Transcript Does Less Lung = More Heart?

Does Less Lung =
More Heart?
Nathaniel Marchetti, DO
Temple University
Philadelphia, PA
Cardiac Effects of COPD
Why do we care about the heart in COPD?
 What does hyperinflation do to the heart?
 Effect of LVRS on cardiac function

Specific Causes of Death in the Lung
Health Study at 14.5 yrs
N=5,887
Anthonisen, et al AIM 2005
COPD Patients Are at Risk for a Range of
Cardiovascular Diseases
Curkendall, et al Annals Epidemiol 2006
Association of CV Mortality and FEV1
Author
Sample
size
Follow-up
(yrs)
Age (yrs)
Relationship
Hole,1977
15,411
15
44-64
Increased RR of 1.56 CV mortality
with lowest quintile FEV1
Ebi-Kryston,1988
17,717
10
40-64
Chronic phlegm associated with
increased all cause & respiratory
mortality
Schunneman,2004
1,195
29
47
Persson,1986
1,462
12
38-60
PEF inversely proportional to AMI
causing death
Truelsen,2001
12,878
17
45-84
Stroke & stroke related mortality
inversely related to FEV1 %
Hozawa,2005
13,842
13
45-64
HR of CV mortality inversely coupled
to FEV1 % predicted
Increased RR of 2.11 in CV mortality
with lowest quintile FEV1
(Modified from McNee PATS 2008)
Vascular Stiffness is Greater in COPD Patients with
Worse Airflow Obstruction and More Systemic
Inflammation
N=60
FEV1
Eickhoff AJRCCM 2008
N=60
CRP
Vascular Stiffness Increases During
AECOPD
Marchetti, et al COPD 2011
Increased Risk of AMI and CVA Following
AECOPD
• Risk AMI
increased 2.27fold 1-5 days post
AECOPD
• Risk CVA
increased 1.26fold 1-49 days
post AECOPD
N=25,857
p=0.03
Donaldson et al, Chest 2010
Troponin T Elevation & Long-term Mortality
after AECOPD
• 396 Hospitalized AECOPD
patients who had
measurements of cardiac specific troponin (cTnT)
• Followed for median 1.9 yrs
• Elevated cTnT associated
with increased all-cause
mortality with a hazard ratio of
1.64 (95% CI 1.15-2.34)
cTnT < 0.01 μgL-1
cTnT 0.01-0.03 μgL-1
cTnT > 0.04 μgL-1
Brekke ERJ 2008
Risk of Death at 30 days Following
Hospitalized AECOPD
Variable
BMI
PaCO2
NT-proBNP
Troponin T >0.03
OR (95% CI)
0.905 (0.83-0.99)
1.041 (1.02-1.07)
9.241 (2.58-33.05)
5.115 (1.73-15.15)
p
0.029
0.002
0.001
0.003
Chang et al, Thorax 2011
Effect of Hyperinflation
on the Heart
Effect of leg elevation on cardiac
function
o EDAI represents LVEDP
o certain increase in preload resulted in more pronounced increase in SVI
o patients on steeper portion of Starling curve suggesting an under filled LV
o SWI/EDAI represents LV systolic function
o No increase in LV EF
Jorgenssen et al Anes & Anal, 2007
? Under filled LV in Emphysema
o Diminished
preload
o ? Lower
intra-thoracic
blood volume
Reduced Intrathoracic Blood Volume and Left
and Right Ventricular Dimensions in Patients
with Severe Emphysema
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Compared cardiac MRI of 13 severely
emphysematous patients to 11 healthy controls
Emphysema patients
FEV1 24%
 TLC 139%
 RV 272%

Jorgenssen et al Chest, 2007
Lower LV
end diastolic
volume in
emphysema
subject
Jorgenssen et al Chest, 2007
Cardiac Function Results
o Emphysematous subjects had
o Lower LV and RV end-diastolic volume index
o Lower LV and RV ejection fraction
o Lower SVI for LV and RV
Jorgenssen et al Chest, 2007
Lower intra-thoracic blood volume
P = 0.001
p = 0.001
Jorgenssen et al Chest, 2007
Percent Emphysema, Airflow Obstruction,
and Impaired Left Ventricular Filling
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Sub study of Multi-Ethnic Study of Atherosclerosis
(MESA)
Measured LV structure and function with MRI in
2,816 patients
Measured extent of emphysema on CT (HU < -910)
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Included 70% of lung since they were cardiac CTs
Spirometry
Barr, et al NEJM, 2010
Effect of percent emphysema on
cardiac measurements
Increasing amounts of emphysema lead to decreased LV volumes but no change in EF
Barr, et al NEJM, 2010
Effect of current smoking
Mean Change in LVEDV for an
increase in emphysema of 10%
Current Smokers
-9.2 mL
Former Smokers
-4.2 mL
Never Smokers
-2.6 mL
Barr, et al NEJM, 2010
Correlation of LVEDV with
Emphysema
Barr, et al NEJM, 2010
Decreasing Cardiac Chamber Sizes and
Associated Heart Dysfunction in COPD.
Role of Hyperinflation
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138 patients with GOLD I-IV disease
Excluded patients with known cardiac disease
Lung volumes and 6MWD
ECHO parameters
Measured cardiac chamber size
 Diastolic dysfunction

Watz, et al Chest, 2010
Chamber size decreased with
increasing GOLD stage
Watz, et al Chest, 2010
Correlation of LVED diameter to
IC/TLC
r = 0.56, p < 0.001
Watz, et al Chest, 2010
IC/TLC was independent predictor
of cardiac chamber size
Watz, et al Chest, 2010
Effects of hyperinflation on the oxygen pulse
as a marker of cardiac performance in COPD
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87 COPD patients compared to 46 healthy
controls
CPET
Measured O2 pulse (VO2/HR)
 Dynamic hyperinflation (IC/TLC)

Vassaux, et al ERJ, 2008
Correlation of O2 pulse with
dynamic and static hyperinflation
Peak O2 pulse vs Static IC/TLC
r = 0.95, p=0.001
Change in O2 pulse vs Change in IC
r = -0.30, p<0.001
Vassaux, et al ERJ, 2008
IC/TLC <25% vs IC/TLC >25%
Difference
Peak Exercise
Rest
Vassaux, et al ERJ, 2008
Summary
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Patients with COPD seem to have diminished
cardiac chamber size
Have decreased intra-thoracic blood volume
with under filled LV
Appears to be related to hyperinflation
Occurs across GOLD stages
Can this be altered?
Effect of LVRS on
Cardiac Function
Extreme example
Effect of Bullectomy on Cardiac
Function
Marchetti, et al J Thorac Cardiovasc Surg 2008
Effects of LVRS on Left Ventricular Diastolic Filling
and Dimensions in Patients With Severe Emphysema

10 patients that had LVRS with FEV1 28%
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Controls = 10 lobectomy patients with FEV1 84%
Performed TEE in OR and measured
LV dimensions
 Mitral flow velocities as a marker of diastolic filling
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TEE done pre-operative but following induction
of anesthesia
TEE repeated at end of case when chest closed
Jorgensen, et al Chest, 2003
Changes in Hemodynamics
LVRS subjects had an increase in CI, SVI, and SWI
Jorgensen, et al Chest, 2003
Effect on Chamber Size
Improved end diastolic size in LVRS group
No change in LVEDS = LV stiffness
Jorgensen, et al Chest, 2003
Mitral Doppler Flow Following
LVRS
E
A
Pre LVRS
Low E-max
Low E/A ratio
Post LVRS
Improved E-wave
Improved E/A ratio
Jorgensen, et al Chest, 2003
Lung Deflation and Oxygen Pulse in COPD:
Results from the NETT Randomized Trial

129 NETT patients that had CPET and arterial
blood gas during exercise
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Divided group in to “deflators” and “nondeflators”
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67 medical
62 LVRS
Deflators defined as the change in RV/TLC by 75% of
subjects
Main outcome was % change in peak O2 pulse from
baseline to 6 months
Come, et al Respir Med 2012
% Change in O2 pulse
52
15
15
47
Come, et al Respir Med 2012
Comparison of baseline to 6 months
Changes in Sx deflators
baseline to 6 months in A-line
patients
Changes in Sx deflators baseline
to 6 months in all patients
Come, et al Respir Med 2012
Increased oxygen pulse after LVRS is
associated with reduced dynamic hyperinflation
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16 patients that had LVRS compared to 6
patients with medical therapy
CPET done baseline and 6 months
O2 pulse and pulse pressure were outcomes
Lammi, et al ERJ 2012 in press
Changes in O2 Pulse
Lammi, et al ERJ 2012 in press
Correlations Between Hyperinflation
and O2 Pulse
75% VCO2 max
Change in O2 pulse (mL/beat)
3
r=-0.391
p=0.07
2
1
0
-1
-2
-0.2
-0.1
0.0
0.1
4
r=-0.487
p=0.02
3
2
1
0
-1
-2
-0.2
Change in EELV/TLC
-0.1
0.0
0.1
Change in EELV/TLC
100% VCO2 max
Change in O2 pulse (mL/beat)
Change in O2 pulse (mL/beat)
50% VCO2 max
6
r=-0.548
p=0.008
4
2
0
-2
-4
-0.2
-0.1
0.0
Change in EELV/TLC
0.1
Lammi,
Lammi,etetalalERJ
ERJ2012
2012ininpress
press
Conclusions
• LVRS improved non-invasive markers of stroke
volume
• Increase in O2 pulse after LVRS correlated with
reductions in static and dynamic hyperinflation
• Strategies to reduce DH might improve exercise
performance in part by ameliorating exerciseinduced cardiac dysfunction
Lammi, et al ERJ 2012 in press
Summary

COPD can impair LV function and it is related
to hyperinflation
Leads to low end-diastolic pressures
 Decreased intra-thoracic blood volumes
 Small cardiac chamber size
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Reducing lung volumes theoretically will help
with improving LV function