Download hartfalen

hartfalen
Mortaliteit door chronisch hartfalen > 70% op 8 jaar.
Harttransplant is de enige mogelijke genezing, maar < 5%
van deze patiënten komen daarvoor in aanmerking.
Palliatieve zorgen wordt bij end-stage hartfalen erg
belangrijk.
Symptomen/klachten van deze patiënten in eindfase (laatste
weken): angst, pijn, dyspnoe, oedemen, vermoeidheid,
depressie, anorexie, incontinentie, constipatie
Farmacotherapie van palliatieve zorgen in deze fase omvat
O2, anxiolytica, morfine of andere narcotica, en
antidepressiva, diuretica, digoxin, ACE inhibitoren, ARBs, en
ß-blockers.
• Small doses of morphine sulfate, such as 2-3 mg taken
orally, may relieve dyspnea and pain. Doses may be
titrated upwards as needed.
Drug Therapy Recommendations for Chronic HF from
the 2005 ACC/AHA Guidelines
Summary
• the importance of
– risk factor modification
– early detection
– therapies proven to prevent and/or reduce morbidity
and mortality.
• HF cannot be cured with drug therapy  lifelong
follow-up and patient education are needed to
promote adherence to diet and medications.
digoxin
• Sinusritme en HF:
-geen impact op mortaliteit
-minder HF hospitalisaties 30% (p < 0.001)
• goede keuze bij VKF en HF (CCB en BB
in voldoende dosis vaak niet verdragen)
• Cave hypokaliëmie
• Cave nauw therapeutisch venster en
interacties
Incidence of Death or Severe Congestive Heart Failure during Six Weeks of Treatment with
Zofenopril or Placebo in Patients with Acute Myocardial Infarction
Ambrosioni E et al. N Engl J Med 1995;332:80-85
Cumulative Mortality during One Year of Follow-up among Patients with Acute Myocardial
Infarction Treated for Six Weeks with Zofenopril or Placebo
Ambrosioni E et al. N Engl J Med 1995;332:80-85
Cumulative Incidence of Death from All Causes after Six Weeks of Treatment with Zofenopril or
Placebo, Regardless of Whether There Was Prior Congestive Heart Failure
Ambrosioni E et al. N Engl J Med 1995;332:80-85
β blockers in heart failure
Potential mechanisms and benefits of β
blockers:
improved left ventricular function;
reduced sympathetic tone; improved
autonomic nervous system balance;
up regulation of β adrenergic receptors;
reduction in arrhythmias, ischaemia,
further infarction, myocardial fibrosis,
and apoptosis
Antithrombotic treatment
• In patients with chronic heart failure the incidence of
stroke and thromboembolism is significantly higher in the
presence of atrial and left ventricular dilatation,
particularly in severe left ventricular dysfunction.
Nevertheless, there is conflicting evidence of benefit
from routine treatment of patients with heart failure who
are in sinus rhythm with antithrombotic treatment,
although anticoagulation should be considered in the
presence of mobile ventricular thrombus, atrial
fibrillation, and severe cardiac impairment. Large scale,
prospective RCT of antithrombotic treatment in heart
failure are in progress, such as the WATCH study (a trial
of warfarin and antiplatelet therapy); the full results are
awaited with interest.
• The combination of atrial fibrillation and heart failure (or
evidence of left ventricular systolic dysfunction on
echocardiography) is associated with a particularly high
risk of thromboembolism, which is reduced by long term
treatment with warfarin.
Chronic heart failure and atrial fibrillation
• Restoration and long term maintenance of sinus
rhythm is less successful in the presence of
severe structural heart disease, particularly
when the atrial fibrillation is longstanding. In
patients with a deterioration in symptoms that is
associated with recent onset atrial fibrillation,
treatment with amiodarone increases the long
term success rate of cardioversion. Digoxin is
otherwise appropriate for controlling ventricular
rate in most patients with heart failure and
chronic atrial fibrillation, with the addition of
amiodarone in resistant cases.
diuretica
•
•
The guidelines note that periodic weight and symptom assessment should direct
diuretic dosage adjustment, based on the patient's fluid status.
In a nurse-driven telephone follow-up program, recently discharged HF patients
were contacted at least weekly. Nurses assessed patients for symptoms of HF
exacerbation and adjusted diuretic doses as appropriate. After one year, this
intervention resulted in a 30% reduction in emergency department visits (p =
0.029) and readmissions (p = 0.045).[45] In another study, a patient-driven
sliding-scale diuretic protocol in patients with NYHA Class II-IV HF resulted in a
90% reduction in emergency department visits (p = 0.015).[46] Diuretic dose
adjustment was based on a 6 point questionnaire that evaluated signs (daily
weights) and symptoms (dyspnea, peripheral edema) of HF. These data suggest
that a flexible dosing strategy could enhance diuretic effectiveness.The
relationship between diuretic use and the efficacy and safety of other HF
therapies is also important. Symptoms of volume overload can arise upon
initiation or dose escalation of a ß-blocker. Some ß-blocker clinical trials
managed this complication by increasing the diuretic dose to regain a euvolemic
state and improve tolerance of the increased ß-blocker dose.[40,43] Diureticinduced volume depletion can negatively impact titration of both ACE inhibitors
and ß-blockers by increasing the risk of hypotension. In the absence of fluid
overload, diuretic dosage reduction should be considered.
Cox-inhibitoren en HF
• Cyclooxygenase (COX) inhibitors (both COX-2 selective
and nonselective) can cause fluid retention and
congestive symptoms, which may attenuate diuretic
efficacy.
• Thus, these agents should be used cautiously or avoided
entirely in HF patients. The renal effects of COX
inhibitors, along with diuretic-associated volume
depletion, may result in additive risks of renal
dysfunction.
diuretica en HF
Diuretic resistance may develop in
-patients taking COX inhibitors
-in those with significant renal impairment or
excess sodium intake
Angor
Met dank aan Professor Dr. Luc Hondeghem
Definitie
Behoefte > Toevoer = Angor
accumulatie metabolieten
zuurstof tekort
Behandeling
Behoefte > Toevoer = Angor
Behoefte
Stress=wandspanning
• volume van ventrikel R2
• druk in ventrikel
• wanddikte
Hartfrequentie
Contractiliteit
Toevoer
 Bloeddruk (perfusiedruk)
 Diastoleduur
 Diameter (weerstand)
Gladde spier
Ca++
i
Ca++-calmodulin
b-receptor
c-AMP
NO
c-GMP
MLCK.PO 4
Myosin-LC-PO4
actin
Contractie
Myosin-LC
MLCK *
actin
Relaxatie
200 ml
100 ml
100 ml
110 ml
10 ml
100 ml
200 ml
110 ml
Dilatatie
10 ml
100 ml
5 ml
195 ml
STEAL
200 ml
110 ml
Dilatatie
10 ml
100 ml
5 ml
195 ml
Angor
klassieke (atherosclerose) .... behoefte
vasospastische (variant, Prinz-metal).
vasodilatatie
onstabiele (dreigend infarct)
Behandeling
Nitraten
b-blokkers
Calciumkanaalblokkers
Behoefte
(
)
Toevoer
Nitraten
nitroglycerine (sublinguaal, oraal, pleister/zalf)
relaxatie (vooral veneus)
... verminderde input ... output
kleiner hart, lagere druk
maar, tachycardie (reflex)
b-blokkers
verhoogde contractiliteit
Opgepast
vers, in glazen flesje en alleen!
orthostatische hypotensie
pulserende hoofdpijn
Monday disease (verminderde tolerantie)
Sunday disease (afhankelijkheid)
 Amylnitriet inhalatie
• Arteriële vasodilatie
• Venoconstriction (reflex)
•Corpus cavernosum
++
Ca -kanaal
blokkers
Phenylalkylamines (Verapamil)
Dihydropyridines (Nifedipine)
Benzothiazepines (Diltiazem)
Selectivity
++
Ca -Kanaal
+
+
+
+
+
N
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
Inactivation
Activation
H2N
HOOC
D+
V-
Weefselspecificiteit
Receptor operated
T-
L-type (voltage operated)
++
Ca
N
Relaxatie
 bloedvaten (N,D,V)
• vooral arteriolen (oedeem vnl. door
extravasatie)
• minder venen (geen orthostatische
hypotensie)
 hart (D,V) (N heeft al perifere effecten bij
dosis die nog geen cardiaal effect heeft)
• SA, AVB, CHF
 skeletspieren 0
 bronchi, GI (constipatie)
Angor
vasodilatatie ... verlaagde bloeddruk
contractiliteit
hartfrequentie ( N, ~ D, V)
coronaire spasmen (vasosp. angor)
angor
acute aanval
Organische
nitraten
CCB
β-blockers
onderhoudstherapie
+
+
(+)
+
-
+
Eerste (thuis)behandeling bij klinisch vermoeden
van acuut myocardinfarct:
• 300 mg (snel resorbeerbaar) ASA po
• nitraten SL (niet teveel)
• morfine iv of sc (niet im)
ALLHAT
Cumulative Event Rates for All-Cause
Mortality by ALLHAT Treatment Group
.3
Cumulative Mortality Rate
.25
HR (95% CI)
p value
A/C
0.96 (0.89-1.02)
0.20
L/C
1.00 (0.94-1.08)
0.90
.2
Chlorthalidone
Amlodipine
Lisinopril
.15
.1
.05
0
0
Number at risk:
Chlor
15,255
Amlo
9,048
Lisin
9,054
1
14,933
8,847
8,853
2
14,564
8,654
8,612
3
4
Years to Death
14,077
8,391
8,318
12,480
7,442
7,382
5
7.185
4,312
4,304
6
3,523
2,101
2,121
7
4288
217
144
ALLHAT
Cumulative Event Rates for All-Cause
Mortality by ALLHAT Treatment Group
.3
Cumulative Mortality Rate
.25
HR (95% CI)
p value
A/C
0.96 (0.89-1.02)
0.20
L/C
1.00 (0.94-1.08)
0.90
.2
Chlorthalidone
Amlodipine
Lisinopril
.15
.1
.05
0
0
Number at risk:
Chlor
15,255
Amlo
9,048
Lisin
9,054
1
14,933
8,847
8,853
2
14,564
8,654
8,612
3
4
Years to Death
14,077
8,391
8,318
12,480
7,442
7,382
5
7.185
4,312
4,304
6
3,523
2,101
2,121
7
4288
217
144