How to strengthen your heart muscle (failing heart)? Daniel Pella, MD, PhD. Professor of Medicine Jan Fedacko, MD, PhD, Lucia Jackova MD, Matej Sajty, MD 1st Dept. of Medicine L. Pasteur University Hospital and Medical Faculty UPJS Košice 7th ICCD, Sofia 24.-26.10.2013 Human heart: how to and what to strengthen ? healthy heart hypertrophic heart (not athletes heart) ischaemic myocardium FAILING HEART Code for healthy heart muscle 0-3-5-140-5-3-0 0 3 5 140 5 3 0 no smoking walking at least 3 km daily or at least 30 minutes of aerobic physical activity daily portions of fruits or vegetables daily systolic blood pressure 140 mm Hg or less total cholesterol below 5.0 mmol/l LDL cholesterol below 3.0 mmol/l no overweight, no obesity and diabetes type 2 Prevalence of hypertension in different regions of the world: Actual figures for 2000 - predicted for 2025 Prevalence of hypertension % 50 Men Women 40 2000 30 20 10 116.2123.3 0 40. 8 52.5 60.4 57.8 60.0 54.3 35.9 37.9 98.5 83.1 38.4 33.0 38.2 41. 6 number of people with HT millions) 50 2025 40 30 20 10 147.9161.8 44. 59.7 0 107.3106.2 102.1 98.5 72.2 80.4 151.7147.5 67.3 62.1 73.6 77. 1 Sa ha Su A f ra b ri n ca O Is Asi the la a r nd & s na Ch i Am Ca er M rib & t ica id be h dl a e e n Cr Ea es ste c e rn nt La ti n In di a Es ta bl Ec M on a ish e Fo om rke d r m ie t er s Ec S on oc om iali ie st s 0 number of people with HT millions) Kearney et al Lancet 2005 Hypertension management: Blood pressure control in various countries <140/90 mm Hg USA 1 <160/95 mm Hg Canada 2 27% England 3 6% Finland 5 22% France 4 24% Spain 5 20,5% 20% Germany 5 Scotland 5 22,5% 17,5% Australia 5 19% India 5 9% sólo > 65 años 1 JNC VI. Arch Intern Med 1997 Joffres et al. Am J Hypertens 1997 3 Colhoun et al. J Hypertens 1998 2 4 5 Chamontin et al. Am J Hypertens 1998 Marques-Vidal P et al. J Hum Hypertens 1997 Progression from hypertension to heart failure Obesity Diabetes Diastolic dysfunction LVH Hypertension Smoking Dyslipidaemia Diabetes HF MI Normal LV structure LV and function remodelling Death Systolic dysfunction Subclinical LV dysfunction Time: decades Overt heart failure Time: months Coronary atherosclerosis starts at very early age and is very common IVUS of coronary arteries Prevalence of atherosclerosis (%) 100% 70% 80% 47% 60% 40% 22% 20% 0% <25 Nissen S. Am J Cardiol. 2001:87(suppl):15A-20A. 25-35 age of heart donor >35 Ischaemia - metabolic definition disproportion between oxygen supply and its consumption Predominant is energetic deficiency (ATP) Intracellular acidosis ↑ H2+, ↑lactate Ion disequilibrium ↑ Ca2+Na+ ↓ K+Mg2+ Human Heart Structure Synthesis of chemical energy (ATP) 30kg/day Conversion (need of coenzyme Q10) to mechanical work (1 contraction/relaxation / 300mg ATP) Resources ATP are sufficient only for 3 heartbeats and are regenerating for every 10-15 sec Heart metabolism: ischaemic conditions ↑Glycolysis Fatty acids ATP ATP + Pi ↑Lactate PDH Pyruvate 60-70% 3-ketoacyl-CoA tiolase (possibly blocked by TRIMETAZIDINE) 30-40% ↓ ATP ↓O2 Mitochondria ADP + Pi Stanley Wiliam C., Eur Heart J,, 2001;Vol 3, Suppl O: 02-07 Active substances supporting myocardial metabolism Treatment target: enhancement of energy production by preference of glucose oxidation leading to decreased O2 consumption For 1 mol O2: + 15 mmol ATP in comparison with fatty acids (used like energy substrate) Guidelines for management of stable angina pectoris, EHJ 2006;27:1341-1381 Trimetazidine – ideal metabolic approach in pts. with stable angina • partially inhibiting 3- ketoacyl CoA tiolase activity by preference of glucose oxidation • especially indicated in metabolic syndrome patients and type 2 DM ( in CHF as well) • type 2 DM pts. – documented decreased activity of SERCA2a – diastolic dysfunction (CHF) • in all patients, who did not tolerate therapy with betablockers, calcium channel blockers or NO donors ( or not able to achieve target doses) Guidelines for management of stable angina pectoris, EHJ 2006;27:1341-1381 Epidemiology of CHF prevalence 2-3% rapidly increases with ageing younger age: more frequent in men 5% of all acute hospitalizations are due to CHF (10% from overall hospitalizations) Anti-ageing medicine: risk of heart failure by age Cumulative risk % 25 Cumulative risk % 25 Men Women 20 20 15 15 10 10 5 5 0 0 40 50 60 70 80 90 40 50 Attained age, year 60 70 80 90 Lloyd-Jones et al Circulation 2002 ...in ...in fact, chronic heart failure is “malignant disease” disease” CHF mortality is 2-times high like in: • • breast cancer urinary bladder cancer higher like in .... • prostate cancer similar like in .... • colon cancer Chronic Heart Failure (CHF) Syndrome high mortality frequent hospitalizations decreased quality of life need for comprehensive management and therapy individual approach CHF - treatment symptomatic CHF + decreased EF diuretics + ACEi (sartans) β-blockers still symptomatic? yes add aldosteron antagonist or sartan ivabradine, digoxin, hydralazine, defibrilator, heart transplantation.... Non-pharmacological management of CHF Risk factors modification decrease of body weight (if overweight) quit smoking control of blood pressure treat dyslipidemia Non- pharmacological management Active immunisation regular vaccination against flu (pneumonia) Regular physical exercise moderate, regular daily activities (depending on severity of CHF) Sexual activity beneficial, but necessary to be consulted with cardiologist Gravidity necessary to consult with cardiologist , during therapy contraceptives needed Depression therapy CHF patients - 20% incidence Dietary recommendations decrease intake of sodium monitoring of fluids intake prevention of malnutrition increase intake of polyunsaturated fatty acids (n-3 PUFA) coenzyme Q10 (probably higher doses) – at least not harmful (studies Q-SYMBIO, KINDA) CoQ10 Body Content Sample Weight of Q10 Content (mg) Plasma 4 1 mg/l Interstitial Volume 11 1 mg/l Heart 28 70 mg/kg Respiratory muscle 60 30 mg/kg Skeletal muscle 1000 40 mg/kg Liver 120 60 mg/kg Fat 200 10 mg/kg Total 1423 Source: Karlsson et al 1993 Mortensen SA, 2008 Mortensen SA, 2008 Mortensen SA, 2008 Goals of pharmacotherapy to decrease mortality, to diminish symptoms improve quality of life eliminate oedemas decrease diziness, number of hospitalizations, improve physical exercise tolerance, improve breathing (breathlessness) prevention of of of of progression of myocardial damage myocardial remodelling new appearance of CHF symptoms re-hospitalizations Background treatment in CHF ACE-inhibitors (IA) β-blockers (IA) perindopril enalapril lisinopril ramipril trandolapril bisoprolol carvedilol metoprolol succinate (ZOK) nebivolol (seniors) AT1 receptor blockers (sartans) (IA-IIB) Aldosteron antagonists (IB) kandesartan valsartan eplerenone spironolactone Therapy for congestion - diuretics Class of reccomendation I Level of evidence B usually administered in combination with ACE-inhibitors (and/or sartans) and betablockers Ivabradine – novel treatment for CHF patients acts specifically in sinoatrial node selective decrease of heart rate no serious adverse effects, no contraindications which are typical e.g. for betablockers Number of heartbeats during the whole life is approximately the same in all animals and human as well 100 Human Expected survival in years 60 Whale Elephant 30 Horse Lion Dog Ape 10 Cat Giraffe Tiger Marmot 5 Rat 2 Hamster Mouse 0 102 104 106 108 Numberof heartbeats/life Levine HJ:.Rest heart rate and life expectancy. J Am Coll Cardiol 1997; 30: 1104-1106 1010 1012 ® Total population: Heart rate and total mortality 60 Heart rate (min-1) Incidence/1000 persons/year 50 30-67 68-75 76-83 84-91 92-220 40 30 20 10 0 Men, 35-64 years old Men, 65-94 years old Kannel WB et al 1987;113:1489 RESULTS OF STUDY In CHF patients and resting heart rate over 75 beats/min. ivabradin decreased: total mortality by 17% cardiovascular mortality by 17% Bohm M, et al. Clin Res Cardiol 2012 New Guidelines for CHF (HF Congress 2012, Beograd) Other therapy anticoagulant drugs warfarin (rivaroxaban, dabigatran, apixaban) antithrombotic drugs aspirin, clopidogrel omega-3 fatty acids statins ??? (if prescribed earlier or indicated due to other reason) GISSI-HF R1 (n=6975) n-3 PUFA 1 g daily (n=3494) Study design Placebo (n=3481) R1 Fish Oil study Placebo (n=2289) R2 statin study R2 (n=4574*) RSV 10 mg daily (n=2285) R1, R2 Visit: Month: Median follow-up 3.9 years 1 2 3 4 5 6 7 8 9 0 1 3 6 12 18 24 30 36 D D D D D D D At each visit, the following assessments were performed: cardiovascular examination, vital signs, 12-lead electrocardiogram, compliance check, serious adverse events assessment and blood chemistry NYHA=New York Heart Association; R1=randomization 1; R2=randomization 2; D=drug distribution Note; 2401 patients were not included in the R2 (rosuvastatin) arm of the study;1576 required statin therapy,395 were contraindicated to statins and 430 were not suitable in the opinion of the investigator. Tavazzi L et al. Eur J Heart Fail 2004; 6: 635–641;GISSI-HF Investigators. Lancet 2008; doi:10.1016/S01.40-6736(08)61240-4 GISSI-HF rosuvastatin : Results – primary endpoints rosuvastatin placebo HR* (n=2285) (n=2289) n (%) n (%) CI p 1.00 [95.5% CI 0.90-1.12] 0.94 1283 (56.1) 1.01 [99% CI 0.91-1.11] 0.90 Primary endpoints total mortality total mortality or CV hospitalizations 657 (28.8) 1305 (57.1) 644 (28.1) HR – Hazard Ratio; CI – Confidence Interval *adjusted HR GISSI-HF Investigators. Lancet 2008; doi:10.1016/S01.40-6736(08)61240-4 GISSI-HF fish oil: Results - primary endpoints n-3 PUFA (n=3494) n (%) placebo HR* (n=3481) n (%) CI p total mortality 955 (27.3) 1014 (29.1) 0.91 [95.5% CI 0.833-0.999] 0.041 total mortality or CV hospitalizations 1981 (57) 2053 (59) Primary endpoints HR – Hazard Ratio; CI – Confidence Interval *adjusted HR 0.92 [99% CI 0.849-0.999] 0.009 Guidelines for resynchronisation treatment in patients class NYHA III-IV with persistent low EF despite optimal pharmacotherapy Recommendation QRS morphology LBBB in pts. with sinus rhythm, QRS ≥120ms, EF≤35%, expected survival more than 1 year (NYHA II - QRS ≥130ms, EF≤30%) QRS non LBBB in pts. with sinus rhythm, QRS ≥150ms, EF≤35%, expected survival more than 1 year (NYHA II - EF≤30%) Class Level of evidence I A IIa A Guidelines for ICD use in CHF patients Recommendations Secondary prevention in pts. with ventricular arrhytmias leading to hemodynamic instability, expected survival more than 1 year, good functional status Primary prevention in pts. with symptomatic CHF, NYHA IIIII, EF≤35%, despite optimal pharmacotherapy, expected survival more than 1 year, good functional status Class Level of evidence I A IIa A Surgical treatment coronary revascularisation (CABG) reconstructions of the left ventricle walls valves surgery mechanical circulatory support heart transplantation But...remember !!! Patient´s education remains basic pillar of potential therapy success diagnosis, etiology, prognosis symptoms monitoring - “self-care“ pharmacotherapy compliance, diet adherence regular physical exercise But...remember !!! Patient´s education remains basic pillar of potential therapy success smoking termination (limited ammounts of alcohol) relax, tourism, entertainment, sexual activity immunisation psychosocial activity, prevention of depression Thank you for your attention !
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