Recommendation provides information to employees of medical departments at any level and primarily primary care about the possible proarrhythmic and adverse effects of drugs used for the treatment of COVID-19 patients and the features of therapy for COVID-19 patients with heart rhythm and conduction disorders receiving permanent antiarrhythmic therapy

For organization of health care, it is important to know the requirement for its individual types, including the number of hospitalizations and the use of expensive technologies. Heart failure (HF) syndrome in patients with cardiovascular diseases often determines their severity and prognosis. However, being a complication of underlying disease, HF is not included into statistical reports and medical bills in the compulsory health insurance system. This article focuses on issues in evaluating HF prevalence and mortality in different countries and provides the authors’ consensus on approaches to HF coding in the informational systems, which record morbidity and mortality.

Aim      To identify new predictors for vulnerability of atherosclerotic coronary plaques in patients with stable ischemic heart disease (sIHD).

Material and methods  This prospective, single-center study included 58 patients with sIHD. Unstable plaques were detected with virtual histology intravascular ultrasound of proximal and medium segments of a coronary artery without significant lesions according to coronarography data. Indexes of inflammation, dyslipidemia and carbohydrate metabolism were considered as candidate predictors for coronary plaque vulnerability.

Results In 56 coronary arteries, 58 plaques were detected, 12 of which (20.7 %) were unstable. Vulnerable plaques differed morphologically from stable ones by a greater size of the necrotic core (35.1±8.5 % vs. 24.0±13.2 %; р=0.008), calcified nodules (2.0 [1.0; 5.0] % vs. 1.0 [0; 2.0] %; р=0.006), and a lower content of fibrous components (54.9±10.2 % vs. 66.4±15.8 %; р=0.02). In addition, vulnerable plaques more frequently narrowed the arterial lumen by >70 % of the lumen area (33.3 % vs. 2.2 %; р=0.0006). Correlation analysis showed a negative correlation between the level of high-density lipoproteins (HDL) and calcium volume (r= –0.4104; р=0.023); a positive correlation between the blood glucose level as determined by the oral glucose tolerance test and the lipid component (r=0.48198; р=0.033); and a negative correlation between the apolipoprotein A level and the calcium volume (r= –0.4297; р=0.008).

Conclusion      The study demonstrated a high prevalence of vulnerable plaques in nontarget coronary arteries in patients with sIHD. In this process, dyslipidemia indexes (LDL, apolipoproteins A) correlate with the calcium volume whereas blood glucose, as measured in the oral glucose tolerance test, correlates with the lipid component of coronary plaque.

 

Over the past few decades, much attention has been paid to the study of the properties of the vascular wall and its role in predicting cardiovascular events. The testing of new indicators characterizing cardiovascular risk is being actively conducted. The study included 288 men aged 40 to 60 years (mean age 51.6 ± 6.2 years). Among the examined 133 people belonged to the category of very high cardiovascular risk (they suffered myocardial infarction for no more than 5 years before inclusion in the study), and 155 patients did not have a history of cardiovascular complications. Using the Fukuda denshi VS-1500 VaSera sphygmograph, a cardio-ankle vascular index (CAVI) and augmentation index (AI) were obtained. A model of multivariate logistic regression was constructed for the probability of assigning the patient to a group of very high risk, as well as ROC analysis. The study demonstrated the statistically significant role of CAVI in predicting the assignment of patients to a group of very high cardiovascular risk (after myocardial infarction). An increase in the odds ratio of assigning a patient to this group with an increase in CAVI per unit is 1.417. According to the results of ROC analysis, the prognostic role of CAVI (AUC 0.70) is slightly inferior to age (AUC 0.75), but exceeds AI (AUC 0.641). The share of variability in the probability of classifying patients as a very high risk group from the influence of the studied factors is 31%. The overall quality of the predictive model can be rated as good (AUC = 0.77).

Aim      To evaluate the effect of combination ivabradine-containing therapy for chronic heart failure (CHF) with preserved ejection fraction on quality of life (QoL) and the primary composite endpoint during a one-year follow-up.

Material and methods  This study included 160 patients aged 45 to 65 years with NYHA functional class (FC) II-III CHF with preserved left ventricular ejection fraction (CHF-PEF) and grade I and II diastolic dysfunction associated with FC III stable angina with sinus rhythm and a heart rate (HR) higher than 70 bpm. Presence of CHF-PEF was confirmed by results of echocardiography and myocardial tissue Doppler imaging. During one year of prospective observation, effects of bisoprolol and ivabradine as a part of the combination therapy on the primary composite endpoint, including death from cardiovascular complications (CVC) and hospitalizations for myocardial infarction (MI) or CHF, were evaluated in patients with CHF-PEF. Patients were randomized to three groups: A, bisoprolol with dose titration from 2.5 to 10 mg; В, combination of bisoprolol 2.5-10 mg and ivabradine 10-15 mg/day; and С, ivabradine 10-15 mg/day. All patients were on a chronic background therapy, including angiotensin-converting enzyme inhibitors (lisinopril) or, if not tolerated, angiotensin II receptor blockers (valsartan), antiaggregants, statins (atorvastatin, rosuvastatin), and short-acting nitrates as required. If edema developed diuretics were added. The follow-up duration was one year.

Results After 12 weeks of follow-up, the achievement of goal HR in group A was associated with a tendency to increased distance in the 6-min walk test from 279±19 to 341±21 m (р>0,05); in group B the distance increased from 243±25 to 319±29 m (р<0.05); and in group C the distance increased from 268±21 to 323±22 m (р<0.05). In the combination ivabradine and bisoprolol treatment group, results of the 24-h electrocardiogram monitoring showed a more pronounced anti-ischemic effect associated with a decrease in the number of myocardial ischemic episodes (p<0.05). QoL was evaluated with the Minnesota questionnaire against the background of treatment. At 12 weeks of observation, the total score decreased from 44.5±2.6 to 38.4±2.1 in group A; from 45±2.9 to 38±2.2 in group B; and from 50.9±3.2 to 42.7±2.8 in group C (р<0.05). The risk of acute MI and repeated hospitalization for CHF during the year of observation, as evaluated according to the Kaplan-Meier method, decreased in both bisoprolol and ivabradine combination treatment groups.

Conclusion      The inclusion of bisoprolol and ivabradine into the background therapy of CHF-PEF patients with stable IHD provided an improvement of QoL and a decrease in the risk of hospitalization for acute MI and CHF during the year of observation.

 

Aim      To compare the accuracy of predicting an in-hospital fatal outcome for models based on current machine-learning technologies in patients with ischemic heart disease (IHD) after coronary bypass (CB) surgery.

Material and methods  A retrospective analysis of 866 electronic medical records was performed for patients (685 men and 181 women) who have had a CB surgery for IHD in 2008–2018. Results of clinical, laboratory, and instrumental evaluations obtained prior to the CB surgery were analyzed. Patients were divided into two groups: group 1 included 35 (4 %) patients who died within the first 20 days of CB, and group 2 consisted of 831 (96 %) patients with a beneficial outcome of the surgery. Predictors of the in-hospital fatal outcome were identified by a multistep selection procedure with analysis of statistical hypotheses and calculation of weight coefficients. For construction of models and verification of predictors, machine-learning methods were used, including the multifactorial logistic regression (LR), random forest (RF), and artificial neural networks (ANN). Model accuracy was evaluated by three metrics: area under the ROC curve (AUC), sensitivity, and specificity. Cross validation of the models was performed on test samples, and the control validation was performed on a cohort of patients with IHD after CB, whose data were not used in development of the models.

Results The following 7 risk factors for in-hospital fatal outcome with the greatest predictive potential were isolated from the EuroSCORE II scale: ejection fraction (EF) <30 %, EF 30-50 %, age of patients with recent MI, damage of peripheral arterial circulation, urgency of CB, functional class III-IV chronic heart failure, and 5 additional predictors, including heart rate, systolic blood pressure, presence of aortic stenosis, posterior left ventricular (LV) wall relative thickness index (RTI), and LV relative mass index (LVRMI). The models developed by the authors using LR, RF and ANN methods had higher AUC values and sensitivity compared to the classical EuroSCORE II scale. The ANN models including the RTI and LVRMI predictors demonstrated a maximum level of prognostic accuracy, which was illustrated by values of the quality metrics, AUC 93 %, sensitivity 90 %, and specificity 96 %. The predictive robustness of the models was confirmed by results of the control validation.

Conclusion      The use of current machine-learning technologies allowed developing a novel algorithm for selection of predictors and highly accurate models for predicting an in-hospital fatal outcome after CB.

 

Aim      To study association of single-nucleotide polymorphisms rs1049255 CYBA and rs2333227 MPO with development of ischemic heart disease (IHD) in Russian residents of Central Russia.

Material and methods  The study material was DNA samples from 436 patients with IHD (265 men, 171 women; mean age, 61 years) and 370 sex- and age-matched arbitrarily healthy volunteers (209 men, 161 women; mean age, 60 years). Genotyping was performed by allelic discrimination with TaqMan probes.

Results Comparative analysis of genotype frequency (log-additive regression model) showed that SNP rs1049255 CYBA (odds ratio, OR, 0.79 at 95 % confidence interval, CI, from 0.65 to 0.96; p=0.02) and rs2333227 MPO (OR 0.72 at 95 % CI from 0.55 to 0.95; p=0.02) were associated with a decreased risk of IHD adjusted for sex and age. Analysis of sex-specific effects showed that the protective effect of rs1049255 CYBA was evident only in men (OR 0.72 at 95 % CI from 0.55 to 0.94; p=0.16).

Conclusion      The study demonstrated a protective effect of rs1049255 CYBA and rs2333227 MPO with respect of IHD in Russians. The protective effect of rs1049255 CYBA was observed only in men.

Aim To evaluate the role of N-terminal pro-hormone brain natriuretic peptide (NT-proBNP) as a predictor of cardiovascular events (CVE) in patients receiving programmed hemodialysis (PHD).
Material and methods This study included 74 patients (men, 64.8 %) older than 18 years receiving PHD. Data were processed using mean values of standard biochemical indexes for 16 months. NT-proBNP level was measured and transthoracic echocardiography (EchoCG) and bioimpedancemetry were performed at the time of inclusion into the study. Cumulative incidence of CVE for 16 months was evaluated in patients with different levels of NT-proBNP (quartile 1: <1127 pg/ml; quartile 1–4: 1127–3210 pg/ml; quartile 4: >3210 pg/ml) using the Kaplan-Meier method. For assessment of NT-proBNP as a CVE predictor, receiver operational characteristic curves (ROC curves) were constructed.
Results The serum concentration of NT-proBNP was 2114.5 [1127; 3210.4] pg/ml. During 16 months, CVE were observed in 25.6 % of patients. The risk of CVE increased with increasing NT-proBNP quartile in the analysis of Kaplan-Meier curves (Log-Rank test, p=0.032). In this process, CVE did not develop in patients with NT-proBNP concentrations lower than 1127 pg/ml. The ROC analysis demonstrated a good predictive value of NT-proBNP (p=0.006, AUC 0.71, 95 % CI: 0.59–0.83). The optimum cut-off threshold of the NT-proBNP level predictive of CVE was 2093 pg/ml (sensitivity, 84.2 %, specificity, 58.2 %). CVE developed in patients with greater values of volumetric myocardial parameters, indirect signs of hyperhydration (higher predialysis sodium level and pulmonary artery systolic pressure), smaller volumes of substituate per dialysis procedure, and left ventricular systolic dysfunction (p<0.05).
Conclusion In patients receiving programmed extracorporeal therapy, the serum concentration of NT-proBNP was considerably higher than mean values in the general population. Apparently, serum NT-proBNP concentrations in the range of 1127–2093 pg/ml can be used as a predictor for a high risk of CVE in the dialysis population. Pronounced structural alterations of the myocardium, left ventricular systolic dysfunction, and hyperhydration are the factors that provide development of CVE on PHD. Large volumes of the PHD substitution solution are associated with a lower incidence of CVE in the dialysis population.

Objectives Radiocontrast agents (RCA) allergy occurs in 0.04 % – 0.22 % of patients. However, the risk of allergic reaction increases as 16 % to 35 % in patients with prior RCA allergy. Herein we reported our experience in patients with a prior history of RCA induced anaphylaxis who underwent coronary angiography (CAG) and intervention.
Methods This retrospective study included 11 patients with prior history of RCA anaphylaxis who underwent CAG and / or intervention at our clinic between May 2016 and September 2019. The mean age of the patients was 61.8±8.99 years, 8 (72.7 %) were female, 9 (81.8 %) had hypertension, 6 (54.5 %) – diabetes mellitus, 11 (100 %) – dyslipidemia, 8 (72.7 %) patients were current smokers, 4 had prior history RCA allergy after i.v. RCA administration in contrast enhanced computed tomography and 7 patients experienced RCA allergy after CAG. All patients had prior severe anaphylaxis reaction. All patients were pretreated with intravenous feniramin maleat 45.5 mg and methylprednizolone 80 mg one hour before the procedure and dexametazon 8 mg after the procedure.
Results CAG and intervention was successfully completed in all patients. Two patients had breakthrough RCA induced anaphylaxis, theyhad urticarial, itching, dyspnea and chest tightness, angioedema during coronary artery stenting. Additional dose of i.v. methylpredinisolene 80 mg, salbutamol nebulae and i.v. adrenalin 1 mg administration rapidly stabilize the patients. All patients were successfully treated and uneventfully discharged after percutaneous coronary intervention.
Conclusion Management of patients with prior RCA adverse drug reaction may be complex. However when CAG and / or intervention is required in such patients it may be safely performed with premedication.

Aim To study long-term compliance with treatment in patients included into the REGistry of pATients after myocArdial infarction (REGATA).
Material and methods In 2012–2013, the study included 481 patients with a history of myocardial infarction (MI) who visited the district outpatient clinic. Median age was 72 [62;78] years; men, 51.4 % (n=247); median time from the last MI to the date of inclusion into the registry was 5 [2;9] years. Compliance with treatment was determined with the Morisky-Green questionnaire during telephone contacts with patients at 36 and 48 months (n=230) after the inclusion. Patients scored 4 were considered compliant; patients scored 3 were low-compliant; and patients scored 0-2 were non-compliant. Statistical significance of differences in compliance at 36 and 48 months was assessed with the McNemar test.
Results There were no significant differences between the proportions of compliant, low-compliant and non-compliant patients for the analyzed period. However, at 48 months after the inclusion, the number of patients who had difficulties in answering the questionnaire questions significantly increased from 15.5 % to 21.6 % (p=0.04). Analysis of changes in compliance with the treatment for only compliant patients showed that at 36 months from the inclusion, 87 patients remained highly compliant (37.8 %) while at 48 months, only 32 (36.8 %) patients remained compliant with the treatment. Proportion of compliant patients did not significantly differ for men and women, patients younger and older than 60 years, patients with primary MI and reinfarction, prone and not prone to self-management, and for those who used or not the medicine assistance.
Conclusion The data obtained as a part of the REGATA registry indicate insufficient long-term compliance with the treatment of after-MI patients with both primary MI and reinfarction, an increasing proportion of patients who are unable to assess their degree of compliance, and decreasing compliance among highly compliant patients during the period between 36 and 48 months of observation. On the whole, there were no significant changes in the compliance with the treatment for 12 months between the first and the second interviews. The proportion of patients compliant with the prescribed drug therapy was significantly lower in the presence of predisposition to self-management.

Aim To study the association between concentrations of endothelial dysfunction (ED) markers and arterial hypertension (AH) in people who were exposed to long-term action of “low-dose” ionizing radiation.
Material and methods The study subjects were men of middle age (45–55 years) who were workers of the Siberian Integrated Chemical Plant with the length of service on the shop floor of at least 5 years. The subjects were divided into the main group (n=96) consisting of workers with grade 1-2 AH and the control group (n=48) consisting of arbitrarily healthy workers. Both groups contained workers who had been exposed to long-term occupational low-intensity irradiation (γ-radiation) and those not exposed to this irradiation. The study evaluated risk factors for cardiovascular diseases, presence of concomitant diseases, blood biochemistry (concentrations of glucose, high-sensitivity C-reactive protein (hsCRP), total cholesterol, low-density lipoproteins, high-density lipoproteins, triglycerides, creatinine, and ED markers, including endothelin, angiotensin II, von Willebrand factor, C-type natriuretic peptide, tissue plasminogen activator, tumor necrosis factor α (TNF-α), and homocysteine, major clinical data, total dose of external irradiation, and the content of 239Pu in the body.
Results AH was associated primarily with excessive body weight and severity of atherogenic dyslipidemia and homocysteinemia. Higher plasma concentrations of TNF-α and a tendency to increasing hsCRP in the AH group, as distinct from the control group of arbitrarily healthy men, indicated a proinflammatory shift. The ED markers were related with clinical data of AH patients and associated with the lipid profile and increased blood concentrations of inflammatory mediators. The radiation exposure did not change the ED marker array in AH patients, which did not allow recommendation of the studied plasma indexes for detection of vascular endothelial injury in workers with AH of the Siberian Integrated Chemical Plant.
Conclusion The study results evidenced the absence of adverse effects of long-term occupational exposure to low-intensity radiation on the vascular endothelium as evaluated by ED markers. In men aged 45–55 years, AH was associated primarily with excessive body weight, homocysteinemia, and atherogenic dyslipidemia.

Aim To study ultrasonic characteristics of lung tissue in patients with heart failure with left ventricular (LV) mid-range ejection fraction (HFmEF) and predictive value of these characteristics after reversing acute decompensated heart failure (ADHF).
Material and methods Ultrasonic characteristics of lung tissue were studied by prospective observation in 71 patients (mean age, 65.2±3.6 years; men, 64.3 %) with HFmEF (LVEF from 40 to 49 %) following ADHF reversal. Semiquantitative evaluation of B-lines was performed by the E. Picano (2016) method at 5+2 days after hospitalization and on discharge from the hospital. The distance between B-lines was 3 mm (В3 lines) and 7 mm (В7 lines). Patients’ catamnesis was studied for determining the predictive value of lung tissue ultrasonic characteristics for two years since the index hospitalization. Statistical analysis was performed using the McNemar’s χ2 test (for evaluation of linked samples and of changes in the presence/absence of B-lines as determined by lung ultrasound examination (USE)) and the Wilcoxon test (for evaluation of quantitative changes). Differences were considered significant at p<0.05.
Results B7-lines characteristic of interstitial component of pulmonary parenchymal edema prevailed in patients with HFmEF. В3-lines characteristic of alveolar edema were found in a small amount. In the anterior-superior segment, B7-lines predominated over B3-lines (80 % vs. 20 %, p<0.01) on the right; however, on the lest, significant differences were not observed (64 % vs. 36 %, p>0.05). In the anterior-inferior segment, В7-lines prevailed over В3-lines on the right (75 % vs. 25 %, p<0.05); however, on the left, the difference was not significant (67 % vs. 33 %, p=0.05). In the lateral superior segment on the right, В7-lines predominated over В3-lines (75 % vs. 25 %, p<0.01); in contrast, on the left, there were no differences (67 % vs. 33 %, p>0.05). In lateral-basal segments on both sides, significant differences were present (73 % vs. 27 % on the right, p<0.05; 72 % vs. 28 % on the lest, p<0.05). The results of lung ultrasound were also used for evaluation of the B-line predictive value in patients with ADHF and mid-range EF on discharge from the hospital after reversal of X-ray and clinical symptoms of pulmonary congestion. In the next two years, 35 patients (49.2 % of sample) were rehospitalized with signs of ADHF (39 hospitalizations, 1.1 hospitalizations per patient). The rehospitalized patients were divided into two subgroups, with an increased number of B-lines and small congestion on discharge (6–15 В-lines) and without signs of congestion (<5 В-lines). For patients with a minimal (small) congestion on pulmonary ultrasound but regression of clinical and X-ray congestion, the number of rehospitalizations was 25 vs. 11 in patients with the number of B7-lines <5. In the ROC-analysis, the area under the curve was 0.706, which corresponded to the expert assessment as “good”. The position sensitivity was 78.6 % and the specificity was 79.7 %.
Conclusion “Ultrasonic pulmonary edema syndrome” in patients with LV mid-range ejection fraction after reversing ADHF was characterized by predomination of the interstitial component, despite the absence of X-ray congestion, correlated with the blood level of NT-proBNP measured at the same time, and was associated with rehospitalizations.

Aim Patients with heart failure with reduced left ventricular (LV) ejection fraction (HFrEF) who have had acute myocardial infarction have an unfavorable prognosis, largely due to ventricular arrhythmias (VA) and risk of sudden cardiac death (SCD). The optimal treatment (triple neurohormonal blockade plus implantable cardioverter defibrillator and cardiac resynchronization therapy) reduced the risk of SCD primarily due to reverse cardiac remodeling, but has not solved this problem completely. Efficacy of purified ω-3 polyunsaturated fatty acid esters (PUFA) in low doses (1 g/day) in reducing VA and risk of SCD in HFrEF patients was demonstrated in two large randomized clinical trials. The PUFA effects was suggested to be related also with increased heart rhythm variability (HRV) and chronotropic action, which might depend on the drug dose. The present open, prospective, randomized, comparative study in parallel groups evaluated the effect of Omacor in different doses on noninvasive markers of SCD risk in patients with ischemic HFrEF receiving the optimal drug therapy.
Methods Patients (n=40) were randomized at a 1:1:2 ratio to the control group (n=10), the Omacor 1 g/day treatment group (n=10), and the Omacor 2 g/day treatment group (n=20) and were followed up for 12 months. Clinical evaluation included changes in the CHF functional class (FC) and Clinical Condition Scale (CCS) score; concentration of N-terminal pro-hormone brain natriuretic peptide (NT-proBNP); and peak oxygen consumption during exercise (peak VO2). The LV function was evaluated by LVEF. Holter ECG monitoring was used for evaluation of HRV (SDNN), average 24-h heart rate (HR), number of ventricular extrasystoles (VE) per hour and severity of VA, and presence of paired VE and VT runs.
Results Improvement of CHF FC became significant only with the high-dose Omacor treatment (2 g/day). The CCS score showed a tendency towards decrease also with a lower dose (1 g/day) whereas the level of NT-proBNP significantly decreased with both Omacor doses. The increase in LV EF was significant only with the use of Omacor 2 g/day (+3 %, р=0.002). A negative chronotropic effect of ω-3 PUFA was observed. Average 24-h HR decreased by 8 bpm (р=0.05) and 11 bpm (р<0.001) with Omacor 1 g/day and 2 g/day, respectively. Either dose of ω-3 PUFA significantly improved VO2, which directly correlated with LV EF and inversely correlated with HR. The decrease in number of VE was associated not only with improved HRV (SDNN) but also with the decrease in 24-h HR, and thus Omacor 2 g/day significantly decreased the number of VE (by 16 per hour) and dangerous VA (paired VE and VT runs ceased to be detected in 40 % of patients).
Conclusion Since HR, HRV, and VA are closely interrelated, the effect of ω-3 PUFA specifically on these noninvasive markers apparently determines its ability to decrease the risk of SCD in patients with ischemic HFrEF. The antiarrhythmic effect of Omacor was greater with higher doses of this drug.

This review focuses on the relevance of sinus rhythm control in patients with atrial fibrillation in real-life clinical practice and specific clinical features of patients with this arrhythmia. The authors presented current guidelines on prevention of thromboembolic complications and a review of results from major clinical studies of direct oral anticoagulants. The search for literature and selection of clinical studies for 2009-2020 were performed on websites of the European and Russian Societies of Cardiology, the All-Russian Scientific Society of Arrhythmologists, and in online databases PubMed, EMBASE, eLibrary, and Google Scholar using the key words atrial fibrillation, anticoagulants, ablation, cardioversion, and efficacy and safety.

The article compares two statistical approaches, which are commonly used in current comparative studies, a hypothesis that a drug is superior over another one (superiority) and a hypothesis that a drug is not inferior to another one in the efficacy and safety (non-inferiority). Using the example of specific studies, the difference between the methods and the tasks, for the solution of which one or another method should be applied, are shown. In order to prove the superiority in efficacy and safety of a new drug over an existing one, only a statistical approach that uses the “superiority” hypothesis is applicable. Studies using the “non-inferiority” hypothesis are generally used for comparing drugs, which are not considerably different in their efficacy, but the study drug has other advantages in the administration, storage, tolerability etc. The choice of statistical method is determined exclusively by the task of the study.

Asymptomatic hyperuricemia (HU) is common in the population and significantly contributes to the general cardiovascular risk. Despite extensive study of this condition there is still no conclusive answers to questions about detection of asymptomatic HU and its effect on the risk for development and progression of cardiovascular and kidney diseases. This review summarizes key information about these issues, which has been accumulated by the present time.

Computed tomography angiography (CT-angiography, CTA) allows noninvasive visualization of coronary arteries (CA). This method is highly sensitive in detecting coronary atherosclerosis. However, standard CTA does not allow evaluation of the hemodynamic significance of found CA stenoses, which requires additional functional tests for detection of myocardial ischemia. This review focuses on possibilities of clinical use, limitations, technical aspects, and prospects of a combination of CT-angiography and CT myocardial perfusion imaging in diagnostics of ischemic heart disease.

Arterial hypertension (AH) and exertional headache (EHA) are comorbidities. The article presents a nonsystematic review focused on studying the AH+EHA phenotype. The authors addressed the history of studying the phenotype, several theories about its pathophysiological causes (psychosomatic, neuroanatomical, and baroreflector). The protective “hypertension-associated hypoalgesia” phenotype, a mechanism of its change in AH chronization, and difficulties of differential diagnosis are described. The AH+EHA phenotype requires further study since its incidence is quite high. This will allow developing an individualized approach in prevention and treatment of EHA attacks, decreasing the risk of life-threatening cardiovascular complications, and avoiding iatrogenic complications in patients with AH. The main way to prevent the development of AH+EHA phenotype is patient’s compliance, which can be provided by using combination hypotensive drugs to reduce the number of pills and dosing. It is important to take into account possible adverse reactions of the nervous system (medication-overuse headache or EHA aggravation). Considering these conditions, the drug Triplixam can be used for prevention of complications in the AH+EHA phenotype. Triplixam is a fixed triple combination of amlodipine/indapamide/perindopril, and its individual components have low and medium risk for development of headache.