asymmetric Dimethylarginine and Components of the Metabolic Syndrome in Nondiabetic Patients (EPICAMP Study): A Double-Blind, Randomized Clinical Trial.

The present trial aimed to investigate the effects of pioglitazone on the serum level of asymmetric dimethylarginine (ADMA), a marker of endothelial function, and some indices of inflammation and glucose and lipid metabolism in nondiabetic metabolic syndrome patients. 104 eligible participants (57% female; age between 20 and 70) were enrolled in a double-blind placebo-controlled trial and were randomized to receive either pioglitazone (uptitrated to 30 mg/day) or matching placebo for 24 weeks. Participants were clinically examined and a blood sample was obtained at baseline and at the end of the trial. Pioglitazone significantly improved C-reactive protein level irrespective of changes in insulin sensitivity. Compared with the placebo group, alanine and aspartate transaminases were decreased and high-density lipoprotein cholesterol was increased after treatment with pioglitazone. A considerably greater weight gain was also recorded in the intervention group. We failed to observe any significant changes in serum ADMA in either group and between groups with and without adjustment for age, sex, and components of the metabolic syndrome. In a nutshell, pioglitazone seems to have positive effects on lipid profile, liver transaminases, and systemic inflammation. However, its previously demonstrated endothelial function-improving properties do not seem to be mediated by ADMA.