Dissecting myocardial mechanics in patients with severe aortic stenosis: 2-dimensional vs 3-dimensional-speckle tracking echocardiography.

BACKGROUND: Aortic stenosis (AS) causes left ventricular (LV) pressure overload, leading to adverse LV remodeling and dysfunction. Identifying early subclinical markers of LV dysfunction in patients with significant AS is critical as this could provide support for earlier intervention, which may result in improved long-term outcomes. We therefore examined the impact of severe AS and its consequent increase in LV afterload on myocardial deformation and rotational mechanics by 2-dimensional (2D) and 3-dimensional (3D) speckle-tracking echocardiography. METHODS: We prospectively measured various strain parameters in 168 patients (42% female, mean age 72 ± 12 years) with severe AS and LV ejection fraction (EF) ≥50%, and compared them to normal values found in literature. 2D and 3D images were analyzed for global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS), basal rotation, apical rotation, and peak systolic twist. We further assessed the degree of concordance between 2D and 3D strain, and examined their association with measures of LV preload and afterload. RESULTS: Patients with severe AS exhibited significantly lower GLS and GRS but higher GCS, apical rotation, and twist by 2D and 3D echocardiography compared with published normal values (P = 0.003 for 3D twist, P < 0.001 for all others). Agreement between 2D- and 3D-GLS by concordance correlation coefficient was 0.49 (95% confidence interval: 0.39-0.57). GLS was correlated with valvulo-arterial impedance, a measure of LV afterload (r = 0.34, p < 0.001 and r = 0.23, p = 0.003, respectively). CONCLUSION: Patients with severe AS demonstrated lower-than-normal GLS and GRS but appear to compensate with higher-than-normal GCS, apical rotation, and twist in order to maintain a preserved LVEF. GLS showed a modest correlation with valvulo-arterial impedance.

A comparison of infarct mass by cardiac magnetic resonance and real time myocardial perfusion echocardiography as predictors of major adverse cardiac events following reperfusion for ST elevation myocardial infarction.

PURPOSE: Infarct mass as assessed by myocardial-delayed enhancement imaging on cardiac magnetic resonance (CMR) and myocardial blood flow as assessed by real time myocardial perfusion echocardiography (RT-MPE) have been shown to predict adverse events following ST elevation myocardial infarction (STEMI). There has been no published comparison of quantitative assessment using these modalities as predictors of clinical outcomes to date. We compared RT-MPE with CMR for prediction of cardiac events in reperfused STEMI patients. MATERIALS AND METHODS: Consecutive STEMI patients with early reperfusion were studied. RT-MPE and CMR were performed. Perfusion score indices (PSIRT-MPE and PSICMR ) were calculated [sum of segmental perfusion scores/number of segments]. CMR infarct mass (g) and RT-MPE myocardial blood flow (MBF dB/s) were quantified. Patients were followed for cardiac events (death, nonfatal MI, revascularization, angina, and heart failure). RESULTS: All 27 patients (age 62±14; follow-up 3.5±2.6 years) had thrombolysis in myocardial infarction (TIMI) grade 3 flow of infarct vessel. Cardiac events occurred in 17 (63%). Cardiac event patients had higher PSIRT-MPE , PSICMR , infarct mass, and lower MBF. PSIRT-MPE cutoff of 0.3 had an AUC of 0.856 (82% sensitivity, 70% specificity), while a PSICMR cutoff of 0.2 had an AUC of 0.765 (76% sensitivity, 60% specificity). Infarct mass and MBF were independent predictors of cardiac events after adjusting for risk factors (hazard ratios: 20.9 [95% CI 1.8-256] P=.02 and 8.1 [95% CI 1.5-78] P=.01, respectively). CONCLUSIONS: Quantitative RT-MPE performed comparably to CMR for prediction of MACE in STEMI patients supporting a prognostic role for this noninvasive, bedside imaging method.

Changes in vascular function and correlation with cardiotoxicity in women with newly diagnosed breast cancer undergoing HER2-directed therapy with and without anthracycline/cyclophosphamide.

Aims: The objective of this study was to assess the effect of HER2-directed therapy (HER2-Tx) on peripheral vasoreactivity and its correlation with cardiac function changes and the additive effects of anthracycline/cyclophosphamide (AC) therapy and baseline cardiovascular risk. Methods and results: Single-centre, prospective cohort study of women with newly diagnosed stage 1-3 HER2-positive breast cancer undergoing HER2-Tx +/- AC. All participants underwent baseline and 3-monthly evaluations with Endo-Peripheral Arterial Tonometry (Endo-PAT), vascular biomarkers [C-type natriuretic peptide (CNP) and neuregulin-1 beta (NRG-1ß)], and echocardiography. Cardiotoxicity was defined as a decrease in the left ventricular ejection fraction (LVEF) of >10% to a value <53%. Of the 47 patients enrolled, 20 (43%) received AC in addition to HER2-Tx. Deterioration of reactive hyperaemia index (RHI) on Endo-PAT by ≥20% was more common in patients receiving HER-Tx plus AC than HER2-Tx alone (65% vs. 22%; P = 0.003). A decrease in CNP and log NRG-1ß levels by 1 standard deviation did not differ significantly between the AC and non-AC groups (CNP: 20.0% vs. 7.4%; P = 0.20 and NRG-1ß: 15% vs. 11%; P = 0.69) nor did GLS (35% vs. 37%; P = 0.89). Patients treated with AC had a significantly lower 3D LVEF than non-AC recipients as early as 3 months after exposure (mean 59.3% (SD 3) vs. 63.8% (SD 4); P = 0.02). Reactive hyperaemia index and GLS were the only parameters correlating with LVEF change. Conclusion: Combination therapy with AC, but not HER2-Tx alone, leads to a decline in peripheral vascular and cardiac function. Larger studies will need to define more precisely the causal correlation between vascular and cardiac function changes in cancer patients.

Characterization of myocardial mechanics and its prognostic significance in patients with severe aortic stenosis undergoing aortic valve replacement.

Aims: Aortic stenosis (AS) induces characteristic changes in left ventricular (LV) mechanics that can be reversed after aortic valve replacement (AVR). We aimed to comprehensively characterize LV mechanics before and after AVR in patients with severe AS and identify predictors of short-term functional recovery and long-term survival. Methods and results: We prospectively performed comprehensive strain analysis by 2D speckle-tracking echocardiography in 88 patients with severe AS and LV ejection fraction ≥50% (mean age 71 ± 12 years, 42% female) prior to and within 7 days after AVR. Patients were followed for up to 5.2 years until death from any cause or last encounter. Within days after AVR, we observed an absolute increase in global longitudinal strain (GLS) (-16.0 ± 2.0% vs. -18.5 ± 2.1%, P<0.0001) and a decrease in apical rotation (10.5 ± 4.0° vs. 8.3 ± 2.8°, P = 0.0002) and peak systolic twist (18.2 ± 5.0° vs. 15.5 ± 3.8°, P = 0.0008). A baseline GLS is less negative than -16.2% was 90% sensitive and 67% specific in predicting a ≥ 20% relative increase in GLS. During a median follow-up of 3.8 years, a global circumferential systolic strain rate (GCSRs) less negative than -1.9% independently predicted lower survival. Conclusion: In patients with severe AS, a reversal in GLS, apical rotation, and peak systolic twist abnormalities towards normal occurs within days of AVR. Baseline GLS is the strongest predictor of GLS recovery but neither was associated with long-term survival. In contrast, abnormal baseline GCSRs are associated with worse outcomes.

Characteristics and Consequences of Work-Related Musculoskeletal Pain among Cardiac Sonographers Compared with Peer Employees: A Multisite Cross-Sectional Study.

BACKGROUND: Work-related musculoskeletal pain (WRMSP) among cardiac sonographers has been incompletely studied. The aim of this study was to compare the frequency, magnitude, and impact of WRMSP among cardiac sonographers with those of a control group of peer employees. METHODS: An electronic survey was sent to cardiac sonographers and peer employees assigned to different occupational exposures within the Department of Cardiovascular Medicine at 10 Mayo Clinic facilities in four states. RESULTS: A total of 416 subjects completed the survey: 111 sonographers (27%) and 305 peer-employee control subjects (73%). The mean age was 43 ± 11 years, and 307 subjects (74%) were women. The sonographers' response rate was 86%. WRMSP was experienced by a large majority of sonographers (95 [86%] vs 140 [46%] for control subjects, P < .001). This association persisted after multivariate adjustment (odds ratio, 8.18; 95% confidence interval, 4.33-15.46; P < .001). Compared with coworkers, sonographers' pain was perceived as more severe (pain score > 5 on a 10-point scale; 62% vs 29%, P < .001) and as getting worse (14% vs 2%, P < .001). The neck (58% vs 25%), shoulder (51% vs 11%), lower back (44% vs 26%), and hand (42% vs 9%) were the most frequently affected body regions (P < .001 for each). The presence of WRMSP in sonographers was more often associated with interference in performance of daily (37% vs 12%, P < .001) and work-related (42% vs 11%, P < .001) activities. Because of pain, sonographers more often sought medical evaluation (27% vs 12%, P < .001), missed work (13% vs 4%, P < .001), had work restrictions (5% vs 0.6%, P = .005), and were considering changing employment (9% vs 0.5%, P < .001) compared with control subjects. CONCLUSIONS: WRMSP in cardiac sonographers is much more prevalent and severe compared with peer employees. WRMSP in sonographers affects daily and work-related activities, as well as future employment plans. Further studies assessing the potential role of preventive interventions are needed.

Echocardiographic Assessment for the Detection of Cardiotoxicity Due to Vascular Endothelial Growth Factor Inhibitor Therapy in Metastatic Renal Cell and Colorectal Cancers.

BACKGROUND: Cardio-oncology is a recently established discipline that focuses on the management of patients with cancer who are at risk for developing cardiovascular complications as a result of their underlying oncologic treatment. In metastatic colorectal cancer (mCRC) and metastatic renal cell carcinoma (mRCC), vascular endothelial growth factor inhibitor (VEGF-i) therapy is commonly used to improve overall survival. Although these novel anticancer drugs may lead to the development of cardiotoxicity, whether early detection of cardiac dysfunction using serial echocardiography could potentially prevent the development of heart failure in this patient population requires further study. The aim of this study was to investigate the role of two-dimensional speckle-tracking echocardiography in the detection of cardiotoxicity due to VEGF-i therapy in patients with mCRC or mRCC. METHODS: Patients with mRCC or mCRC were evaluated using serial echocardiography at baseline and 1, 3, and 6 months following VEGF-i treatment. RESULTS: A total of 40 patients (34 men; mean age, 63 ± 9 years) receiving VEGF-i therapy were prospectively recruited at two academic centers: 26 (65%) were receiving sunitinib, eight (20%) pazopanib, and six (15%) bevacizumab. The following observations were made: (1) 8% of patients developed clinically asymptomatic cancer therapeutics-related cardiac dysfunction; (2) 30% of patients developed clinically significant decreases in global longitudinal strain, a marker for early subclinical cardiac dysfunction; (3) baseline abnormalities in global longitudinal strain may identify a subset of patients at higher risk for developing cancer therapeutics-related cardiac dysfunction; and (4) new or worsening hypertension was the most common adverse cardiovascular event, afflicting nearly one third of the study population. CONCLUSIONS: Cardiac dysfunction defined by serial changes in myocardial strain assessed using two-dimensional speckle-tracking echocardiography occurs in patients undergoing treatment with VEGF-i for mCRC or mRCC, which may provide an opportunity for preventive interventions.

Rationale for Cardio-Oncology Units.

With the rapidly rising number of patients surviving cancer, often in the setting of new or pre-existing cardiovascular disease and risk factors, a need has arisen for a specialty within the realm of cardiovascular care that can evaluate and manage these patients along with our colleagues in oncology and hematology. By the same token, all health care providers involved in the care of cancer patients with heart disease must be fully aware of the impact of adverse cardiovascular effects on the survival of these patients. Collaboration is required to mitigate the effect of cardiovascular toxicity associated with these necessary life-saving cancer therapies. The cardio-oncologist plays a pivotal role in bridging the 2 specialties, by creating a comprehensive plan to address the comorbidities as well as to provide guidance on the optimal choice of therapy. In this 3-part review, we will outline: a) the significant impact of cancer therapies on the cardiovascular health of patients with cancer and cancer survivors, b) the advantage of a multidisciplinary team in addressing these cardiovascular complications, and c) the delivery of clinical care to patients with cancer and heart disease.

Prognosis of Light Chain Amyloidosis With Preserved LVEF: Added Value of 2D Speckle-Tracking Echocardiography to the Current Prognostic Staging System.

OBJECTIVES: This study evaluated whether 2-dimensional speckle-tracking echocardiography (2D-STE) has incremental value for prognosis over traditional clinical, echocardiographic, and serological markers-with main focus on the current prognostic staging system-in light-chain (AL) amyloidosis patients with preserved left ventricular ejection fraction. BACKGROUND: Cardiac amyloidosis (CA) is the major determinant of outcome in AL amyloidosis. The current prognostic staging system is based primarily on serum levels of cardiac troponin T (cTnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and free light chain differential (FLC-diff). METHODS: Consecutive patients with biopsy-proven AL amyloidosis and left ventricular ejection fraction ≥55% were divided into group 1 with CA (n = 63) and group 2 without CA (n = 87). Global longitudinal strain (GLS) by 2D-STE was performed with Vivid E9 (GE Healthcare Co., Milwaukee, Wisconsin) and syngo Velocity Vector Imaging (VVI) software (Siemens Medical Solutions USA, Inc., Malvern, Pennsylvania) (GLSGE and GLSVVI, respectively). RESULTS: Thirty-two deaths (51%) occurred in group 1 and 13 (15%) in group 2 (p ≤ 0.001). Group 1 had thicker walls, lower early diastolic tissue Doppler velocity at septal mitral annulus, and greater left ventricular mass, left atrial volume, glomerular filtration rate, FLC-diff, cTnT, and NT-proBNP (p < 0.001). For the entire cohort, GLSGE ≥ -14.81, GLSVVI ≥-15.02, cTnT, NT-proBNP, FLC-diff, age, left ventricular wall thickness, early diastolic tissue Doppler velocity at septal mitral annulus, diastolic dysfunction grade, glomerular filtration rate, deceleration time, and left atrial volume were univariate predictors of death. In a multivariate Cox model, GLSGE ≥-14.81 (hazard ratio [HR]: 2.68; 95% confidence interval [CI]: 1.07 to 7.13; p = 0.03), FLC-diff, NT-proBNP, and age were independent predictors of survival. There was also a strong trend for GLSVVI ≥-15.02 (HR: 2.44; 95% CI: 0.98 to 6.33; p = 0.055). Using a nested logistic regression model, GLSGE (p = 0.03) and GLSVVI (p = 0.05) provided incremental prognostic value over cTnT, NT-proBNP, and FLC-diff. For survival analysis limited to group 2 (non-CA), GLSGE and GLSVVI both predicted all-cause mortality (GLSGE HR: 1.23; 95% CI: 1.03 to 1.47 [p = 0.02]; GLSVVI HR: 1.22; 95% CI: 1.01 to 1.49 [p = 0.04], respectively). CONCLUSIONS: 2D-STE predicted outcome and provided incremental prognostic information over the current prognostic staging system, especially in the group without CA.

Detection of Carotid Atherosclerotic Plaque Neovascularization Using Contrast Enhanced Ultrasound: A Systematic Review and Meta-Analysis of Diagnostic Accuracy Studies.

BACKGROUND: Intraplaque neovascularization is considered an important indicator of plaque vulnerability. Contrast-enhanced ultrasound (CEUS) of carotid arteries improves imaging of carotid intima-media thickness and permits real-time visualization of neovascularization of the atherosclerotic plaque. The authors conducted a systematic review and meta-analysis to evaluate the accuracy of CEUS-detected carotid atherosclerotic plaque. METHODS: A systematic search was performed to identify studies published in the MEDLINE, Embase, Scopus, and Web of Science databases from 2004 to June 2015. Studies evaluating the accuracy of quantitative analysis and qualitative analysis (visual interpretation) for the diagnosis of intraplaque neovascularization compared with histologic specimens and/or clinical diagnosis of symptomatic plaque were included. Parameters evaluated were plaque quantitative CEUS intensity and the visual grading of plaque CEUS. A random-effects meta-analysis was used to pool the likelihood ratios (LRs), diagnostic odds ratios, and summary receiver operating characteristic curves. Corresponding areas under the curves were calculated. RESULTS: The literature search identified 203 studies, 20 of which were selected for systematic review; the final meta-analysis included seven studies. For qualitative CEUS, pooled sensitivity was 0.80 (95% CI, 0.72-0.87), pooled specificity was 0.83 (95% CI, 0.76-0.89), the pooled positive LR was 3.22 (95% CI, 1.67-6.18), the pooled negative LR was 0.24 (95% CI, 0.09-0.64), the pooled diagnostic odds ratio was 15.57 (95% CI, 4.94-49.03), and area under the curve was 0.894. For quantitative CEUS, pooled sensitivity was 0.77 (95% CI, 0.71-0.83), pooled specificity was 0.68 (95% CI, 0.62-0.73), the pooled positive LR was 2.34 (95% CI, 1.69-3.23), the pooled negative LR was 0.34 (95% CI, 0.25-0.47), the pooled diagnostic odds ratio was 7.06 (95% CI, 3.6-13.82), and area under the curve was 0.888. CONCLUSIONS: CEUS is a promising noninvasive diagnostic modality for detecting intraplaque neovascularization. Standardization of quantitative analysis and visual grading classification is needed to increase reliability and reduce technical heterogeneity.

Relationship between glycosylated hemoglobin A1c and coronary flow reserve in patients with Type 2 diabetes mellitus.

Type 2 diabetes mellitus patients are at increased risk for macrovascular and microvascular complications. Both in vivo and in vitro studies of small arteries and arterioles of diabetic subjects demonstrate impaired endothelial function without anatomic lesions. Coronary flow reserve (CFR) is a surrogate marker of coronary microcirculatory endothelial function in diabetic patients without significant stenosis of the associated epicardial coronary artery. Glycosylated hemoglobin A1c is related to likelihood of occurrence of microvascular events. The objective of this article is to report on recent developments in multiple noninvasive techniques to assess CFR and their use in aiding the understanding of the relationship of CFR, glycemic control and cardiovascular outcomes.

Regadenoson Stress Real-Time Myocardial Perfusion Echocardiography for Detection of Coronary Artery Disease: Feasibility and Accuracy of Two Different Ultrasound Contrast Agents.

BACKGROUND: The aim of this study was to compare the efficacy of myocardial perfusion (MP) and wall motion (WM) analysis obtained with real-time myocardial contrast echocardiography (RTMCE) and two widely used contrast agents in detecting coronary artery disease after injection of the vasodilator regadenoson. METHODS: One hundred fifty patients were studied at two academic centers using regadenoson (400-µg intravenous bolus) vasodilator stress RTMCE (7.5% Optison infusion [n = 50] or 1.5% Definity infusion [n = 100]). Both MP and WM with RTMCE were analyzed at rest and after regadenoson bolus. Comparisons of WM and MP sensitivity, specificity, and accuracy were made. Quantitative angiography was performed in all patients within 1 month of the regadenoson stress study (>50% and >70% diameter stenosis was considered significant). Reviewers were blinded to all clinical and quantitative angiographic data. RESULTS: Rate-pressure product after regadenoson was higher in Optison than Definity patients (P = .004). Using a 50% diameter stenosis on quantitative angiography as a reference standard, overall sensitivity, specificity, and accuracy for combined WM and MP analysis were not different for both agents (Optison, 77%, 64%, and 73%; Definity, 80%, 74%, and 78%; P = NS). The sensitivity, specificity, and accuracy of WM analysis alone for Optison were 68%, 71%, and 69% compared with 60%, 72%, and 66% for Definity (P = NS). Adding MP analysis improved the sensitivity and accuracy of Definity for detecting both >50% and >70% stenoses (P < .001 vs WM), while MP analysis did not improve the sensitivity of Optison for detecting either >50 or >70% stenoses. CONCLUSIONS: RTMCE during regadenoson stress using either Optison or Definity is a rapid and effective method for the detection of coronary artery disease. The ability of MP imaging to improve WM accuracy may depend on the rate-pressure product achieved.

Relationship between HgbA1c and myocardial blood flow reserve in patients with type 2 diabetes mellitus: noninvasive assessment using real-time myocardial perfusion echocardiography.

To study the relationship between glycosylated hemoglobin (HgbA1c) and myocardial perfusion in type 2 diabetes mellitus (T2DM) patients, we prospectively enrolled 24 patients with known or suspected coronary artery disease (CAD) who underwent adenosine stress by real-time myocardial perfusion echocardiography (RTMPE). HgbA1c was measured at time of RTMPE. Microbubble velocity (ß min(-1)), myocardial blood flow (MBF, mL/min/g), and myocardial blood flow reserve (MBFR) were quantified. Quantitative MCE analysis was feasible in all patients (272/384 segments, 71%). Those with HgbA1c > 7.1% had significantly lower ßreserve and MBFR than those with HgbA1c ≤ 7.1% (P < 0.05). In patients with suspected CAD, there was a significant inverse correlation between MBFR and HgbA1c (r = -0.279, P = 0.01); however, in those with known CAD, this relationship was not significant (r = -0.117, P = 0.129). Using a MBFR cutoff value > 2 as normal, HgbA1c > 7.1% significantly increased the risk for abnormal MBFR, (adjusted odds ratio: 1.92, 95% CI: 1.12-3.35, P = 0.02). Optimal glycemic control is associated with preservation of MBFR as determined by RTMPE, in T2DM patients at risk for CAD.