MCV1
This presentation is the property of its rightful owner.
Sponsored Links
1 / 53

Pisa PowerPoint PPT Presentation


  • 99 Views
  • Uploaded on
  • Presentation posted in: General

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.

Download Presentation

Pisa

An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -

Presentation Transcript


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


Pisa

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.


Relationship between heart rate and mortality in the general population

Relationship Between Heart Rate and Mortality in the General Population

Gillman MW et al. Am Heart J1993;93:1148-1154.


Heart rate and mortality in patients with ischemic hf

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.


Pisa

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.


Pisa

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.


Pisa

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.


Pisa

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


Pisa

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.


Pisa

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].


Pisa

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].


Pisa

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].


Pisa

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].


Pisa

Cardiovascular Effects of Increasing Heart Rate

Cardiac work

MVO2

Filling time

Myocardial perfusion

Efficiency

Endothelial function

Oxygen delivery

Myocardial blood flow

ENERGY


Relationship of heart rate with sympathetic activity and nor epinephrine levels

Relationship of Heart Rate With Sympathetic Activity and Nor-epinephrine Levels

Grassi G, al. J Hypertens 1998;16:1635-1639.


Pisa

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


Pisa

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.


Pisa

Living organisms constantly need to expend energy to perform vital life functions

Everything that happens is caused by an energy change


Pisa

Energy

Klabunde, RE, 2005.


Pisa

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.


Pisa

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


Pisa

  • 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.


Pisa

Energy Trasformations in Energy Systems

Energy Storage

Useful Output

Energy Source

Energy Loss as Heat


Pisa

Energy Trasformations in Energy Systems

Energy Storage

Useful Output

Energy Source

Energy Loss as Heat


Pisa

Energy Trasformations in Energy Systems

Energy Storage

Useful Output

Energy Source

Energy Loss as Heat


Pisa

Energy Trasformations in Energy Systems

Energy Storage

Useful Output

Energy Source

Energy Loss as Heat


Pisa

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.


Pisa

Where does the entropy come from?


Pisa

.

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).


Oxidative phosphorylation

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.


Pisa

Mitochondria as generators of oxygen free radical species


Pisa

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.


Pisa

Multiple sites of replacement fibrosis in the noninfarcted viable left ventricular tissue

Diffuse interstitial fibrosis


Pisa

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.


Pisa

ISO-STROKE CURVE

LV EDV (ml)

EF,%

www.cardiodinamica.it


Pisa

ISO-STROKE CURVE

MVO2

Efficiency

www.cardiodinamica.it


Pisa

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


Pisa

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


Pisa

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.


Pisa

Granville Sewell: Appl Math Letts 2011.


Pisa

Entropy

Throughlungs and kidney

WORK

Energy

Entropy

Throughmuscolar work

ORGANIC FUELS, OXYGEN

BIOSPHERE

Carboncycle

Water and energy cycle

Nitrogen cycle


Pisa

Expiration

CO2 Trasport

CO2 Production

VCO2

VENTILATION

CIRCULATION

MUSCLE

VO2

Inspiration

ENTROPY

NEGATIVE ENTROPY

Life-driven anti-entropic processes

O2 Trasport

O2 Consumption


Pisa

"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."


Pisa

Thermodynamic Systems

THE HEART LIKE AN OVEN


Pisa

LEONARDO DA VINCI – Codice Arundel

The heart like an oven

Dissipative

OPEN

OPEN

THE HEART LIKE A DISSIPATIVE SYSTEM


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


Stay hungry

STAY HUNGRY

STAY FOOLISH …

Steve Jobs


Pisa

The Heart as a Toothpaste


Pisa

Dini FL. Future Cardiology 2011;7:347-356.


Pisa

m/sec

IVT

LVOT

VTI

Cardiac output

Blood pressure (mean)

3D LV mass


Pisa

100

80

60

Sensitivity

40

20

Ejection fraction

p=0.002

Power-to-LV mass

0

0

20

40

60

80

100

100-Specificity

Dini FL, et al. J Am Soc Echocardiogr 2010;23:1259-1265.


  • Login