Physiologic effects of stress dose corticosteroids in in-hospital cardiac arrest (CORTICA): A randomized clinical trial.

Aim: Postresuscitation hemodynamics are associated with hospital mortality/functional outcome. We sought to determine whether low-dose steroids started during and continued after cardiopulmonary resuscitation (CPR) affect postresuscitation hemodynamics and other physiological variables in vasopressor-requiring, in-hospital cardiac arrest. Methods: We conducted a two-center, randomized, double-blind trial of patients with adrenaline (epinephrine)-requiring cardiac arrest. Patients were randomized to receive either methylprednisolone 40 mg (steroids group) or normal saline-placebo (control group) during the first CPR cycle post-enrollment. Postresuscitation shock was treated with hydrocortisone 240 mg daily for 7 days maximum and gradual taper (steroids group), or saline-placebo (control group). Primary outcomes were arterial pressure and central-venous oxygen saturation (ScvO2) within 72 hours post-ROSC. Results: Eighty nine of 98 controls and 80 of 86 steroids group patients with ROSC were treated as randomized. Primary outcome data were collected from 100 patients with ROSC (control, n = 54; steroids, n = 46). In intention-to-treat mixed-model analyses, there was no significant effect of group on arterial pressure, marginal mean (95% confidence interval) for mean arterial pressure, steroids vs. control: 74 (68-80) vs. 72 (66-79) mmHg] and ScvO2 [71 (68-75)% vs. 69 (65-73)%], cardiac index [2.8 (2.5-3.1) vs. 2.9 (2.5-3.2) L/min/m2], and serum cytokine concentrations [e.g. interleukin-6, 89.1 (42.8-133.9) vs. 75.7 (52.1-152.3) pg/mL] determined within 72 hours post-ROSC (P = 0.12-0.86). There was no between-group difference in body temperature, echocardiographic variables, prefrontal blood flow index/cerebral autoregulation, organ failure-free days, and hazard for poor in-hospital/functional outcome, and adverse events (P = 0.08->0.99). Conclusions: Our results do not support the use of low-dose corticosteroids in in-hospital cardiac arrest.Trial Registration:ClinicalTrials.gov number: NCT02790788 ( https://www.clinicaltrials.gov ).

Dimethylarginines in acute myocardial infarction: Association with lifestyle, sociodemographic, and somatometric factors.

BACKGROUND: Recent findings associate asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) with the prognosis of acute myocardial infarction (AMI). The purpose of the current study was to associate patients' lifestyle, sociodemographic, and somatometric characteristics with the time course of ADMA and SDMA concentrations in the serum of AMI patients. PATIENTS AND METHODS: In the serum of 66 AMI patients, ADMA, SDMA, troponin T, and C-reactive protein (CRP) were measured upon hospital admission (<24 h) and on the 3rd day following. Lifestyle, sociodemographic, and somatometric characteristics were obtained through a questionnaire, filled on patient discharge. RESULTS: ADMA concentrations on the 1st day positively correlated with daily reported hours of sleep (+0.497, P < 0.001) and delivery or eating out frequency (+0.285, P = 0.02), whereas it negatively correlated with reported physical condition (-0.304, P = 0.013). A personal history of hypertension indicated higher 1st-day ADMA concentration (1.818 vs 1.568, P = 0.042). Age positively correlated with 1st-day SDMA (+0.320, P = 0.009). All of the biomarker concentrations were reduced on the 3rd day measurements (P < 0.001). Self-reported lifetime minimum BMI positively correlated with either absolute (r = +0.366, P = 0.009) or percentage (r = +0.262, P = 0.045) ADMA reduction. A daily sleep in 5-8-h range was inversely correlated with percentage (-0.410, P = 0.001) or absolute (r = -0.369, P = 0.002) SDMA reduction. CONCLUSIONS: Modifiable factors such as BMI, eating habits, physical condition, and sleep seem to affect the baseline levels or time course of ADMA and SDMA in AMI patients. Changes in these factors may affect AMI prognosis by altering dimethylarginine levels.

Impact of ß-thalassemia trait carrier state on inflammatory status in patients with newly diagnosed hypertension.

BACKGROUND: B-thalassemia carrier state or thalassemia minor confers cardiovascular protection through favorable lipidemic and blood pressure profile. However, its impact on inflammatory status-a common denominator of the above conditions-has not been addressed. METHODS: We investigated a wide range of inflammatory markers [white blood cell (WBC) count, homocysteine, C-reactive protein (CRP), serum amyloid A (SAA), fibrinogen, plasminogen, fibronectin, plasminogen activator inhibitor-1 (PAI-1), and uric acid] in a large cohort of 15 805 newly diagnosed hypertensive patients (8299 men, 7506 women); 626 of them (4.0%) had thalassemia minor. RESULTS: The levels of WBC, homocysteine, CRP, SAA, fibrinogen, and PAI-1 were significantly lower in thalassemia minor patients, but not of plasminogen, fibronectin, and uric acid. In multivariate linear regression analyses, the lower values of WBC (<0.001), CRP (<0.001), homocysteine (<0.001), fibrinogen (<0.001), and PAI-1 (0.008), but not of SAA, were independently associated with thalassemia minor. The interaction between thalassemia minor and body mass index had a significant impact only on WBC and CRP (P for the interaction 0.010 and 0.005, respectively), whereas the interaction between thalassemia minor and sex had a significant impact only on fibrinogen (P for the interaction 0.007). CONCLUSION: Thalassemia minor is followed by a favorable inflammatory profile that may contribute to the overall better cardiovascular health of the carriers.

Pre-loading therapy with statins in patients with angina and acute coronary syndromes undergoing PCI.

Statins constitute the most powerful class of drugs for cardiovascular risk reduction associated to atherosclerosis. Their important pharmacological properties include reduction of serum lipid concentrations and non-lipid related, pleotropic effects such as anti-inflammatory action. Previous largescale randomized studies have demonstrated the beneficial effects of statin loading prior to elective percutaneous coronary intervention (PCI) for the reduction of periprocedural myocardial infarction and prevention of major adverse cardiac events at 30 days. The present review summarizes the data from major randomized trials that evaluated the clinical benefit of statin pretreatment in the setting of PCI resulting in a better understanding of their impact on reduction of interventional complications.

Celiac Artery Avulsion Secondary to Blunt Trauma: A Case Report.

Celiac artery (CA) injuries are very rare and are often associated with high mortality. These injuries are associated more often with penetrating trauma rather than blunt trauma injury. Our case highlights a blunt trauma injury of CA in a hemodynamically stable patient without any symptoms that was treated conservatively.

Association between anxiety and depression in patients with acute coronary syndromes due to financial crisis.

BACKGROUND: The effect of anxiety and depression on patients with acute coronary syndromes (ACS) warrants investigation, especially during periods of economic crisis. AIM: To investigate the relation between anxiety and depression in patients presenting with ACS due to financial crisis and to investigate whether these two entities could predict long-term cardiovascular mortality. METHODS AND RESULTS: Anxiety and depression symptoms were assessed in 350 patients (210 men) presenting with ACS, with 70 (20%) patients showing elevated scores (Hellenic Heart Failure Protocol). Over a mean follow-up of 48 months there were 36 (10%) cardiovascular deaths. Cox proportional hazards models adjusted for other prognostic factors (including age, sex, marital status, creatinine levels, left ventricular ejection fraction, heart failure, atrial fibrillation, previous hospitalisation, and baseline medications) showed that elevated anxiety and depression scores significantly predicted cardiovascular mortality (primary outcome) and all-cause mortality. CONCLUSIONS: Elevated anxiety and depression symptoms are related to cardiovascular mortality due probably to financial crisis, even after adjustment for other prognostic indicators in patients with ACS, who received optimised medical treatment.

Diagnosis and Treatment of Left-Sided Prosthetic Paravalvular Regurgitation.

Paravalvular leak (PVL) is a complication related to the surgical implantation of left-sided prosthetic valves. The prevalence of paravalvular regurgitation ranges between 5 and 20%. Left-sided prosthetic paravalvular regurgitation presents with a wide constellation of signs and symptoms ranging from asymptomatic murmur to heart failure, hemolysis and cardiac cachexia. Echocardiography plays a key role in imaging the PVL and can help in guiding the closure procedure with both transesophageal and intracardiac probes. Transcatheter closure of paravalvular regurgitations is an appealing prospect.

Transforming growth factor-ß inhibition and endothelin receptor blockade in rats with monocrotaline-induced pulmonary hypertension.

Transforming growth factor-ß (TGF-ß) inhibition is an investigational therapy for pulmonary arterial hypertension with promising results in experimental studies. The present work compared this approach with endothelin-receptor blockade and evaluated the effects of combined administration. Pulmonary arterial hypertension was induced by single monocrotaline injection (60 mg/kg) in 75 Wistar rats and 15 rats served as controls. Intervention groups consisted of treatment with an antibody against TGF-ß-ligand, bosentan, both or none, initiated four weeks after monocrotaline injection. Right ventricular systolic pressure, pulmonary vascular remodeling, and exercise tolerance were evaluated eight weeks after monocrotaline injection. Either treatment, alone or in combination, lowered mortality. Comparable efficacy was found in the three treatment groups in terms of right ventricular systolic pressure (~45% decrease) and hypertrophy (~30% decrease), as well as exercise capacity. The three treatment groups equally ameliorated pulmonary vascular remodeling, evidenced by decreased vessel-wall thickness (in vessels 50-200 µm) and a smaller number of pre-capillary arterioles (< 50 µm) with a muscularized media. Treatment either with an antibody against TGF-ß or with endothelin receptor blockade are equally effective in experimental pulmonary hypertension. Their combination provides no added benefit, indicating common mechanisms of action.

Transforming growth factor-ß inhibition attenuates pulmonary arterial hypertension in rats.

The role of transforming growth factor-ß in the pathogenesis of pulmonary arterial hypertension is unclear. We examined the effects of T9429, an antibody against transforming growth factor-ß receptors, on hemodynamic, histological and functional parameters in the rat model of monocrotaline-induced pulmonary hypertension. One week after monocrotaline injection (60 mg/kg) in 28 Wistar rats, T9429 (0.1mg/kg daily) was administered intraperito-neally in 19 rats (268±10g) via an osmotic mini-pump for 7 days. One week thereafter, right ventricular systolic pressure, pulmonary vascular remodeling and exercise tolerance were evaluated. Compared to the monocrotaline group (25.5±1.9mmHg), right ventricular systolic pressure was lower (p=0.0014) in the monocrotaline+antibody group (18.4±0.8mmHg). This was translated into attenuated right ventricular hypertrophy (p=0.0063) and longer (p=0.0155) exercise duration (2.08±0.29min versus 6.19±1.02min). Pulmonary arterial wall thickness (in vessels 50 -200µm) was comparable between the two groups, but the monocrotaline+antibody group displayed lower number (p<0.0001) of pre-capillary arterioles (<50µm, in 20 randomly selected fields) with a muscularized media (23.33±3.15 versus 6.64±0.75). Our results suggest that transforming growth factor-ß receptor blockade improves vascular remodeling and attenuates pulmonary hypertension, a finding with potential therapeutic implications.

Endothelin-B receptors and ventricular arrhythmogenesis in the rat model of acute myocardial infarction.

The arrhythmogenic effects of endothelin-1 (ET-1) are mediated via ETA-receptors, but the role of ETB-receptors is unclear. We examined the pathophysiologic role of ETB-receptors on ventricular tachyarrhythmias (VT/VF) during myocardial infarction (MI). MI was induced by coronary ligation in two animal groups, namely in wild-type (n = 63) and in ETB-receptor-deficient (n = 61) rats. Using a telemetry recorder, VT/VF episodes were evaluated during phase I (the 1st hour) and phase II (2-24 h) post-MI, with and without prior beta-blockade. Action potential duration at 90% repolarization (APD90) was measured from monophasic epicardial recordings and indices of sympathetic activation were assessed using fast-Fourier analysis of heart rate variability. Serum epinephrine and norepinephrine were measured with radioimmunoassay. MI size was similar in the two groups. There was a marked temporal variation in VT/VF duration; during phase I, it was higher (p = 0.0087) in ETB-deficient (1,519 +/- 421 s) than in wild-type (190 +/- 34 s) rats, but tended (p = 0.086) to be lower in ETB-deficient (4.2 +/- 2.0 s) than in wild-type (27.7 +/- 8.0 s) rats during phase II. Overall, the severity of VT/VF was greater in ETB-deficient rats, evidenced by higher (p = 0.0058) mortality (72.0% vs. 32.1%). There was a temporal variation in heart rate and in the ratio of low- to high-frequency spectra, being higher (<0.001) during phase I, but lower (p < 0.05) during phase II in ETB-deficient rats. Likewise, 1 h post-MI, serum epinephrine (p = 0.025) and norepinephrine (p < 0.0001) were higher in ETB-deficient (4.20 +/- 0.54, 14.24 +/- 1.39 ng/ml) than in wild-type (2.30 +/- 0.59, 5.26 +/- 0.67 ng/ml) rats, respectively. After beta-blockade, VT/VF episodes and mortality were similar in the two groups. The ETB-receptor decreases sympathetic activation and arrhythmogenesis during the early phase of MI, but these effects diminish during evolving MI.