How to strengthen your heart muscle (failing heart)? Daniel Pella, MD, PhD.

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 !