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Pisa

MCV1. Pisa. Nebula. Congresso Regionale ANMCO 2011 “Il Cuore in Versilia” Viareggio, 7-8 Ottobre 2011. Frank L. Dini UO Cardiologia Universitaria Dipartimento Cardio Toracico - Pisa. 1000. 600. Mouse. Hampster. 300. Rat. Monkey. Marmot. Cat. Dog. 100. Giraffe. Tiger. Horse.

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  1. MCV1 Pisa Nebula Congresso Regionale ANMCO 2011 “Il Cuore in Versilia” Viareggio, 7-8 Ottobre 2011 Frank L. Dini UO Cardiologia Universitaria Dipartimento Cardio Toracico - Pisa

  2. 1000 600 Mouse Hampster 300 Rat Monkey Marmot Cat Dog 100 Giraffe Tiger Horse 50 Man Donkey Elefant Lion Whale 20 Whale Levine HJ. J Am Coll Cardiol 1997;30:104-106.

  3. Relationship Between Heart Rate and Mortality in the General Population Gillman MW et al. Am Heart J1993;93:1148-1154.

  4. Heart Rate and Mortality in Patients With Ischemic HF Mortalità (%) 1.0 > 91 bpm81-91 bpm71-80 bpm40-70 bpm 0.8 0.6 0.4 N=1518 P<0.0001 0.2 0.0 Anni 0 2 4 6 8 10 Fosbol EL, et al. Int J Cardiol 2010;140:279-286.

  5. Systolic Heart failure treatment withthe Ifinhibitor ivabradine Trial Study Design • SHIFT was a randomised, double-blind, placebo-controlled trial in 6505 pts with chronic HF, LVEF ≤ 35%, sinus rhythm and heart rate (HR)  70 bpm • Aim: to evaluate if reduced HR can translate into reduced CV mortality or hospitalizations for worsening HF • Patients were randomized to ivabradine 5 mg bid or placebo Swedberg K, et al. Lancet 2010;376:875-885.

  6. Primary composite endpointCV mortality or hospitalisation for HF worsening HR = 0.82 (0.75-0.90) p<0.0001 Cumulative frequency (%) 40 Placebo -18% 30 Ivabradine 20 10 0 Months 0 6 12 18 24 30 Swedberg K, et al. Lancet 2010;376:875-885.

  7. Hospitalization for worsening heart failure HR = 0.74 [95% CI 0.66-0.83]p<0.0001 Cumulative frequency (%) 30 Placebo -26% 20 Ivabradine 10 0 Months 0 6 12 18 24 30 Swedberg K, et al. Lancet 2010;376:875-885.

  8. Kindermann W, Eur Heart J 2002;23:1301-1308.

  9. Heart rate achieved on ivabradine treatment as a predictor of outcomes Patients with CV death and hosp. for worsening HF (%) 50 P<0.0001 40 ≥75 bpm 70-<75 bpm 30 60-<65 bpm 65-<70 bpm <60 bpm 20 10 0 Months 0 6 12 18 24 30 Primary composite end point according to heart rate achieved at day 28. Böhm M, et al. Lancet 2010;376:886-894.

  10. Primary endpoint: change in LVESV index from baseline to 8 months Left ventricular end-systolic volume index ∆ -5.8,P=0.0002 75 70 D - 7.0 ± 16.3 D - 0.9 ± 17.1 65 mL/m2 60 55 50 0 Baseline 8 months Baseline 8 months Ivabradine (n=208) Placebo (n=203) Tardif JC, et al. Eur Heart J 2011 [ePub head of print].

  11. D -7.9 ± 18.9 D -1.8 ± 19.0 Secondary endpoint: change in LVEDV index from baseline to 8 months Left ventricular end-diastolic volume index ∆ -5.5, P=0.0019 100 95 90 mL/m2 85 80 75 0 Baseline 8 months Baseline 8 months Ivabradine (n=204) Placebo (n=199) Tardif JC, et al. Eur Heart J 2011 [ePub head of print].

  12. D 2.4 ± 7.7 D - 0.1 ± 8.0 M008 M008 Baseline Baseline Secondary endpoint: change in LVEF from baseline to 8 months ∆ + 2.7,P=0.0003 Left ventricular ejection fraction 40 35 30 65.2 ± 29.1 25 % 20 15 10 5 0 Baseline 8 months Baseline 8 months Ivabradine (n=204) Placebo (n=199) Tardif JC, et al. Eur Heart J 2011 [ePub head of print].

  13. Relative change in LVESV index from baseline to 8 months 60 Ivabradine Placebo P=0.005 49% 50 48% 40 38% 30 25% 27% 20 13% 10 0 ≤-15% >-15% to <+15% ≥+15% Tardif JC, et al. Eur Heart J 2011 [ePub head of print].

  14. Cardiovascular Effects of Increasing Heart Rate Cardiac work MVO2 Filling time Myocardial perfusion Efficiency Endothelial function Oxygen delivery Myocardial blood flow ENERGY

  15. Relationship of Heart Rate With Sympathetic Activity and Nor-epinephrine Levels Grassi G, al. J Hypertens 1998;16:1635-1639.

  16. Survival benefit of b-blockers in heart failure is statistically signicantly associated with the magnitude of heart rate reduction …

  17. Heart rate and cardiac rhythm relationships with bisoprolol benefit in chronic heart failure in CIBIS II Trial. One year Mortality (%) 18 Bisoprolol N=2593 Placebo 16 14 12 10 8 6 4 2 0 Basal HR 72 bpm Basal HR 72-84 bpm Basal HR >84 bpm Lechat, et al. Circulation 2001;103:1428-1433.

  18. Living organisms constantly need to expend energy to perform vital life functions Everything that happens is caused by an energy change

  19. Energy Klabunde, RE, 2005.

  20. The 2nd LawofThermodynamicsdescribesbasicprinciplesfamiliar in everyday life. Itispartially a universallawofdecay; the ultimate cause ofwhyeverythingultimatelyfallsapart and disintegratesovertime. Evendeathis a manifestationofthislaw. The effectsof the 2nd Law are allaround, touchingeverything in the universe.

  21. Intake Compression Power Exhaust Machines, engines, etc, breakdown faster if one uses them frequently and more intensively. The same theory might be applicable to human life. ENTROPY

  22. Electromagnetic • Thermodynamic • Universal expansion • Kaon decay • Human body The ARROW of time Time goes from the past to the future where the entropy is greater than it was before.

  23. Energy Trasformations in Energy Systems Energy Storage Useful Output Energy Source Energy Loss as Heat

  24. Energy Trasformations in Energy Systems Energy Storage Useful Output Energy Source Energy Loss as Heat

  25. Energy Trasformations in Energy Systems Energy Storage Useful Output Energy Source Energy Loss as Heat

  26. Energy Trasformations in Energy Systems Energy Storage Useful Output Energy Source Energy Loss as Heat

  27. Cardiac Reserve and Remodeling 100 80 60 Cardiac reserve 40 Adaptive Maladaptive 20 0 20 60 40 80 Years Swan HJC, et al. Eur Heart J 1993;14 (Suppl A):45-46.

  28. Where does the entropy come from?

  29. . Reduction involves a decrease in oxidation state H+ + e- Oxidation involves an increase in oxidation state Mitochondria are an important source of reactive oxygen species (ROS).

  30. Oxidative Phosphorylation Citric Acid Cycle Electron Transport Chain ATP Electrons are transferred from electron donors to electron acceptors such as oxygen, in redox reactions. These redox reactions release energy, which is used to form ATP.

  31. Mitochondria as generators of oxygen free radical species

  32. Collagen Collagen Fibroblasts Collagen Extracellular matrix alterations during episodes of ischemia-reperfusion and stunning. B A C D Zhao M et al. J Am Coll Cardiol 1987;10:1322-1328.

  33. Multiple sites of replacement fibrosis in the noninfarcted viable left ventricular tissue Diffuse interstitial fibrosis

  34. Sarcomeres are confined to the sarcolemmal margins. In addition mitochondria are virtually absent and those that are present are small and round. Furthermore, there is a marked glycogen accumulation. Redwood S R et al. Heart 1998;80:218-222.

  35. ISO-STROKE CURVE LV EDV (ml) EF,% www.cardiodinamica.it

  36. ISO-STROKE CURVE MVO2 Efficiency www.cardiodinamica.it

  37. Neglia D, et al: Am J Physiol 2007;293:H3270-3278.

  38. Neglia D, et al: Am J Physiol 2007;293:H3270-3278.

  39. Cumulative Entropy Generation for Different Physical Activity Levels (PAL) 100 Veryactive PAL 80 Low active PAL 60 Entropy generation 40 Sedentary PAL 20 0 20 60 40 80 Time Silva C., Annamalai K: Entropy 2008;10:100-123.

  40. Granville Sewell: Appl Math Letts 2011.

  41. Entropy Throughlungs and kidney WORK Energy Entropy Throughmuscolar work ORGANIC FUELS, OXYGEN BIOSPHERE Carboncycle Water and energy cycle Nitrogen cycle

  42. Expiration CO2 Trasport CO2 Production VCO2 VENTILATION CIRCULATION MUSCLE VO2 Inspiration ENTROPY NEGATIVE ENTROPY Life-driven anti-entropic processes O2 Trasport O2 Consumption

  43. "It is by avoiding the rapid decay into the inert state of 'equilibrium' that an organism appears so enigmatic....What an organism feeds upon is negative entropy."

  44. Thermodynamic Systems THE HEART LIKE AN OVEN

  45. LEONARDO DA VINCI – Codice Arundel The heart like an oven Dissipative OPEN OPEN THE HEART LIKE A DISSIPATIVE SYSTEM

  46. MCV1 Pisa Nebula Congresso Regionale ANMCO 2011 “Il Cuore in Versilia” Viareggio, 7-8 Ottobre 2011 Frank L. Dini UO Cardiologia Universitaria Dipartimento Cardio Toracico - Pisa

  47. STAY HUNGRY STAY FOOLISH … Steve Jobs

  48. The Heart as a Toothpaste

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