Infective Endocarditis in Moscow General Hospital: Clinical Characteristics and Outcomes (Single-Center 7 Years' Experience).

AIM: to investigate clinical properties of course and outcomes of infective endocarditis (IE) depending on source of infection, to find predictors of mortality in a Moscow general hospital. MATERIALS AND METHODS: We included in this study 176 patients with definite and possible infective endocarditis (the Duke criteria), admitted in our hospital in 2010-2017. Patients were divided in three groups according to source of infection. All patients underwent standard clinical and laboratory assessment, echocardiography, blood culture test combined with blood PCR with sequencing. Inhospital and 1-year outcome were evaluated. RESULTS: Among 176 patients with IE 65.3 % were men (median age 57 [35-72] years), most patients (n=149, 84.7 %) had native valve IE. Etiological factor was identified in 127 (72.2 %) cases. Gram-positive infective agents prevailed (54 %). Surgery in active phase of the disease was performed in 30 (17 %) patients. Among patients with healthcare-associated IE (n=76, 43.9 %) prevailed those older than 60 years, with high Charlson comorbidity index, with culture-negative IE, and complicated clinical course (mainly progressing heart failure). Patients with intravenous drug use associated IE (n=50, 28.4 %) had low Charlson index, association with hepatitis C viral infection, involvement of tricuspid valve with big vegetations, high frequency of embolic complications, and low inhospital mortality. Group of patients with community acquired IE (n=50, 28.4 %) more often had uncommon causative microorganisms, and had better long-term outcome. In-hospital mortality was 30.1 % (n=53) mostly due to sepsis with multi-organ failure, and heart failure. Risk factors of inhospital death were history of cardiovascular diseases, old age, kidney damage, methicillin-resistant Staphylococcus aureus (MRSA) infection, uncontrolled infection, and embolic events. Risk factors of 1-year mortality were history of stroke, and heart failure as IE complication. Independent predictors of in-hospital death were MRSA infection (odds ratio [OR] 50.32, 95 % confidence interval [CI] 1.66-213.92; p=0.002), persistent infection (OR 18.6, 95 %CI 5.37-64.40; p=0.001), duration of fever >7 days after initiation of antibacterial therapy (OR 13.41, 95 %CI 3.51-51.24; p=0.001); and of death during first year - history of cerebral infarction (OR 4.39, 95 %CI 1.32-14.70; p=0.016)), and heart failure as IE complication (OR 8.1, 95 %CI 1.97-67.09; p=0.016). Among patients subjected to surgery there were no fatal outcomes during 1 year after hospital discharge, while among conservatively treated patients were 21 (14.4 %) deaths (p<0.009). CONCLUSION: Main clinical features of IE course in patients urgently admitted to a general hospital was dominance of healthcare-associated  IE among patients, who were older than 60 years with severe comorbidities. These patients had more complications and worse outcome. Modeling of prognosis identified uncontrolled infection as key factor of unfavorable outcome. Surgery significantly reduced long-term mortality.

[Infective endocarditis: Importance of molecular biological techniques in etiological diagnosis]. / Infektsionnyi endokardit: znachenie molekulyarno-biologicheskikh metodov v etiologicheskoi diagnostike.

AIM: To investigate the specific features of conventional bacteriological methods and current molecular biological techniques for the etiological diagnosis of infective endocarditis (IE). SUBJECTS AND METHODS: Examinations were made in 53 patients treated at City Clinical Hospital Sixty-Four, Moscow Healthcare Department, in 2012-2015 who underwent simultaneous bacteriological and molecular biological (polymerase chain reaction (PCR) or PCR with further sequencing) examinations of blood or resected cardiac valve tissues. RESULTS: The investigation included 53 patients (31 men; median age, 62 years) with IE (Duke 2009); its primary form was observed in 32 (60.4%) patients. Blood bacteriological tests and PCR assays were positive in 28 (52.8%) and 34 (64.2%) patients, respectively. There were concordant results in 21 of the 28 positive blood culture cases and discordant results in 7 (25%); at the same time 3 cases showed a compete discordance in the detected causative agents (the growth of Enterococcus spp. was revealed by bacteriological examination and that of Staphylococcus spp., Streptococcus spp., and Escherichia coli by DNA PCR) and a pathogen could not be identified by DNA PCR in 4 patients who had positive blood bacteriological results. The positive PCR results for cocci and fungi were obtained in 10 of the 25 (47.2%) examinees with culture-negative IE. Rare causative agents were not revealed. The tissues obtained from 8 resected damaged heart valves displayed a wider spectrum of pathogens than did blood samples, which was associated with the formation of bacterial films. CONCLUSION: The etiological agent of IE was revealed in venous blood by bacteriological examination in 52.8% of the examinees, by PCR in 64.2%, and by either in 71.7%. There were concordant and discordant results in 67.9 and 32.1% of the patients, respectively; among whom 18.9% were found to have pathogen DNA revealed by PCR in culture-negative IE.

[Cardiac damage in liver cirrhosis in alcohol abusers]. / Porazhenie serdtsa pri tsirroze pecheni u bol'nykh, zloupotreblyayushchikh alkogolem.

AIM: to estimate the contribution of liver cirrhosis (LC) to the development of heart diseases in alcohol abusers. SUBJECTS AND METHODS: The investigation included 80 patients with alcoholic LC without a history of cardiovascular and respiratory diseases and, as a control group, 32 alcohol abusers without a history of chronic diseases of the liver and cardiovascular and respiratory systems; 45 patients with alcoholic cardiomyopathy (ACM) and congestive heart failure without a history of coronary heart disease and valvular diseases, among whom 11 patients were found to have LC. In addition to standard clinical examination, all the patients underwent electrocardiography, by estimating the corrected QT interval (QTc), standard echocardiography; and those without ACM underwent estimation of left ventricular (LV) kinetics using speckle-tracking echocardiography. RESULTS: The patients with alcoholic LC were found to have a higher LV ejection fraction and a more obvious impairment of LV global longitudinal deformity, and more commonly LV diastolic dysfunction. 16 of the 80 patients with LC were observed to have moderate pulmonary hypertension while the mean pulmonary artery pressure (MPAP) was within the normal range in all the patients without LC. A prolonged QTc interval was revealed in the patients with LC. The duration of QTc was directly correlated with the MELD severity of LC. The patients with chronic heart failure in the presence of ACM and CL showed a more obvious LV diastolic dysfunction, as estimated by E/E', a greater LV mass index, and a higher MPAP than those with ACM without LC. CONCLUSION: The LC patients both with ACM and without a history of diseases of the heart were noted to have its more evident disorders as diastolic dysfunction and elevated MPAP. Those without ACM were observed to have impaired LV global deformity and a prolonged QTc interval.

[The concurrence of kidney and liver dysfunctions in decompensated heart failure].

AIM: To study the incidence, pattern, and predictive factors of concurrent kidney and liver dysfunctions in patients with decompensated heart failure (HF). SUBJECTS AND METHODS: The kidney and liver function indicators were estimated in 322 patients aged 69.5±10.6 years with decompensated HF (hypertension in 87%, myocardial infarction in 57%, atrial fibrillation in 65%, chronic kidney disease in 39%, type 2 diabetes in 42%, a left ventricular ejection fraction (EF) of 38±13%, EF <35% 39%, NYHA Functional Class IV in 56%). Cardiohepatic syndrome (CHS) was diagnosed if at least one indicator of liver function was increased; acute kidney injury (AKI) was diagnosed using the KDIGO criteria. RESULTS: AKI and CHS had been previously diagnosed in 60 (18.6%) and 274 (85.1%) patients, respectively. Among the patients with signs of kidney and/or liver dysfunction, the incidence of isolated CHS, concurrent AKI and CHS, and isolated AKI was 78.4, 20.1, and 1.5%, respectively. The patients with concurrent kidney and liver dysfunctions were observed to have more profound systemic hemodynamic changes (hypoperfusion and congestion). The risk of concurrent AKI and CHS increased glomerular filtration rate (GFR) <45 ml/min/1.73 m2, admission systolic blood pressure <110 mm Hg, needs for vasopressors, hydropericardium, and EF <35%. The concurrence of AKI and CHS was associated with longer hospital stay (15.7±6.5 and 13.5±4.8 days, respectively; p<0.05). CONCLUSION: The incidence of concurrent AKI and CHS in patients with decompensated HF is 20.1%. Concurrent kidney and liver dysfunctions is associated with more obvious signs of hypoperfusion and congestion and characterized by worse prognosis.

[Blood Content of Markers of Inflammation and Cytokines in Patients With Alcoholic Cardiomyopathy and Ischemic Heart Disease at Various Stages of Heart Failure].

We conducted a comparative study of content proinflammatory cytokines, biomarkers of inflammatory process, biochemical indicators of congestive heart failure (CHF) and hemodynamic parameters in patients with alcoholic cardiomyopathy (ACMP) and ischemic heart disease (IHD) with various NYHA classes. We examined 62 men with ACMP (n = 45) and IHD (n = 17) and NYHA class III-IV CHF. Patients of both groups had lowered ejection fraction (EF), dilated cardiac chambers, and increased left ventricular (LV) myocardial mass index (MMI). Relative LV wall thickness was within normal limits but in the ACMP group it was significantly lower than in IHD group what corresponded to the eccentric type of myocardial hypertrophy. Higher NYHA class was associated with lower EF and larger end diastolic and end systolic LV dimensions. In ACMP it was also associated with larger dimension of the right ventricle while in IHD--with substantially larger (by 30%) dimension of atria. Substantial amount of endotoxin found in blood plasma of patients with IHD corresponded to the conception of increased intestinal permeability of in CHF. Alcohol abuse was an aggravating factor of endotoxin transmission and its concentration in patients with ACMP was 3 times higher than in patients with IHD. Patients with ACMP had substantially elevated blood concentrations of interleukins (IL) 6, 8, 12, tumor necrosis factor α (TNF-α), and its soluble receptor s-TNF-R; they also had twofold elevation of C-reactive protein concentration. ACMP was associated with manifold rise of blood content of brain natriuretic peptide (BNP). Patients with IHD also had elevated blood concentrations of IL 6, 8 and 12 but their values were 1.5-2 times lower than ACMP group. Blood content of TNF-α and s-TNF-R in IHD group was within normal limits. Higher NYHA class in ACMP patients was associated with higher concentrations of IL 6 and 8, TNF-a, and BNP. In both groups of patients contents of IL-12, s-TNF-R, TGF-1ß and factors of acute phase of inflammation did not reflect severity of CHF. Functional insufficiency of myocardium in IHD patients was best characterized by blood content of IL-6 while in ACMP patients--of BNP.

[Contrast-induced acute kidney injury after primary percutaneous coronary interventions: Prevalence, predictive factors, and outcomes].

AIM: To study the incidence, severity, predictive factors, and prognostic value of contrast-induced acute kidney injury (CIAKI) in patients with ST-segment elevation acute coronary syndrome (STSEACS), who have undergone primary percutaneous coronary intervention (PCI). SUBJECTS AND METHODS: The 2012 KDIGO criteria were used to estimate the incidence of CIAKI in 216 patients (mean age, 64 ± 13 years) admitted to Moscow City Clinical Hospital Sixty-Four and underwent primary PCI for STSEACS (hypertension in 90%, prior myocardial infarction in 27%, chronic kidney disease in 7%, type 2 diabetes mellitus in 21%). Logistic regression analysis was performed to identify predictive factors for CIAKI; following 12 months, its prognosis was assessed by phone. RESULTS: Forty-three (20%) patients were diagnosed with Stages I (81%) and II (19%) CIAKI. The patients with CIAKI were older; they had higher baseline serum creatinine levels, a higher volume of contrast agent, a higher ratio of contrast medium volume to glomerular filtration rate, and lower left ventricular ejection fraction. Independent predictive factors for CIAKI were identified; these were chronic kidney disease, multivascular injury in the coronary bed, hospital therapy with loop diuretics, nephrotoxic antibiotics, or mineralocorticoid receptor antagonists. CONCLUSION: The development of CIAKI is associated with poor outcomes, such as higher 30-day mortality and more frequent cardiovascular disease readmissions.

[Clinical pharmacology and pharmacotherapy: Problems and disputable issues]. / Problemy i spornye voprosy klinicheskoi farmakologii i farmakoterapii.

The paper discusses the current problems of internal medicine: the use of biologicals not only in rheumatology, but also in cardiology and pulmonology; current antiviral therapy for diseases of not only the liver, but also the heart (controversial issues); recent clinical data regarding LCZ (versus enalapril) and ivabradine (heart rate reduction).

[Blood Content of Markers of Inflammation and Cytokines in Patients With Alcoholic Cardiomyopathy and Ischemic Heart Disease at Various Stages of Heart Failure].

We conducted a comparative study of content proinflammatory cytokines, biomarkers of inflammatory process, biochemical indicators of congestive heart failure (CHF) and hemodynamic parameters in patients with alcoholic cardiomyopathy (ACMP) and ischemic heart disease (IHD) with various NYHA classes. We examined 62 men with ACMP (n=45) and IHD (n=17) and NYHA class III-IV CHF. Patients of both groups had lowered ejection fraction (EF), dilated cardiac chambers, and increased left ventricular (LV) myocardial mass index (MMI). Relative LV wall thickness was within normal limits but in the ACMP group it was significantly lower than in IHD group what corresponded to the eccentric type of myocardial hypertrophy. Higher NYHA class was associated with lower EF and larger end diastolic and end systolic LV dimensions. In ACMP it was also associated with larger dimension of the right ventricle while in IHD - with substantially larger (by 30%) dimension of atria. Substantial amount of endotoxin found in blood plasma of patients with IHD corresponded to the conception of increased intestinal permeability of in CHF. Alcohol abuse was an aggravating factor of endotoxin transmission and its concentration in patients with ACMP was 3 times higher than in patients with IHD. Patients with ACMP had substantially elevated blood concentrations of interleukins (IL) 6, 8, 12, tumor necrosis factor (TNF-), and its soluble receptor s-TNF-R; they also had twofold elevation of C-reactive protein concentration. ACMP was associated with manifold rise of blood content of brain natriuretic peptide (BNP). Patients with IHD also had elevated blood concentrations of IL 6, 8 and 12 but their values were 1.5-2 times lower than ACMP group. Blood content of TNF- and s-TNF-R in IHD group was within normal limits. Higher NYHA class in ACMP patients was associated with higher concentrations of IL 6 and 8, TNF-, and BNP. In both groups of patients contents of IL-12, s-TNF-R, TGF-1 and factors of acute phase of inflammation did not reflect severity of CHF. Functional insufficiency of myocardium in IHD patients was best characterized by blood content of IL-6 while in ACMP patients - of BNP.

[First Experience of Clinical Application of LCZ696 an AT1-angiotensin Receptors and Neprilysin Inhibitor in Patients With Chronic Heart Failure and Reduced Ejection Fraction].

Simultaneous inhibition of the renin-angiotensin-aldosterone system and the system of degradation of natriuretic peptides can potentially provide unique therapeutic effects in patients with chronic heart failure (CHF) with reduced ejection fraction (EF). Aim of this study was to assess tolerability of therapy with LCZ696 - first representative of a class of inhibitors of angiotensin receptor and neutral endopeptidase neprilysin - and to study its pharmacodynamic effects. METHODS: We included into open uncontrolled study 30 patients with stable functional class II-III CHF and EF less or equal 40%. After 24-hour run-in period during which angiotensin converting enzyme inhibitors (ACEI) were withdrawn the patients were given LCZ696 (100 mg/day for 7 days followed by 200 mg/day for 14 days). Other CHF therapy remained unchanged. RESULTS: Transition from therapy with ACEI to LCZ696 was well tolerated. Three patients were excluded because of hyperkalemia more or equal 5mmol/l. After 21 days of treatment elevation of plasma biomarkers of inhibition of neprilysin and angiotensin receptors occurred: cyclic guanosine monophosphate, renin concentration and activity rose 1.38, 3.50, and 2.27 times from baseline level (<0.05 for all). After 7 and 21 days of LCZ696 administration we noted significant lowering of NT-proBNP; significant lowering of aldosterone and endothelin-1 in blood plasma was observed on day 21. CONCLUSION: Administration of LCZ696 to patients with CHF with reduced ejection fraction (EF) was well tolerated and associated with potentially favorable for this category of patients dynamics of biomarkers.

[Left Atrial Remodeling and Thromboembolic Risk in Patients With Recurrent Atrial Fibrillation].

PURPOSE: To assess the relationship between left ventricular and left atrial (LA) structural and functional characteristics and thromboembolic (TE) risk in patients (pts) with recurrent atrial fibrillation (AF). MATERIAL AND METHODS: Sixty pts (mean age 65 [61; 72] years, 42% men) with nonvalvular paroxysmal and persistent AF during sinus rhythm were divided into three groups based on CHA2DS2-VASc score: 1, 2, and ≥ 3. All pts underwent conventional and speckle tracking echocardiography. Apical four- and two-chamber views images of 6 myocardial segments in the filling phase were obtained to assess global peak left atrial longitudinal strain (PALS) in the reservoir (r) and contractile (c) phase. RESULTS. Patients with paroxysmal AF had significantly higher PALSr compared with patients with persistent AF (15.1 vs 11.2%, p = 0.0002) and PALSc (-15.0 vs -12.0%; p = 0.0002]. In logistic regression analyses, only higher PALSr was significantly associated with lower CHA2DS2-VASc score (OR 0.61; 95% Cl 0.38-0.97; p = 0.03). In order to distinguish patients with moderate and high TE risk we performed ROC curve analysis. Effective PALSr cut-off point was 16.7% with sensitivity of 62.5%, specificity of 39.0% and an area under the curve of 0.85 (95% Cl 0.72-0.98; p = 0.002). CONCLUSIONS: In patients with AF PALSr was independently associated with CHA2DS2-VASc score. Use of a PALSr threshold allows to detect patients with moderate and high TE risk and can be considered in the process of decision making on initiation of anticoagulation treatment in patients with AF and CHA2DS2-VASc score of 1.

[Biomarkers of acute kidney injury: current views and prospects].

In the past decades, the incidence of acute kidney dysfunction has been steadily increasing, which is mainly due to rises in the prevalence of cardiovascular diseases and the survival of cardiac patients and to more common use of intervention examination and treatment methods. The early diagnosis of acute kidney injury (AKI) is made difficult by the delay in clinical symptoms and the elevated serum levels of creatinine as to cell damage, which chiefly appears as the expression of biomarkers. The new AKI biomarkers whose concentration changes significantly earlier than the serum creatinine levels increase have been recently identified. This has allowed Acute Dialysis Quality Initiative (ADQI) experts to develop consensus on the use of the biomarkers to diagnose AKI; a new concept of the diagnosis of AKI, by assessing not only the markers of renal function (serum creatinine and diuresis), but also those of injury, and the conceptual model of AKI are proposed.

[Giant abdominal urate tumor-like mass with multiple crystalline deposits in the bowel and lung walls in a patent with terminal heart failure].

The paper describes a unique case of a large abdominal urate mass with a peculiar inflammatory process with giant cells and smaller urate deposits in the lung and small bowel without articular changes and kidney injury in a patient with terminal heart failure.

[Immunoinflammatory changes (myocarditis?) in chronic heart failure in alcoholic patients].

AIM: To estimate the contribution of immuno-inflammatory changes to the formation of clinical and hemodynamic features in alcoholic patients with chronic heart failure (CHF). SUBJECTS AND METHODS: Forty-five males with CHF in the presence of alcohol-induced heart damage (AIHD) who had been admitted to therapeutic units for decompensated heart failure were examined. A control group consisted of 20 men with the CHF severity comparable with the NYHA classification in the presence of prior myocardial infarction. All the patients underwent examination of the immune-inflammatory status--the cytokines: interleukin (IL) 6, IL-8, IL-12, tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta1, endotoxin, cellular immune parameters, and cardiac structure and function by echocardiography. RESULTS: The patients with CHF in the presence of AIHD, as compared to those with ischemic cardiomyopathy, showed the higher levels of inflammatory cytokines (IL-6, TNF-alpha, IL-12, and endotoxin) and cell-mediated immunity changes (the smaller count of suppressor T cells, natural killer cells, and a shift of the T-helper/T-suppressor ratio towards the T-helper population). The magnitude of these changes correlated with the severity of CHF and cardiac morphofunctional changes. CONCLUSION: The relationship of immuno-inflammatory changes to the severity of CHF and the morphofunctional state of the heart irrespective of the etiology of heart failure demonstrated the role of immune inflammation in its pathogenesis particularly in alcoholic patients who were found to have more marked immuno-inflammatory changes than in those with ischemic cardiomyopathy.

[Echocardiographic assessment of myocardial fibrosis in young men with arterial hypertension and different types of left ventricular remodeling].

In order to study structural functional characteristics of myocardium including parameters of myocardial fibrosis according echocardiography data in men with various levels of arterial pressure (AP) we examined 215 men aged 18-25 (mean 21.1+/-0,1) years with history of elevated AP at casual measurement. AP phenotype (normotension, stable arterial hypertension [AH], unstable AH) was determined on the basis of multiple measurements of clinical AP and 24 hour AP monitoring. At echocardiography we assessed presence of left ventricular (LV) hypertrophy (LVH), type of LV geometry, proportionality of LV myocardial mass (LVMM), diastolic function. Myocardial fibrosis was assessed by pixel density distribution range (PDDR) with the use of analysis of reflected signal. There were no manifestations of LV remodeling in subjects with normal AP. Concentric LV remodeling was found in 27.5 and 60.5% of patients with unstable and stable AH, respectively. Concentric LVH was found only in patients with stable AH (4.8%). Disproportionally high LVMM was found in 16.1% of subjects with stable AH. In a combined group with concentric LV remodeling and LVH rate of disproportionally high LVMM was 20.8%. We noted significant (p<0.001) increase of PDDR in stable AH (181.4+/-2.2) compared with PDDR in normal AP (164.6+/-4.6) and unstable AH (160.1+/-2.7). In stable I degree AH PDDR (177.3+/-2.2) was insignificantly lower than in II degree AH (185.7+/-3.9). PDDR in concentric LV remodeling was 180.5+/-2.3, in concentric LVH- 166.8+/-13.2, in normal LV geometry - 168.4+/-2.5. PDDR in disproportionally high LVMM was higher than in proportional LVMM. Independent interrelationship was found between PDDR and body mass index (r=0.17; p=0.03), duration of AH (r=0.17; p=0.03), isovolumic relaxation time (r= 0.15; p=0.04). In young men LV remodeling can be detected at the stage of unstable AH. In stable AH degree of myocardial fibrosis was associated with higher AP level, concentric LV geometry, disproportionally high LVMM, lowering of diastolic function.

[Cardiorenal syndromes: pathogenetic, clinico-diagnostic, prognostic and therapeutic aspects].

Current information on cardiorenal and renocardial relations with clinicopathophysiological disorders in which primary impairment of the heart or kidneys leads to secondary functional and morphological abnormality in the other organ is analysed. Acute decompensation of cardiac failure is wide spread pathology which can be complicated by both acute and chronic lesion of the kidneys. Acute renal failure in cardiogenic shock in patients with ST elevation acute myocardial infarction deteriorates prognosis and raises lethality. Administration of radiopharmaceutical in patients with myocardial infarction and coronary heart disease with stents may induce nephropathy. Synergic affection of the heart and kidneys is observed in diabetes mellitus, systemic lupus erythematosus, amyloidosis, infectious endocarditis and some other diseases.

[Efficacy of ivabradin in combined treatment of patients with postinfarction systolic chronic cardiac failure].

AIM: To study effects of ivabradin on clinicohemodynamic and prognostic parameters in patients after myocardial infarction (MI) with systolic chronic cardiac failure (SCCF). MATERIAL AND METHODS: A population-based randomized prospective trial enrolled 49 patients (40 males--81.6%, mean age 63.1 +/- 8.1 years) with sinus rhythm and a longer than 3 month history of MI. The patients were randomized into 2 groups: 23 patients of group 1 received standard treatment plus ivabradin, 26 patients of group 2 received standard treatment alone. Follow-up was 36.1 +/- 6.2 months. We analysed the trend in heart rate (HR), blood pressure (BP), parameters of echocardiography, ECG, levels of electrolytes, creatinin in blood plasma, frequency of hospitalizations, recurrent non-fatal MI and lethality (combined endpoint). RESULTS: In the end of the trial ivabradin significantly decreased HR from 71 to 64 b/m. Frequency of combined end point of efficacy was 30.4 and 50% in group 1 and 2, respectively. In group 1 primary end point in high baseline HR occurred more frequently than in HR < 70 b/m in 6 (50%) and 1 (9.1%) cases, respectively, but these differences were not significant (p = 0.068). In group 2 the differences were significant--9 (90%) and 4 (25%) cases, respectively (p = 0.004). By none of the parameters of ECG, plasma electrolytes, creatinine level significant intergroup differences were found. CONCLUSION: In the same trend in BP and ECG, group 1 patients showed significant and more pronounced HR lowering than group 2 patients. Addition of ivabradin to standard treatment of SCCF after MI promoted less frequency of hospitalizations, recurrent non-fatal MI, fatal cardiovascular events. This effect was especially strong in high baseline HR.