Download Myocardial contraction fraction: Ideas for analysis

Myocardial contraction fraction:
Ideas for analysis
Eric Steidley, USA
The Myocardial Contraction Fraction (MCF): A Volumetric Index for Predicting Mortality in Cardiac Transthyretin Amyloidosis
Mat Maurer, MD (Columbia)
D. Eric Steidley, MD (Mayo)
Julius Miller
Using the THAOS Database!
Hypothesis of Study
• Myocardial Contraction Fraction (MCF) will be superior to Left Ventricular Ejection Fraction in predicting survival in TTR Amyloidosis
• MCF will be associated with cardiac phenotype in patients with TTR Amyloidosis Rationale and Background
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History of EF
Physiologic Basis of MCF
Prior Application of MCF in Cardiac Disease
Analysis Plan and Methods for Study
Implications and Limitations
History of Ejection Fraction
• 1950s ‐ physiologists wanted to know EDV and ESV and SV, but no methods for quantification available
• Fluoroscopic techniques could measure outline or area of ventricular chambers
• “Fractional” ejection found to be ~46% and constant across species
Circulation: 1951: The Mechanics of Ventricular Contraction: A
Cinefluorographic Study
Constancy of EF Across Mammals
• In mammals varying 54‐fold in body weight, there is a linear relationship between EDV and ESV and between EDV and SV
• Residual fraction of the left ventricle is ~ the same for all of these animals
• The relationship holds throughout the entire range of mammalian hearts
• All normal mammalian left ventricles in the control state, regardless of the size of the animal, have a residual fraction of approximately 57 per cent, and to eject approximately 43 per cent of the EDV with each beat of the heart
Circulation Research, May 1962
Advantages of Ejection Fraction
• Unit‐less
• Does not need to be indexed
– Thus, independent of •
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Age Gender
Race
Body Size
• Easy to calculate
• Became a well‐established metric
Disadvantages of Ejection Fraction
• Affected by loading conditions
– Afterload sensitive (e.g. mitral regurgitation)
• Not an accurate estimate of chamber contractility
• Not able to differentiate physiologic from pathologic hypertrophy
• Often preserved in patients with heart failure
– Thus, EF fails to predict incident HF especially among individuals with preserved EF (heart failure with preserved EF; HFpEF)
Physiologic vs. Pathologic Hypertrophy
HFpEF
(Hypertensive
hypertrophy)
Normal
(Sedentary)
Athlete
(Athletic Heart –
Physiologic
hypertrophy)
Physiologic vs. Pathologic Hypertrophy
Pathologic
Hypertrophy
Normal
(Sedentary)
Athlete
Physiologic
hypertrophy
55-70%
55-70%
55-70%
Definition of MCF
• Defined as:
MCF = Stroke volume / Myocardial volume
• Myocardial volume is constant from end diastole to end systole
• Epicardial and endocardial SV are equal
• Thus indexing stroke volume to myocardial volume is a novel index of myocardial function that delineates a volumetric index of myocardial shortening
J Am Coll Cardiol 2002;40:325-9
Incompressibility of Myocardium
= Endocardial Volume
= Myocardial Volume
Myocardial Mass is constant from diastole to systole and since density of myocardium constant so is myocardial volume
=
EDV
minus
J Am Soc Echocardiogr 2002;15(12):1503‐6.
ESV
=
Stroke
Volume
Basis for MCF
= Endocardial Volume
= Myocardial Volume
minus
Epicardial
ESV =
EDV
minus
ESV
Epicardial
SV
= Epicardial
EDV
= Epicardial Volume
=
Endocardial
SV
Physiologic vs. Pathologic Hypertrophy
Pathologic
Hypertrophy
Normal
(Sedentary)
Athlete
Physiologic
hypertrophy
55-70%
55-70%
55-70%
Myocardial Contraction Fraction: Differentiating Physiologic and Pathologic Hypertrophy
J Am Coll Cardiol 2002;40:325-9
MCF in Cardiac Amyloid
• Amyloid causes thickening of the ventricular wall and increased myocardial mass that results in a reduction in EDV
• Thus, despite declines in SV that accompany disease progression, the ejection fraction (EF) remains ‘‘normal’’ or ‘‘preserved’’ even in advanced stages because of progressive reductions in ventricular chamber capacitance
• MCF should be superior to EF, the conventional measure of left biventricular function, in predicting survival among patients with cardiac amyloidosis
Amyloid 2014 Dec 16:1-6
66 patients with cardiac amyloid:
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34 AL
32 TTR
No difference in baseline LVEF 54% vs 49%
MCF in Cardiac Amyloid
Amyloid 2014 Dec 16:1-6
MCF in Cardiac Amyloid
Amyloid 2014 Dec 16:1-6
MCF in Cardiac Amyloid
Amyloid 2014 Dec 16:1-6
Analysis and Methods
• Echo data in THAOS will allow calculation of Myocardial Volume (LV Mass/density of muscle)
• LV End Systolic Dimension
• LV End Diastolic Dimension
• Interventricular septal thickness
• Posterior wall thickness
• Stroke Volume = EDV‐ ESV
• MCF = SV / MV
Potential Covariates
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Age
Gender
Race/Ethnicity
mBMI
Mean Arterial BP and HR
Renal Function (eGFR)
voltage of ECG
Mutation and phenotype
Outcome: Death or CV Transplant
• Examination of baseline covariates • Evaluate continuous relationships across quintiles for MCF
• Cox Models to calculate Hazard ratios
• Construct a multivariate analysis after adjusting for any other variables that are found to be predictive of outcome (i.e. age, race, BP)
Implications & Limitations
• MCF may reflect the impact of amyloid on cardiac function better than EF
• Simple, “low tech” method • Useful too for large database work
• MCF can be calculated using Cardiac MR
• Missing data on MCF component measures