considerar otros diagnósticos

Considerar otros

diagnósticos

normalDeterminar la presencia de

cardiopatía mediante ECG, RX-tórax,

Péptidos natriuréticos

Guías para el diagnóstico de IC aguda de la ESC

Guías para el diagnóstico de IC aguda de la ESC

Nieminen MS et al. Eur Heart J 2005; 26:384

Sospecha de IC en base a signos y síntomas

anormal

Ecocardiografía-Doppler

..continuar

ANP y BNP: comparación fisiológicaANP y BNP: comparación fisiológica

InestableEstableEstabilidad mRNA

RápidaLentaRespuesta de la transcripción genética al estímulo

++++Aumento en relación con la insuficiencia cardíaca

(+)++Secreción cardíaca basal

BajaElevadaConcentración auricular

Aurícula y ventrículo AurículaLocalización cardíaca

BNPANP

cardiomiocito

pre-proBNP

sangre

signalproBNP

NT-proBNP BNP

-26 amino acid 108

-26 -11 108

1 76 77 108

Péptidos natriuréticos: SintesisPéptidos natriuréticos: Sintesis

BNP- Diagnosis of acute dyspneaBNP- Diagnosis of acute dyspnea

Maisel et al, NEJM 2002;347:161

BNP Study:Breathing Not Properly

Estudio ICONEstudio ICON

• Número total=1256 pacientes

• No ICC=536 pacientes

– Antecedentes de ICC=55– No antecedentes de ICC=481

• IC aguda=720 pacientes

Diagnostico y NT-proBNP ICONICON

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Area under the curve=0.94P<0.00001

Optimal cut: 1160 pg/ml

Effect of Age on Cut-point Performance

• Age <50 yearsAge <50 years

– 84% sensitive/97% specific84% sensitive/97% specific

• Age 50-75 yearsAge 50-75 years


• Age >75 yearsAge >75 years


ICONICON

ROC Analysis: Age<50 yearsROC Analysis: Age<50 years

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Optimal cut: 450 pg/ml97% sensitive, 93% specific

ROC Analysis: Age 50-75 yearsROC Analysis: Age 50-75 years

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ROC Analysis: Age >75 yearsROC Analysis: Age >75 years

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0.0041.00-1.021.01Frecuencia cardiaca

<0.00011.3-1.81.6Edad

<0.00011.7-4.02.6Ausencia de fiebre

<0.00011.7-4.62.8Antecedentes de ICC

<0.00011.8-4.42.8Uso de diuréticos de asa

<0.000012.0-4.53.0Crepitantes pulmonares

<0.000012.2-5.53.5Ortopnea

0.00021.85-7.73.7Ausencia de tos

<0.00013.5-12.86.7Edema intersticial en RX

<0.00001<0.0000112.6-39.312.6-39.324.224.2NT-proBNP elevadoNT-proBNP elevado**

P95% CIORPredictor

*NT-proBNP elevado definido como >450 para pacientes <50 años, >900 pg/ml para pacientes 50-75 años, y >1800 pg/ml para pacientes >75 años

Análisis de regresión logística MV

ICONICON

22%

36%

Rule Out Cutoff PointsRule Out Cutoff Points

International NT-proBNP Collaboration

300 pg/ml, age independent

99% sensitive60% specific

98% NPV

Punto de corte recomendado en las nuevas guías de la ESC

Patient attending the ED with breathlessness

History taking, physical exam, ECG, chest X-ray and NTproBNP

Acute CHF

unlikely

Acute CHFlikely

Acute CHF less likely

Additional tests

NTproBNP<300pg/mL

NTproBNPbetween 2 cut-

points

NTproBNP>450g/mL - patients <50 a>900pg/mL - patients 50-75 a>1800pg/mL - patients >75a

Understanding NT-proBNP in Obesity

Understanding NT-proBNP in Obesity

The obesity paradox ¿?

• Plasma levels of natriuretic peptides appear inversely associated with BMI in both subjects with and without HF.

• Natriuretic peptides are lower in overweight and obese patients compared with lean patients

Mehra MR et al. JACC 2004;43:1590Kistorp C et al. Circulation 2005;112:1756.StPeter JV. Clin Chemistry 2006;52:680Rivera M et al. Eur J Heart Fail 2005;7:1168.

Mechanisms of low NP in obesity Is it a matter of Increased degradation?

Mechanisms of low NP in obesity Is it a matter of Increased degradation?

22 pts underwent bariatric surgery

Parallel increases of BNP and NT-proBNP after weight loss

These data refutes the hypothesis that negative correlation between BNP and BMI is due to upregulation of NPR-C

because NPR-C do not clear NT-proBNP

Mechanisms of low NP in obesityMechanisms of low NP in obesity

• Increased degradation– BNP is cleared by NPR-C, abundantly expressed in human

adipocytes.– NT-proBNP is not cleared by NPR-C

• Reduced synthesis• altered neurohormonal interactions ¿?• Sex steroid hormones ¿?• Substance produced in the lean mass that

suppresses either synthesis or release of NP from cardiomyocytes ¿?

Das SR et al. Circulation 2005;112:2163van Kimmenade R et al. JACC 2006;47:886

Obesity, NT-proBNP and DiagnosisObesity, NT-proBNP and Diagnosis

How obesity affects NT-proBNP in the diagnosis of acute HF?

ICON BMI- substudy

How obesity affects NT-proBNP in the diagnosis of acute HF?

ICON BMI- substudy

BMI, NT-proBNP and diagnosisBMI, NT-proBNP and diagnosis

ROC curves for NT-proBNP / BMIROC curves for NT-proBNP / BMI

Utility of recommended NT-proBNP rule-in and rule-out HF cut-points as a function of

BMI

Utility of recommended NT-proBNP rule-in and rule-out HF cut-points as a function of

BMI

NP and obesity for diagnosing acute HF

NP and obesity for diagnosing acute HF

• Age-adjusted rule-in and age-independent rule-out cut-points for NT-proBNP are equally useful for obese and lean patients

Bayes-Genis et al. Arch Intern Med 2006: In press

• BMI influences the selection of cut-points for BNP in diagnosing acute HF:

• 170 ng/L - lean• 54 ng/L - obese

Daniels LB et al. Am Heart J 2006;151:999

Obesity, NT-proBNP and PrognosisObesity, NT-proBNP and Prognosis

How obesity affects the prognostic value of NT-proBNP

ICON BMI - substudy

How obesity affects the prognostic value of NT-proBNP

ICON BMI - substudy

BMI, NT-proBNP and prognosisBMI, NT-proBNP and prognosis

Hazard ratios across BMI adjusted for NT-proBNP > 986 ng/L

Hazard ratios across BMI adjusted for NT-proBNP > 986 ng/L

Optimal long-term (1 year) NT-proBNP cut-point: 986ng/L

Januzzi JL et al. Arch Intern Med 2006;166:315

K-M survival curves across BMI categories

K-M survival curves across BMI categories

Bayes-Genis et al. Arch Intern Med 2006: In press

What about BNP?What about BNP?

BMI, BNP and prognosisBMI, BNP and prognosis

Horwich TB et al. JACC 2006;47:85

Diferent prognostic cut-points across BMI

Diferent prognostic cut-points across BMI


• One single prognostic cut-point for NT-proBNP (986ng/L) is useful across all BMI categories.

Januzzi JL et al. Arch Intern Med 2006;166:315

Bayes-Genis A et al. Arch Intern Med 2006;In press

• Optimal BNP cut-points for prediction of death or urgent transplantation are different in the three BMI strata:

• 590 ng/L - lean • 491 ng/L - overweight• 343 ng/L - obese


NP and obesity for long-term risk stratification

NP and obesity for long-term risk stratification

In univariable analysis, higher BMI was an independent predictor of survival, with a 4% reduction in the risk of death with every increase of 1 BMI unit (95% CI=0.94-0.99, p=0.002). However, greater BMI was not significantly associated with 1-year mortality once age was added to the model.

Thus, the apparent obesity paradox in HF represents an association that is unlikely to be

causal

The obesity paradoxREVISITED

Riñón y NT-proBNPRiñón y NT-proBNP

Subestudio Renal de ICONSubestudio Renal de ICON

• 720 pacientes con IC aguda

• FGR calculado mediante ecuación MDRD

• Supervivencia a 60 días• 84 pacientes fallecieron• 606 pacientes vivos

Levey et al. Ann Intern Med 1999;130:461-470

Supervivencia a 60 díasSupervivencia a 60 díasCharacteristic Alive

(n=606)Deceased

(n=84)p-value

Age (mean±SD) 74.4±11.7 78.5±10.6 0.002

Male Gender 51.2% 52.4% 0.833

Past medical history HT CAD Prior MI Prior HF Prior COPD

62.0%50.7%33.3%51.7%29.3%

51.2%65.5%42.2%54.8%26.2%

0.0560.0110.1120.5930.561

Symptoms/signs Orthopnea Edema NYHA Class 4

51.6%46.5%44.2%

48.4%45.2%50.0%

0.6350.8230.319

Characteristic Alive (n=606)

Deceased (n=84)

p value

Physical Examination Pulse rate (mean±SD) Jugular venous distension S3 gallop Rales

92.8±25.848.8%6.9%

68.7%

95.5±26.056.0%8.3 %

67.9 %

0.3810.2220.6390.882

Chest X-ray findings Infiltrate Pleural effusion Cardiomegaly

11.7%26.6%37.0%

16.7%22.6%39.3%

0.1960.4400.680

ECG findings AF/AFl LBBB LVH

34.5%15.0%10.7%

32.1%25.0%8.3%

0.6710.0200.499

Supervivencia a 60 díasSupervivencia a 60 días

Characteristic Alive (n=606)

Deceased (n=84)

p value

Laboratory findings Creatinine, mg/dl (median, IQR) GFR (ml/min/1.73m²)(median, IQR) TropT >0.01 ng/ml NT-proBNP, pg/ml (median, IQR)

1.12 (0.87-1.50)61 (43-79)

47.5%4077 (1740-9989)

1.41 (1.02-2.10) 44 (31-64)

77.3% 9448 (3805-22179)

<0.001<0.001<0.001<0.001

Supervivencia a 60 díasSupervivencia a 60 días

• Los pacientes fueron dicotomizados

– Según los niveles de NT-proBNP– Concentración mediana = 4647 pg/mL (=548 pmol/L)

– Según FGR – > / < 60 ml/min/1.73m²

– 51.8% had GFR < 60 ml/min/1.73m²

Subestudio Renal de ICONSubestudio Renal de ICON

Predictores independientes de mortalidad en el análisis multivariado


Predictor Odds Ratio

95% CI P Value

Age 1.02 0.99 -1.05 0.08

Prior HF 0.78 0.48-1.27 0.31

Prior MI 1.36 0.84-2.22 0.22

NYHA class 1.26 0.86-1.86 0.24

Hemoglobin 0.94 0.88-1.01 0.07

GFR < 60 ml/min/1.73 m² 2.03 1.18-3.49 <0.01

NT-proBNP > 4647 pg/mL 2.67 1.58-4.51 <0.01

Predictor Odds Ratio 95% CI P Value

Age 1.02 0.99 -1.05 0.06

Prior HF 0.78 0.48-1.27 0.31

Prior MI 1.37 0.84-2.24 0.20

NYHA class 1.24 0.84-1.83 0.28

Hemoglobin 0.94 0.88-1.01 0.07

GFR < 60 ml/min/1.73 m² &

NT-proBNP > 4647 pg/mL 3.46 2.13-5.63 <0.001



Curvas de K-M según FGR y NT-proBNPCurvas de K-M según FGR y NT-proBNP

Van Kimmenade R et al. JACC 2006 In Press

NT-proBNP monitoringNT-proBNP monitoring

ER ER ER7 d 7 d 7 d

Death ofCV origin

Death ofnon CV

origin

Survivors

P=0.004

- 15% - 75% - 50%

Percent NTproBNP reduction during admission and prognosisPercent NTproBNP reduction during admission and prognosis

1 - Specificity

1,00,80,50,30,0

Sen

sitiv

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1,0

0,8

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0,0

AUC 0.79 (0.69-0.94)p=0.001

ROC for NTproBNP reduction during hospitalizationROC for NTproBNP reduction during hospitalization

Sens: 70%

Spec: 84%

PPV: 47%

NPV 94%

Accuracy 82%

- 30%

Prognosis of NTproBNP reduction during hospitalization for CHF

Prognosis of NTproBNP reduction during hospitalization for CHF

Bettencourt P et al. Circulation 2004;110:2168

N=182

Decrease 30% - 25%

Decrease <30% - ~50%

Increase 30% - 80%

6 months

A

Baseline W1 W2 W3 W4 M3

UneventfulFollow-up

LVEDD: 69 mmLVEF: 16%

Patient with no events during follow-upPatient with no events during follow-up

Baseline W1 W2 W3 W4 M3

Hospitaladmission

deathLVEDD: 73 mmLVEF: 20%

Patient with events during follow-upPatient with events during follow-up

What’s next?What’s next?

Worsening HF

Good prognosisoutpatient follow-up

Adverse prognosis

Resynchronization?i.v. inotropes?

???????

considerar otros diagnósticos

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