Myocardial ischemia – reperfusion injury

Aim. To summarize and broaden the idea about mechanisms of acute coronary insufficiency development and pathophysiological features of myocardial reperfusion injury. Today, in the event of acute coronary syndrome, according to the latest recommendations for myocardial revascularization, percutaneous coronary intervention should be performed to determine the anatomy of coronary artery lesions and further percutaneous therapy. But in some patients, after blood flow restoration, reperfusion injury occurs, which is primarily related to the duration of ischemia, infarct size, and the myocardial resistance to ischemia. Treatment of myocardial infarction, like any treatment method, has evolved. In the 60s of the previous century, it included morphine, oxygen, warfarin and bed rest for 4–6 weeks. Then, during the 70s, it consisted of morphine, oxygen, lidocaine, warfarin, bed rest for 2–3 weeks and possibly coronary angiography for the further bypass surgery. The late 1970s saw the rapid progress in thrombolysis, first intravenous and then intracoronary. And starting in the early 1980s, since G. Hartzler performed the first balloon angioplasty for acute coronary artery occlusion, the stage of mechanical myocardial reperfusion has come. At the same time, knowledge about the pathophysiology of acute coronary ischemia was deepened. The World Health Organization developed ECG criteria for acute myocardial infarction using population-based studies in the 1950s–1970s, and additional four normative European regulations since then were issued defining concepts, key points of diagnosis and possible complications of myocardial infarction. Conclusions. The development of myocardial ischemic-reperfusion injury is a staged process that has a complex pathogenesis, its own clinical manifestations, and an association with more negative long-term outcomes of myocardial infarction treatment. Its main components are myocardial swelling involving cardiomyocytes, endotheliocytes, and the interstitial space; downregulation of cytoskeleton and disruption of sarcolemma integrity; increased vascular wall permeability; spasm of arterioles; intravascular accumulation of platelets and leukocytes, and the resultant the most severe form of myocardial damage is intramyocardial hemorrhage. Clinically, this is manifested by the no-reflow phenomenon following percutaneous coronary intervention

Increasing Physical Tolerance during Cardiac Rehabilitation Helps to Restore Endothelial Function in Patients after Acute Coronary Syndrome

In recent years, many studies have been aimed at exploring the possibilities of cardiac rehabilitation as a tool to improve the prognosis in patients after acute coronary syndrome (ACS). Endothelial dysfunction is one of the initiating mechanisms of cardiovascular diseases, and myocardial infarction in particular, so it is important to assess the dynamics of changes in the number of endothelial progenitor cells (EPCs) in patients during cardiac rehabilitation with the increase in physical activity. The aim. To establish the relationship between the level of recovery of exercise tolerance and the recovery of endothelial function by determining the number of EPCs in patients undergoing cardiac rehabilitation after ACS. Materials and methods. The study included 44 patients with ST-elevation myocardial infarction who underwent urgent stenting of the infarct-related artery, with a mean age of 59 years (Q1-Q3; 51-64). All the study participants underwent laboratory tests (CD45+/CD34+ cell count before and after the exercise test) and instrumental tests (echocardiography, bicycle ergometry, coronary angiography). Statistical processing was carried out using SPSS Statistics 23 (trial version). Results. According to the results of the exercise test at the first examination, the patients were divided into 2 groups: group 1 with low exercise tolerance (≤50 W) and group 2 with high exercise tolerance (>50 W). The data obtained indicate a link between better recovery of exercise tolerance after ACS and recovery of endothelial func-tion in patients with high exercise tolerance during follow-up compared to the patients whose exercise tolerance did not exceed 50 W, as evidenced by a statistically higher number of EPCs after exercise in patients with a favor-able course and high exercise tolerance (3633 vs. 2400 cells/ml) (p=0.006). Patients with low exercise tolerance were more likely to be diagnosed with lesions of left anterior descending coronary artery (96% vs. 70%, p=0.02). More severe coronary vascular lesions with stenosis of 75% of two or more arteries showed lower pre-exercise EPCs, but increased post-exercise EPCs (+228 cells/ml), whereas in the group with stenosis of more than 75% of one vessel, a decrease in post-exercise EPCs (–604 cells/ml) was observed (p=0.004). If patients have more than one stent, there is a 2.5-fold increased risk of decreased exercise tolerance to values of 25-50 W (relative risk = 1.8; 95% confidence interval: 1.3-2.4). Conclusions. The data obtained indicate that there is an association between a better recovery of exercise tolerance after ACS and recovery of endothelial function in patients with a favorable course at repeated examination, compared to patients whose level of exercise tolerance did not exceed 50 W (low exercise tolerance), as evidenced by a statistically greater number of EPCs after exercise test in patients with favorable course and high exercise tolerance compared with patients with unfavorable course and low exercise tolerance

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

ТРИ ДЕСЯТИЛЕТИЯ ТРАНСПЛАНТАЦИИ СЕРДЦА В ФНЦТИО ИМЕНИ АКАДЕМИКА В.И. ШУМАКОВА: ОТДАЛЕННЫЕ РЕЗУЛЬТАТЫ

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Two-year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD-AF.

AIMS: The relationship between outcomes and time after diagnosis for patients with non-valvular atrial fibrillation (NVAF) is poorly defined, especially beyond the first year. METHODS AND RESULTS: GARFIELD-AF is an ongoing, global observational study of adults with newly diagnosed NVAF. Two-year outcomes of 17 162 patients prospectively enrolled in GARFIELD-AF were analysed in light of baseline characteristics, risk profiles for stroke/systemic embolism (SE), and antithrombotic therapy. The mean (standard deviation) age was 69.8 (11.4) years, 43.8% were women, and the mean CHA2DS2-VASc score was 3.3 (1.6); 60.8% of patients were prescribed anticoagulant therapy with/without antiplatelet (AP) therapy, 27.4% AP monotherapy, and 11.8% no antithrombotic therapy. At 2-year follow-up, all-cause mortality, stroke/SE, and major bleeding had occurred at a rate (95% confidence interval) of 3.83 (3.62; 4.05), 1.25 (1.13; 1.38), and 0.70 (0.62; 0.81) per 100 person-years, respectively. Rates for all three major events were highest during the first 4 months. Congestive heart failure, acute coronary syndromes, sudden/unwitnessed death, malignancy, respiratory failure, and infection/sepsis accounted for 65% of all known causes of death and strokes for <10%. Anticoagulant treatment was associated with a 35% lower risk of death. CONCLUSION: The most frequent of the three major outcome measures was death, whose most common causes are not known to be significantly influenced by anticoagulation. This suggests that a more comprehensive approach to the management of NVAF may be needed to improve outcome. This could include, in addition to anticoagulation, interventions targeting modifiable, cause-specific risk factors for death. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Improved risk stratification of patients with atrial fibrillation: an integrated GARFIELD-AF tool for the prediction of mortality, stroke and bleed in patients with and without anticoagulation.

OBJECTIVES: To provide an accurate, web-based tool for stratifying patients with atrial fibrillation to facilitate decisions on the potential benefits/risks of anticoagulation, based on mortality, stroke and bleeding risks. DESIGN: The new tool was developed, using stepwise regression, for all and then applied to lower risk patients. C-statistics were compared with CHA2DS2-VASc using 30-fold cross-validation to control for overfitting. External validation was undertaken in an independent dataset, Outcome Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). PARTICIPANTS: Data from 39 898 patients enrolled in the prospective GARFIELD-AF registry provided the basis for deriving and validating an integrated risk tool to predict stroke risk, mortality and bleeding risk. RESULTS: The discriminatory value of the GARFIELD-AF risk model was superior to CHA2DS2-VASc for patients with or without anticoagulation. C-statistics (95% CI) for all-cause mortality, ischaemic stroke/systemic embolism and haemorrhagic stroke/major bleeding (treated patients) were: 0.77 (0.76 to 0.78), 0.69 (0.67 to 0.71) and 0.66 (0.62 to 0.69), respectively, for the GARFIELD-AF risk models, and 0.66 (0.64-0.67), 0.64 (0.61-0.66) and 0.64 (0.61-0.68), respectively, for CHA2DS2-VASc (or HAS-BLED for bleeding). In very low to low risk patients (CHA2DS2-VASc 0 or 1 (men) and 1 or 2 (women)), the CHA2DS2-VASc and HAS-BLED (for bleeding) scores offered weak discriminatory value for mortality, stroke/systemic embolism and major bleeding. C-statistics for the GARFIELD-AF risk tool were 0.69 (0.64 to 0.75), 0.65 (0.56 to 0.73) and 0.60 (0.47 to 0.73) for each end point, respectively, versus 0.50 (0.45 to 0.55), 0.59 (0.50 to 0.67) and 0.55 (0.53 to 0.56) for CHA2DS2-VASc (or HAS-BLED for bleeding). Upon validation in the ORBIT-AF population, C-statistics showed that the GARFIELD-AF risk tool was effective for predicting 1-year all-cause mortality using the full and simplified model for all-cause mortality: C-statistics 0.75 (0.73 to 0.77) and 0.75 (0.73 to 0.77), respectively, and for predicting for any stroke or systemic embolism over 1 year, C-statistics 0.68 (0.62 to 0.74). CONCLUSIONS: Performance of the GARFIELD-AF risk tool was superior to CHA2DS2-VASc in predicting stroke and mortality and superior to HAS-BLED for bleeding, overall and in lower risk patients. The GARFIELD-AF tool has the potential for incorporation in routine electronic systems, and for the first time, permits simultaneous evaluation of ischaemic stroke, mortality and bleeding risks. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier for GARFIELD-AF (NCT01090362) and for ORBIT-AF (NCT01165710)

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362