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]
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
• ELECTROCARDIOGRAPHYST 116x/min, RAD, RVH, ST ↓in II, III, aVF, poor R wave pro-gression V1-V6
• ECHOCARDIOGRAPHYEF 18 %, TAPSE 1.3 cm, Severe Global HypokineticModerate Mitral RegurgitationModerate Tricuspid RegurgitationModerate Pulmonary hypertension Thrombus (+) at the apical LV
Hospitalized Heart Failure on NCVC
January – December 2012
Janu
ary
Febr
uary
Mar
chAp
rilMay
June Ju
ly
Augu
st
Sept
embe
r
Octob
er
Novem
ber
Decem
ber
0
50
100
150
200
250
122
89 82
130
212
133
20
70 72
122
9170
Total: 1243 patient
67.9%
32.1%
MaleFemale
Previous HF history
30.3%
35.2%
34.5%
No HF history Previous HF History (+)Prior Hospitalization in PJNHK
Etiology of Heart Failure at NCCHK 2012
Ischemic heart disease docu-
mented by coronary an-
giography; 20.2
Ischemic heart disease
not docu-mented by
coronary an-giography;
37.6 %
Dilated Car-diomyopathy;
3.4
Valve disease; 12.7
Tachycardia re-lated car-
diomyopathy; 0.2
HFPEF Syn-drome; 17.8
Other; 8.2
Precipitating Factors for hospitalization in HF
Myocardial Ischemia
Acute Coronary Syndromes
Atrial Fibrillation
Bradycardia
Ventricular Arrythmia
Infection
Hypertension
Non Compliance
Renal Dysfunction
Anemia
Diuretic as Decongestive Ther-apy
No Yes0
102030405060708090
100 No; 91.2
Yes; 8.8
IV Nitrate
No Yes0
102030405060708090
100
No; 10.5
Yes; 89.5
IV Diuretics
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
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
• 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
Resistance Etiology-based Strategies to Restoring DU Efficacy
► 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
V2 Receptor Mediates Hyponatremia and Volume Overload:Role of Vaptans
V2RAVP
HypoNa+
Congestion,
edema
H2O
VaptansSIADH
Cirrhosis/Ascites
HeartFailure
42
Tolvaptan Site of Action
Verbalis JG, et al. Am J Med 2007;120(11 suppl 1):S1-S21. Knoers NVAM. N Engl J Med. 2005;352(18):1847-50.
44
Aquaresis is More Than Free Water Clearance
44
Aquaretic effect without increasing urinary electrolyte excretion
Potential role of Tolvaptan based on clinicaland preclinical studies
Maintains its aquaretic effect in combination with saluretic drugs
Does not affect neurohormonal factors, renal function, or hemodynamic parameters, such as blood pressure and heart rate
Hori M. Cardiovasc Drugs Ther. 2011;25(suppl 1):S1-S4.
45
Effect of Tolvaptan on Urine Volume
Udelson et al. J Am Coll Cardiol 2008;52;1540-1545.
Mean change from baseline in urine volume in the first 8 h after treatment administration
300
-2000 82 3 4 5 6 7
200
100
0
-100
1
Placebo Samsca® 15 mg Samsca® 30 mg Samsca® 60 mg
Mea
n C
hang
e F
rom
Bas
elin
e In
Urin
e V
olun
e (m
L)
Time (hrs)
A dose-dependent increase in urine output was observed among the tolvaptan-treated groups.
Bloods test results of Mr A, M, 40 yo1 Haemoglobin 13.2 g/dL
2 Leukocyte 5870 /uL
3 Hematocrit 39%
4 Thrombosis 179,000 /uL
5 GFR 36
6 Serum Blood Glucose 95 mg/dL
7 Ureum 100 mg/dL
8 BUN 47 mg/dL
9 Creatinine 2.02 mg/dL
10 Sodium 126 mEq/dL
11 Potasium 4.8 mEq/dL
12 Calcium total 2.35 mEq/dL
13 Chloride 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
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/kgof BW
25mg/kgof 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 - 56.5 kg
MANAGEMENT SUMMARY
M, 44 years
Serum sodium level was corrected, Negative Fluid balance >>>, Body
Weight <<<,, General condition was improved
Tolvaptan + furosemide drip
Post Tolvaptan Treatment Patient was
admitted in with ADHF Edema (+)
Conclusion• The initial evidence based management strategy sug-
gested that an initial “high dose” IV bolus injection con-tinued with moderate dose continuous infusion is likely to be more successful than a slower approach.
• In cases of diuretic resistance, adding a thiazide or thi-azide like diuretic or K sparring diuretic, or spironolac-tone 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 pa-tients with significant renal dysfunction.
• Low dose (renal dose) dopamine infusion can im-prove 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 Hy-ponatremia and Diuretic Resistance will lead to the risk of Osmotic Demyelination Syndrome