What do the new ESC Guidelines for the treatment of heart failure bring to internists?

Chronic heart failure is in european countries in 0,4-2,0% population with an increase with age. The improved care of acute cases enables to decrease the number of patients with chronic heart failure.The disease has a bad prognosis, the diagnosis therapy are demanding. European guidelines for diagnosis and treatment heart failure stress, that patients should have all 4 drugs with class 1 reccomendation (ACE I/ARNI, betablockers, MRA and SGLT2) in reccomended doses. These drugs will be given step by step with dose titration.

Betablockers after myocardial infarction and chronic coronary heart disease.

Treatment with beta-blockers has been an essential part of secondary prevention after myocardial infarction or chronic CHD for several decades. Studies that have shown a beneficial prognostically beneficial effect of beta-blockers were conducted in the period prior to the routine use of reperfusion therapy. In patients who have been treated with fibrinolytic therapy, their contribution is less pronounced. The situation is even less clear in patients who are treated with primary percutaneous coronary intervention, as prospective studies and observational data from registries do not yet give a clear view of the indications and clinical contribution of beta-blockers, especially in the group with normal ejection fraction, without signs of heart failure. Here are the latest different studies from the South Korean and Danish national registries in patients with CHD without heart failure and the effect of beta-blockers on the long-term prognosis.

EMPEROR reduced - empagliflozin in patients with heart failure and reduced ejection fraction.

Type 2 diabetes mellitus (T2DM) is common in patients with chronic heart failure and is associated with high morbidity and mortality. Significant advances have recently occured in the treatment of diabetes mellitus type 2 (T2DM) and cardiovascular diseases. Several new glucose lowering drugs have shown either neutral or positive cardiovascular effect especially on hospitalisations, but also on mortality. Some of these drugs have safety characteristics with strong practical implication in heart failure, for example sodium-glucose co-transporters type 2 inhibitors (SGLT-2). Position paper of the European Society of Cardiology/Heart Failure Association was published in October 2019 and in June 2020. The results of EMPEROR reduced study were presented on European congress in september 2020. In this phase III, placebo-controlled trial, 3730 patients with New York Heart Association class II, III, or IV heart failure and an ejection fraction of 40% or less were randomly assigned to receive either empagliflozin (10 mg once daily) or placebo, in addition to recommended therapy. Over a median of 16 months, the primary outcome (cardiovascular mortality and hospitalisation for heart failure) occurred in 361 of 1863 patients (19.4%) in the empagliflozin group and in 462 of 1867 patients (24.7%) in the placebo group (hazard ratio, 0.75; 95% confidence interval [CI], 0.65 to 0.86; P.

Vericiguat in patients with heart failure and reduced ejection fraction.

BACKGROUND: The effect of vericiguat, a novel oral soluble guanylate cyclase stimulator, in patients with heart failure and reduced ejection fraction who had recently been hospitalized or had received intravenous diuretic therapy is unclear. METHODS: In this phase 3, randomized, double-blind, placebo-controlled trial, we assigned 5 050 patients with chronic heart failure (New York Heart Association class II, III, or IV) and an ejection fraction of less than 45% to receive vericiguat (target dose 10 mg once daily) or placebo, in addition to guideline-based medical therapy.The primary outcome was a composite of death from cardiovascular causes or first hospitalization for heart failure. RESULTS: Over a median of 10.8 months, a primary-outcome event occurred in 897 of 2 526 patients (35.5%) in the vericiguat group and in 972 of 2 524 patients (38.5%) in the placebo group (p = 0.02). A total of 691 patients (27.4%) in the vericiguat group and 747 patients (29.6%) in the placebo group were hospitalized for heart failure. Death from cardiovascular causes occurred in 414 patients (16.4%) in the vericiguat group and in 441 patients (17.5%) in the placebo group. The composite endpoint of death from any cause or hospitalization for heart failure occurred in 957 patients (37.9%) in the vericiguat group and in 1 032 patients (40.9%) in the placebo group (p = 0.02). Symptomatic hypotension occurred in 9.1% of the patients in the vericiguat group and in 7.9% of the patients in the placebo group (p = 0.12), syncope occurred in 4.0% of the patients in the vericiguat group and in 3.5% of the patients in the placebo group (p = 0.30). CONCLUSION: Among patients with high-risk heart failure, the incidence of death from cardiovascular causes or hospitalization for heart failure was lower among those who received vericiguat than those who received placebo.

Innovations in pharmacological treatment of heart failure.

The main goal of the heart failure treatment is the decrease of mortality and morbidity, especially improvement of quality of life and decrease of hospitalisations. ACE inhibitors are the cornerstone of the treatment, MRA should be added to ACEI. Angiotensin receptor blockers (ARB) are indicated in the case of ACE inhibitors intolerance. Betablockers in maximal tolerated doses should be added to the renin angiotensin blockade. Diuretics are given to the symptoms relieve - dyspnoe or oedema. Digoxin is indicated in selected patients. There are 3 new promising groups of drugs: (1) Angiotensin Receptor-Neprilysin Inhibitor - ARNI - Sacubitril/Valsartan can replace the ACEI according to the results of the PARADIGM-HF trial. (2) Sodium-glucose co-transporter-2 (SGLT2) inhibitors in patients with diabetes mellitus. (3) A hughe clinical research is done with omecamtiv mecarbil and others perspective drugs.

Pathophysiology, causes and epidemiology of chronic heart failure.

The prevalence of heart failure in developed countries is about 1-2 % in general and in patients above 70 years over 10 %. HFpEF is the cause of heart failure from 22 to 73 %, exact data are not available. If compared with HFrEF, patients with HFpEF are older, more frequent women with hypertension and atrial fibrillation, but less myocardial infarction in their history. Heart failure is a hemodynamic disorder and the pathophysiologic basis is cardiac output, cardiac contractility, filling pressures, wall stress during systolic and diastolic function and heart rate. The neurohumoral activation is very important for the diagnosis as well as prognosis and the most sensitive seems to be brain natriuretic peptide (BNP), respectively the precursor NT-proBNP, which become a part of the new diagnostic classification and are a part of modern treatment. Key words: heart failure - hemodynamics - neurohumoral activation.

The heart transplantation.

The article reviews history, indication and follow-up after heart transplantation, including the mechanical assist devices. Various complications of posttransplant follow-up are mentioned, e.g. rejection, infection, vasculopathy, meta-bolic disorders, hypertension or malignities. Pharmacotherapy used for immunosuppression is discussed. Heart transplantation improves the prognosis of patients with previous heart failure and also their quality of life. Key words: heart transplantation - immunosuppression - mechanical assist devices - rejection - terminal heart failure.

Comorbidities in heart failure.

Comorbidities are important parts of care in patients with heart failure. Comorbidities, as well as their treatments, directly influence the course of heart failure. We present the most comorbidities a their therapy with regard to left ventricular dysfunction. Key words: comorbidities - heart failure.

Arrhythmias and conductance disturbances and heart failure.

Arrhythmias and conductance disturbances and heart failure have a close relation. Arrhythmias are serious complication, but also etiology of heart failure. So it is not clear, what is the cause and what is a consequence. Atrial fibrillation is a frequent cause, ventricular arrhythmias a frequent consequence and ventricular fibrillation a frequent cause of death in patients with heart failure. Overview are about frequent arrhythmias as well as their therapy with regard to left ventricular dysfunction. Key words: arrhythmias - heart failure.

[What are the effects of fixed-dose combination of candesartan and amlodipine]. / Co prinásí fixní kombinace kandesartanu a amlodipinu?

We are presenting a current view on a fixed-dose combination of amlodipine and candesartan in the treatment of hypertension. Major studies on the individual preparations as well as studies examining their combination are included. This fixed-dose combination expands our possibilities with regard to attaining the blood pressure target values, in particular in patients with risk factors or patients with comorbidities. Finally, the benefit mainly consists in the greater compliance of the patient with a minimum adverse effects.

[Heart failure with preserved ejection fraction]. / Srdecní selhání se zachovanou ejekcní frakcí.

UNLABELLED: Heart failure with preserved ejection fraction occurs almost with the same frequency as heart failure with reduced ejection fraction. The diagnosis is based on echocardiography with evidence-based ejection fraction over 50 %, or with left atrial enlargement and left ventricular hypertrophy, and specification of natriuretic peptides. BNP 35 pg/ml and NT-proBNP 125 pg/ml are considered the limits of the norm for chronic heart failure. The treatment of heart failure with preserved ejection fraction lacks clear evidence of mortality reduction, diuretics are recommended to remove symptoms, ACE inhibitors or sartans and beta-blockers to improve the prognosis. Anticoagulation treatment is recommended for atrial fibrillation and possibly digoxin, hypolipidemics for patients in secondary prevention. An important goal of the treatment is the control of accompanying diseases such as hypertension, diabetes mellitus and ischemic heart disease. KEY WORDS: accompanying diseases - treatment - heart failure - heart failure with preserved ejection fraction.

[The TECOS, EXAMINE and SAVOR studies--how do they differ and what are their outcomes?]. / Studie TECOS, EXAMINE a SAVOR--cím se lisí a co prinásejí?

The treatment of diabetes mellitus type 2 is effective, but still is not optimal. DPP4 inhibitors (gliptins) are a new group of peroral antidiabetic drugs. The third clinical mortality study with gliptins in patients with diabetes mellitus type 2 was finished in 2015. The studies are known under acronym TECOS, SAVOR and EXAMINE and the tested drugs are sitagliptin, saxagliptin and alogliptin. The studies included about 37,000 patients. The studies confirmed the cardiovascular safety of the DPP4 inhibitors, but the question about increased heart failure remains open. The effectiveness of lowering glycaemia (glycated haemoglobin) was confirmed and also the pancreatic safety is confirmed.

[Inhibition of renin-angiotensin-aldosterone system in heart failure, or from CONSENSUS to PARADIGM-HF]. / Inhibice systému renin-angiotenzin-aldosteron u srdecního selhání aneb od obecného souhlasu (CONSENSUS) po vzorec myslení (PARADIGM-HF).

An historical survey is presented of mortality trials on angiotensin-aldosteron system inhibition in patients with chronic heart failure. From the CONSENSUS trial up to the PARADIGM-HF trial, ACE inhibitors/angiotensin II receptor antagonists (AT1-blockers, ARBs, sartans), along with mineralocorticoid receptor blockers, have been the gold standard of treatment. Both direct renin blocker aliskiren and dual blocker enalapril + neprilysin proved ineffective; on the other hand, the new dual inhibitor valsartan + neprilysin LCZ 696 is a new and promising therapeutic agent for future treatment of chronic heart failure.

[PEGASUS - Ticagrelor in secondary prevention on patients after a myocardial infarction]. / Pegasus - Tikagrelor v sekundární prevenci u nemocných po infarktu myokardu.

BACKGROUND: Ticagrelor is a P2Y12 receptor antagonist that has been shown to reduce ischemic events for up to a year after an acute coronary syndrome. The efficacy and safety of long-term ticagrelor therapy beyond 1 year after a myocardial infarction is unknown. METHODS: We randomized 21,162 patients with a history of myocardial infarction within the prior 1-3 years in a double-blind 1 : 1 : 1 fashion to ticagrelor 90 mg twice daily, ticagrelor 60 mg twice daily, or placebo, all with low-dose aspirin, and followed them for a median of 33 months. The primary efficacy endpoint was the composite of cardiovascular death, myocardial infarction, or stroke. The primary safety endpoint was TIMI major bleeding. RESULTS: Both doses of ticagrelor significantly reduced the primary combined efficacy endpoint compared to placebo with Kaplan-Meier rates at 3 years of 7.85 % with ticagrelor 90 mg, 7.77 % with ticagrelor 60 mg, and 9.04 % with placebo (HR for ticagrelor 90 mg vs placebo 0.85, 95% CI 0.75-0.96, p = 0.0080; HR for ticagrelor 60 mg vs placebo 0.84, 95% CI 0.74-0.95, p = 0.0043). Rates of TIMI major bleeding were higher with ticagrelor (2.60 % for 90 mg, 2.30 % for 60 mg and 1.06 % for placebo, p < 0.001 for each dose against placebo); the rates of intracranial hemorrhage or fatal bleeding were 0.63 %, 0.71 % and 0.60 % in the 3 arms, respectively. CONCLUSIONS: Treatment of patients more than 1 year after a myocardial infarction with ticagrelor reduces the risk of cardi-ovascular death, myocardial infarction, or stroke, and increases the risk of major bleeding.Key words: myocardial infarction - secondary prevention - ticagrelor.

[Combination treatment of hypertension in 2015]. / Kombinacní lécba hypertenze 2015.

We present an overview of the present views on combination treatment and on fixed combinations in the treatment of hypertension according to guidelines of ESH/ESC and CSH from 2013. The most frequently recommended dual combinations include a blocker of the renin-angiotensin system (ACEI or sartan) and a calcium channel blocker, and further a blocker of the renin-angiotensin system and a diuretic and a calcium channel blocker and a diuretic. In 2014 a fixed-dose combination of an ACE inhibitor (perindopril), a calcium channel blocker (amlodipine) and an diuretic (indapamide) appeared on the Czech market. Within the PIANIST study including 4 731 insufficiently controlled hypertensives, a fixed-dose triple combination of perindopril, amlodipine and indapamide led to a decrease in blood pressure by 28.3/13.8 mm Hg and to a sufficient control of hypertension in 92 % of patients. The advantage of fixed combinations primarily consists in greater compliance of patients and thereby in a better control of hypertension. About 1/3 of hypertensives need a triple combination for a satisfactory blood pressure control.

[Do natriuretic peptides have a new chance in treatment of heart failure?]. / Mají natriuretické peptidy novou sanci v lécbe srdecního selhání?

The effect of natriuretic peptides on cardiovascular and renal system offers a potential benefit in therapy of hypertension and heart failure; however the current results of clinical trials are not encouraging. Synthetic B natriuretic peptide has demonstrated short-term hemodynamic improvement in patients, but in terms of renal function and long-term prognosis the effect was questionable. Nevertheless, new hope is ularitid a dual inhibitor of neprilysin and ARB: LCZ 696, the ongoing clinical studies and previous data from pilot studies appear promising.

[IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (studie IMPROVE-IT)]. / IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (studie IMPROVE-IT).

BACKGROUND: The IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) is evaluating the potential benefit for reduction in major cardiovascular (CV) events from the addition of ezetimibe versus placebo to 40 mg/d of simvastatin therapy in patients who present with acute coronary syndromes and have low-density lipoprotein cholesterol (LDL-C) 125 mg/dl. METHODS: Randomized double blind clinical trial in patients with acute coronary syndrome and low cholesterol level. The simvastatin monotherapy arms LDL-C target was < 70 mg/dl, the comparison arm was simvastatin + ezetimibe. Ezetimibe was assumed to further lower LDL-C by 15 mg/dl and produce an estimated ~ 8 % to 9 % treatment effect. The primary composite end point was CV death, nonfatal myocardial infarction (MI), nonfatal stroke, rehospitalization for unstable angina (UA), and coronary revascularization ( 30 days postrandomization). The targeted number of events was 5,250. RESULTS: 18,144 patients were enroled with either ST segment elevation MI (STEMI, n = 5,192) or UA/non-ST segment elevation MI (UA/NSTEMI, n = 12,952) from October 2005 to July 2010. Primary endpoint occured in 2 742 patients (34.7 %) treated with simvastatin in monotherapy and in 2 572 patients (32.7 %) (p = 0.016) treated with combination. Compared to patients with coronary heart disease given the drug simvastatin plus a placebo, those given both simvastatin and the non-statin drug, ezetimibe, had a 6.4 % lower combined risk of subsequent heart attack, stroke, cardiovascular death, rehospitalization for unstable angina and procedures to restore blood flow to the heart. Heart attacks alone were reduced by 13 %, and non-fatal stroke by 20 %. Deaths from cardiovascular disease were statistically the same in both groups. Patients were followed an average of approximately six years, and some as long as 8.5 years. Approximately 2 patients out of every 100 patients treated for 7 years avoided a heart attack or stroke [Number Needed to Treat (NNT) = 50/7 years]. CONCLUSIONS: The study has shown a claer benefit from combination treatment with simvastatin and ezetimibe in patients with acute coronary syndrome and low LDL-C.

[Palliative care and chronic heart failure]. / Paliativní péce a chronické srdecní selhání

Heart failure is a very common clinical syndrome in cardiology which reduces life expectancy and has a significant impact on the quality of life. The treatment of heart failure improves survival thus the number of patients who reach the terminal state increases with this diagnosis. Major symptoms and psychosocial difficulties begin to appear during therapy which aims to prolong life or cure the life limiting illnesses. The World Health Organization (WHO) changed its definition in 2002 and concluded that palliative care should be provided "in the early stages of disease, together with another treatment that prolongs life." Palliative care involves multiple disciplines in order to solve problems caused by the symptoms of the disease and other related aspects of the patient and family who are considered as a one subject, because a feeling of well-being has an impact on others.Key words: heart failure - non-pharmacological treatment - palliative care.

[Comparison of American and European (Czech) guidelines for diagnosis and treatment of chronic heart failure]. / Srovnání amerických a evropských (ceských) doporucení pro diagnostiku a lécbu chronického srdecního selhání

The new Czech and European recommendations for diagnosis and treatment of heart failure were published in 2012. The American guidelines ACCF/AHA were published in 2013. Main difference between them is presentation of acute and chronic heart failure in the European guidelines while the American and the Czech guidelines include only chronic heart failure. The American recommendations distinguish heart failure with reduced ejection fraction and with remained ejection fraction. In the beginning, the American guidelines introduce A-D classification which doesn´t figure in the European neither Czech guidelines. Class A patients are ill with risk factors, but without heart failure. In contrast, class D patients are decompensated with symptoms in the rest. Epidemiologic data shows interesting results with prevalence about 0.2% in 60-69 years old subjects and 80% in subjects older than 85 years. 5 year mortality is 50%. The American guidelines start to treat class A which is in fact prevention and treatment of risk factors. There is mentioned inevitably treatment of hypertension, both systolic and diastolic which decrease risk of heart failure up to 50%. There is almost no difference in pharmacotherapy. Noteworthy, the American guidelines introduce also ACE inhibitors - fosinopril and quinapril, on the other hand beta-blockers don´t involve nebivolol. Wide range of diuretics are mentioned, some of them aren´t registered in the Czech Republic. European and Czech guidelines involve ivabradin. Neither nesiritid nor levosimendan for inpatients aren´t involved. There is briefly mentioned surgery and cardiac mechanical support, moreover there are references for guidelines for heart transplantation.

The Lesser Egyptian Gerbil (Gerbillus gerbillus) is a suitable host for the long-term propagation of Cryptosporidium andersoni.

We describe the course of infection of Cryptosporidium andersoni LI03, originally isolated from cattle, in outbred Gerbillus gerbillus (Lesser Egyptian Gerbil), Meriones unguiculatus (Mongolian gerbil), and Meriones tristrami (Tristram's jird). While both Meriones spp. partially cleared the infection and shed a low number of oocysts (less than 15,000 oocysts per gram (OPG)), chronic infection with a mean infection intensity reaching 200,000 OPG was observed in G. gerbillus. These data suggest that G. gerbillus can be used as a laboratory model for the long-term maintenance and study of C. andersoni without the need for host immunosuppression.