Clinical trials and regulatory science in cardiology最新文献

Objective

The objective of this study was the determination of the diagnostic value of Copeptin as a novel biomarker in early diagnosis of acute myocardial infarction.

Background

Copeptin is a strong marker for mortality and morbidity in patients with heart failure after an acute myocardial infarction (AMI). It is released very early during the onset of an AMI, raising the question of its potential value in the diagnosis of AMI and particularly in ruling-out AMI. Indeed, Copeptin is released much earlier than troponin making the interpretation of their complementary kinetics a useful tool to rule-out AMI. [1]

Method

This Prospective Comparative Analytical cohort study included 56 patients with Patients with acute myocardial infarction (STEMI) and 15 healthy controls who were admitted to the Cardiology Department, Menoufiya University from January 2014 to December 2014. All patients were subjected to full medical history taking, general examination, local cardiac examination, resting 12 leads ECG and laboratory investigations (including CK-T, cTnT and Copeptin).

Results

Our study showed non-significant differences regarding age, sex, blood pressure and hypertension between patient group and control group, but there was statistically significant difference as regards heart rate, smoking, diabetes mellitus, CK-T, (cTnT) and Copeptin.

Conclusion

Adding Copeptin to CK-T, cardiac troponin T (cTnT) allowed safe rule out of AMI with a negative predictive value (NPV) > 99% in patients presenting with suspected acute coronary syndromes. This combination has the potentiality to rule out AMI in 58% of patients without serial blood draws.

Background

Rheumatic fever recurrence (RFrec) contributes to the worsening of rheumatic valve disease. There are few studies describing the factors associated with recurrence.

Objectives

To analyze the potential risk factors for RFrec in an outpatient cohort.

Methods

We evaluated 148 patients from a cohort of 218 patients treated at rheumatic fever (RF) clinics of the University Hospital Prof. Edgard Santos (Salvador-BA), with at least two years of follow-up.

Results

The mean age was 29.7 ± 12.7 years, with 64% female. RFrec occurred in 14.2% of patients. Patients with and without recurrence differed in age (23.4 ± 9.9 × 30.8 ± 12.7 years, p = 0.024), age ≤ 23 years (82.3% vs 39.6%, p = 0.001), non-adherence to prophylaxis (36.8% vs 15.5%, p = 0.027), prior heart failure (HF) (38% vs. 17%, p = 0.03), presence of aortic regurgitation on echocardiography (71% vs. 44%, p = 0.05) and diastolic dimension of the left ventricle (58.0 ± 16.2 × 51.6 ± 8.6 mm, p = 0.025). Estimated relative risk of RFrec were: age ≤ 23 years RR 5.6 (95% CI 1.7 to 18.5) — p = 0.001; non-adherence to prophylaxis RR 2.6 (95% CI 1.1 to 5.9) — p = 0.027; prior HF RR 2.4 (95% CI 1.1 to 5.2) — p = 0.03. In multivariate analysis, these three parameters showed significant independent association with RFrec.

Conclusions

RFrec occurred in 14.2% of patients. Age ≤ 23 years, lack of adherence to secondary prophylaxis and prior HF were independent predictors of recurrence.

Background

Deep vein thrombosis (DVT) after total knee arthroplasty (TKA) often results in a fatal pulmonary thromboembolism (PTE). Edoxaban is an activated factor X inhibitor, which has been shown to prevent thromboembolic events in venous thromboembolism (VTE). Recently, the Total-Thrombus-formation Analysis System (T-TAS™), a microchip-based flow chamber system capable of evaluating thrombogenicity, was developed. In this study, utilizing the T-TAS™, we will examine the incidence of VTE after TKA and evaluate how thromboses form.

Methods/design

This study will be a prospective, single-center, open-label, randomized, controlled clinical trial aimed at exploring the efficacy of edoxaban in reducing the incidence of VTE after TKA.

A total of 80 patients who will undergo TKA will be randomly and evenly divided into groups receiving edoxaban plus physiotherapy or physiotherapy alone. The primary outcome measures will include the incidence rate of VTE as detected by ultrasonography 7 days after TKA and the changes in T-TAS™ parameters. The secondary outcome measures will include the changes in prothrombin time and activated partial thromboplastin time, incidence of major/minor bleeding events and adverse effects of edoxaban.

Discussion

This study will provide clinical evidence on the combined efficacy and safety of edoxaban and physiotherapy compared with that of physiotherapy alone. This is will be the first prospective trial designed to explore how thrombus formation after TKA can be predicted by the T-TAS™.

Aim

Low adherence to cardiovascular medications is often difficult to monitor and is associated with adverse outcomes. We investigated whether there is a difference between the estimated adherence (EA) of the two-dosed regimens of apixaban (A) and the one-dosed regimen of rivaroxaban (R) for stroke prophylaxis in patients with non-valvular atrial fibrillation (AF).

Method and results

This is a retrospective cohort study of AF patients referred to a well-structured nurse-based AF unit for the initiation of anticoagulation therapy. The adherence data was extracted from the Swedish national prescribed drug register. EA was calculated by dividing the number of daily doses dispensed from the prescription that occurred closest after 3 months from the first dispensed prescription of the respective agent until (but excluding) the last refill by the number of days in the interval. The study included 123 patients on A and 227 patients on R with a 12-month follow-up period. There were no significant demographic differences between the two patient groups except for previous vitamin K antagonist treatment, in the A patient group (n = 29, 24%) and in the R (n = 31, 14%), p = 0.025. The mean ± SD of EA after 3 months was high for both A 97 ± 7 (n = 112) and R 97 ± 9 (n = 197) p = 0.97. The EA ≥ 80% was for A 97% (n = 109) and for R 96% (n = 189) p = 0.43.

Conclusion

The two dosed regimens of apixaban and the one dosed regimen of rivaroxaban showed similar high estimated adherence when administered for stroke prophylaxis in patients with AF in a well-structured nurse-based AF clinic.

Background

Host genetic factors of interleukin (IL)-1 polymorphisms influence Helicobacter pylori infection pathogenic activity. We examined whether H. pylori-infected patients with IL-1 polymorphisms are associated with myocardial infarction (MI).

Materials and methods

We recruited 594 consecutive coronary artery disease patients and excluded those who met exclusion criteria. After matching age and sex, 82 cases with MI and 82 controls were enrolled. Immunoglobulin G antibodies against H. pylori and IL-1 polymorphisms (IL-1 beta-511 base pairs and IL-1 receptor antagonist) were analyzed. We assessed high sensitivity C-reactive protein (hs-CRP) level and reactive hyperemia-peripheral arterial tonometry (RH-PAT) index (RHI) using the EndoPAT2000 system.

Results

The simultaneous prevalence of H. pylori-seropositivity and IL-1 polymorphisms was 45.1% and 19.5% in the cases and controls, respectively (P = 0.001). H. pylori-positive patients with IL-1 polymorphisms showed significantly higher serum levels of natural logarithm of hs-CRP in the cases and controls (− 2.8 ± 1.0 vs. − 3.4 ± 0.6, respectively; P = 0.003 and − 2.8 ± 0.9 vs. − 3.2 ± 0.6, respectively; P = 0.02) and significantly lower levels of natural logarithm of RHI in the cases and controls (0.51 ± 0.13 vs. 0.61 ± 0.23, respectively; P = 0.039 and 0.47 ± 0.13 vs. 0.69 ± 0.23, respectively; P = 0.005). H. pylori-seropositivity with IL-1 polymorphisms was significantly associated with MI by logistic regression analysis (odds ratio, 4.83; 95% confidence interval, 1.99–11.7; P < 0.001).

Conclusions

H. pylori-positive patients with IL-1 polymorphisms showed higher levels of hs-CRP and lower levels of RHI, and were significantly correlated with the MI.

Background

Trials of remote ischemic pre-conditioning (RIPC) have suggested this intervention reduces complications of angioplasty and coronary artery by-pass grafting (CABG). The aim of this work was to conduct a systematic review and meta-analysis of the effects of RIPC on mortality and myocardial damage in patients undertaking coronary artery bypass grafting with/without valve surgery.

Methods

A systematic review and subsequent meta-analysis of randomized controlled trials of RIPC versus usual care or sham RIPC was performed.

Results

Eighteen studies, totalling 4551 participants were analysed. RIPC reduced post troponin release as indicated by area under the curve at 72 h (μg·L^− 1) Mean Difference (MD) − 3.72 (95% CI − 3.92 to − 3.53, p < 0.00001). However there was no significant difference between RIPC and control when mortality odds ratio (OR) 1.27 (95% CI 0.87 to 1.86, p = 0.22); the incidence of new onset atrial fibrillation OR 0.82 (95% CI 0.67 to 1.01, p = 0.06); inotropic support OR 1.27 (95% CI 0.84 to 1.91, p = 0.25); intensive care unit stay in days MD − 0.02 (95% CI − 0.12 to 0.07, p = 0.61); Hospital stay in days MD 0.18 (95% CI − 0.30 to 0.66, p = 0.47) and serum creatinine MD − 0.00 (95% CI − 0.07 to 0.07, p = 0.97) were compared.

Conclusions

RIPC reduces does not confer any clinical benefit in patients undertaking CABG with/without valve surgery.

Background

The Universal Definition for type 5 myocardial infarction (MI) applies to coronary artery bypass grafting (CABG), while MIs for other cardiac surgery are not specifically defined. We assessed whether elevated high-sensitivity troponin (hs-TnT), with electrocardiogram (ECG) changes and/or new wall motion abnormalities on echocardiography as defined by the Universal Definition, predicted mortality and/or morbidity after aortic valve replacement (AVR) (n = 219).

Methods

Consecutive patients with isolated AVR performed during July 2010–December 2012 and followed-up for 2.3 ± 0.8 years. Hs-TnT was measured 12–24 h post-operatively. ECG and/or echocardiographic changes with hs-TnT > 140 ng/L (10 times 99th percentile upper reference limit and > 500 ng/L (10 times the coefficient of variation of 10% for 4th generation troponin T applied to hs-TnT) were pre-specified as the criteria for MI diagnosis.

Results

There were 9.1% (20) and 3.7% (8) patients with ECG and/or echocardiographic changes and hs-TnT > 140 ng/L and hs-TnT > 500 ng/L respectively. Neither criterion was independently associated with 30-day mortality (2.7%). Hs-TnT > 500 ng/L and ECG and/or echocardiographic changes was independently associated with mortality (5.5%) during follow-up, hazards ratio 5.23, 95% confidence interval 1.09–25.2, p = 0.039. Hs-TnT per 100 ng/L as a continuous parameter was independently associated with 30-day mortality, mortality during follow-up and composite morbidity.

Conclusion

The Universal Definition of MI, using 10 times the URL for the 4th generation troponin T and 35 times the URL for hs-TnT with a cutpoint of > 500 ng/L with ECG and/or echocardiographic changes, independently predicted median term mortality after AVR. Hs-TnT as a continuous parameter was independently associated with mortality at both time points and morbidity.

Background

Anemia is found to be an independent risk factor of morbidity, mortality and hospitalization among patients with heart failure. The prevalence, as the potential treatment options of anemia in HF has received increasing clinical interest and epidemiological studies have indicated a variation in the prevalence of anemia in patients with HF.

Method

Electronic search took place in the databases: Pubmed, Cochrane and CINAHL to locate studies in English that investigated the effect of anemia in patients with HF. The overall pooled effect (relative risk, RR) of anemia as comorbid factor compared with HF patients without anemia was estimated by using a random effects analysis (95% confidence interval (CI) for the outcomes of HF — related mortality rate, re-hospitalization and physical condition.

Results

Twenty-six studies were selected. In the overall RR of mortality, re-hospitalization and extended hospitalization was 1.70, 95% CI (1.47–1.98), p < 0.00001, for readmission rate 1.57, 95% CI (1.17, 2.10), p = 0.003 and 1.25, 95% CI (0.59–1.90), p = 0.0002 respectively in behalf of heart failure patients without anemia. Likewise, patients with anemia tend to have worse functionality according to NYHA classification 1.23, 95% (CI 0.99–1.52), p = 0.06. A meta-regression analysis conducted in an effort to explain the heterogeneity of mortality.

Conclusion

The meta-analysis gives an outline profile of patients with the co-morbidity HF and anemia in terms of clinical outcomes. The results point out worse prognosis in HF patients with anemia. Nevertheless, the available data did not allow the extraction of a conclusion in which exact Hb levels anemia becomes a negative predictor of prognosis.

Background

Asymmetric dimethylarginine (ADMA), and its symmetrical stereoisomer (SDMA) — as methylated products of l-arginine, decrease nitric oxide (NO) availability. Their elevated levels in diabetes increase the risk of acute myocardial infarction (MI), through endothelial dysfunction.

Aims

We investigated the relationship between circulating levels of ADMA, SDMA and functional relevant parameters in patients with acute MI.

Methods

Prospective study from 31 MI patients hospitalized < 12 h after symptom onset. Blood samples were taken on admission and serum levels of ADMA, SDMA and l-arginine were determined using high-performance liquid chromatography (HPLC).

Results

Mean age was 65y, most were male, hypertensive, 1/3rd were current smokers, or had a history of CAD and 23% were diabetic. ADMA and l-arginine values were similar whatever the risk factor, except for ADMA that was positively correlated with blood glucose (r = 0.37). In contrast, SDMA was correlated with age (r = 0.43), and admission glucose (r = 0.57). SDMA was elevated in hypertension, prior CAD, statin therapy and showed a trend toward an increase in diabetic patients (p = 0.191). Moreover, there was a trend toward an elevation of SDMA with decreased LVEF (r = − 0.25). In multivariate linear regression analysis, blood glucose was an estimate of SDMA (ß = 0.373, p = 0.025), beyond traditional markers of dimethylarginines including kidney failure.

Conclusion

Our study showed that in patients with acute MI, SDMA, and only weakly ADMA, are associated with admission blood glucose, beyond traditional dimethylarginine determinants and may therefore have biological activity beyond renal function.

Background

We analyzed the literature to assess the coincidental impact on migraines of transcatheter patent foramen ovale (PFO) closure performed for secondary stroke prevention.

Methods

We searched Medline, EMBASE, and the Cochrane database for studies published up until August 2013. We included English-language studies that provided information on complete resolution or improvement in migraine headaches following PFO closure. Two study authors identified 375 original articles and both independently reviewed 32 relevant manuscripts. Data including study methodology, inclusion criteria, PFO closure and migraine outcomes were extracted manually from all eligible studies. Pooled odds (and probability) of resolution or improvement of migraine headaches were calculated using random-effects models.

Results

Twenty studies were analyzed. Most were uncontrolled studies that included a small number of patients with cryptogenic stroke who had undergone PFO closure and had variable time of follow-up. The probability of complete resolution of migraine with PFO closure (18 studies, 917 patients) was 0.46 (95% confidence interval 0.39, 0.53) and of any improvement in migraine (17 studies, 881 patients) was 0.78 (0.74, 0.82). There was evidence for publication bias in studies reporting on improvement in migraines (Begg's p = 0.002), but not for studies on complete resolution of migraine (p = 0.3). In patients with aura, the probability of complete resolution of migraine post-PFO closure was 0.54 (0.43, 0.65), and in those without aura, complete resolution occurred in 0.39 (0.29, 0.51).

Conclusions

Among patients with unexplained stroke and migraine undergoing transcatheter PFO closure, resolution of headaches occurred in a majority of patients with aura and for a smaller proportion of patients without aura.