Takotsubo cardiomyopathy. Literature review: concept, epidemiology, pathogenesis. Part I

Up-to-date data on the problem of takotsubo cardiomyopathy, including key issues of epidemiology, clinical presentation, diagnostic criteria, and general pathophysiological mechanisms of the disease is presented in review

Takotsubo cardiomyopathy. Literature review: clinical performance, diagnostic algorithm, treatment, prognosis. Part II

Up-to-date data on the problem of takotsubo cardiomyopathy, including data on the clinical manifestations, diagnostic algorithm and treatment approaches, as well as the prognosis of possible complications is presented in review

Acute Heart Failure in a Pregnant Woman with Preeclampsia: a Rare Case of Takotsubo Syndrome

The mechanisms of takotsubo syndrome, better known as stress-induced cardiomyopathy, are not fully understood. The article presents a clinical case of the development of acute left ventricular failure in a 39-year-old pregnancy against the background of severe preeclampsia. Echocardiography revealed a decrease in global myocardial contractility, hypo-akinesia of the apex and all median parts of the left ventricle, hyperkinesis of the basal parts. After 2 weeks, myocardial contractility was normal, no contractility impairment was found. Two months after the acute episode of the disease, magnetic resonance imaging of the heart was performed, according to which no pathological changes were detected. Based on the clinical picture, electrocardiogram changes, laboratory data and typical transient echocardiographic changes, it was suggested that the patient had takotsubo syndrome

The effect of rs776746 polymorphism in the <i>CYP3A5</i> gene on heart rate when using bisoprolol in patients with acute coronary syndrome

Aim. The aim of this work was to study the occurrence of the rs776746 allelic variant of the CYP3A5 gene and its effect on heart rate (HR) when using bisoprolol in patients hospitalized with acute coronary syndrome (ACS).Materials and methods. The study included patients with ACS who were prescribed bisoprolol for clinical indications. All patients underwent molecular genetic testing. In order to evaluate the effectiveness of the therapy with bisoprolol, all patients underwent Holter electrocardiogram (ECG) monitoting on days 10, the following parameters were assessed: minimum, average, maximum heart rate and heart rate during an exercise test. The stress test was performed as a ladder test.Results. The study involved 97 patients (63,5±10,5 years), including 60 men and 37 women. The frequency of occurrence of the desired alleles of the CYP3A5 gene was: CYP3A5*3 - 93%, and CYP3A5*1 - 7%, which corresponds to its prevalence in the European population. 84 carriers of the CYP3A5*3*3 genotype (87%), 12 heterozygous carriers of the *1 allele (12%) and one patient with the *1*1 genotype (1%) were identified. In order to search for differences in the effects of bisoprolol depending on the genetically predetermined activity of CYP3A5, we divided the general group of patients into two subgroups: subgroup 1 (CYP3A5*3*3), represented by carriers of the genotype associated with the synthesis of the inactive form of CYP3A5, and subgroup 2 (CYP3A5*1*3 and CYP3A5*1*1), represented by carriers of at least one allele encoding the synthesis of a fully functional protein CYP3A5, coupled with an increased metabolic rate. Patients did not differ in clinical and demographic characteristics. By the time of daily ECG monitoring, both groups reached comparable heart rate values. In carriers of at least one CYP3A5*1 allele (n = 13), associated with an increased metabolic rate, the daily dose of bisoprolol on the 10th day of hospitalization was significantly higher (p &lt;0.05). The only carrier of the homozygous CYP3A5 *1*1 variant receives bisoprolol at a daily dose of 10 mg. Taking into account the close to significant differences in glomerular filtration rate (GFR) in patients in the groups with the studied genetic variants, and the known eliminating role of the kidneys for bisoprolol, a linear regression model was built with the inclusion of factors that could affect the dose of bisoprolol: GFR, functional class of chronic heart failure, gender, age, number of simultaneously assigned CYP3A5 substrates. Of the parameters listed, only the CYP3A5 genotype significantly predicted the dose of bisoprolol (F=8.5; p&lt;0.005; R2=0.096).Conclusion. In this study, it was demonstrated for the first time that patients with different genetic variants of CYP3A5, in particular with respect to the rs776746 polymorphism, may differ in individual requirements for the dose of bisoprolol

International longitudinal registry of patients with atrial fibrillation and treated with rivaroxaban: RIVaroxaban Evaluation in Real life setting (RIVER)

Background Real-world data on non-vitamin K oral anticoagulants (NOACs) are essential in determining whether evidence from randomised controlled clinical trials translate into meaningful clinical benefits for patients in everyday practice. RIVER (RIVaroxaban Evaluation in Real life setting) is an ongoing international, prospective registry of patients with newly diagnosed non-valvular atrial fibrillation (NVAF) and at least one investigator-determined risk factor for stroke who received rivaroxaban as an initial treatment for the prevention of thromboembolic stroke. The aim of this paper is to describe the design of the RIVER registry and baseline characteristics of patients with newly diagnosed NVAF who received rivaroxaban as an initial treatment. Methods and results Between January 2014 and June 2017, RIVER investigators recruited 5072 patients at 309 centres in 17 countries. The aim was to enroll consecutive patients at sites where rivaroxaban was already routinely prescribed for stroke prevention. Each patient is being followed up prospectively for a minimum of 2-years. The registry will capture data on the rate and nature of all thromboembolic events (stroke / systemic embolism), bleeding complications, all-cause mortality and other major cardiovascular events as they occur. Data quality is assured through a combination of remote electronic monitoring and onsite monitoring (including source data verification in 10% of cases). Patients were mostly enrolled by cardiologists (n = 3776, 74.6%), by internal medicine specialists 14.2% (n = 718) and by primary care/general practice physicians 8.2% (n = 417). The mean (SD) age of the population was 69.5 (11.0) years, 44.3% were women. Mean (SD) CHADS2 score was 1.9 (1.2) and CHA2DS2-VASc scores was 3.2 (1.6). Almost all patients (98.5%) were prescribed with once daily dose of rivaroxaban, most commonly 20 mg (76.5%) and 15 mg (20.0%) as their initial treatment; 17.9% of patients received concomitant antiplatelet therapy. Most patients enrolled in RIVER met the recommended threshold for AC therapy (86.6% for 2012 ESC Guidelines, and 79.8% of patients according to 2016 ESC Guidelines). Conclusions The RIVER prospective registry will expand our knowledge of how rivaroxaban is prescribed in everyday practice and whether evidence from clinical trials can be translated to the broader cross-section of patients in the real world

Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients

Background Patients with acute medical illnesses are at prolonged risk for venous thrombosis. However, the appropriate duration of thromboprophylaxis remains unknown. Methods Patients who were hospitalized for acute medical illnesses were randomly assigned to receive subcutaneous enoxaparin (at a dose of 40 mg once daily) for 10±4 days plus oral betrixaban placebo for 35 to 42 days or subcutaneous enoxaparin placebo for 10±4 days plus oral betrixaban (at a dose of 80 mg once daily) for 35 to 42 days. We performed sequential analyses in three prespecified, progressively inclusive cohorts: patients with an elevated d-dimer level (cohort 1), patients with an elevated d-dimer level or an age of at least 75 years (cohort 2), and all the enrolled patients (overall population cohort). The statistical analysis plan specified that if the between-group difference in any analysis in this sequence was not significant, the other analyses would be considered exploratory. The primary efficacy outcome was a composite of asymptomatic proximal deep-vein thrombosis and symptomatic venous thromboembolism. The principal safety outcome was major bleeding. Results A total of 7513 patients underwent randomization. In cohort 1, the primary efficacy outcome occurred in 6.9% of patients receiving betrixaban and 8.5% receiving enoxaparin (relative risk in the betrixaban group, 0.81; 95% confidence interval [CI], 0.65 to 1.00; P=0.054). The rates were 5.6% and 7.1%, respectively (relative risk, 0.80; 95% CI, 0.66 to 0.98; P=0.03) in cohort 2 and 5.3% and 7.0% (relative risk, 0.76; 95% CI, 0.63 to 0.92; P=0.006) in the overall population. (The last two analyses were considered to be exploratory owing to the result in cohort 1.) In the overall population, major bleeding occurred in 0.7% of the betrixaban group and 0.6% of the enoxaparin group (relative risk, 1.19; 95% CI, 0.67 to 2.12; P=0.55). Conclusions Among acutely ill medical patients with an elevated d-dimer level, there was no significant difference between extended-duration betrixaban and a standard regimen of enoxaparin in the prespecified primary efficacy outcome. However, prespecified exploratory analyses provided evidence suggesting a benefit for betrixaban in the two larger cohorts. (Funded by Portola Pharmaceuticals; APEX ClinicalTrials.gov number, NCT01583218. opens in new tab.

Cause of Death and Predictors of All-Cause Mortality in Anticoagulated Patients With Nonvalvular Atrial Fibrillation : Data From ROCKET AF

M. Kaste on työryhmän ROCKET AF Steering Comm jäsen.Background-Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all-cause mortality may guide interventions. Methods and Results-In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all-cause mortality in the 14 171 participants in the intention-to-treat population. The median age was 73 years, and the mean CHADS(2) score was 3.5. Over 1.9 years of median follow-up, 1214 (8.6%) patients died. Kaplan-Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all-cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33-1.70, P= 75 years (hazard ratio 1.69, 95% CI 1.51-1.90, P Conclusions-In a large population of patients anticoagulated for nonvalvular atrial fibrillation, approximate to 7 in 10 deaths were cardiovascular, whereasPeer reviewe

Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease

BACKGROUND: The cholesteryl ester transfer protein inhibitor evacetrapib substantially raises the high-density lipoprotein (HDL) cholesterol level, reduces the low-density lipoprotein (LDL) cholesterol level, and enhances cellular cholesterol efflux capacity. We sought to determine the effect of evacetrapib on major adverse cardiovascular outcomes in patients with high-risk vascular disease. METHODS: In a multicenter, randomized, double-blind, placebo-controlled phase 3 trial, we enrolled 12,092 patients who had at least one of the following conditions: an acute coronary syndrome within the previous 30 to 365 days, cerebrovascular atherosclerotic disease, peripheral vascular arterial disease, or diabetes mellitus with coronary artery disease. Patients were randomly assigned to receive either evacetrapib at a dose of 130 mg or matching placebo, administered daily, in addition to standard medical therapy. The primary efficacy end point was the first occurrence of any component of the composite of death from cardiovascular causes, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina. RESULTS: At 3 months, a 31.1% decrease in the mean LDL cholesterol level was observed with evacetrapib versus a 6.0% increase with placebo, and a 133.2% increase in the mean HDL cholesterol level was seen with evacetrapib versus a 1.6% increase with placebo. After 1363 of the planned 1670 primary end-point events had occurred, the data and safety monitoring board recommended that the trial be terminated early because of a lack of efficacy. After a median of 26 months of evacetrapib or placebo, a primary end-point event occurred in 12.9% of the patients in the evacetrapib group and in 12.8% of those in the placebo group (hazard ratio, 1.01; 95% confidence interval, 0.91 to 1.11; P=0.91). CONCLUSIONS: Although the cholesteryl ester transfer protein inhibitor evacetrapib had favorable effects on established lipid biomarkers, treatment with evacetrapib did not result in a lower rate of cardiovascular events than placebo among patients with high-risk vascular disease. (Funded by Eli Lilly; ACCELERATE ClinicalTrials.gov number, NCT01687998 .)

Complicated Course of Coronavirus COVID-19 Infection in the old Patient with Severe Cardiac Pathology: a Clinical Case Study

The article describes a clinical case of the COVID-19 viral infection complicated with severe pneumonia, “cytokine storm”, bacteriemia, and acute myocardial injury with decompensated chronic heart failure, ventricular arrhythmias, and formation of an intracardiac thrombus in an elderly patient with underlying clinically significant cardiovascular pathology.

Prognostic value of atrial fibrillation in group of patients with myocardial infarction. Long-term observation results

Purpose. To assess the effect of preexisting atrial fibrillation (AF) on prognosis in patients with type 1 myocardial infarction (MI).Material and methods. These patients were selected from 1660 patients with MI admitted to cardiology department of the NWSMU named after I.I. Mechnikov in 2013-2018. They formed the main group (100 patients). The control group included 200 patients with type 1 MI without AF with the same gender, age. In order to balance groups by prognostically significant factors propensity score matching was carried out. Тhen effect of AF on endpoints was assessed.Results. Patients with type 1 MI and preexisting AF have higher comorbidity, lower ejection fraction. In this group in-hospital pulmonary embolism (PE) (9 % versus 1 % in patients without AF, p=0,0011), minor bleeding (21 % versus 9,5 %, p=0,0057), combined endpoint (stroke + PE + mortality) (19 % versus 10,5 %, p=0,0415) were more common. In the long-term period patients with AF had a higher rate of hospitalizations due to decompensation of chronic heart failure (CHF) (OR=2,47 (95 % CI =1,20–5,08), p=0,0137) and higher incidence of minor bleeding (OR=10,77 (95 % CI =2,36–49,24), p=0,0022). Preexisting AF in patients with type 1 MI (after adjustment for prognostically significant factors) increased the risk of all-cause (OR=5,0 (95 % CI =1,5-17,1), p=0,0072) and cardiovascular mortality (OR=4,1 (95 % CI =1,1-14,9), p=0,0236), increased the risk of CHF III-IV (OR=4,9 (95 % CI =1,2–20,4), p=0,0147), but had no effect on the frequency of ischemic events.Сonclusion. In patients with type 1 MI and pre-existing AF in-hospital and long-term prognosis is worse than in patients without AF. Preexisting AF in these patients is an independent predictor of severe CHF at discharge, cardiovascular and all-cause mortality over follow-up period