Myocardial Contraction Fraction Research Articles

Abstract 13456: Screening for Transthyretin Cardiac Amyloidosis Using 99mTc-Pyrophosphate Scintigraphy in Patients Undergoing Transcatheter Aortic Valve Replacement

Background: Transthyretin cardiac amyloidosis (ATTR-CA) is an increasingly recognized cause of heart failure with preserved ejection fraction (EF). Bone scintigraphy has emerged as a non-invasive imaging approach that is highly sensitive and specific for identifying ATTR-CA. We conducted a prospective cohort study using 99m Tc-pyrophosphate scintigraphy ( 99m Tc-PYP) to determine the prevalence of ATTR-CA and other clinical associations with 99m Tc-PYP positivity in older patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). Methods: A total of 40 patients (53% men) with severe AS underwent 99m Tc-PYP planar cardiac imaging within 30 days of TAVR. Myocardial uptake was assessed with both a semi-quantitative visual score (range 0: no uptake to 3: uptake greater than bone) and by quantitative analysis by drawing a region of interest over the heart, mirroring it to the contralateral chest, and calculating a heart-to-contralateral ratio (HCL). Semi-quantitative score ≥ 2 and HCL ≥ 1.5 were considered positive for ATTR-CA. Demographics and pre-TAVR clinical history, laboratory values, EKG, and echocardiographic data were also analyzed for association with 99m Tc-PYP positivity. Results: Among 40 patients (mean age 85.2 + 5.3 years), 99m Tc-PYP uptake was found in 10% (n=4), all men. Mean semi-quantitative score was 2.8±0.5 and HCL was 1.6±0.1. Elevated BNP (1379±689 vs 438±483 pg/ml, p=0.02), decreased serum albumin (3.2±0.5 vs 3.8±0.5 g/dL, p=0.02), and both larger interventricular septal wall (1.3±0.4 vs 1.0±0.2 cm, p=0.01) and left posterior wall thickness (1.3±0.6 vs 0.9±0.2 cm, p=0.04) at diastole were associated with 99m Tc-PYP positivity. There was no difference in EF, but myocardial contraction fraction, the ratio of stroke volume to myocardial volume, was significantly lower, 24±12% vs 45±18%, in 99m Tc-PYP positive patients (p=0.03). Conclusions: 99m Tc-PYP has potential as a screening tool for ATTR-CA in high-risk populations. Our data suggest that ATTR-CA may be prevalent in patients undergoing TAVR, particularly men, 20% of whom had a positive 99m Tc-PYP scan. Identifying specific etiologies of heart failure in TAVR patients may be important for prognostication and response to therapy.

Cardiologic Phenotypes and Natural History of FAC

Fifty years ago, the focus on the Val30Met type of the disease, in which neurologic manifestations predominate, led to the widespread notion that hereditary transthyretin-related amyloidosis (ATTR) was essentially a neurologic disease. It is now clear that ATTR is extremely heterogeneous on both genotypic and phenotypic grounds. The clinical spectrum of the disease ranges from an almost exclusive neurologic involvement to strictly cardiac manifestations. This heterogeneity is linked to several factors including specific transthyretin mutations, geographic distribution and endemic vs. non-endemic aggregation type. The existence of exclusively or predominantly cardiac phenotypes makes the recognition of the disease very challenging since it can mimic other more common causes of left ventricular “hypertrophy”. Assessment of such patients should include an active search for possible red flags that can indicate the correct final diagnosis. More in general the clinician must be aware that: • Cardiac amyloidosis (CA) should be suspected in any patient with heart failure, unexplained increased LV wall thickness and non-increased end systolic left ventricular volume • In a patient with an initial diagnosis of hypertrophic cardiomyopathy (HCM), look for the infiltrative phenotype hidden beneath the hypertrophic one! • A distinctive sign of CA is the abnormal ratio between left ventricular thickness and QRS voltages rather than low QRS voltages, alone. The absence of low QRS voltages doesn’t rule out a CA if the context is otherwise fitting and up to 20% of subjects with CA can have electrocardiographic evidence of left ventricular hypertrophy. • In an elderly man with unexplained concentric left ventricular hypertrophy, especially in the absence of hypertension, always consider the possibility of wtTTR CA! • Amyloidotic cardiomyopathy in an elderly patient with monoclonal gammopathy is not necessarily related to AL: consider the possibility of wTTR + MGUS • Longitudinal LV function can be severely depressed despite a normal LVEF and the myocardial contraction fraction is often low suggesting reduced global myocardial shortening. • Myocardial deformation is reduced in amyloidotic cardiomiopathy but the apex is generally spared • In CA, Gadolinium distribution at MRI is heterogeneous: subendocardial late gadolinium enhancement (LGE) is not the only diagnostic pattern and the absence of LGE does not exclude CA. • Bilateral carpal tunnel syndrome in a man with HCM-like phenotype on echo is highly suggestive of TTR-related CA The natural history of ATTR is only partially known, due to the rarity of the disease and its high genotypic heterogeneity. Patients with ATTR cardiomyopathy have a much more indolent course than those with AL etiology. Progression of neurological disease and heart failure are the leading causes of death. As in AL amyloidosis, in ATTR the presence of cardiac involvement is an incremental risk factor for overall and cardiovascular events. Consequently, non-Val30Met mutations, in which cardiac involvement is more frequent and severe, appear to be associated with a particularly poor prognosis, even after successful OLT . Very little is known about the underlying cause and the incidence of sudden death, which has been reported to be associated with the occurrence of advanced atrioventricular blocks, ventricular tachycardia/fibrillation, or, probably more frequently, electromechanical dissociation.

The myocardial contraction fraction is superior to ejection fraction in predicting survival in patients with AL cardiac amyloidosis

Cardiac amyloidosis is a cause of diastolic heart failure in which ejection fraction (EF) remains “normal” despite progression of disease. The myocardial contraction fraction (MCF) is an index of myocardial function, defined as stroke volume (SV) over myocardial volume (MV). We hypothesized that MCF would be superior to EF, the conventional measure of left ventricular function, in predicting survival among patients with cardiac amyloidosis. Sixty-six subjects (mean age = 67 ± 12 years; 20% women) with cardiac amyloidosis (34 with light-chain amyloid and 32 with transthyretin amyloid) underwent two-dimensional echocardiography to determine left ventricular structure and function. Cox proportional hazard modeling was used to determine the association of MCF and EF with survival. Over a mean follow-up of 1.86 ± 1.78 years (range 0.03–7.36 years), 37 subjects (56.1%) died. Mean EF of the study population was 51 ± 13%. There was no significant difference in EF between patients who survived the study period and those who died (54 ± 11% versus 49 ± 14%; p = 0.1196) while there was a significant difference in MCF (35 ± 19% versus 23 ± 10%, p = 0.0065). Using Cox proportional hazards modeling, MCF was associated with death (HR = 0.953, 95% CI of 0.932–0.984, p = 0.0031) while EF was not (HR = 0.991, 95% CI of 0.968–1.014, p = 0.4320). In a multivariate model, amyloid light-chain (AL) amyloid type was an independent risk predictor of death with a HR of 2.841 (95% CI of 1.214–6.648, p = 0.0161) along with a MCF < 30 with a HR of 2.567 (95% CI of 1.197–5.508, p = 0.0155), which was driven by a higher risk in AL subjects with a MCF < 30, HR of 3.39 (95% CI of 1.20–9.55, p = 0.021) than TTR subjects with a MCF < 30, HR of 1.26 (95% CI of 0.36–3.28, p = 0.87). In conclusion, MCF, a novel measure of myocardial chamber function, is superior to EF in predicting overall survival among patients with AL cardiac amyloidosis.

Abstract P322: Myocardial Contraction Fraction is an Independent Predictor of Incident Adverse Cardiovascular Events; The Framingham Heart Study

Introduction: Myocardial contraction fraction (MCF) is the ratio of left ventricular (LV) stroke volume to myocardial volume, and thus a measure of LV pumping capacity per unit of myocardium. We sought to determine whether MCF measured using current steady-state free precession (SSFP) cardiac magnetic resonance (CMR) sequences was an independent predictor of incident “hard” cardiovascular disease (CVD) events, defined by myocardial infarction (MI), stroke, unstable angina (UA), hospitalized heart failure (HF) or CVD death in a community dwelling cohort initially free of these CVD events. Methods: 1794 members of the Framingham Heart Study Offspring cohort (aged 65±9 years) underwent CMR between 2002-2006 using a 1.5-Tesla system with contiguous multislice SSFP cine imaging to encompass the left ventricle. MCF was determined from the cine images by a single observer blinded to participant characteristics. We tracked incident hard CVD events over median 6.5-year follow up and used Cox proportional hazards models (adjusted for age, sex, body mass index, systolic blood pressure, diabetes, dyslipidemia, smoking, treatment for hypertension) to determine hazard of hard CVD events per increment (0.10) of MCF. Results: MCF was determined in 1776 (99%) Offspring (835 men). Overall, MCF was greater in women (0.92±0.14 vs. 0.78±0.15 for men), p&lt;0.0001. There were 60 incident hard CVD events during follow up. Incident hard events included 26 MI, 2 UA, 13 stroke, 14 hospitalized HF and 5 CVD deaths. Offspring experiencing an incident event had lower MCF (0.78±0.19 vs. 0.86±0.15 for those free of events), p=0.002. On MV-adjusted Cox proportional hazards analyses, a greater MCF was protective against hard CVD events, HR [95% confidence intervals] = 0.76 [0.63 - 0.93] per 0.10 increment of MCF. Conclusion: Over 6.5-year follow-up, greater MCF is protective against major adverse CVD events, even after adjustment for traditional CVD risk factors in a community dwelling cohort of middle-aged and older predominantly European-descended adults. Determination of MCF requires only knowledge of LV stroke volume and myocardial volume, both of which are routinely determined in a standard CMR examination of the left ventricle, and thus imposes no additional scan-time or analysis burden. While MCF may be clinically useful for prediction of risk for incident hard CVD events, its potential value in younger age groups and other ethnicities remains to be determined.

Early post-contrast T1 mapping yields maximal discriminatory capacity for detection of cardiac amyloid - influence of temporal T1 differences on MOLLI imaging

Methods Myocardial T1 mapping was performed in two cohorts (1) “amyloid +” subjects, defined by biopsy-proven systemic amyloid with associated remodeling suggestive of cardiac involvement (left ventricular [LV] hypertrophy and/or atrial dilation); (2) normative controls without risk factors for amyloid or cardiovascular disease. CMR (1.5T) included 2 components cine-CMR (SSFP) for cardiac structure/function, and T1 mapping for myocardial tissue characterization. T1 mapping was performed using a conventional modified look locker inversion recovery (MOLLI) sequence (flip angle = 30°; matrix 256 × 128; parallel imaging reduction factor =1.5; linear view ordering; 6 Kaiser-Bessel ramp preparation; 17 heart beat acquisition), with T1 calculated using an established formula (T1 = T1* (B/A-1), T1*, A, and B obtained via three-parameter exponential fit). To test time dependent differences in myocardial T1, MOLLI was acquired at sequential time points (3,5,10,14, 20 minutes) following intravenous administration of gadolinium (0.2 mmol/kg). Results 10 subjects (5 amyloid, 5 controls) were studied (44 ± 21 years, 40% male); all amyloid affected subjects had biopsyconfirmed disease (4 light chain type, 1 transthyretin). Amyloid subjects had higher LV mass (200 ± 34 vs. 101 ± 34 gm, p = 0.004), lower myocardial contraction fraction (32 ± 8 vs. 88 ± 27, p = 0.002), and larger left atrial area (26 ± 5 vs. 18 ± 5 cm2, p = 0.03) than controls, but similar LV end-diastolic volume (120 ± 24 vs. 133 ± 45 ml, p = 0.61), stroke volume (66 ± 10 vs. 86 ± 30 ml, p = 0.20), and LVEF (56 ± 10 vs. 65 ± 4%, p = 0.11). MOLLI was successfully acquired in all subjects at each time point: T1 differed significantly (all p ≤ 0.05) between amyloid and control groups at all times (Figure 1). However, magnitude of difference temporally decreased following gadolinium administration (Figure 2): T1 differences between patients and controls were maximal at 3 minutes post-contrast (135 ± 15 vs. 310 ± 61 msec, p = 0.004) with progressive decrements thereafter, as evidenced by 57% relative difference between groups at 3 minutes and only a 36% difference at 20 minutes following gadolinium infusion.

Abstract P243: Myocardial Contraction Fraction, Diabetes, and Heart Failure: The Multi-Ethnic Study of Atherosclerosis

Background: Persons with diabetes mellitus (DM) have altered cardiac structure and function, which increases heart failure (HF) risk. Myocardial contraction fraction (MCF) is an echocardiographic global measure of fractional shortening recently applied to cardiac MRI. We sought to determine if MCF differed by DM status and if MCF predicts HF in the Multi-Ethnic Study of Atherosclerosis, a cohort which enrolled ethnically diverse adults aged 45-84 who were free of clinical CVD. Methods: Analyses included 4991 with MRI data for whom DM status could be ascertained. Left ventricle (LV) volumes and mass (LVM) were calculated by the summation of disks method from cine short axis images. Ejection fraction (EF) is defined as LV stroke volume (SV) / end diastolic luminal volume. MCF is defined as LV SV/ end diastolic myocardial volume. DM was defined as using hypoglycemic drugs or a fasting glucose&gt;125mg/dl. Linear regression was utilized for cross sectional analyses of the association between MCF and DM status, adjusting for age, gender, race/ethnicity, BMI, systolic BP, BP drugs, and smoking. Cox proportional hazards modeling was used to compare MCF, EF and LV mass quartiles as predictors of HF, adjusting for the above variables and DM. Results: At baseline the mean age was 61.5 (SD 10), 52% were female, 39% white, and 61% minorities; 13% had impaired fasting glucose (IFG) and 12% DM. The table indicates LV measurements. After adjustment, DM status remained associated with a lower MCF (IFG -0.02, 95% CI -0.03,-0.01; DM -0.032, 95%CI -0.04, -0.02). There were 96 incident HF events. Compared to the 4 th quartile, the 1 st MCF quartile was associated with HF (adjusted HR 2.2; 95%CI 1.13, 4.43) as was 1 st EF quartile (adjusted HR 2.9; 95%CI 1.6, 5.2) and 4 th quartile LVM (adjusted HR 5.4; 95%CI 2.2, 13.2). Among those with DM, 39% were in the 1 st MCF quartile, compared to 27% in the 1 st EF and 33% in the 4 th LVM quartile. Conclusions: Incident HF is predicted by MCF. MCF may be a more sensitive marker for diabetic cardiomyopathy than EF or LVM. Ventricular Measures by Diabetes Status Glucose Category Parameter Normal 100-125 mg/dl Diabetes p-value MCF 0.66 (0.14) 0.61 (0.14) 0.59 (0.14) &lt;0.001 EF, % 69 (7) 69 (8) 68 (9) 0.11 SV (ml) 87 (20) 86 (19) 86 (19) 0.05 LMV (g) 142 (38) 153 (41) 157 (43) &lt;0.001 Mean (Std Dev)

Usefulness of the Left Ventricular Myocardial Contraction Fraction in Healthy Men and Women to Predict Cardiovascular Morbidity and Mortality

We sought to determine whether depressed myocardial contraction fraction (MCF; ratio of left ventricular [LV] stroke volume to myocardial volume) predicts cardiovascular disease (CVD) events in initially healthy adults. A subset (n = 318, 60 ± 9 years old, 158 men) of the Framingham Heart Study Offspring cohort free of clinical CVD underwent volumetric cardiovascular magnetic resonance imaging in 1998 through 1999. LV ejection fraction (EF), mass, and MCF were determined. "Hard" CVD events consisted of cardiovascular death, myocardial infarction, stroke, or new heart failure. A Cox proportional hazards model adjusting for Framingham Coronary Risk Score was used to estimate hazard ratios for incident hard CVD events for gender-specific quartiles of MCF, LV mass, and LVEF. The lowest quartile of LV mass and highest quartiles of MCF and EF served as referents. Kaplan-Meier survival plots and log-rank test were used to compare event-free survival. MCF was greater in women (0.58 ± 0.13) than in men (0.52 ± 0.11, p <0.01). Nearly all participants (99%) had EF ≥0.55. During an up to 9-year follow-up (median 5.2), 31 participants (10%) developed an incident hard CVD event. Lowest-quartile MCF was 7 times more likely to develop a hard CVD (hazard ratio 7.11, p = 0.010) compared to the remaining quartiles, and increased hazards persisted even after adjustment for LV mass (hazard ratio 6.09, p = 0.020). The highest-quartile LV mass/height 2.7 had a nearly fivefold risk (hazard ratio 4.68, p = 0.016). Event-free survival was shorter in lowest-quartile MCF (p = 0.0006) but not in lowest-quartile LVEF. In conclusion, in a cohort of adults initially without clinical CVD, lowest-quartile MCF conferred an increased hazard for hard CVD events after adjustment for traditional CVD risk factors and LV mass.

P18.04: Application of 3D/4D cardiac functional parameters to evaluation and management of MCBA twins

Background: We recently presented several 3D/4DUS-based fetal cardiac functional measures: end-diastolic and end-systolic ventricular volume and myocardial mass, ejection fraction (obtained by 3DUS), contraction fraction (CF), and 4D-MPI in uncomplicated cases. Management decisions in MCBA twins are traditionally based on degrees of poly/oligohydramnios and Quintero staging, as well as fetal 2DUS-Doppler based measures, myocardial performance index (MPI), or mid-cerebral artery measures. We now applied the above 3D/4DUS-based measures to the evaluation and management of MCBA twins. Methods: During a 12 month period, 15 MCBA twin pregnancies were followed in our center with both classic U/S parameters and 3D/4DUS cardiac functional parameters. During bi-weekly (or more as indicated) examinations, Quintero staging and other 2DUS Doppler parameters including umbilical artery, MCA, and aorta Doppler, shunt determination, and others were evaluated, and in addition 3D/4D based measures: cardiac volumes and mass, EF, CF, and 4D-MPI. Results: 15 MCBA twins were followed. Group I: 6 cases with TTTS (Quintero stage 2–3, 4 of whom eventually required laser ablation); Group II: 4 cases that developed selective IUGR; and 5 MCBA pregnancies progressed normally. In Group II we observed intermittent absent or reversed diastolic flow in the UA, but no other pathologies were noted in 2D or 3D/4D examination. In all Group I cases we observed that in the recipient and the donor, 3D/4D measures: ventricular mass, IVS, EF and 4D-MPI were consistently outside normal range (1–2 SD). Appearance of cardiac functional pathology preceded the appearance of Quintero stage parameters. Following laser ablation, cardiac functional parameters, except for ventricular mass, returned to normal within 96 hours, preceding normalization of Quintero parameters. Conclusions: 3D/4DUS cardiac function surveillance may add to the armamentarium of the evaluation and management of MCBA pregnancies, may be more sensitive to developing or resolving pathology.

133 Obesity is associated with decreased myocardial contraction fraction despite preserved ejection fraction

133 Obesity is associated with decreased myocardial contraction fraction despite preserved ejection fraction

Combined first-pass perfusion and viability study at MR imaging in patients with non-ST segment-elevation acute coronary syndromes: feasibility study.

To assess the feasibility of combined perfusion and viability testing by using magnetic resonance (MR) imaging in one setting in patients with non-ST segment-elevation acute coronary syndromes. The data of 13 patients (mean age, 68 years; range, 40-85 years) at high risk for myocardial infarction who underwent MR imaging at 1.5 T were reviewed. Risk factors were increased troponin T levels in seven, reversible ST depression on an electrocardiogram in four, history of myocardial infarction in two, and presence of heart failure in four. Cine imaging of the left ventricle was performed with a true-fast imaging with steady-state precession (FISP) sequence to assess the regional myocardial contraction and ejection fraction. After injection of 0.1 mmol per kilogram of body weight of gadopentetate dimeglumine, first-pass MR images were obtained by using an inversion-recovery true-FISP sequence at rest and during infusion of adenosine (140 microg/kg/min). Resting and stress images were assessed qualitatively for abnormal regional perfusion (hypoenhancement). The myocardium was divided into three radial segments corresponding to the three coronary artery territories. Delayed (after 15 minutes) contrast material-enhanced images were acquired with use of a segmented inversion-recovery fast low-angle shot sequence. Conventional coronary angiograms were compared with the first-pass images. A more than 50% stenosis in diameter in any coronary artery was considered substantial. Mann-Whitney test was used to assess any significant difference between the left ventricular ejection fraction (LVEF) in patients with and those without myocardial infarct. Mean LVEF was 51.5% (range, 30%-77%). First-pass stress perfusion studies depicted 25 segments of hypoenhancement in 11 patients. Comparison of first-pass perfusion defects with findings on coronary angiograms indicated an overall sensitivity of 92% (24 of 26) and specificity of 92% (12 of 13) in detection of substantial coronary artery disease. Infarcts detected from hyperenhancement on delayed contrast-enhanced images were present in eight segments (four were transmural) in five patients. No significant difference was noted in the LVEF between patients with and those without infarct (P =.724). Combined stress perfusion and viability MR imaging was feasible in patients with acute coronary syndromes. First-pass MR perfusion defects compare well with the presence of substantial coronary artery stenosis on conventional angiograms.

Myocardial contraction fraction: a volumetric index of myocardial shortening by freehand three-dimensional echocardiography.

This study sought to evaluate myocardial contraction fraction (MCF) as an index of myocardial shortening by comparison to conventional shortening indices in patients with hypertensive hypertrophy, athletes with physiologic hypertrophy and sedentary normal adult subjects. A significant percentage of patients with hypertensive hypertrophy have "normal" or "preserved" left ventricular (LV) systolic function by conventional echocardiographic measures whereas their systolic function is depressed when measured by the two-dimensional echocardiographic mid-wall shortening fraction (MWSF). A three-dimensional echocardiographic measure of myocardial shortening analogous to MWSF has been lacking. We describe a volumetric measure of myocardial shortening, the MCF, as the ratio of stroke volume (SV) to myocardial volume (MV), and hypothesize that it may be useful to compare myocardial performance in patients with different degrees and types of hypertrophy. We compared the MCF using freehand three-dimensional echocardiographic reconstruction of the LV to conventional measures of LV function (ejection fraction [EF], endocardial shortening fraction [SF] and MWSF) in subjects with pathologic hypertensive hypertrophy, heart failure symptoms and preserved EF (n = 17), athletes with physiologic hypertrophy (n = 41) and normal sedentary adults (n = 80). The EF was in the normal range for all three groups. The MCF was lower in hypertensive hypertrophy compared with normal subjects (0.33 +/- 0.05 vs. 0.44 +/- 0.07, p < 0.01). It also successfully differentiated physiologic hypertrophy from normal subjects (0.50 +/- 0.05 vs. 0.44 +/- 0.07, p < 0.01). The endocardial SF did not distinguish athletes from normal subjects and the MWSF did not distinguish hypertensive from physiologic hypertrophy. The MCF, a volumetric measure of myocardial shortening, demonstrates that myocardial shortening is decreased in hypertensive hypertrophy and increased in physiologic hypertrophy. The MCF may be useful in assessing differences in myocardial performance in patients with similar degrees of hypertrophy.