Patients with stable coronary artery disease and diabetes with previous percutaneous coronary intervention (PCI), particularly those with previous stenting, are at high risk of ischaemic events. These patients are generally treated with aspirin. In this trial, we aimed to investigate if these patients would benefit from treatment with aspirin plus ticagrelor. The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) was a phase 3 randomised, double-blinded, placebo-controlled trial, done in 1315 sites in 42 countries. Patients were eligible if 50 years or older, with type 2 diabetes, receiving anti-hyperglycaemic drugs for at least 6 months, with stable coronary artery disease, and one of three other mutually non-exclusive criteria: a history of previous PCI or of coronary artery bypass grafting, or documentation of angiographic stenosis of 50% or more in at least one coronary artery. Eligible patients were randomly assigned (1:1) to either ticagrelor or placebo, by use of an interactive voice-response or web-response system. The THEMIS-PCI trial comprised a prespecified subgroup of patients with previous PCI. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke (measured in the intention-to-treat population). Between Feb 17, 2014, and May 24, 2016, 11 154 patients (58% of the overall THEMIS trial) with a history of previous PCI were enrolled in the THEMIS-PCI trial. Median follow-up was 3·3 years (IQR 2·8-3·8). In the previous PCI group, fewer patients receiving ticagrelor had a primary efficacy outcome event than in the placebo group (404 [7·3%] of 5558 vs 480 [8·6%] of 5596; HR 0·85 [95% CI 0·74-0·97], p=0·013). The same effect was not observed in patients without PCI (p=0·76, pinteraction=0·16). The proportion of patients with cardiovascular death was similar in both treatment groups (174 [3·1%] with ticagrelor vs 183 (3·3%) with placebo; HR 0·96 [95% CI 0·78-1·18], p=0·68), as well as all-cause death (282 [5·1%] vs 323 [5·8%]; 0·88 [0·75-1·03], p=0·11). TIMI major bleeding occurred in 111 (2·0%) of 5536 patients receiving ticagrelor and 62 (1·1%) of 5564 patients receiving placebo (HR 2·03 [95% CI 1·48-2·76], p<0·0001), and fatal bleeding in 6 (0·1%) of 5536 patients with ticagrelor and 6 (0·1%) of 5564 with placebo (1·13 [0·36-3·50], p=0·83). Intracranial haemorrhage occurred in 33 (0·6%) and 31 (0·6%) patients (1·21 [0·74-1·97], p=0·45). Ticagrelor improved net clinical benefit: 519/5558 (9·3%) versus 617/5596 (11·0%), HR=0·85, 95% CI 0·75-0·95, p=0·005, in contrast to patients without PCI where it did not, pinteraction=0·012. Benefit was present irrespective of time from most recent PCI. In patients with diabetes, stable coronary artery disease, and previous PCI, ticagrelor added to aspirin reduced cardiovascular death, myocardial infarction, and stroke, although with increased major bleeding. In that large, easily identified population, ticagrelor provided a favourable net clinical benefit (more than in patients without history of PCI). This effect shows that long-term therapy with ticagrelor in addition to aspirin should be considered in patients with diabetes and a history of PCI who have tolerated antiplatelet therapy, have high ischaemic risk, and low bleeding risk. AstraZeneca.

The combination of heart failure and renal failure is called cardiorenal syndrome. It is a stage of the cardiorenal continuum and, possibly, a small link of the cardiorenal-cerebral-metabolic axis. Despite the fact that the phrase “cardiorenal syndrome” and its five types have become a part of the medical lexicon, many aspects of this problem are still not clear. Cardiorenal syndrome can be diagnosed in 32-90.3% of patients with heart failure. Cardiorenal syndrome type 1 or 2 develops in most cases of heart failure: cardiorenal syndrome presents with the development ofchronic kidney disease in patients with chronic heart failure and acute kidney injury in patients with acute heart failure. Impaired renal function has an unfavorable prognostic value. It leads to an increase in the mortality of patients with heart failure. It is necessary to timely diagnose the presence of cardiorenal syndrome and take into account its presence when managing patients with heart failure. Further researches are needed on ways toprevent the development and prevent the progression of kidney damage in patients with heart failure, to which the efforts of the multidisciplinary team should be directed. The first part of this review examines the currently definition, classification, pathogenesis, epidemiology and prognosis of cardiorenal syndrome in patients with heart failure.

Cardiac amyloidosis (amyloid cardiomyopathy) is a disease damage to the heart caused by extracellular amyloid deposition. In some cases, there may be local damage to the structures of the heart, for example, the atria; more often, heart damage is part of a systemic (generalized) pathology. Depending on the amyloid precursor protein, 36 types of amyloidosis are described, among which hereditary and acquired forms are distinguished. Cardiac amyloidosis is diagnosed 1) in the case of the amyloid infiltration in the myocardial bioptates or 2) in the case of non-cardiac amyloid deposition and the left ventricular wall thickening >12 mm without arterial hypertension and other reasons. The heart is most often affected in AL-, ATTR-, AA-, AANF-types of amyloidosis. Cardiac amyloidosis should be considered in patients with a heart failure with an unclear etiology, especially with preserved left ventricular ejection fraction, refractory to treatment, with proteinuria and CKD 4-5, in patients with idiopathic atrial fibrillation and conduction disturbances, in patients with left ventricular wall thickening of unclear etiology, low ECG voltage, unexplained arterial hypotension and pulmonary hypertension. Screening for cardiac amyloidosis should include non-invasive methods such as electrophoresis and immunofixation of blood and urine proteins, the free light lambda and kappa chains of immunoglobulins, 99Tc-DPD scintigraphy, genetic testing (if hereditary variants of amyloidosis are suspected), as well as a histological examination of biopsy samples stained with Congo red and polarizing microscopy.

Heart failure is an important medical, social and economic problem around the world. In recent years, a number of diagnostic and prognostic biological markers of blood in cardiovascular diseases have been studied. Identification of new biological markers, analysis of their pathophysiological aspects and changes in concentration under the influence of various treatment options, allow us to understand many pathogenetic features of the development and course of heart failure. In recent decades, natriuretic peptides have been introduced into clinical practice, which are widely used as reliable markers for diagnostic and prognostic assessment. Growth differentiation factor-15 is a cytokine belonging to the family of transforming growth factors, the activity of which is significantly increased under stress and inflammation. In patients with chronic heart failure, the concentration of this marker is associated with an increased risk of overall mortality and adverse cardiovascular events; in patients with heart failure with preserved left ventricular ejection fraction, the use of the marker showed prognostic and diagnostic significance. Data from the Framingham Heart Study showed that growth differentiation factor-15 was the only marker in multivariate analysis that showed a statistically significant association with all adverse cardiovascular events. Eight studies showed that overexpression of growth differentiation factor-15 was associated with an increased risk of mortality in patients with heart failure. It was shown that growth differentiation factor-15 as a prognostic marker in patients with acute heart failure is not inferior to the brain natriuretic peptide precursor. To confirm the value of this marker in blood in patients with heart failure, it is necessary to conduct extensive prospective randomized clinical trials.

Aim. To assess the healthcare system costs for the management of patients with heart failure (HF) based on a retrospective analysis of primary medical documentation.Material and methods. We performed the analysis of outpatient records of 1000 patients, followed up for 1 year by a general practitioner or cardiologist in ambulatory clinic in 7 Russian regions. The study included men and women over 18 years of age with an established class II-IV HF and at least one hospitalization due to acute decompensated HF within 12-month follow-up.Results. The final analysis included 888 patients (men, 52,9%; women, 47,1%; mean age, 69 [61; 78] years). The preserved ejection fraction (EF) was detected in 47,86% of patients, mid-range — in 40,54%, reduced — in 11,6%. Only in 16% of patients, there was improved by 1 or more HF. Hypertension and coronary artery disease were predominant in etiology pattern of HF. Preserved EF was more often detected in women over 60 years of age, with HTN and obesity, as well as with HF with mid-range and reduced EF in men in the same age group. There was sufficient follow-up rate, but the extent examinations do not correspond to the recommended one. The prescription rate of renin-angiotensin-aldosterone system (RAAS) inhibitors corresponds to the recommended one, but there is a high frequency of prescribing angiotensin II receptor blockers (ARBs). The prescription rate of β-blockers and loop diuretics (mainly torasemide) increased in comparison with previous studies, while thiazide diuretics — decreased. In patients with reduced EF, the prescription rate of sacubitril/valsartan was only 14,7%, β-blockers — 83,3%, mineralocorticoid receptor antagonists (MCRA) — 72,5%. In patients with midrange EF, there was a sharp decrease in prescription rate of RAAS inhibitors, β-blockers, MCRA.Conclusion. The practical follow-up of patients with HF differs significantly from clinical guidelines. Due to inadequate pharmacotherapy, as well as insufficient noncompliance with the recommended extent of investigations, 1-year HF therapy does not lead to a pronounced improvement in the patients' class.

Infiltrative cardiomyopathies are a group of diseases characterized by the deposition of abnormal substances in heart tissues, which leads to thickening of the walls or dilation of chambers with a secondary decrease in wall thickness and the development of diastolic, less often systolic, ventricular dysfunction. Most often, these are progressive diseases that, in the absence of adequate therapy, have an unfavorable prognosis. Clinical manifestations of infiltrative cardiac diseases are variable, which often leads to diagnostic difficulties and errors. In most cases, specific laboratory and morphological tests are required to confirm or clarify the diagnosis. Early diagnosis is critical to initiating therapy and improving patient prognosis. This article provides characteristic signs and symptoms, the so-called "red flags", making it possible to suspect infiltrative cardiomyopathies, diagnose them at an early stage and start life-saving therapy.