PRESSURE AND VOLUME OVERLOAD. REMODELLING OF THE HEART. CHRONIC HEART FAILURE VLA 3. 10. 2017 NORMAL CARDIAC FUNCTION  Cardiac Output = Heart rate x Stroke volume  Heart rate – controled by SNS and PNS  Stroke – dependent on preload, afterload and contractility  Preload = LVEDP and is measured as PCWP (Pulmonary Capillary Wedge Pressure)  Afterload = SVR  Contractility: ability of contractile elements to interact and shorten against a load (+ inotropy- inotropy) Angiotensinogen Renin Angiotensin I Angiotensin II Angiotensin (1-9) Necrotic lesions Cardiac, renal arterial Angiotensin (1-7) Cardiac and renal protective function ACE ACE2 ACE2 ACE ACE2? ? Danilczyk and Penninger, 2006 Phillips MI et al., 2008 MASR is highly expressed in myelinrich tissue, especially in peripheral nerves. Myelin formation marker? Working diagram Sum of the external and internal work represents the total mechanical work of contraction and this is directly proportional to oxygen consumption of the myocardium. Pressure work of the heart consumes more oxygen than volume work, so that the effectivity of the former is lower than that of the latter. SYSTOLIC DYSFUNCTION  Impairment of the contraction of the left ventricle such that stroke volume (SV) is reduced for any given end-diastolic volum (EDV)  Ejection fraction (EF) is reduced (below 40-45%)  EF=SV/EDV SYSTOLIC DYSFUNCTION-ETIOLOGY  Dilated Cardiomyopathy - Ischemic disease myocardial ischemia myocardial infarction - Non-ischemic disease Primary myocardium muscle dysfunction Valvular abnormalities Hypertension Alcohol and drug-induced Idiopathic DIASTOLIC DYSFUNCTION  Ventricular filling rate and the extent of filling are reduced or a normal extent of filling is associated with an inappropriate rise in ventricular diastolic pressure. DIASTOLIC DYSFUNCTION-ETIOLOGY  Hypertrophic Cardiomyopathy - Hypertension - Myocardial ischemia and infarction - Restrictive Cardiomyopathy - Amyloidosis - Sarcoidosis COMPENSATORY MECHANISMS FOR DECREASED CARDIAC OUTPUT  Increased SNS activity Increase HR and SVR which increases BP  Frank-Starling mechanism: LVEDP = SV  Activation of Renin-angiotensin-aldosterone system (RAAS)  Myocardial Remodeling - Concentric hypertrophy - Eccentric hypertrophy Pathological hypertrophy of the myocardium CARDIOMYOPATHIES CLASSIFICATION  Dilated (congestive)  Hypertrophic  Restrictive CARDIOMYOPATHIES DILATED (CONGESTIVE) Ejection fraction-- <40%  Mechanism of failure--  Impairment of contractility (systolic dysfunction)  Causes--  Idiopathic, alcohol, peripartum, genetic, myocarditis, hemochromatosis, chronic anemia, doxorubicin, sarcoidosis  Indirect causes (not considered cardiomyopathies)--  Ischemic heart disease, valvular disease, congenital heart disease Cross section of a normal heart, with right and left ventricles (R &L) having normal myocardial thickness and chamber size. normal thickness LV 1.3-1.5 cm; RV 0.3-0.5 cm Dilated cardiomyopathy (cross section), with both right and left ventricular chambers showing dilatation. The myocardium appears to be normal or slightly thin in this case. CARDIOMYOPATHIES HYPERTROPHIC  Ejection fraction-- 50-80%  Mechanism of failure-- impairment of compliance (diastolic dysfunction)  Causes-- Idiopathic, genetic, Friedreich ataxia, storage diseases, DM mother  Indirect causes– hypertesion heart, aortic stenosis CARDIOMYOPATHIES RESTRICTIVE  Ejection fraction-- 45-90%  Mechanisms of failure-- Impairment of compliance (diastolic dysfuntion)  Causes-- Idiopathic, amyloidosis, radiation-induced fibrosis  Indirect causes-- pericardial constriction ETIOLOGY Familial in ~ 55% of cases with autosomal dominant transmission Mutations in one of 4 genes encoding proteins of cardiac sarcomere account for majority of familial cases Remainder cases are spontaneous mutations  -MHC  cardiac troponin T  myosin binding protein C  -tropomyosin RESTRICTIVE (INFILTRATIVE) CARDIOMYOPATHY-ETIOLOGY  Infiltration of the myocardium with something other than muscle  Stiff heart that cannot fill or pump well (Filling appears to be the main problem) ETIOLOGIES HEART FAILURE  A condition that exist when the heart is unable to pump sufficient blood volume to meet the metabolic needs of the body.  Heart failure (HF) is a growing health problem and a major cause of mortality and morbidity in the world. HEART FAILURE  The pathophysiological concept of HF has changed dramatically during the last decade with an increased understanding of the heart as an endocrine organ, leading to a multiorgan neurohormonal response and an activation of systemic inflammation. HEART FAILURE  Gut microbiota play critical physiological roles in the extraction of energy from our food and in the control of local or systemic immunity. Curr Heart Fail Rep. 2016 Apr;13(2):103-9. doi: 10.1007/s11897-016-0285-9. HEART FAILURE  Gut microbiota and microbiome compositions appear to be involved in the pathogenesis of diverse diseases such as obesity, diabetes, gastrointestinal diseases, cancer and cardiovascular (CV) diseases, including HF. Curr Heart Fail Rep. 2016 Apr;13(2):103-9. doi: 10.1007/s11897-016-0285-9.F. HEART FAILURE  Trimethylamine N-oxide (TMAO), which is derived from gut microbiota produced metabolites of specific dietary nutrients, has emerged as a key contributor to CV disease pathogenesis.  Changes in composition of gut microbiota, called dysbiosis, can contribute to higher levels of TMAO and the generation of uremic toxins, progressing to both HF and renal impairment. Currently, antibiotics, prebiotics, probiotics and symbiotics are the instruments utilized in clinical practice to modulate the intestinal microbiota both in healthy and pathologic conditions. Curr Heart Fail Rep. 2016 Apr;13(2):103-9. doi: 10.1007/s11897-016-0285-9. GUT MICROBIOTA  Gut microbiota participates in food digestion through two main catabolic pathways.  In the saccharolytic pathway, the gut microbiota is responsible for production of short-chain fatty acids, which are known to exert a protective action and a positive immune-modulating activity, guaranteeing a general healthy status.  The second catabolic pathway is represented by protein fermentation, which also induces short-chain fatty acid formation and leads to other co-metabolites such as ammonia, amines, thiols, phenols and indoles, some of which are potentially toxic and are considered microbial uremic toxins.  The microbiota exerts a fundamental influence on systemic immunity and metabolism. A healthy gut microbiota is largely responsible for the overall health of the host. Curr Heart Fail Rep. 2016 Apr;13(2):103-9. doi: 10.1007/s11897-016-0285-9. TYPES OF HEART FAILURE  Systolic & Diastolic  High Output Failure  Pregnancy, anemia, thyreotoxicosis  Low Output Failure  Acute  large MI, aortic valve dysfunction---  Chronic Precipitating causes of heart failure 1. ischemia 2. change in diet, drugs or both 3. increased emotional or physical stress 4. cardiac arrhythmias (eg. atrial fib) 5. infection 6. concurrent illness 7. uncontrolled hypertension 8. new high output state (anemia, thyroid) 9. pulmonary embolism 10. mechanical disruption HEART FAILURE CLINICAL MANIFESTATIONS Symptoms  dyspnea  fatigue  exertional limitation  weight gain  poor appetite  cough Signs  tachycardia, tachypnea  edema  jugular venous distension  pulmonary rales  pleural effusion  hepato/splenomegaly  ascites  cardiomegaly  S3 gallop LEFT VS. RIGHT HEART FAILURE Left Heart Failure  pulmonary congestion Right Heart Failure  peripheral edema  sacral edema  elevated JVP  ascites  hepatomegaly  splenomegaly  pleural effusion COMPENSATORY MECHANISMS IN HEART FAILURE  increased preload  increased sympathetic tone  increased circulating catecholamines  increased renin-angiotensin-aldosterone  increased vasopressin ( CRH)  increased atrial natriuretic factor Current Heart Failure Reports October 2017, Volume 14, Issue 5, pp 393–397 Heart failure according to the compensation state PATHOPHYSIOLOGY OF ACUTE CONGESTIVE HEART FAILURE Acute failure PATHOPHYSIOLOGIC RESPONSE TO HEART FAILURE LV Dysfunction Renal-Adrenal Carotid and LA Baroreceptors Renin- Angiotensin Aldosterone Sympathetic Output Sodium and fluid retention tachycardia vasoconstriction NEUROHUMORAL MECHANISMUS DURING CHRONIC HEART FAILURE (CHF)  Direct toxic effects of Norepinephrine (NE) and AngiotensinII (AII) (Arrhythmias, Apoptosis)  Impaired diastolic filling  Increased myocardial energy demand  Increased pre- and after-load  Platelet aggregation  Desensitization to catecholamines NEUROHORMONAL MECHANISM OF CHF  Components  Endothelin  Vasopressin (ADH)  Natriuretic Peptides  Endothelium-Derived Relaxing Factor  RAAS  SNS  Cytokines NYHA FUNCTIONAL CLASSIFICATION  Class I: patients with cardiac disease but no limitation of physical activity  Class II: ordinary activity causes fatigue, palpitations, dyspnea or anginal pain  Class III: less than ordinary activity causes fatigue, palpitations, dyspnea or angina  Class IV: symptoms even at rest STAGES OF HEART FAILURE  Stage A  High risk for development of heart failure  Stage B  Structural heart disease  No symptoms of heart failure  Stage C  Symptomatic heart failure  Stage D  End-stage heart failure THE VICIOUS CIRCLE IN CARDIOGENIC SHOCK Ann Intern Med 131:47–59, 1999 DĚKUJI ZA POZORNOST!