Heart failure api

Prof. U. C. SAMALMD, FICC, FACC, FIACM, FIAE, FISE, FISC, FAPVSEx- Prof. Cardiology & Ex-HOD Medicine Patna Medical College, Patna, BiharPast President, Indian College of CardiologyPermanent & Chief Trustee, ICC-Heart Failure FoundationNational Convener Heart Failure Sub Specialty, CSIExecutive Member (National), Cardiological Society of IndiaPresident, CSI Bihar / Vice President, API Bihar 1

HEART FAILURE

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

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Total Population of India - 1.16 Billion (2009 Est)

Classification of Heart FailureACCF/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.

Stages, Phenotypes and Treatment of HF

STAGE AAt high risk for HF but without structural heart

disease or symptoms of HF

STAGE BStructural heart disease

but without signs or symptoms of HF

THERAPYGoals· Control symptoms· Improve HRQOL· Prevent hospitalization· Prevent mortality

Strategies· Identification of comorbidities

Treatment· Diuresis to relieve symptoms

of congestion· Follow guideline driven

indications for comorbidities, e.g., HTN, AF, CAD, DM

· Revascularization or valvular surgery as appropriate

STAGE CStructural heart disease

with prior or current symptoms of HF

THERAPYGoals· Control symptoms· Patient education· Prevent hospitalization· Prevent mortality

Drugs for routine use· Diuretics for fluid retention· ACEI or ARB· Beta blockers· Aldosterone antagonists

Drugs for use in selected patients· Hydralazine/isosorbide dinitrate· ACEI and ARB· Digoxin

In selected patients· CRT· ICD· Revascularization or valvular

surgery as appropriate

STAGE DRefractory HF

THERAPYGoals· Prevent HF symptoms· Prevent further cardiac

remodeling

Drugs· ACEI or ARB as

appropriate · Beta blockers as

appropriate

In selected patients· ICD· Revascularization or

valvular surgery as appropriate

e.g., Patients with:· Known structural heart disease and· HF signs and symptoms

HFpEF HFrEF

THERAPYGoals· Heart healthy lifestyle· Prevent vascular,

coronary disease· Prevent LV structural

abnormalities

Drugs· ACEI or ARB in

appropriate patients for vascular disease or DM

· Statins as appropriate

THERAPYGoals· Control symptoms· Improve HRQOL· Reduce hospital

readmissions· Establish patient’s end-

of-life goals

Options· Advanced care

measures· Heart transplant· Chronic inotropes· Temporary or permanent

MCS· Experimental surgery or

drugs· Palliative care and

hospice· ICD deactivation

Refractory symptoms of HF at rest, despite GDMT

At Risk for Heart Failure Heart Failure

e.g., Patients with:· Marked HF symptoms at

rest · Recurrent hospitalizations

despite GDMT

e.g., Patients with:· Previous MI· LV remodeling including

LVH and low EF· Asymptomatic valvular

disease

e.g., Patients with:· HTN· Atherosclerotic disease· DM· Obesity· Metabolic syndrome orPatients· Using cardiotoxins· With family history of

cardiomyopathy

Development of symptoms of HF

Structural heart disease

2013 ACCF/AHA Guideline for the Management of Heart Failure

• 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

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SIGNS/SYMPTOMS CONGESTION:DYSPNOEA/( EXERTION /REST)ORTHOPNEA PNHJV DISTENSIONRALES (uncommon in chronic cases)LOUD P2 INCREASING S3PEDAL OEDEMAABDOMINOJUGULAR REFLUXASCITESVALSALVA SQUARE WAVE

POSSIBLE EVIDENCE OF LOW PERFUSION:SLEEPY / OBTUNDEDCOOL EXTREMITIESNARROW PULSE PRESSUREHYPOTENSION WITH ACE INHIBITORLOW SERUM SODIUMAKI / RENAL DYSFUNCTIONELEVATED LFTsPULSUS ALTERNANS

67%

28%5%

67%

28%5%

ACE-I / ARB/ BB/ MRA MM/ MN

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

activationMechanisms which

can be targetedMetabolic

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

Diagnosis of HF in untreated patients with symptoms suggestive of HF using natriuretic peptides

Clinical examinationECG, Chest X-rayEchocardiography

Natriuretic peptides

BNP < 100pg/mlNT-proBNP <

400pg/ml

BNP < 100-400 pg/mlNT-proBNP 400-2000

pg/ml

BNP > 400 pg/mlNT-proBNP > 2000

pg/ml

Chronic HF likely Uncertain diagnosis Chronic HF likely

“HF management ‘guided’ by natriuretic peptides would be superior to standard HF therapy alone.”

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van Kimmenade, R. R. & Januzzi, J. L. Jr. Clin. Chem. 58, 127–138 (2012).

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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

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 factorsAge, 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) p46513

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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).

NeurohormonesNorepinephrine

ReninAngiotensin II

CopeptinEndothelin

Vascular systemHomocysteine

Adhesion molecules(ICAM, P-selectin)

EndothelinAdiponectin

C-type natriuretic peptide

InflammationC-reactive protein

sST2Tumor necrosis factor

FAS (APO-1)GDF-15

Pentraxin 3AdipokinesCytokines

ProcalcitoninOsteoprotegerin

Myocardial stressNatriureticpeptides

Mid-regional pro-adrenomedullin

NeuregulinsST2

Myocardial injuryCardiac troponins

High sensitivity cardiac troponinsMyosin light-chain kinase 1

Heart-type fatty acid binding proteinPentraxin 3

Matrix and cellularremodelingGalectin-3

sST2GDF-15MMPsTIMPs

Collagen propeptidesOsteopontin

Cardio-renal syndromeCreatinineCystatin C

NGALß-Trace protein

Oxidative stressOxidized LDL

MyeloperoxidaseUrinary biopyrrins

Urinary and plasma isoprostanes

Plasma malondialdehyde

HF as a systemic illness.

15Nature Review Cardiology Vol.9 June 12 pg 349

“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 RangeCKMB 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

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6 Biomarkers 750 +750 bucks

* Galectin3/BNP+NGAL being uploaded to the test platform

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SOB TRIAGE METER PLATFORM

Parameters Normal Range

Cost(Rs.) Timing

CKMB 0.0-4.3SOB

PANEL

Rs. 750

10-15 MinMYO 0.0-107

TNI 0.00-0.40

BNP 0.00-100

DDIM 0.1-400

NAGAL 0-149 Rs. 850 15 Min

Triage® Meter: Three Simple Steps

1. Add whole blood to Test Device

2. Insert Test Device into Meter

3. Read results

Intelligent Nephelometry TechnologySmart Card CalibrationEconomic 10 Parameter Assay Panelser- friendly 3 Step Assay ProcedureNo 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” MeasuresACR

&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

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

1st Ht Consult

Parameters Pack size Test Range Normal Range Price TimingASO 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

Possible future strategies for biomarker-guided therapies in chronic HF. 2013-14 Optimism :

Ahmad T et al Nat. Rev. Cardiol.9,347-359(2012)

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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

Chan

ge in

Odd

s of

24-

Mon

th M

orta

lity

(%)

-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

Number needed to treat for mortality

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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

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…

“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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HF----

We are all equals but some are better equalsHeart Failurists are less equal

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