Stress (Takotsubo) cardiomyopathy and

heart failure: clinical predictors.

I. Nuñez-Gil1, JC. Garcia Rubira1, M. Luaces2, D. Vivas1, B. Ibanez1, B. Ruiz Mateos1,

A. De Agustin1, N. Gonzalo1, C. Macaya1, A. Fernandez Ortiz1

(1) Hospital Clínico San Carlos, Madrid, Spain

(2) Hospital de Fuenlabrada, Fuenlabrada, Spain.

No conflicts of interest.

Partially supported by a grant:

Mutua Madrileña

DISCLOSURES

Takotsubo syndrome (TS) presents features mimicking

acute coronary syndromes.

It is characterized by transient regional systolic

dysfunction of the LV, in the absence of obstructive

coronary artery disease.

Systolic heart failure (HF) is the most common

complication.

INTRODUCTION

Our aim was to examine:

Frequency of HF

Risk factors for HF

Prognosis of HF

Risk Score for..

patients with acute in stay HF complicating TS

(Killip≥2).

OBJETIVES

Retrospective analysis was conducted among 100 patients

prospectively registered between 2002 and 2010.

Inclusion criteria were (Mayo Clinic Crit. , mod. 2008):

Presentation mimicking acute coronary syndrome;

Transient dys/akinesis of LV segments, without significant coronary artery

narrowing;

ECG abnormalities and elevated cardiac troponin/CK;

Absence of: intracranial disease, pheochromocytoma …

… and no previous obstructive coronary artery disease.

METHODS

HF was assesed by means of the Killip classification (I-IV).

K2- dyspnea, pulmonary rales, elevated CVP, S3

K3- pulmonary edema depicted in chest X ray.

K4- SHOCK trial criteria+.

Cardiac cath and complete echocardiogram (<24hrs of admission)

were performed in 100%.

LV recovery was probed by echocardiogram (± CMRI), 100%.

METHODS II

+Hochman, NEJM, 1999.

LV DISFUNCTION

LV RECOVERY

Variables are presented as mean±standard deviation, counts (%),

or median with interquartile range (IQR).

Independent predictors for the development of HF were

estimated by means of a multivariate regression model.

The variables included in the multivariate analysis were chosen

because of the univariate results.

Goodness of fit: Hosmer Lemeshow.

Scores: ROC.

Follow up Events : Kaplan Meier (Breslow).

All analysis were performed using the software package SPPS, v15

(SPPS 2006, Ill, USA)

For all, a p-value<0.05 (two sided), was considered significant.

STATISTICAL ANALYSIS

RESULTS

BASAL FEATURES I OVERALL %, N= 100 NO HF %, N=70 HF %, N= 30 P*

Female 89 87.1 93.3 0.36

HTN 68 71.4 60.0 0.26

DLP 50 51.4 46.7 0.66

DM 18 12.9 30.0 0.04

SMOKER 31 30.0 33.3 0.74

CAD Fam Hist 19 26.5 3.7 0.01

Obesity 24 19.1 37.9 0.04

Hiperuricaemia 3 1.4 6.9 0.15

OSA 1 1.5 0 0.51

Previous NYHA

- I

- II

- III

64

31

5

77.1

21.4

1.5

33.3

53.3

13.3

<0.01

Trigger

- Psychological

- Physical

- NO

43

10

47

44.3

8.6

47.1

40.0

13.3

46.7

0.75

Chest pain **

Yes

No

88

12

95,7

4.3

70.0

30.0

<0.01 * Test: χ2

** consult in ER

mainly due to…

BASAL FEATURES II

OVERALL*

N= 100

NO HF *

N= 70

HF *

N= 30

P **

Age (yrs) 68.0±13.2 66.0±13.2 72.9±12.0 0.01

SBP (mmHg) 143.0±35.8 150.1±32.6 127.0±38.0 0.04

HR (bpm) 86.0±21.0 81.4±16.5 96.8±27.3 0.02

Temp (Celsius) 36.2±0.4 36.2±0.4 36.4±0.5 0.43

Creatinine 0.95±0.4 .90±0.2 1.00±0.3 0.10

Leucocyte 9.8±3.3 9.5±2.9 10.6±3.9 0.15

Hb 13.5±1.4 13.5±13.0 13.5±15.0 0.89

Platelets 250.0±70.0 249.1±67.8 251.3±77.3 0.80

Max .Tn I *** 4.2 (2.0-8.9) 3.9 (2.1-7.8) 6.6 (1.8-11.9) 0.27

Max. CK *** 200.5 (123.5-329.8) 196 (121-325) 234 (140-462) 0.23

* Mean ± SD

** Test: Student’s-t.

*** Expressed as median (IQR). Test: Mann Whitney’s -U.

TEST FINDINGS

OVERALL

N= 100

NO HF

N= 70

HF

N= 30

P*

Sinus Rhythm 96 % 95.7 % 96.7 % 0.82

Onset ST elevation 58 % 59.7 % 62.1 % 0.82

ST Elevation 60 % 62.1 % 65.5 % 0.75

ST depression 5 % 3.2 % 10.7 % 0.13

Neg. T waves 87 % 86.4 % 89.3 % 0.69

Max. QTc (V3) 512.8±72.0 499.5±67.8 543.3±73.6 0.01

Onset LVEF (Echo, %)** 48.1±11.0 50.9±10.1 41.8±11.8 <0.01

Valve disease (>mild) 25 % 18.6 % 40.0 % 0.02

LVOT gradient (> 25mmHg) 9 % 7.1 % 13.3 % 0.32

LVEF after F-up (Echo, %)** 63.9±7.2 65.3±7.3 60.4±5.9 <0.01

Emergent cath 33 % 32.3 % 34.5 % 0.83

Right dominance 79 % 81.5 % 75.9 % 0.02

LVEF (Cath, %)** 53.5±11.0 55.3±11.5 48.8±10.1 0.01

* Test: χ2

** Test: Student’s-t.

EKG

TT

Echo

Cardiac

Cath

PREVIOUS TREATMENT

OVERALL

N= 100

NO HF

N= 70

HF

N= 30

P*

ASA 16 17.1 13.3 0.63

Clopidogrel 2 1.4 3.3 0.53

Anticoagulants 10 11.4 6.7 0.46

Nitroglicerine 2 1.4 3.3 0.55

Diuretics 16 14.3 20 0.47

Statins 14 10 23.3 0.07

Calcium Channel Blockers 10 10 10 1

Betablockers 11 10 13.3 0.62

ARBs-ACEIs 29 28.6 30 0.88

Glucocorticoids 6 7.1 3.3 0.46

Ansiolitics 12 11.4 13.3 0.78

Antidepressant 8 7.1 10 0.62

Oral antidiabetics 9 8.6 10 0.81

Insulin 5 4.3 6.7 0.61

* Test: χ2

CCU -TREATMENT

OVERALL , %

N= 100

NO HF, %

N= 70

HF , %

N= 30

P*

Inotropic drugs 11 1.4 * * 33.3 <0.001

IABP 2 0 6.7 0.02

Non invasive

Mechanical Ventilation.

3 0 10 0.007

Mechanical Ventilation. 6 1.4 16.7 0.003

Gp IIb/IIIa inhibitors 31 35.7 20.0 0.11

Fibrinolisis 3 4.3 0.0 0.25

* Test: χ2

* * Diuretic Dopamine.

DISCHARGE-TREATMENT

OVERALL

N= 100

NO HF

N= 70

HF

N= 30

P*

ASA 95 95.7 93.3 0.61

Clopidogrel 44 41.4 50.0 0.42

Anticoagulants 90 90.0 90.0 1

Nitroglicerine 64 64.4 63.3 0.92

Diuretics 36 15.7 83.3 <0.001

Statins 71 72.9 66.7 0.53

Calcium Channel Blockers 21 17.1 30.0 0.14

Betablockers 69 70.0 66.7 0.74

ARBs-ACEIs 70 68.6 73.3 0.63

Glucocorticoids 9 8.6 10.0 0.81

Ansiolitics 76 78.6 70.0 0.35

Antidepressant 10 10.0 10.0 1

Oral antidiabetics 9 8.6 10.0 0.73

Insulin 18 17.1 20.0 0.73

* Test: χ2

MAX. KILLIP

IN STAY EVENTS

OVERALL

N= 100

NO HF

N= 70

HF

N= 30

P*

LV Thrombus 5 2.9 10.0 0.14

Arrhythmias 32 27.1 44.3 0.27

New episode 11 10.0 14.8 0.53

Others (infection,

vascular, …)

20 13.6 35.7 0.01

Death 0 0.0 0.0 1

* Test: χ2

TIMES

OVERALL

N= 100

NO HF

N= 70

HF

N= 30

P*

FOLLOW UP 1380 (755-1941) 1534 (822-2109) 1075 (633-1622) 0.04

IN STAY 7 (5-10) 6 (4-9) 9.5 (7-14) <0.001

TIME TO 1ST ECHO 0 (0-1) 0 (0-1) 0 (0-1) 1

TIME TO CATH 1 (0-2) 1 (0-2) 1 (0-2) 0.72

TIME TO F-UP ECHO

(Full LV recovery)

74 (9-174) 74 (6-160) 73 (11-186) 0.15

* Expressed as median (IQR). Test: Mann Whitney’s -U.

MULTIVARIATE MODEL

HF *

OR 95% CI P **

DM 4.20 0.77-22.96 0.09

Obesity 3.60 0.03-15.99 0.08

Onset Chest pain 0.07 0.01-0.45 0.005

Valve disease 4.23 1.02-17.49 0.04

SBP>140 0.31 0.08-1.20 0.09

HR>100 7.71 1.44-41.30 0.01

LVEF <45% 4.94 1.09-22.32 0.038

Age > 70 2.03 0.48-8.45 0.33

Previous NYHA 8.30 2.04-33.74 0.003

* Variables in the model: Diabetes, Family history, Obesity (BMI>30), Previous NYHA,

Chest pain on admission, Age>70yrs, SBP>140mmHg, HR>100bpm, LVEF (echo)<45%,

Valve disease (>mild).

** Goodness of fit: Hosmer Lesmeshow-test, p=0.903 – adequate.

HF predictors

DM

Obesity

Onset Chest pain

Valve disease

SBP>140

HR>100

LVEF <45%

Previous NYHA

FOLLOW UP

OVERALL

N= 100

NO HF

N= 70

HF

N= 30

P*

MACE 20 15.7 30.0 0.10

READMISSION 16 14.3 20.0 0.47

RECURRENCE 4 1.4 10.3 0.04

DEATH 6 1.4 16.7 0.03

CV DEATH 3 1.4 6.7 0.15

* Test: χ2

FOLLOW UP

Time (days)

MA

CE

F

ree S

urv

ival

No

Yes

Censored

Censored

HF (Killip≥2)

p * =0.034

* Test: Breslow

Time (days)

Su

rviv

al

No

Yes

Censored

Censored

HF (Killip≥2)

FOLLOW UP

p * =0.01

* Test: Breslow

MAX KILLIP NSTEMI

CAD ABSENT CAD PRESENT

70

15

5 10

I II III IV

TS

SCORE MAYO*

Simple.

C-statistic=0. 77, p<0.001

1Point each.

Physical trigger (present).

Age > 70yrs.

LVEF< 40%.

*Madhavan et al. JACC, 2011.

S

1-E

C= 0.741

p< 0.001

SCORE TAKO-SCO I

Simple.

1Point each.

Previous NYHA class.

Onset Chest pain (absent).

HR> 100 bpm.

Valve disease (>mild).

LVEF< 45%.

S

1-E

C= 0.866

p< 0.001

Tako-Sco

Mayo

SCORE TAKO-SCO II

2 Points each.

Previous NYHA class.

Onset Chest pain (absent).

HR > 100 bpm.

Valve disease (>mild).

LVEF< 45%.

1 Point each

DM

Obesity

S-BP<140

S

1-E

C= 0.908

p< 0.001

CONCLUSIONS

In spite of coronary arteries without significant

obstructions, TakoTsubo cardiomyopathy is not lacking

of in-hospital complications.

The most frequent is HF.

HF could be related with future CV events during F-up

and merits early detection and treatment.

Patients with lower previous NYHA class, absent chest

pain at admission, HR> 100 bpm, valve disease

(>mild), LVEF< 45% have an increased probability to

present HF.

We developed a simple score to predict HF.

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