Transcript The use of diuretics in acute heart failure: Evidence based

DIURETIC RESISTANCE IN HEART FAILURE:
Pathophysiology & Cases Discussion
Bambang Budi Siswanto
Prof MD, PhD, FIHA, FAsCC, FAPSC, FESC, FACC, FSCAI
Dept Cardiology and Vascular Medicine University Indonesia
Medical Research Unit & Medical Education Unit & Coordinator Collaboration FKUI
Email : [email protected]
Disclosure :
• This symposium is sponsored by Otsuka
• Speakers sponsored by Otsuka
* Median Total Hospital LOS in the Asia Pacific Region excludes Philippines
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MEDIAN TOTAL HOSPITAL LENGTH OF STAY BY COUNTRY
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Indonesia
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ADHERE- Indonesia vs. AP vs. Europe vs.US (2006)
Siswanto BB et.al, CVD Prevention and Control (2010) 5, 35-38
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* United States Most Recent 12 Months (04.01.05-03.31.06)
** United States Cumulative (01.01.01-03.31.06)
Lesson learned 2006-2009
Compared to the ADHERE Registry - US ® and EuroHeart
Survey II, the ADHERE ® International - APLA data
suggest:
1. A younger patient population than in the US and Europe
2. More patients exhibiting severe clinical signs and symptoms.
3. Higher rates of mechanical ventilation (compared to the US)
4. More frequent use of inotropic drugs
5. Underutilization of baseline heart failure medications such as
ACEI or ARB, beta blocker and low dose spironolactone
6. Higher rates of In-hospital mortality and readmission rate
RISK OF DEATH RELATED WITH NYHA CLASS & GFR
STAGE OF HEART FAILURE & THE TREATMENT
(Jessup M, Brozena S. N Engl J Med 2003; 348: 2007-18.)
(2013 ACCF/AHA Guideline for the Management of Heart Failure)
Case discussion on Advanced HF
•
A 44 years old male was admitted to Emergency Room
• increasing dyspnea at rest a week prior with edema & decreased urine pr
oduction..
•
•
History of recurrent admission with dilated cardiomyopathy,
Poor EF complicated with right pleura effusion, ascites, swollen anklean
d left ventricle thrombus
•
He was on poly pharmacies ( multiple drugs) after being discharged
and denied of non compliance ( before this admission )
1. furosemide 2x40mg mane
2. bisoprolol fumarate 1,25 mg mane
3. spironolactone 1x50mg mane
4. warfarin 1x1 mg nochte
5. ramipril 1x7.5mg nochte
RISK FACTORS for CAD
•
•
•
•
Hypertension (-)
Diabetes Melitus (-)
Smoking (-)
Dyslipidemia (-)
PHYSICAL EXAMINATION
20 May 2015
VITAL SIGNS
•
•
•
•
•
Consciousness : compos mentis
Blood Pressure : 70/50mmHg,
Heart Rate
: 100x/min/regular
Respiratory Rate: 24x/min,
O2 Saturation
: 98%
PHYSICAL EXAMINATION
• Conjunctiva was not pale nor anemic
• Jugular Venous Distended
• Chest
– Heart
1st and 2nd heart sound were normal, Pan Syst gr 3/6 at LSB
i.c.s. 5, radiated to axilla.
gallop (-)
– Lung
Vesicular with soft rales on the base of lung, wheezing (-)
• Abdomen
Liver was palpable 2 cm below processus xiphoideus,
Ascites (+)
• Extremities : Pitting Edema (+) on both sides
Supporting diagnostic :
• A-P CHEST X-RAY
CTR > 55%, aorta segment normal
pulmonal segment normal, downward apex, congestion (+),
infiltrate (-), right pleural effusion (+)
• ELECTROCARDIOGRAPHY
ST 116x/min, RAD, RVH, ST ↓in II, III, aVF, poor R wave progression V
1-V6
• ECHOCARDIOGRAPHY
EF 18 %, TAPSE 1.3 cm, Severe Global Hypokinetic
Moderate Mitral Regurgitation
Moderate Tricuspid Regurgitation
Moderate Pulmonary hypertension
Thrombus (+) at the apical LV
Hospitalized Heart Failure on NCVC
January – December 2012
250
212
200
150
133
130
122
Male
122
89 82
100
91
70 72
50
70
20
December
November
October
September
August
July
June
May
April
March
February
January
0
Total: 1243 patient
Female
67.
32.
9%
1%
Previous HF history
No HF history
Previous HF History (+)
Prior Hospitalization in PJNHK
30.3%
34.5%
35.2%
Etiology of Heart Failure at NCCHK 2012
Ischemic heart
Tachycardia related
Other, 8.2
cardiomyopathy,
0.2
disease
documented
HFPEF Syndrome,
by coronary
17.8
angiography,
20.2
Valve disease, 12.7
Ischemic heart
disease not
documented
Dilated
by coronary
Cardiomyopathy,
angiography;
3.4
37.6 %
Precipitating Factors for hospitalization in HF
Anemia
Renal Dysfunction
Non Compliance
Hypertension
Infection
Ventricular Arrythmia
Bradycardia
Atrial Fibrillation
Acute Coronary Syndromes
Myocardial Ischemia
Diuretic as Decongestive Therapy
No,
100
IV Nitrate
91.2
IV Diuretics Yes,
100
80
80
60
60
40
40
Yes,
20
8.8
0
No
Yes
89.5
No,
20
10.5
0
No
Yes
EVIDENCE BASE FOR THE USE OF DIURETICS IN ACUTE HEART FAILURE
Edema of the Gut, Edema of the Kidney
By Pressure Overload
Diuretic Resistance
• Related to Cardio-renal Syndrome or Worsening
Renal Function
– Often associated with renal insufficiency (acute and/or
chronic)
• Definitions vary
– Persistent edema despite adequate diuretic doses
– Diminished natriuretic response to repeated doses
– Daily furosemide doses > 80mg1
• Prevalence
– Chronic use of loop diuretic : 35%1
– Acute: unknown
1Neuberg GW, et al. Am Heart J 2002;144:31-8.
Mechanism of DU resistance
• Decrease drug bioavailability
• Reduced glomerular filtration rate
• Excessive sodium uptake in the proximal tubule and the loop
of Henle
• Renal adaptation
• Excessive sodium and water retention in the distal nephron
and collecting ducts
• Drug interaction
• Pseudoresistance
Resistance Etiology-based Strategies to Restoring DU Efficacy
•
Loop DU Pharmacodynamics
- Reduction in preload to the LV by diuresis & vasodilation
- Diuretic effect of Loop DU; conc.-dependent
1) the rate of urinary excretion
2) the natriuretic response after binding to the target receptor
- Loop DU’s D-R curve; sigmoidal pattern
►
ADHF pts require a higher drug conc. to achieve the DU threshold and have a diminished response to ceiling doses.
⇒Administer higher dose / Increase the frequency of administration
Journal of Cardiac Failure, Accepted Date: 22 May 2014
Resistance Etiology-based Strategies to Restoring DU Efficacy
•
Loop DU Pharmacology & Pharmacokinetics
- Absorption
- Metabolism
- Distribution
- Excretion
- 50% inactivated by renal
glucoronidation
- 50% secreted as parent
compound by OAT-1
system
Journal of Cardiac Failure, Accepted Date: 22 May 2014
OVERCOMING DIURETIC RESISTANCE
• Diuretic Strategies
- Sequential nephron blockade/
Multiple sites of diuretic MOA
- Renal Dose Dopamine
- Osmotic Diuretic
- Thiazides / Thiazides Like diuretic
- Aldosterone antagonis = MRA
Vasopressine Antagonist Aquaretics
. Non Diuretic Strategies = Expensive Devices
- Ultrafiltration : Neutral results
Bloods test results of Mr A, M, 40 yo
1 Haemoglobin
2 Leukocyte
13.2 g/dL
5870 /uL
3 Hematocrit
4 Thrombosis
5 GFR
39%
179,000 /uL
36
6 Serum Blood Glucose
7 Ureum
95 mg/dL
100 mg/dL
8 BUN
9 Creatinine
10 Sodium
47 mg/dL
2.02 mg/dL
126 mEq/dL
11 Potasium
12 Calcium total
13 Chloride
4.8 mEq/dL
2.35 mEq/dL
94 mEq/dL
Working DIAGNOSIS
• Acute Decompensated Heart Failure Wet and
Warm.
• Recurrent admission of Dilated Cardiomio
pathy with Left Ventricle Thrombus
• Right Pleural Effusion
• Moderate Mitral Regurgitation
• Acute Kidney Injury DD/ CKD St 3
M, 44 years
MANAGEMENT SUMMARY
Date
6/5
7/5
8/5
9/5
10/5
Post Samsca
Treatment
Natrium
127
-
-
137
-
141mmol/L
Furosemide
10mgkg of
Body Weight
(BW)
10mg/kg
of BW
25mg/kg
of BW
25mg/kg
of BW
25mg/kg
Of BW
per oral
Tolvaptan
-
15 mg
15 mg
15 mg
-
Input
1447
322
2244
2391
1148
-
Output
1500
50
4800
5400
5300
-
Fluid balance (-)
-53
+ 272
-2556
-3009
-4152
-
Dyspnea
+
++
↓
↓↓
↓↓
No Dyspnea
Body Weight
60kg
64 kg
-
Patient was
admitted in
with ADHF
Edema (+)
56.5 kg
Tolvaptan + furosemide drip
Serum sodium level was corrected,
Negative Fluid balance >>>, Body Weight
<<<,, General condition was improved
Post Tolvaptan
Treatment
Conclusion
• The initial evidence based management strategy suggested
that an initial “high dose” IV bolus injection continued with
moderate dose continuous infusion is likely to be more
successful than a slower approach.
• In cases of diuretic resistance, adding a thiazide or thiazide
like diuretic or K sparring diuretic, or spironolactone or
osmotic diuresis can enhance diuresis, but no Evidence
based. Close monitoring of fluid balance and Na & K is
mandatory. This strategy can not done in patients with
significant renal dysfunction.
• Low dose (renal dose) dopamine infusion can improve
the effectiveness of diuretic therapy, and help maintain
renal function, or increased BP but increased HR,
although the evidence base for this is limited.
• Tolvaptan is a new & the only aquaretic drug with
novel MOA by vasopressin antagonist pathway that
appropriate to treat diuretic resistance
• The infusion of Na Cl 0,3 % for correction of
Hyponatremia and Diuretic Resistance will lead to the
risk of Osmotic Demyelination Syndrome