Gli scores di rischio nello scompenso cardiaco:tra teorica utilita' e reale applicabilita

Michele Senni - Bergamo

Get the core: advancing in risk stratification and

treatment in heart failure

Michele SenniUnità Complessa di Medicina Cardiovascolare

Dipartimento CardiovascolareClinico e di RicercaOspedali Riuniti

Bergamo

Gli scores di rischio nello scompenso cardiaco:tra teorica utilita' e reale applicabilita'

Michele Senni - Bergamo

Key Points:

1. La stratificazione prognostica e' importante

2. Diversi livelli di stratificazione

3. Gli scores clinici sono fondamentali

Sig. F.R., 68 aa, DM, neuropatia diabetica, IMA ant 2003, episodio di SC 2008, IRC (creat 1.8 mg/dl), anemia (Hb 10.5 gr/dl)

NYHA IIIFA non databileNon segni di stasi, ss 2/6 apicale, PA 95/60

mmHgVSx DTD/DTS 68/60 mm, FE 20%,

TAPSE 18 mm, PAPs 40 mmHg

“Dottore, per motivi familiari, vorrei sapere quale è la mia aspettativa di vita ad 1 anno”

La probabilità di sopravvivenza ad 1 anno di F.R. può essere stimata attorno a :

20%55%90%75%

Prognostic Markers in HFInvasive haemodynamic

CO, CI, PACWP, LVEDPNon invasive

LVEF, LV volumes, dimensionsFunctional

Peak VO2, functional capacityClinical

NYHA ClassNeurohumoral

Na, creatinine, catecholamines, endothelin, cytokines, natriuretic peptides

Prognosis

Prognosis in Heart Failure

Risk stratification remains one of the major limits in HF.

In recent clinical guidelines, estimating prognosis is a key element of HF management.

PROGNOSTIC STRATIFICATION in HEART FAILURE (HF)

Identification of patients at high risk of mortality

in HF by:

? a single marker

? multiparametric approach

> Composite Survival Score

Prognostic ModelsAuthor Year N°

variab.Population/ HF type

Validat. Prognosticprediction

Lee 2003 11 Registro retrospet. MulticenAHF/ SHF + PrEF HF

Indep.cohort

30 d.-1 y.

Felker 2004 5 Trial / SHF Bootstr. 60 d.

Fonarow 2005 3 Registro MulticentricoAHF/ SHF + PrEF HF

Indep.cohort

Intrahosp.

Levy 2006 14 4 Trials + 2 RegistriAHF + ChHF/ prevalente SHF

Indep.cohort.

1-2-3-5 ys.

Krumholtz 2006 24 Database amministrativo Indep.cohort

30 d

Senni 2006 13 Registro retrospet. MonocenAHF + ChHF/ SHF + PrEF HF

Indep.cohort.

1 y

Abraham 2008 7 Registro retrospet. MulticenAHF/ SHF + PrEF HF

Indep.cohort

IntraHhosp.

At admission

Duringhospitalization

At discharge

Outpatientvisit

Levels of Prognostic stratification

Tarantini  

Euro Heart Failure Survey - II%

Mor

talit

y

Follath WCC 2006

At admission

Duringhospitalization

At discharge

Outpatientvisit

Levels of Prognostic stratification

Heart Failure Risk Scoring System

Lee DS et al. JAMA 2003

Enhanced Feedback for Effective Treatment (EFFECT) Study

Limitations:

- No data on ventricular function (only vital signs)

- Score not at bedside (Website)

Heart Failure Risk Scoring System

Lee DS et al. JAMA 2003

AUC = 0.78

At admission

Duringhospitalization

At discharge

Outpatientvisit

Levels of Prognostic stratification

ADHERE CART: Predictors of Mortality

SYS BP 115n=24,933

SYS BP 115n=7,150

6.41%n=5,102

15.28%N=2,048

21.94%n=620

12.42%n=1,425

5.49%n=4,099

2.14%n=20,834

BUN 43N=33,324

Greater thanLess than

2.68%n=25,122

8.98%n=7,202

Cr 2.752,045

Highest to Lowest Risk CohortOR 12.9 (95% CI 10.4-15.9)

Fonarow Circulation 2003;108:IV-693

>>

><

<<

1,84,7

1,84,3

25,6

8,0

14,1

23,8

7,9

14,2

0

5

10

15

20

25

30

Low Intermediate

3Intermediate

2Intermediate

1High

DerivationCohortValidationcohort

In‐Hospital M

ortality%

ADHERE CART

Gregg et al. JAMA 2005

The Seattle Heart Failure Score was derived in the PRAISE 1 database (n= 1.125)

and validated prospectively in 5 additional databases (n=9.942):

Study N. Exclusion criteria for entry

ELITE2 RCT 2.987 Yes

Val-HeFT RCT 5.010 Yes

RENAISSANCE RCT 925 Yes

Univ Washington HF Clinic 148 No

IN-CHF HF Clinic 872 No

Circulation. 2006;113:1424-1433.

10%

Total population AUC = 0.73

www.SeattleHeartFailureModel.org.

Limitations:

- Less than 300 DHF pts

- Score not at bedside (Website)

- Trial limitations

Differences between CHF patients enrolled in Clinical Trials and those of Clinical Practice

Variable RCT/Cardiology Community

Mean Age 57-64 70-75Gender M:F 4:1 1:1EF >40% exclusion criteria >40%Atrial Fibrillation 20% 40%Severe Renal Dysfun. exclusion criteria 20-30%Comorbidities exclusion criteria frequentDrug Dosage at target lowCompliance high lowTreatment Duration 1-3 years life long1-year Mortality 9-12% 25-30%

Vazquez R et al. Eur Heart J 2009*AVE = Atherosclerotic Vascular Event

*

N° of pts 992

Vazquez R et al. Eur Heart J 2009

Limitations:

- Small number of patients

- Relatively young pts (mean age 65 yo)

- No derivation and validation cohorts

- Limited comorbidities in the variables

AUC 0.76

AUC 0.78

AUC 0.80

AUC 0.77

24.7%10.5%7.2%Renal Failure

38.4%27.1%29.1%Diabetes

TemistocleCardiology

TemistocleMedicine

16.1%11.7%15.2%Anemia

29.7%35.7%44.5%COPD

Di Lenarda A et al. Am Heart J 2003Tavazzi L et al. Eur Heart J 2006

Comorbidities in hospitalized patients

ItalianSurvey AHF

Comorbidities and survival

754 HF ptsCreatinine Clearance (CrCl): ≤ 30 ml/min in 16%30-59 ml/min in 40%

Median Follow-up: 926 days

Death in 385 pts (37%)

Survival significantly associated with Renal Function (p=0.002), even after adjustement for all other prognostic factors.

1% increase in Mortality for each1ml/min decrease in CrCl.

Varela et Al. Eur J Heart Fail 2005;7:859– 864

Influence of diabetes on the survival of patients hospitalized with heart failure: A 12-year study

Kaplan–Meier survival curves of diabetic (DM) and non-diabetic (non-DM) subgroups HF patients hospitalized with LVEF ? 50% (n=498) and < 50% (n=754)

0

10

20

30

40

50

without COPD COPD

without COPD 7 8 9 10 11COPD 20 20 18 20,5 41

1979- 1984- 1988- 1992- 1996-

COPD and COPD and MortalityMortality

Holguin F et al.CHEST,2005,128,2005-2011

Quintiles of Hematocrit< 38.2 38.2-41.3 41.4-43.7 43.8-46.8 > 46.8

Pump Failure Death (p for trend < 0.001)

Sudden Death

Other Deaths

Anemia Predicts Mortality in Severe Heart Failure. The Prospective Randomized Amlodipine Survival Evaluation (PRAISE)

Mozaffarian D et al. J Am Coll Cardiol 2003; 41: 1933-9

1,130 pts with LVEF < 30% and NYHA Class IIIB or IV, treated with ACEI, diuretics and digoxin.

Anemia is a significant independent risk factor for Death.

Within the lowest quintile of Hct:- Pts had a 52% higher risk of Death (HR 1.52, 95% CI 1.1- 2.1)- Each 1% decrease in Hct was associated with an 11% higher risk of Death (p<0.01).

Selected and trained in large, multicenter patient groups similar to those described in population-based studies.

Crucial characteristics of a prediction model

Accurate prediction should be balanced againstpracticality (i.e. VO2 max or right catheterization).

Accurate prediction across the entire spectrum of LV systolic dysfunction.

Incorporation of medications.

Adequate statistical approach to the analysis

24 Centers

Italy

France

Germany

Greece

Poland

5 European Countries

Bergamo Cardiac and Comorbid Conditions Heart Failure (3C-HF) Score

Senni M et al. (submitted)

Bergamo 3C-HF score

0.5Atrial fibrillation0.5Severe valvular disease0.5No β-Blocker0.5LVEF ≤ 20%1No ACEi/ARBs2NYHA class III-IV

0.5Complicated diabetes0.5Moderate to severe renal failure0.5Anemia2Metastatic cancer/2 cancers

0.5 per decade > 40Age

Variables Points

Non cardiac

Cardiac

Demographic -

Senni M et al. (submitted)

At discharge and out-patients = 6398 HFpEF 2670 (42%)

1,00,80,60,40,20,0

1 - Specificity

1,0

0,8

0,6

0,4

0,2

0,0

Sens

itivi

ty

ROC CurveROC Curve

AUC 0.865(95% CI 0.847 to 0.882)

It is similar to that of Pap smears (AUC 0.85) and superior to that of mammography (AUC 0.70) and Framingham Score (AUC 0.74 in men and 0.77 in women).

3C-HF Score

Calibration

0 – 2.5

3 - 5

5.5 -7

>7

3C-HF Score

0.920.090.8651482 (23.1)Internal medicine

0.920.070.8564916 (76.9)Cardiology

0.830.090.8343323 (76.9)Outpatient

0.780.060.87330.75 (48.1)Discharged

0.630.070.8321869(42.1)

Reduced LV

0.820.080.8754530 (57.8) Preserved LV

0.870.080.8573679 (29.2)Retrospective

0.830.060.8732670(70.8)

Prospective

P valueBrier scoreAUCN°(%)

Subgroup

3C-HF Score

The Relevanceof

Prognosis

Permette di discriminare i pazienti in:

- a rischio basso: MMG

- a rischio intermedio: approccio multidisciplinare diagnostico e terapeutico aggressivo

- ad elevatissimo rischio: cure palliative

3C-HF Score

KD Aaronson et al.: Circulation 1997

Heart Failure Scoring System

Criteria for heart trasplantation

KD Aaronson et al.: Circulation 1997

Heart Failure Scoring System

Criteria for heart trasplantation

Low risk: HFSS > 8.10Medium risk: HFSS 7.20 to 8.09

High risk: HFSS < 7.19

HF patientcandidate to some cardiac surgery procedure

One of the most frequent question is:

“If I do not undergo to operation whatis my future?”

… more than 60 prognostic factors in HF

Own clinician’s experience

Approximately X% survival at 1-year??

HF patientcandidate to some cardiac surgery procedure

One of the most frequent question is:

“If I do not undergo to operation whatis my future?”

1-year mortality with Medical RX only (Bergamo 3C-HF score)

30 days operative mortality (EuroSCORE logistic + Bergamo 3C-HF score)

Patient’s choice

Complexity of HF patients admitted to CardioVascular Medicine Unit

Mea

nB

erga

mo

3C-H

F sc

ore

2003 2004 2005 2006 2007

5

10

4.86.8

8.09.2 9.5

“Dottore, per motivi familiari, vorrei sapere quale è la miaaspettativa di vita ad 1 anno”

La probabilità di sopravvivenza ad 1 anno di F.R. può essere stimata attorno a :

20%55%90%75%

Sig. F.R., 68 aa, DM, neuropatia diabetica, IMA ant 2003, episodio di SC 2008, IRC (creat 1.8 mg/dl),anemia (Hb 10.5 gr/dl)