Cardioprotection Using Strain-Guided Management of Potentially Cardiotoxic Cancer Therapy: 3-Year Results of the SUCCOUR Trial.

BACKGROUND: Global longitudinal strain (GLS) can predict cancer therapeutics-related cardiac dysfunction and guide initiation of cardioprotection (CPT). OBJECTIVES: In this study, the authors sought to determine whether echocardiography GLS-guided CPT provides less cardiac dysfunction in survivors of potentially cardiotoxic chemotherapy, compared with usual care at 3 years. METHODS: In this international multicenter prospective randomized controlled trial, patients were enrolled from 28 international sites. All patients treated with anthracyclines with another risk factor for heart failure were randomly allocated to GLS-guided (>12% relative reduction in GLS) or ejection fraction (EF)-guided (>10% absolute reduction of EF to <55%) CPT. The primary end point was the change in 3-dimensional (3D) EF (ΔEF) from baseline to 3 years. RESULTS: Among 331 patients enrolled, 255 (77%, age 54 ± 12 years, 95% women) completed 3-year follow-up (123 in the EF-guided group and 132 in the GLS-guided group). Most had breast cancer (n = 236; 93%), and anthracycline followed by trastuzumab was the most common chemotherapy regimen (84%). Although 67 (26%) had hypertension and 32 (13%) had diabetes mellitus, left ventricular function was normal at baseline (EF: 59% ± 6%, GLS: 20.7% ± 2.3%). CPT was administered in 18 patients (14.6%) in the EF-guided group and 41 (31%) in the GLS-guided group (P = 0.03). Most patients showed recovery in EF and GLS after chemotherapy; 3-year ΔEF was -0.03% ± 7.9% in the EF-guided group and -0.02% ± 6.5% in the GLS-guided (P = 0.99) group; respective 3-year EFs were 58% ± 6% and 59% ± 5% (P = 0.06). At 3 years, 17 patients (5%) had cancer therapeutics-related cardiac dysfunction (11 in the EF-guided group and 6 in the GLS guided group; P = 0.16); 1 patient in each group was admitted for heart failure. CONCLUSIONS: Among patients taking potentially cardiotoxic chemotherapy for cancer, the 3-year data showed improvement of LV dysfunction compared with 1 year, with no difference in ΔEF between GLS- and EF-guided CPT. (Strain Surveillance of Chemotherapy for Improving Cardiovascular Outcomes [SUCCOUR]; ACTRN12614000341628).

Speckle tracking global strain rate E/E' predicts LV filling pressure more accurately than traditional tissue Doppler E/E'.

BACKGROUND: The ratio of early diastolic transmitral flow velocity (E) to tissue Doppler (TD) mitral annular early diastolic velocity (E/E'(VEL-TD)) has been widely used for the noninvasive assessment of LV diastolic filling pressures. However, it has been reported that E/E'(VEL-TD) is not accurate particularly when being applied to patients with advanced heart failure. METHODS: Fifty-six ICU patients with decompensated heart failure underwent simultaneous echocardiography and PCWP measurements. Patients with elevated PCWP (n = 41) were compared with patients normal PCWP (n = 15) as well as age-matched healthy controls (n = 32). In the apical 4-chamber view, the ratio of E to speckle tracking (ST) mitral annular velocity (E/E'(VEL-ST)) and early diastolic global LV longitudinal strain rate (E/E'(SR-ST)) were evaluated as new surrogate markers of elevated PCWP. RESULTS: Correlations with PCWP were observed for speckle tracking derived E/E'(VEL-ST) (r = 0.40,P = 0.002) and E/E'(SR-ST) (r = 0.56, P < 0.001), although the traditional E/E'(VEL-TD) did not show a significant correlation (r = 0.23, P = 0.082). Compared with controls, patients with elevated PCWP had significant increases in all variables. The best cutoff values and diagnostic accuracies for identifying elevated PCWP were E/E'(VEL-TD) >12 (Sensitivity/Specificity/area under the ROC curve: 0.58/0.90/0.78), E/E'(VEL-ST) > 14 (0.60/0.85/0.80), and E/E'(SR-ST) > 93 (0.80/0.88/0.89). CONCLUSION: Speckle tracking derived E/E'(SR-ST) may be a robust surrogate marker of elevated LV filling pressure. In ICU patients, E/E'(SR-ST) showed better correlation with PCWP and higher diagnostic accuracy than the tissue Doppler approach.

Early increase in serum fatty acid binding protein 4 levels in patients with acute myocardial infarction.

BACKGROUND: Acute myocardial infarction (AMI) induces marked activation of the sympathetic nervous system. Fatty acid binding protein 4 (FABP4) is not only an intracellular protein, but also a secreted adipokine that contributes to obesity-related metabolic complications. Here, we examined the role of serum FABP4 as a pathophysiological marker in patients with AMI. METHODS AND RESULTS: We studied 106 patients presenting to the emergency unit with a final diagnosis of AMI, including 12 patients resuscitated from out-of-hospital cardiac arrest (OHCA) caused by ventricular fibrillation. FABP4 levels peaked on admission or just after percutaneous coronary intervention and declined thereafter. Regression analysis revealed no significant correlation between peak FABP4 and peak cardiac troponin T determined by Roche high-sensitive assays (hs-TnT). Notably, FABP4 levels were particularly elevated in AMI patients who were resuscitated from OHCA (median 130.2 ng/mL, interquartile range (IQR) 51.8-243.9 ng/mL) compared with those without OHCA (median 26.1 ng/ml, IQR 17.1-43.4 ng/mL), while hs-TnT levels on admission were not associated with OHCA. Immunohistochemistry of the human heart revealed that FABP4 is abundantly present in adipocytes within myocardial tissue and epicardial adipose tissue. An in vitro study using cultured adipocytes showed that FABP4 is released through a ß3-adrenergic receptor (AR)-mediated mechanism. CONCLUSIONS: FABP4 levels were significantly elevated during the early hours after the onset of AMI and were robustly increased in OHCA survivors. Together with the finding that FABP4 is released from adipocytes via ß3-AR-mediated lipolysis, our data provide a novel hypothesis that serum FABP4 may represent the adrenergic overdrive that accompanies acute cardiovascular disease, including AMI.

Improvement in Strain Concordance between Two Major Vendors after the Strain Standardization Initiative.

BACKGROUND: Disagreement of strain measurements among different vendors has provided an obstacle to the clinical use of strain. A joint standardization task force between professional societies and industry was initiated to reduce intervendor variability of strain. Although feedback from this process has been used in software upgrades, little is known about the effects of efforts to improve conformity. The aim of this study was to assess whether intervendor agreement for global longitudinal strain (GLS) has improved after standardization initiatives. METHODS: Eighty-two subjects (mean age, 52 ± 21 years; 55% men) prospectively underwent two sequential examinations using two most common ultrasound systems (Vivid E9 and iE33). GLS was calculated using proprietary software (EchoPAC-PC BT12 [E12] and BT13 [E13] vs QLAB version 8.0 [Q8], QLAB version 9.0 [Q9], and QLAB version 10.0 [Q10]). Agreements in GLS were evaluated with Bland-Altman plots. Coefficients of variation (CVs) were compared using the Friedman test and compared with CVs of left ventricular volumes and ejection fraction (LVEF). RESULTS: Median GLS using E12 was -19.2% (interquartile range [IQR], -15.2% to -23.2%), compared with -19.3% (IQR, -14.9% to -23.7%) for E13, -15.7% (IQR, -11.4% to -20%) for Q8, -19% (IQR, -15.7% to -22.3%) for Q9, and -18.7% (IQR, -15.7% to -21.7%) for Q10. The CVs of prestandardization GLS (12 ± 8% [E12/Q8] and 14 ± 8 [E13/Q8]) were significantly larger than that of LVEF (5 ± 5) (P < .001). Since standardization, the CVs of GLS have shown improvement (6 ± 4 [E12/Q9], 7 ± 4 [E12/Q10], 6 ± 4 [E13/Q9], and 7 ± 4 [E13/Q10]) and are similar to those of LVEF. CONCLUSIONS: Subsequent to the joint standardization task force, there has been improvement in between-vendor concordance in GLS between two leading ultrasound manufactures, the variability of which is now analogous to that of LVEF. The removal of concerns about measurement variability should allow wider use of GLS.

Three cases of vasospastic angina that developed following the initiation of corticosteroid therapy.

Three patients diagnosed as having remitting seronegative symmetrical synovitis with pitting edema syndrome, pemphigus erythematosus and idiopathic interstitial pneumonia were treated with oral prednisolone. Several weeks after starting the treatment, they experienced repeated chest pain attacks between midnight and early morning, although none of the patients had a past history of ischemic heart disease. One of the patients exhibited aggravation of symptoms soon after increasing the dose of prednisolone. A definitive diagnosis of vasospastic angina was made using electrocardiograms, coronary angiography and vasospasm provocation tests. These cases emphasize that clinicians should be aware of the possible occurrence of vasospastic angina following the initiation of corticosteroid therapy.

Prolonged vortex formation during the ejection period in the left ventricle with low ejection fraction: a study by vector flow mapping.

PURPOSE: Vortex formation in the left ventricle (LV) can be visualized by novel vector flow mapping (VFM) based on color Doppler and speckle tracking data. The aim of this study was to evaluate the impact of a vortex during the ejection period using VFM. SUBJECTS AND METHODS: Color Doppler images were obtained to produce VFM images in 80 subjects (20 normal, 29 with dilated cardiomyopathy, and 31 with old myocardial infarction). The duration of the LV vortex was measured and expressed as the ratio to the ejection time (VTRe). RESULTS: The VTRe showed significant correlations with EDV (ρ = 0.672, p < 0.001), ESV (ρ = 0.772, p < 0.001), EF (ρ = -0.783, p < 0.001), left atrium diameter (LAd) (ρ = 0.302, p = 0.007), stroke volume (ρ = -0.600, p < 0.001), e' (ρ = -0.389, p < 0.001), a' (ρ = -0.314, p = 0.005), s' (ρ = -0.512, p < 0.001), and E/e' (ρ = 0.330, p = 0.003). The diastolic parameters (e', a', E/e', LAd) were not correlated when they were adjusted by EF. CONCLUSIONS: In the normal LV, a vortex existed for only a limited time during the early ejection period. In contrast, the lower the EF was, the longer the vortex remained during systole. Evaluation of vortices by VFM may noninvasively provide novel insights into the pathophysiology of impaired cardiac function.

Estimation of the left ventricular diastolic function with cardiac MDCT: correlation of the slope of the time-enhancement-curve with the mitral annulus diastolic velocity.

Patients with diastolic heart failure tend to have a poor outcome, similar to that for patients with systolic heart failure. The aim of this study was to explore the ability of MDCT to estimate the left ventricular diastolic function. Thirty patients with suspected coronary artery disease underwent MDCT and echocardiography. The early transmitral flow velocities (E) and the velocity of mitral annulus early diastolic motion (e') were measured in order to evaluate the diastolic function. The scanning delay of CT was determined using a test injection technique. The aortic enhancement was measured over the aortic-root lumen, and it was plotted over time to yield a time-enhancement-curve. A gamma variate function was then fit to the time-enhancement-curve and thereafter both the 'slope' of enhancement for each patient and the region of interest [ROI] were calculated. According to a univariate analysis, the slope of the time-enhancement-curve was found to correlate with the e' (r = 0.686, P = 0.000) and E/e' (r = -0.482, P = 0.007), however, no significant correlation was observed with the systolic parameters of the left ventricle. These results indicate that the slope of the time-enhancement-curve in the aorta significantly correlates with e', i.e. the diastolic parameters, which are independent of the systolic parameters. Based on these findings, we propose that the slope of the time-enhancement-curve may serve as a parameter for the left ventricular diastolic function on MDCT.

Prediction of coronary artery stenosis using strain imaging diastolic index at rest in patients with preserved ejection fraction.

BACKGROUND: Post-ischemic myocardial diastolic stunning persists for a long time after transient ischemia even after systolic function has recovered. We sought to identify coronary artery stenosis in clinical patients using strain imaging diastolic index (SI-DI) at rest. METHODS: We retrospectively examined 85 patients with suspected coronary artery disease and preserved ejection fraction (EF; >50%) who underwent both echocardiography and coronary angiography. Speckle tracking strains were measured in 3 apical views and parasternal left ventricular (LV) short-axis views at the papillary muscle level. LV segments with inadequate image quality and deficit segments in the movie were excluded by the blinded observer. After strain analysis, LV segments were classified into no stenosis (≤ 50%), mild stenosis (51-75%), and severe stenosis (>75%) groups on the bases of the coronary angiogram. RESULTS: SI-DI decreased significantly in severe stenosis segments (p<0.05, ANOVA), but none of the peak strains showed significant difference. The area under the curve for predicting severe stenosis in radial, longitudinal, and transverse SI-DI was 0.72, 0.74, and 0.80, respectively. A cut-off value of 49 for transverse SI-DI can predict LV segments with severe stenosis with sensitivity of 0.79 and specificity of 0.73. A screening cut-off value of 63 for transverse SI-DI shows sensitivity of 0.95 and specificity of 0.50. CONCLUSION: SI-DI at rest is a novel marker in predicting coronary stenosis even in patients with preserved EF. This index can be used to screen patients with suspected coronary artery disease in routine echocardiography and does not require stress provocation.

The seabed-like appearance of atherosclerotic plaques: three-dimensional transesophageal echocardiographic images of the aortic arch causing cholesterol crystal emboli.

Cholesterol crystal embolism (CCE) is a rare but important complication of endovascular procedures or anticoagulation therapy. An 84-year-old man was referred to the Gunma University Graduate School of Medicine with the diagnosis of acute myocardial infarction. After successful emergency coronary angioplasty, his serum creatinine level increased continuously. A subsequent skin biopsy confirmed that the patient had CCE. Transesophageal echocardiography (TEE) clearly demonstrated the mobile mass protruding from the complex atheroma. Three-dimensional TEE provides more precise and attractive volumetric images of the atherosclerotic plaque than two-dimensional TEE. In addition, the findings of this case revealed contrast media-induced nephropathy and CCE as possible causes of renal dysfunction after endovascular procedures.