DAILY CHANGES OF CENTRAL HEMODYNAMICS IN PATIENTS WITH CHRONIC HEART FAILURE WITH NIGHT-TIME DYSPNOEA ATTACK

Aim. To study daily changes of central hemodynamics (CHD) in patients with chronic heart failure (CHF) and the effects of therapy. Materials and methods. 22 patients with ischemic heart disease and CHF of III-IV functional class (FC) by NYHA, age 60,5±10,5 were observed. Patients were suffering from night-time dyspnoea attacks and had pulmonary artery occlusion pressure (PAOP) 15-20 mm Hg. CHD was monitored invasively before the treatment and after 4 weeks of CHF treatment. Results. According to the cardiac index (CI) at admission patients were split into two groups. 9 patients of group-I had CI ≤2,15 l\min\m2, and 13 patients of group-II had CI >2,15 l\min\m2. In patients of group-I CI increased in 4 weeks of treatment. The treatment caused considerable clinical improvement in all patients. The CHD indexes also improved. Initially evening-night-time peaks of PAOP (р≤0,002), systolic (SBP) (р≤0,003), diastolic (DBP) (р=0,002) and average (BPa) (р=0,0007) blood pressure (BP) as well as double multiplication (DM) (р≤0,008) were registered in patients of group-I. At the end of treatment only evening-night increase in DBP (р=0,002) and BPa (р≤0,006) were noted. In patients of group-II after 4 weeks of treatment CI decreased or didn’t change. Towards 28-th day of treatment 10 patients had clinical improvements. Only one patient’s FC NYHA increased. At the end of treatment the normalization of CHD was registered totally in group. Initially evening-night-time peaks of PAOP (р≤0,002), SBP (р≤0, 0001), CI (р=0,057) and DM (р=0,084) were registered in patients of group-II. At the end of treatment evening-night-time peaks of PAOP (р≤0,015), SBP (р≤0,044), CI (р≤0,005) and DM (р≤0,044) still remained. Besides, evening-night-time peaks of cardiac output (р≤0,01) and systolic index (р≤0, 06) have added. Conclusion. In patients with CHF with initial CI ≤2,15 l\min\m2 treatment results in the normalization of CHD and its daily rhythm. In patients with CHF with initial CI >2,15 l\min\m2 the treatment leads to the normalization of CHD, though it doesn’t correct daily rhythm disturbances of circulation

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Heart valve calcification in patients with coronary heart disease

Aim. To study mitral and aortic valve calcification prevalence in patients with coronary heart disease (CHD), and its influence on myocardial status. Material and methods. Echocardiography was performed in 214 CHD patients (119 females, 95 males; mean age 59.0±8.3 years). Mitral and aortic valve calcification, regurgitation, ejection fraction, diastolic dysfunction, left cardiac chamber sizes, and atherosclerosis risk factors were studied. Results. Calcification of aortial and mitral valves was found in 74 (34.5%) patients with CHD. All of them were above 40, 46% - older than 70; 50 (68%) patients were females. Combination of CHD and arterial hypertension (AH) was observed in 26 (35%) patients. Aortic or mitral valve calcification was found in 86% and 53% of the cases, respectively. Regurgitation was observed in 17 (23%) participants, left atrial dilatation and diastolic dysfunction – in 89%, left ventricular hypertrophy – in 74%. Conclusions: Aortic and mitral valve calcification was observed in 74 (35.5%) participants with CHD. Most of these patients were above 60 years, females, suffering from AH and diabetes mellitus. Aortic valve was affected in 86% of the cases; frequency of mitral calcification increased with age. The prevalence of left atrial dilatation, left ventricular hypertrophy and diastolic dysfunction was higher by 8%, 19%, and 13%, respectively, than that in individuals with intact valves. Ejection fraction did not differ in both groups

Prevalence of rheumatic diseases in North Osetia-AIania and their medical and social significance

Statistical analysis of annual republic accounts of North Osetia-Alania Ministry of public health showed increase of musculoskeletal diseases (MSD) prevalence on 68,3% and incidence - on 42,7% among adult population. MSD are on the 6th place in the general structure of morbidity. Regions with high and relative low levels of these indices were revealed. The data of the present study show that MSD prevalence has similar tendency to increase as in Russian Federation as in North Osetia but rate of increase and absolute increase of MSD prevalence in North Osetia-Alania are respectively 2,85 and 1,79 times higher than in Russian Federation. High increase of MSD incidence and prevalence among children and teenagers (152,0% and 345,8% respectively) causes especial concern. During 5 years temporary working losses connected with MSD increased on 12,8% in cases and on 3,8% in days of disability per 100 working people. Primary invalidity increased to 2002 on 69,5% in comparison with 1998

Antiinflammatory therapy with canakinumab for atherosclerotic disease

BACKGROUND: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. METHODS: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P=0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P=0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P=0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P=0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P=0.31). CONCLUSIONS: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. Copyright © 2017 Massachusetts Medical Society

Cardiac myosin activation with omecamtiv mecarbil in systolic heart failure

BACKGROUND The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown. METHODS We randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes. RESULTS During a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P = 0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro-B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups. CONCLUSIONS Among patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo. (Funded by Amgen and others; GALACTIC-HF ClinicalTrials.gov number, NCT02929329; EudraCT number, 2016 -002299-28.)