Authors

• Jozica Šikić — University Hospital “Sveti Duh”, Zagreb, Croatia — ORCID: 0000-0003-4488-0559

Abstract

Heart failure (HF) is a disorder in the structure or function of the heart that prevents it from maintaining adequate oxygen supply to other tissue. It manifests with symptoms and signs of damage to almost all target organs. The most common cause is damage of the systolic function of the left ventricle, but causes include disrupted diastolic function, valvular diseases, pericardial and endocardial diseases, and heart rhythm disorders. The diagnosis of HF can be established using both invasive and non-invasive techniques. The goal of HF treatment is to reduce the symptoms and signs of the disease, reduce rehospitalization, and improve the quality and length of the patient’s life. Three neurohormonal antagonists play a key role in the treatment: angiotensin-converting enzyme inhibitors (or angiotensin receptor blockers), beta-blockers, and mineralocorticoid receptor antagonists. Refractory HF in the terminal phase can be treated with heart transplants and cardiac support pumps, which can be uni- or biventricular and either temporary or permanent.

Keywords

heart failure, diagnosis, therapy

DOI

Full Text

Heart failure (HF) can be defined as a disorder in the structure or function of the heart which, despite normal pressure flow, prevents it from maintaining adequate oxygen supply for normal tissue metabolism. (1) It is a syndrome that can manifest manifests with symptoms and signs of damage to almost all target organs. The most common cause is damage of the systolic function of the left ventricle, but disrupted diastolic function, valvular diseases, pericardial and endocardial diseases, and heart rhythm disorders also play a significant role. (2) To establish a diagnosis of systolic HF, in addition to typical symptoms and signs, ultrasound verification of reduced ejection fraction is necessary as well, whereas diagnosis of HF with preserved systolic function is much more complex and requires, other than the typical signs and symptoms, normal ejection fraction of the non-dilated left ventricle combined with relevant structural heart defects such as left ventricular hypertrophy and diastolic dysfunction. (3) The severity of the disease and the survival rate correlates better with signs and symptoms than measurement of ejection fraction, so the severity of the disease is usually assessed using the NYHA classification. About 1 – 2% of the population of developed countries suffers from HF, for which the coronary heart disease is the underlying condition in two thirds of cases. (1) When diagnosing HF, in addition to chest X-ray, a 12-lead ECG is also needed to determine heart rhythm as well as the QRS complex width (in order to make prognostic estimates but also for indication for the implantation of resynchronizing electrostimulators). Transthoracic echocardiography is the basic method for assessment of the myocardium and valves. (4-6) This method can be supplemented with magnetic resonance imaging of the heart, which provides a better and more detailed image of heart structure and functions. Biochemical analysis provides insight into damage to target organs (the kidneys, liver, thyroid, etc.), with hyponatremia and increased creatinine levels being important though negative prognostic signs. BNP and nT-proBNP values are also important diagnostic markers, but also markers of HF outcomes. (7) Coronarography is indicated in patients where coronary heart disease is suspected, and can be supplemented with catheterization of the right side of the heart in patients scheduled for heart transplants or ventricular assist device implantation. ## Treatment of heart failure The goal of HF treatment is to reduce the symptoms and signs of the disease, reduce rehospitalization, and improve the quality and length of the patient’s life. Three neurohormonal antagonists play a key role in the treatment: angiotensin-converting enzyme (ACE) inhibitors (or angiotensin receptor blockers), beta-blockers, and mineralocorticoid receptor antagonists (Table 1). ### Table 1: Pharmacological treatments indicated in potentially all patients with symptomatic (NYHA functional class II-IV) systolic heart failure. | RECOMMENDATIONS | Class of recommendation | Level of evidence | | --- | --- | --- | | An ACE inhibitor is recommended, in addition to beta-blocker, for all patients with an EF ≤40% to reduce the risk of HF hospitalization and the risk of premature death | I | A | | A beta-blocker is recommended in addition to an ACE inhibitor (or ARB if ACE i not tolerated) for all patients with an EF ≤40% to reduce the risk od HF hospitalization and the risk of premature death | I | A | | An MRA is recommended for all patients with persisting symptoms (NYHA class II-IV) and an EF ≤35% despite treatment with an ACE inhibitor (or ARB if ACE i not tolerated) and a beta-blocker to reduce the risk of HF hospitalization and the risk of premature death | I | A | [†] ACE = angiotensin-converting enzyme, ARB= angiotensin receptor blocker, EF= ejection fraction; HF= heart failure, MRA = mineralocorticoid receptor antagonist, NYHA = New York Heart Association. Adapted from: Eur Heart J. 2012;33:1787-847. ## 1) Angiotensin-converting enzyme inhibitors Angiotensin-converting enzyme (ACE) inhibitors have been shown to improve the signs and symptoms of HF, reduce rehospitalization, and improve survival rates, and should thus be introduced as soon as the diagnosis is established. Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS) that included patients with severe HF found a 27% reduction in mortality, while the Studies of Left Ventricular Dysfunction (SOLVD) on patients with mild to moderate HF symptoms showed a 16% reduction in mortality. (8-10) These results have been confirmed in numerous smaller studies and meta-analyses. (1) During treatment with ACE inhibitors, kidney function must be carefully monitored, since there is a chance of deterioration and hypercalcemia. Studies on patients with symptomless HF showed similar results. ## 2) Beta-blockers Beta-blockers are a heterogeneous group of medications and can be classified as non-selective and selective. Metoprolol, carvedilol, and bisoprolol have been shown to reduce total mortality, rehospitalization, and left ventricle dysfunction (LVEF, 35 – 40%). (11, 12) Bisoprolol (e.g. Sobycor®) has a 20 times greater selectivity to B1 receptors than to B2 receptors, and no significant side-effect are expected in the respiratory system. It has no intrinsic sympathomimetic activity, a negative chronotropic effect, and no significant metabolic effect on lipids and glucose. There have been numerous studies on treatment of HF using these medications. The most important are: Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS), Cardiac Insufficiency Bisoprolol Study II (CIBIS II), and Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MEIT-HF). More than 90% of patients received these medications in addition to ACE inhibitors. (13-17) These studies found a reduction of mortality of approximately 34%, whereas a study on the effects of nebivolol (SENIORS) found a reduction in rehospitalization, but not mortality. (18) Beta-blockers are introduced during the stable phase of the disease; during deterioration, i.e. decompensation, a reduction of the dosage is recommended, while the treatment should be discontinued during cardiogenic shock. ## 3) Mineralocorticoid receptor antagonists Aldosterone receptor blockers have been found effective in treating patients with systolic HF. Two basic studies, Randomized Aldactone Evaluation Study (RALES) and Epleronon in Mild Patients Hospitalization and Survival Sudy in Heart Failure (EMPHASIS-HF) showed a significant reduction in mortality and rehospitalization, at approximately 35%. These medications can cause hypercalcemia and require renal function monitoring. (19-21) ## 4) Other medication In addition to the above medication, HF is also treated with angiotensin receptor antagonists (most commonly when ACE cause coughing), and ivabradine in patients with a sinus rhythm and EF of 120ms. (28-33) Patients in the terminal phase of HF with no comorbidities that are a contraindication can receive heart transplants. Recently, a number of heart pumps has been developed, which can be uni- or biventricular and either temporary or permanent. These circulatory supports can serve as a bridge to decision, bridge to candidacy for heart transplants, a bridge to transplantation, a bridge to recovery after cardiac surgery or myocarditis, and as a permanent support to the heart (destination therapy). (1) Thanks to the development of medicine and technology, many very active treatment methods are available to these patients today, resulting in not only improved quality of life but also in longer lives as well.

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