cardiac investigation in heart failure

Cardiac Investigation in Cardiac Investigation in Heart FailureHeart Failure

What Internist Needs to What Internist Needs to knowknow

Sarinya Puwanant, MD, FASESarinya Puwanant, MD, FASE

Evaluation /InvestigationEvaluation /Investigation

How do I assess CAD in HF ?How do I assess CAD in HF ? When should I do endomyocardial biopsy ?When should I do endomyocardial biopsy ? When should I order BNP?When should I order BNP? When shouldWhen should I screen for rare disease and I screen for rare disease and

comorbidities?comorbidities? When should I get metabolic stress testing ?When should I get metabolic stress testing ? When should I use echo for guiding management?When should I use echo for guiding management? When should I place CRT/ICD?When should I place CRT/ICD?

Assessment of CAD in HFAssessment of CAD in HF

Is the patient a potential Is the patient a potential revascularization candidate?revascularization candidate?

Recommendations linked to proof Recommendations linked to proof that revasc alters outcomes.that revasc alters outcomes.

ESTPerfusionStress Echo

Get Angiogram FirstGet Angiogram First

Angina (I)Angina (I) Atypical Chest Pain (IIa)Atypical Chest Pain (IIa) Known CAD + No chest pain (IIa)Known CAD + No chest pain (IIa) Suspected CAD with Chest pain (IIa)Suspected CAD with Chest pain (IIa)

Stress Test, Viability, Stress Test, Viability, Perfusion StudyPerfusion Study

Known CAD (extent) (IIa)Known CAD (extent) (IIa) Diagnostic CAD (IIb)Diagnostic CAD (IIb)

Spotty DiseaseSpotty Disease Sensitivity 50%Sensitivity 50% False negative 40%False negative 40%

No specific Rx even immunosuppressive Rx No specific Rx even immunosuppressive Rx does not improved outcomesdoes not improved outcomes

Giant Cell Myocarditis Giant Cell Myocarditis

Trial ImmunosuppressiveTrial Immunosuppressive

LVADLVAD

OHTxOHTx GCM- Young, Female, rapid deterioration GCM- Young, Female, rapid deterioration

(VT, CHB, rapid drop of EF)(VT, CHB, rapid drop of EF)

Biopsy is useful forBiopsy is useful for

Confirm diagnosis (Strongly suspected)Confirm diagnosis (Strongly suspected) Altered managementAltered management

– Anthracycline toxicityAnthracycline toxicity– Affect Suitability for OHTX ( Amyloid)Affect Suitability for OHTX ( Amyloid)– GCMGCM

B-Natriuretic Peptide in HFB-Natriuretic Peptide in HF

PhysiologyPhysiology

Caveats of Natriuretic PeptideCaveats of Natriuretic Peptide

Clinical Utility of Natriuretic Peptide Clinical Utility of Natriuretic Peptide and and

Landmark TrialsLandmark Trials

When should we order Natriuretic When should we order Natriuretic Peptide?Peptide?

BNP Release BNP Release

Atrial Atrial stretchstretch Not always = Not always = pressurepressure

i.e., tamponadei.e., tamponade

Increased LV wall Increased LV wall stressstress

ProBNPProBNP

NT-ProBNP

BNP

Pre-ProBNPPre-ProBNP

-In-active-Half Life 90 90 min

-Active-Half Life 2020 min



CaveatCaveatSS of Natriuretic Peptide of Natriuretic Peptide




High BNPHigh BNP

ElderlyElderly FemaleFemale Pulmonary EmboliPulmonary Emboli Renal FailureRenal Failure H/o HF w/ undiagnosed H/o HF w/ undiagnosed

dyspneadyspnea AnemiaAnemia Hyperthyroid (NT)Hyperthyroid (NT)

Low BNP Tamponade Constriction Obesity –NPR-C

400 pg/ml pg/ml-se 87, sp 76

NT 1200 pg/ml-se 89, sp 72



Caveat of Natriuretic PeptideCaveat of Natriuretic Peptide

Clinical Utility of Natriuretic Clinical Utility of Natriuretic Peptide Peptide

and Landmark Trialsand Landmark Trials


Clinical Utility of Natriuretic Clinical Utility of Natriuretic Peptide in Heart FailurePeptide in Heart Failure

1. 1. Diagnosis Diagnosis Ruling out Ruling out

2. Risk Stratification2. Risk Stratification

3. Screening Cardiac Dysfunction3. Screening Cardiac Dysfunction

4. Guiding Management of Heart 4. Guiding Management of Heart FailureFailure


1.1. Diagnosis Diagnosis Ruling out Ruling out



4. Guiding Management of Heart Failure4. Guiding Management of Heart Failure


ConfirmConfirm or or Rule outRule out HF HF DiagnosisDiagnosis

AmbiguousAmbiguous signs and symptoms signs and symptoms

AcuteAcute Setting Setting

BNPBNP Cut – Off Cut – Off

Maisel. N Engl J Med 2002;347:161-7

BNP StudyN=1586

References Ranges References Ranges BNP (pg/ml)BNP (pg/ml)

767 Subjects w/o CV diseases or LV dysfunction 767 Subjects w/o CV diseases or LV dysfunction (5(5thth-95-95thth percentile) percentile)

Age 45-54 55-64 65-75 74-83Age 45-54 55-64 65-75 74-83

Female Female 8-73 10-93 13-120 16-1558-73 10-93 13-120 16-155

Male Male 4-40 5-52 7-67 9-86 4-40 5-52 7-67 9-86

Redfield JACC 2002

NT-Pro BNPNT-Pro BNP Cut - Off Cut - Off

PRIDE STUDY

N=600

Am J Cardiol 2005;95:948

Pro-NT BNPPro-NT BNP Cut - Off Cut - Off

Januzzi EHJ 2006:27:330

The International Collaborative of NT-proBNP Study

N=1256

Preserved EF HF - BNP Sub-Preserved EF HF - BNP Sub-studystudy

JACC 2003;41:2010 –7

BASEL STUDY

• N=452, ER w/ acute dyspnea, Biosite Essay

• 2 Diagnostic strategies- BNP and no BNP

• BNP group - Less need for hospitalization (75% vs. 85%, p< 0.05) - Less need for intensive care (15 vs. 24%, p<0.05) - Rapid time to discharge (8 vs. 11 days, p<0.05) - Less total cost of treatment (5410 $ vs. 7264$, p<0.05) - Similar 30- day mortality


ConfirmConfirm or or Rule outRule out HF HF DiagnosisDiagnosis

AmbiguousAmbiguous signs and symptoms signs and symptoms

NonNon- Acute- Acute Setting Setting

Clinical Utility of Natriuretic Peptide in Diagnosis of Heart Failure in Non-Acute Setting

1. Class II a, Level of evidence C

2. Skeptical, various cut-off values (80-300 pg/ml)

3. Lack of good prospective randomized control trials

4. Presently, NT pro-BNP improved HF diagnostic accuracy (21 vs. 8%, p<0.002). Number needed to Dx =7

5. Great impact on ruling out HF

6. Lower cut-off compared to those in acute setting

Zaphirio European Journal of Heart Failure 7 (2005) 537– 541

N=306ESC HF criteria

Nielsen et al. The European Journal of Heart Failure 6 (2004) 63–70

NT-pro BNP <17 pg/mlAge >=50

NT-pro BNP <11 pg/mlAge >=50

N= 345, ESC HF Dx

Sens 95% Spect 68% PPV 54% NPV 97%

• N=558, Chronic stable systolic HF

• Asymptomatic (n=60) BNP 5-572 pg/ml, median 147

• Symptomatic (n=498) 21% had BNP <100 pg/ml

r=0.32 r=0.69

• Weak correlation of BNP and PCWP in ICU pts with LV dysfx -Circulation. 2004;109:2432-2439

• Poor correlation of BNP, pro BNP and LVEDP (r=0.05-0.08)

-Am Heart J 2006; 152:107126

Risk Stratification• Provide robust prognostic information - Normal Population - ACS - CAD - CRT - HF - PE

for both BNP and proBNP for both absolute values and delta values on F/U

• Provide incremental prognostic information

• Lack of clear clinical utility of guiding of clinical management

(Circulation. 2003;107:1278-1283.)

N=4300 HF patientsValheft Study

• N= 72, NYHA class 3-4• Last BNP strongly associate combine endpoints (death, re-HF hospitalization)• BNP @ DC = strong predictor of re-admission

J Am Coll Cardiol 2001;37:386 –91

Screening for Cardiac Dysfunction

CV Risk Factors

Asymptomatic LV dysfx

Overt Heart Failure

Advanced/Terminal Heart Failure

AHA/ACC Stage

A

B

C

D

?

Screening for Cardiac Dysfunction

Approach 1 – Post MI w/o overt HF

Approach 2- Other Population Olmsted Higher BNP, higher LV abn.

• Inconclusive data (vary ranges, cost effectiveness)

• Pro and Con• Class II b• Still not warranted/recommended

LV diastolic dysfunctionLV diastolic dysfunction

N=294

Circulation. 2002;105:595-601

N=220NYHA 2-3LVEF <45%BNP <100 = targetMedian 15 months FU

JACC 2007;49:1733–9


? Track changes in Clinical Status? Track changes in Clinical Status

Track changes in Risk and Clinical Status

• BNP falls rapidly after diuretics

• BNP correlates w/ functional status in OPD pts.

- Independent of hemodynamic status - vary widely - Lag period?

- High intra-individual variability

•Pre DC BNP is superior to Admission BNP in predicting of death, HF hospitalization in pts with acute LVF

• BNP is not a perfect surrogate for intravascular volume • Driving down BNP at all costs may be potentially harmful • NT pro-BNP comes down slower than BNP• What is optimal level?• Therefore … at best this is an unproven concept



Caveats of Natriuretic PeptideCaveats of Natriuretic Peptide




When Should we order When Should we order BNP/NT- proBNP ?BNP/NT- proBNP ?

1. To exclude or diagnose HF patients presented with acute dyspnea and ambiguous signs and symptoms of HF (Ruling out > Diagnose)

2. To exclude HF in patient presented with non-acute dyspnea and ambiguous signs and symptoms of HF in some patients (not routine !)

3. To assess risk stratification if needed in selected patients (not routine !)

Adapted from Tang Circulation July 31, 2007

Not Recommend Not Recommend ordering BNP/NT-ordering BNP/NT-PBNP :PBNP :

1. Routine BNP/NT-pro BNP testing for screening of asymptomatic LV dysfunction

2. Routine blood biomarker testing for the sole purpose of risk stratification in patients with HF

3. Routine blood BNP or NT-proBNP testing for making specific therapeutic decisions for patients with acute or chronic heart failure

(Reasons: still emerging but incomplete data as well as intra- and inter-individual variations)

Adapted from Tang Circulation July 31, 2007

Have to ask before Have to ask before interpretationinterpretation

1. NT pro BNP vs. BNP?

2. What kind of essay?

Research [Shionogi®] vs. Commercial [Abbots®, Biosite®]

3. Any factors affecting BNP/ pro BNP level?

4. Is ordering physician clever ? Why did he/she order?


How do I assess CAD in HF ?How do I assess CAD in HF ? When should I do endomyocardial biopsy ?When should I do endomyocardial biopsy ? When should I order BNP?When should I order BNP? When shouldWhen should I screen for rare diseases and I screen for rare diseases and


When shouldWhen should I screen for rare I screen for rare diseases and comorbidities?diseases and comorbidities?

AnthracyclineAnthracycline HerceptinHerceptin CyclophosphamideCyclophosphamide ChloroquineChloroquine ETOH, CocainETOH, Cocain NSAIDS-Cox2NSAIDS-Cox2 XRTXRT Premature CADPremature CAD Valvular diseaseValvular disease CPCP RCMRCM

HF and systemic diseaseHF and systemic disease

Recognize Clinical Recognize Clinical ClueClue Routine screening not Routine screening not

recommended if nothing recommended if nothing suggested in clinical historysuggested in clinical history

HemochromatosisHIVCNTDAmyloidPheochromocytomaFamilial CM

ROUTINE LAB:CBC, UA, BUN, Cr, ElyteBG, Lipid, LFT, TSH12 lead EGCXR PA, lat



comorbidities?comorbidities? When should I get metabolic stress testing ?When should I get metabolic stress testing ? When should I use echo for guiding management?When should I use echo for guiding management? When should I place CRT/ICD?When should I place CRT/ICD? Hot Topic-Sleep and HFHot Topic-Sleep and HF

When should I get metabolic When should I get metabolic stress testing ?stress testing ?

Vo2 max < 14 ml/k/min orVo2 max < 14 ml/k/min or <50% age and sex matched<50% age and sex matched RER >=1.15RER >=1.15 Don’t do until medical Rx optimized. Don’t do until medical Rx optimized.

Heart Failure

Diastolic dysfunction- LV filling pressure- Exercise/rest

Systolic dysfunction Structural Abnormalities

•RV•Pericardial disease

E/e’ = 22

Mitral e’ = 5 cm/s

Mitral E = 110 cm/s

110/5

Diastolic LV filling pressure ?

Critical LM CADLVEDP 28 mmHg

Estimation of Estimation of LV Filling PressureLV Filling Pressure

mLAP

LVEDP

PCWP

E / E’ ratioE / E’ ratio

E/E’ < 8

M-LVDP (mmHg)

40

35

30

25

20

15

10

5

0

40

35

30

25

20

15

10

5

0E/E’ 8-15 E/E’ > 15

M-LVDP (mmHg)

E/E’ < 8 E/E’ 8-15 E/E’ > 15

Patients with EF < 50% Patients with EF > 50%Patients with EF < 50% Patients with EF > 50%

M-LVDP vs. Groups Defied M-LVDP vs. Groups Defied byby

Values of Septal E/E’Values of Septal E/E’

Ommen et al. Circulation 2000 110-103

Omens SR Circ 102: 10/10/2000

Septal vs. LateralSeptal vs. Lateral

Omens SR Circ 102: 10/10/2000

Diastolic Diastolic DysfunctionDysfunction

Lateral E/E’ >10 predicts Lateral E/E’ >10 predicts LVEDP >12 mmHgLVEDP >12 mmHg

Sensitivity 91%Sensitivity 91% Specificity 81%Specificity 81%

Nagueh et al. JACC 1997; 30:1527-33

Correlations between Correlations between PCWP and BNP vs. PCWP and BNP vs.

Mitral E/e’Mitral E/e’

Echocardiography is now able to estimated LV filling pressure under various conditions

RA pressureRA pressure

Note in intubated patients, IVC size is not reliable for RA pressure assessment (unless it is small).

IVC ∆ with respRA

pressure

<1.5 cm collapse 0-5 mmhg

nl (1.5-2.5) >50% 5-10

nl <50% 11-15

>2.5 <50% 16-20

>2.5 no change >20

RVSP-RASP = Peak gradient TR= 85 mmHgRVSP = 85 + RASP

= 85+5= 90

RV

RA

mRAP =5 mmHg

Right AtrialLead

Right VentricularLead

Left VentricularLead

COMPANION study N Engl J Med 2004;350:2140-50.

(Death and hospitalization) (Death from any cause)

•NYHA class III•QRS 120

•PR 150 •LVEF < 35%

•NSR•VDD pacing

CARE-HF N Engl J Med 2005;352:1539-49.

•NYHA class III•LVEF < 35%

•QRS 120-149 plus echo criteria•LVEDD 30 mm

•QRS > 149

Cardiac Resynchronization Therapy* Cardiac Resynchronization Therapy* in Patients With Severe Systolic in Patients With Severe Systolic

Heart FailureHeart Failure

I IIa IIb III

III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII

III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII 1. LVEF <=35%2. QRS >=120 ms3. Sinus rhythm4. NYHA III or ambulatory IV5. Optimal medical Rx

1. LVEF <=35%2. QRS >=120 ms3. AFib4. NYHA III or ambulatory IV5. Optimal medical Rx

1. LVEF <=35%2. QRS >=120 ms3. V pacing dependent4. NYHA III or ambulatory IV5. Optimal medical Rx

Cardiac Resynchronization Cardiac Resynchronization Therapy* in Patients With Severe Therapy* in Patients With Severe

Systolic Heart FailureSystolic Heart Failure

For patients with LVEF less than or equal to 35% with For patients with LVEF less than or equal to 35% with NYHA functional Class I or II symptoms who are NYHA functional Class I or II symptoms who are receiving optimal recommended medical therapy and receiving optimal recommended medical therapy and who are who are undergoing implantation of a permanent undergoing implantation of a permanent pacemaker and/or ICD with anticipated frequent pacemaker and/or ICD with anticipated frequent ventricular pacing, CRT may be considered.ventricular pacing, CRT may be considered.

CRT is not indicated for asymptomatic patients with CRT is not indicated for asymptomatic patients with reduced LVEF in the absence of other indications for reduced LVEF in the absence of other indications for pacing. pacing.

CRT is not indicated for patients whose functional status CRT is not indicated for patients whose functional status and life expectancy are limited predominantly by and life expectancy are limited predominantly by chronic noncardiac conditions. chronic noncardiac conditions.




N Engl J Med 2005;352:225-37

N=2521LVEF 35%NYHA class II

Sleep and HFSleep and HF

OSAOSA Central Apnea- Chyne Central Apnea- Chyne

stroke Respstroke Resp

Sleep Disordered Breathing (SDB)Sleep Disordered Breathing (SDB)

[Apnea-Hypopnea syndrome][Apnea-Hypopnea syndrome] SDB – apnea or hypopneaSDB – apnea or hypopnea

AH index (Apnea/hypopnea index)AH index (Apnea/hypopnea index)งง 5-15 Mild5-15 Mild >15 Moderate or severe>15 Moderate or severe

AH syndrome (SDB)AH syndrome (SDB) Daytime somnolence Daytime somnolence


PolysomnogramPolysomnogram


General popGeneral pop SDB 24% men, 9% womenSDB 24% men, 9% women

OSAH syndrome 4% male, 2 % female.OSAH syndrome 4% male, 2 % female.

HF with low LVEFHF with low LVEF Prevalence is higherPrevalence is higher SDB = 51%SDB = 51%

(78% CSA, 22% OSAH)(78% CSA, 22% OSAH)


CSA caused by HFCSA caused by HF OSA caused HFOSA caused HF


OSAHSOSAHS Weight LossWeight Loss CPAPCPAP

CSR-CSACSR-CSANocturnal O2Nocturnal O2

CPAP needed?CPAP needed?

TheophyllineTheophylline

ASV-Alternating servo ventilationASV-Alternating servo ventilation

Sleep and HF RxSleep and HF Rx

cardiac investigation in heart failure

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