Heart failure api

1. Prof. U. C. SAMAL
MD, FICC, FACC, FIACM, FIAE, FISE, FISC, FAPVS
Ex- Prof. Cardiology & Ex-HOD Medicine
Patna Medical College, Patna, Bihar
Past President, Indian College of Cardiology
Permanent & Chief Trustee, ICC-Heart Failure Foundation
National Convener Heart Failure Sub Specialty, CSI
Executive Member (National), Cardiological Society of India
President, CSI Bihar / Vice President, API Bihar 1
HEART FAILURE

2. Heart failure -- Epidemiology
Prevalence • > 2% - 3% overall; 10% - 20% at > 70 yrs
• European society of cardiology countries : > 15
milion patients with heart failure and increasing
Burden • Primary cause of 5% of hospital admissions
• Present in 10% of hospitalized patients
• 2% of national health expenditure [60% - 70% of cost
due to heart failure hospitalization]
• 40% of patients admitted to hospital with heart
failure are dead or readmitted within 1 yr
Mcmurray J J Et Al Eur Heart J 2013; 33 [14]: 1787-1847
Dickstein K Et Al Eur Heart J 2006; 29: 2388-2442
FinalPathwaysDisease

3. Total Population of India - 1.16 Billion (2009 Est)

4. Classification of Heart Failure
ACCF/AHA Stages of HF NYHA Functional Classification
A At high risk for HF but without
structural heart disease or symptoms
of HF.
None
B Structural heart disease but without
signs or symptoms of HF.
I No limitation of physical activity.
Ordinary physical activity does not
cause symptoms of HF.
C Structural heart disease with prior or
current symptoms of HF.
I No limitation of physical activity.
Ordinary physical activity does not
cause symptoms of HF.
II Slight limitation of physical activity.
Comfortable at rest, but ordinary
physical activity results in symptoms
of HF.
III Marked limitation of physical activity.
Comfortable at rest, but less than
ordinary activity causes symptoms of
HF.
IV Unable to carry on any physical
activity without symptoms of HF, or
symptoms of HF at rest.
D Refractory HF requiring specialized
interventions.

5. Stages, Phenotypes and Treatment of HF
2013 ACCF/AHA Guideline for the Management of Heart Failure

7. • diuretics
• ultrafiltration
Vasodilators
• nitroglycerin
• nesiritide
• nitroprusside
INOTROPES
• dobutamine
• dopamine
• levosimendan
• nitroprusside
Fluid retention or redistribution ? Pulmoedema??
“dry out”
“warm up & “dry out”
Assessment of hemodynamic profile : therapeutic implications
Adapted from Stevenson L W, Eur Heart j
7
SIGNS/SYMPTOMS
CONGESTION:
DYSPNOEA/( EXERTION /REST)
ORTHOPNEA
PNH
JV DISTENSION
RALES (uncommon in chronic cases)
LOUD P2
INCREASING S3
PEDAL OEDEMA
ABDOMINOJUGULAR REFLUX
ASCITES
VALSALVA SQUARE WAVE
POSSIBLE EVIDENCE OF LOW PERFUSION:
SLEEPY / OBTUNDED
COOL EXTREMITIES
NARROW PULSE PRESSURE
HYPOTENSION WITH ACE INHIBITOR
LOW SERUM SODIUM
AKI / RENAL DYSFUNCTION
ELEVATED LFTs
PULSUS ALTERNANS
67%
28%5%
67%
28%5%
ACE-I / ARB/
BB/ MRA
MM/ MN

9. Linking Short- term intervention with long-term benefit:
What is needed?
Better understanding of Acute Heart Failure pathophysiology
MORTALITY
• Myocardial injury [Tn
release]
• Renal dysfunction [CRS]
• Liver dysfunction
PREVENTION OF END-
ORGAN DAMAGE
Congestion
Viable but
dysfunctional
myocardium
Neurohormonal
& inflammatory
activation
Mechanisms which
can be targeted
Metabolic
factors
Hemodynamic
deterioration
[↑LVFP,↓ CO, ↓ PERFUSION]
Vascular resistance
/stiffness ↑
ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012 Reviewed by Ponikowski

10. Diagnosis of HF in untreated patients with symptoms
suggestive of HF using natriuretic peptides
Clinical examination
ECG, Chest X-ray
Echocardiography
Natriuretic peptides
BNP < 100pg/ml
NT-proBNP <
400pg/ml
BNP < 100-400 pg/ml
NT-proBNP 400-2000
pg/ml
BNP > 400 pg/ml
NT-proBNP > 2000
pg/ml
Chronic HF likely Uncertain diagnosis Chronic HF likely

11. “HF management ‘guided’ by natriuretic peptides would be superior
to standard HF therapy alone.”
11
van Kimmenade, R. R. & Januzzi, J. L. Jr. Clin. Chem. 58, 127–138 (2012).

12. 12
Clinical Value of diagnostic testing modality : BNP/ NT-BNP
Adapted and reprinted with permission from Januzzi JL,Camargo CA, Anwarudding S ,et al. The N-terminal Pro-
BNP investigation of Dyspnea in the Emergency Department (PRIDE) Study. Am J Cardiol 2005;95:948-954

13. Effect of cardiac and extra cardiac
parameters on BNP and NT-proBNP
Raised in
Cardiac Factors
Lower Ejection Fraction, Larger Left ventricular mass, Atrial size, Atrial
fibrillation, Coronary heart disease , Valvular heart disease, Acute coronary
syndrome, Cor pulmonale (acute/ chronic), COLD (right heart strain)
Extra Cardiac factors
Age, Female gender, Low glomerular filtration, Hematocrit low, Hyperthyroidism,
Cushing syndrome. Liver cirrhosis with ascites, paraneoplastic syndrome,
Subarachnoidal bleeding, Sepsis, Rheumatic diseases, Stroke
Reduced in
Extra Cardiac factors
Obesity,ACE-I/ARB, Diuretics, Hypothyroidsm, Primary hyperaldosteronism
Biomarkers in medicine 3.5 (Oct 2009) p465
13

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“For example, over the past 2 decades, the once-held
view of chronic HF as a syndrome of disordered
hemodynamics and fluid balance caused by alterations
in the structure of the heart has been succeeded by a
view of the disease that involves molecular pathways in
disarray. Chronic HF is now seen as a systemic illness
that involves interplay between myocardial factors,
systemic inflammation, renal dysfunction, and
neurohormonal activation. Our assessment and
treatment of patients with chronic HF has, thus,
progressed from a focus on improving hemodynamics
to measuring and modifying the maladaptive molecular
processes that contribute to progression of disease”
Braunwald, E. N. Engl. J. Med. 358, 2148–2159 (2008).

15. Neurohormones
Norepinephrine
Renin
Angiotensin II
Copeptin
Endothelin
Vascular system
Homocysteine
Adhesion molecules
(ICAM, P-selectin)
Endothelin
Adiponectin
C-type natriuretic
peptide
Inflammation
C-reactive protein
sST2
Tumor necrosis factor
FAS (APO-1)
GDF-15
Pentraxin 3
Adipokines
Cytokines
Procalcitonin
Osteoprotegerin
Myocardial stress
Natriuretic
peptides
Mid-regional
pro-adrenomedullin
Neuregulin
sST2
Myocardial injury
Cardiac troponins
High sensitivity cardiac troponins
Myosin light-chain kinase 1
Heart-type fatty acid binding protein
Pentraxin 3
Matrix and cellular
remodeling
Galectin-3
sST2
GDF-15
MMPs
TIMPs
Collagen propeptides
Osteopontin
Cardio-renal syndrome
Creatinine
Cystatin C
NGAL
ß-Trace protein
Oxidative stress
Oxidized LDL
Myeloperoxidase
Urinary biopyrrins
Urinary and plasma
isoprostanes
Plasma malondialdehyde
HF as a systemic illness.
15
Nature Review Cardiology
Vol.9 June 12 pg 349

16. “HF-CBS-SRS”
Quantitative results in~ 15 minutes! EDTA Whole Blood , No Centrifugation
Anywhere, anytime, in time
Point of Care System for rapid, accurate
results
• Easy
• Portable
• Reliable Results in about minutes
Fluorescence Sandwich
immunoassay
Test Normal Range
CKMB ng/mL (0.0 - 4.3)
MYO ng/mL (0.0 – 107)
TNI ng/mL (0.00 - 0.40)
BNP pg/mL (0.00 - 100)
DDIM ng/mL (0.0 - 400)
NGAL* ng/mL (0-149)
PANEL OF SOB TRIAGE/
AMI/ AKI
15
6 Biomarkers 750 +750 bucks
* Galectin3/BNP+NGAL being
uploaded to the test platform
16

17. SOB TRIAGE METER
PLATFORM
Parameters Normal
Range
Cost(Rs.) Timing
CKMB 0.0-4.3
SOB
PANEL
Rs. 750
10-15 Min
MYO 0.0-107
TNI 0.00-0.40
BNP 0.00-100
DDIM 0.1-400
NAGAL 0-149 Rs. 850 15 Min

18. Triage® Meter: Three Simple Steps
1. Add whole blood to Test Device
2. Insert Test Device into Meter
3. Read results

19. Intelligent Nephelometry Technology
Smart Card Calibration
Economic 10 Parameter Assay Panel
ser- friendly 3 Step Assay Procedure
No Sample dilution
Test Normal Range
ASO I/mL (50 - 1000)
CRP mg/L (0.5 - 320)
RF I/mL (10-120)
HbA1c % (3-13%)
IgE I/mL (1-1000)
MICROALBMIN mg/L (5-200)
Lp(a) Mg/dl (1-100)
CYSTATIN C mg/L (0.0-10)
FERRITIN I/mL (1-1000)
D-DIMER ng/mL
REPORT OF MISPA PANEL SERUM / URINE
“HF-CBS-SRS” Measures
ACR
&
Routine rine
Parameters
• 95% Correlation with conventional immunoturbidimetric test
• Analyze spot rine sample
• Works on batteries or power cable
• Provides Printed report
“15/23 Minutes Exercise”
10 Biomarkers 1000
Bucks
19

20. Agappe Mispa carries
ISO 13485:2003 and CE marking; GMP and
FDA compliant ISO 9001: 2008 certified

21. 1st Ht Consult

22. Parameters Pack size Test Range Normal Range Price Timing
ASO 30 Test 50-1000 IU/ml 0-200 IU/ml 62 5 Min
CRP 30 Test 0.5-250 mg/L 0.000-6.000mg/L 51 5Min
RF 30 TEST 10-120 IU/ml 0.000-20.000/IU/ml 46 6 min
CYSTATIN C 30 TEST 0.1-10 mg/L 0.000-1.149 mg/L 161 6 min
HbA1C 30 TEST 3-13% 4.000-6.000 % 160 7 min
D-DIMER 30 TEST 0-400 ng/mL 0.000-400 ng/ml 160 7 min
IgE 30 TEST 0-1000 IU/mL 0.000-400 IU/mL 180 6 min
FERRITIN 30 TEST 0-1000 ng/mL 0.000-230 ng/mL 200 6 min
Lp(a) 30 TEST 1-100 mg/dL 0-30 mg/dL 180 7 min
MICROALBUMIN 30 TEST 5-200 mg/L 0.000-25.000 mg/L 101 5 min
Intelligent Double Chanel Nephlometry Technology

23. Possible future strategies for biomarker-guided
therapies in chronic HF. 2013-14 Optimism :
Ahmad T et al Nat. Rev. Cardiol.9,347-359(2012)
23

24. Cumulative benefits of medical therapy on mortality. Adapted, with permission, from Fonarow GC, et al.
Potential impact of optimal implementation of evidence-based heart failure therapies on mortality. Am
Heart J 2011;161:1024-30.
Heart Failure Therapies
Beta-blocker
Beta-blocker +
ACEI/ARB
Beta-blocker +
ACEI/ARB+ ICD
Beta-blocker +
ACEI/ARB+ ICD+
HF education
Beta-blocker +
ACEI/ARB+ ICD+
HF education+
anticoagulation for
AF
Beta-blocker +
ACEI/ARB+ ICD+
HF education+
anticoagulation
for AF +CRT
ChangeinOddsof24-MonthMortality(%)
-39%
[-28% to -49%]
P < 0.0001
-63%
[-54% to -71%]
P < 0.0001 -76%
[-68% to -81%]
P < 0.0001
-81%
[-75% to -86%]
P < 0.0001
-83%
[-77% to -88%]
P < 0.0001
-81%
[-72% to -87%]
P < 0.0001

25. Number needed to treat for mortality
25
Guideline
recommended
therapy
Relative risk
reduction in
mortality
Number needed
to treat for
mortality
Number
needed to treat
for mortality
[ standardized
to 36 mths]
Relative risk
reduction in HF
hospitalisations
ACEI / ARB 17% 22 over 42 mths 26 31%
Beta blocker 34% 28 over 12 mths 9 41%
Aldosterone
antagonist
30% 9 over 24 months 6 35%
Hydralazine /
nitrate
43% 25 over 10 mths 7 33%
CRT 36% 12 over 24 mths 8 52%
ICD 23% 14 over 60 mths 23 NA
Reproduced with permission from Fonarow GC et al Am Heart j 2011; 161: 1024-30

26. Milton Packer 2008 JCF
• … Yet, despite substantial advances in our understanding and
management of heart failure, we have had
• few successes and many failures.
• Nearly 1,000 new drugs and devices have been developed for
the treatment of heart failure duringthe past 20 years, but only
9 have received regulatory approval and are being used in the
clinical setting.
• Most of our efforts to correct fluid retention, stimulate the
inotropic state of the heart, and modulate neurohormonal
systems have not predictably improved the condition of
patients with HF…

27. “Poly Client Challenge”
• Poly co-morbidities
• Poly – pharmacy
• Poly - side effects
• Poly – healthcare providers
• Poly - clinics
• Poly-labs / investigation
• POLY – CONFUSION…….
END RESULT You must have patience to find
little pink hope!!!
Yes , a Pandora’s box !
but
Heart Failure Care is always rewarding

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31. HF----
We are all equals but some are better equals
Heart Failurists are less equal

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