Susan E. Wiegers

Assessment of Echocardiography and Biomarkers for the Extended Prediction of Cardiotoxicity in Patients treated with Anthracyclines, Taxanes and Trastuzumab

Background—Because cancer patients survive longer, the impact of cardiotoxicity associated with the use of cancer treatments escalates. The present study investigates whether early alterations of myocardial strain and blood biomarkers predict incident cardiotoxicity in patients with breast cancer during treatment with anthracyclines, taxanes, and trastuzumab. Methods and Results—Eighty-one women with newly diagnosed human epidermal growth factor receptor 2–positive breast cancer, treated with anthracyclines followed by taxanes and trastuzumab were enrolled to be evaluated every 3 months during their cancer therapy (total of 15 months) using echocardiograms and blood samples. Left ventricular ejection fraction, peak systolic longitudinal, radial, and circumferential myocardial strain were calculated. Ultrasensitive troponin I, N-terminal pro–B-type natriuretic peptide, and the interleukin family member (ST2) were also measured. Left ventricular ejection fraction decreased (64 ± 5% to 59 ± 6%; P<0.0001) over 15 months. Twenty-six patients (32%, [22%–43%]) developed cardiotoxicity as defined by the Cardiac Review and Evaluation Committee Reviewing Trastuzumab; of these patients, 5 (6%, [2%–14%]) had symptoms of heart failure. Peak systolic longitudinal myocardial strain and ultrasensitive troponin I measured at the completion of anthracyclines treatment predicted the subsequent development of cardiotoxicity; no significant associations were observed for left ventricular ejection fraction, N-terminal pro–B-type natriuretic peptide, and ST2. Longitudinal strain was <19% in all patients who later developed heart failure. Conclusions—In patients with breast cancer treated with anthracyclines, taxanes, and trastuzumab, systolic longitudinal myocardial strain and ultrasensitive troponin I measured at the completion of anthracyclines therapy are useful in the prediction of subsequent cardiotoxicity and may help guide treatment to avoid cardiac side-effects.

Echocardiography for hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a genetic cardiomyopathy. The prevalence of phenotypic expression, in the absence of another systemic or cardiac disease causing increased left ventricular (LV) wall thickness, is estimated to be 1:500. The frequency of clinical presentation is far less, highlighting the need for a non-invasive diagnostic imaging tool. Echocardiography is readily available and allows for structural characterization and hemodynamic assessment of the hypertrophic heart and to screen patients at-risk for HCM, such as first degree relatives of affected individuals, and differentiate HCM from the athletic heart. Echocardiography can also be used to assess for anatomic abnormalities of the mitral valve apparatus that may exacerbate LV outflow track obstruction and to further risk stratify patients during exercise. Finally, echocardiography plays an integral role in guiding alcohol septal ablation procedures.

Symptomatic Low Gradient Severe Aortic Stenosis with Preserved Left Ventricular Ejection Fraction: Now Less of a Clinical Conundrum

Accurate assessment of aortic stenosis (AS) severity is one of the more technically demanding studies in echocardiography. This is reflected in the Intersocietal Accreditation Commission for Echocardiography standards that specify that AS gradients must be measured from at least 3 different transducer positions and with a nonimaging, dedicated, continuous-wave Doppler transducer (Pedhoff). The standards do not specify the measurement of any other valvular lesion. Submission and review of AS cases is required for laboratory accreditation by that body. Given the complexity in echocardiographic assessment, the determination that a patient has severe AS (defined as a valve area ≤1 cm2 or an indexed area ≤0.6 cm2/m2) but a mean gradient <40 mm Hg despite a preserved left ventricular (LV) ejection fraction (LVEF) is often met with skepticism by our interventional colleagues. Low-gradient severe AS resulting from decreased LV systolic function can be assessed by dobutamine protocols intended to increase the flow across the valve and to distinguish true AS from pseudo-AS.1 Such is usually not the case in patients with preserved LVEF. Article see p 622 Work by a group in Quebec has highlighted the existence of paradoxical low-gradient severe AS (LGSAS) in patients with preserved LVEF but paradoxically low stroke volume.2 The low stroke volume is presumably attributable to a small LV cavity that has been infringed on by LV hypertrophy and decreased myocardial function that has not yet resulted in a decreased LVEF. Milano et al3 performed intraoperative myocardial biopsies on patients undergoing aortic valve replacement (AVR) for AS and demonstrated that those patients with moderate fibrosis had much poorer long-term outcome despite normal LVEF compared with patients with no or mild fibrosis. Other groups have confirmed fibrosis and myocardial dysfunction in these patients with magnetic resonance imaging to assess …

Left Ventricular Remodeling in Human Heart Failure: Quantitative Echocardiographic Assessment of 1,794 Patients

Background: The left ventricle (LV) undergoes significant architectural remodeling in heart failure (HF). However, the fundamental associations between cardiac function and LV size and performance have not been thoroughly characterized in this population. We sought to define the adaptive remodeling that occurs in chronic human HF through the detailed analyses of a large quantitative echocardiography database. Methods: Baseline echocardiograms were performed in 1,794 patients with HF across a broad range of ejection fraction (EF), from less than 10% to greater than 70%. Core lab measurements of LV volumes and length were made, from which EF, mass, sphericity indices, stroke volume (SV), and stroke work were derived. Spearman correlation coefficients and linear regression methods were used to determine the relationships between remodeling parameters. Results: The median EF was 28.6% (IQR 21.9–37.0). Across a multitude of parameters of cardiac structure and function, indexed end‐systolic volumes (ESVs) explained the greatest proportion of the variance in EF (R =−0.87, P < 0.0001). Systolic sphericity index and LV mass were also strongly correlated with EF (R =−0.62 and −0.63, P < 0.0001), reflective of the alterations in LV shape and size that occur as EF declines. SV was rigorously maintained across a broad spectrum of EF, until the EF fell below 20%, at which point SV decreased significantly (P < 0.0001). Conclusions: In chronic HF, the LV undergoes extensive structural adaptive remodeling in order to maintain SV across a broad range of EF. However, when the EF falls below 20%, further modulation of SV is no longer possible through alterations in ventricular architecture.

A Metric‐Based System for Evaluating the Productivity of Preclinical Faculty at an Academic Medical Center in the Era of Clinical and Translational Science

Academic medical centers are faced with increasing budgetary constraints due to a flat National Institutes of Health budget, lower reimbursements for clinical services, higher costs of technology including informatics and a changing competitive landscape. As such, institutional stakeholders are increasingly asking whether resources are allocated appropriately and whether there are objective methods for measuring faculty contributions and engagement. The complexities of translational research can be particularly challenging when trying to assess faculty contributions because of team science. For over a decade, we have used an objective scoring system called the Matrix to assess faculty productivity and engagement in four areas: research, education, scholarship, and administration or services. The Matrix was developed to be dynamic, quantitative, and able to insure that a fully engaged educator would have a Matrix score that was comparable to a fully engaged investigator. In this report, we present the Matrix in its current form in order to provide a well‐tested objective system of performance evaluation for nonclinical faculty to help academic leaders in decision making.

Next Steps in Modeling the Tricuspid Valve

In an era where cardiovascular imaging has allowed us to develop robust models of the aortic and mitral valves that guide cardiac interventions, our attention has now been drawn to the tricuspid valve. Tricuspid regurgitation (TR) is a common finding, present in many normal patients. However, moderate or worse TR is associated with a poor prognosis independent of left ventricle systolic function or the presence of pulmonary hypertension.1 See Article by Utsunomiya et al Functional TR is the result of uncoupling the right heart valvulo-ventricular complex. Although the leaflets are normal, the regurgitant orifice develops from annular dilatation (>40 mm) and valvular deformation or leaflet tenting (>8 mm).2 Patients experiencing right ventricular dilatation and dysfunction will have functional TR primarily because of tenting. Those without significant ventricular remodeling from left heart disease or pulmonary hypertension, but significant tricuspid annular dilatation as seen with atrial fibrillation, will have functional TR primarily because of annular dilatation. In this issue of Circulation: Cardiovascular Imaging , Utsunomiya et al3 were able to achieve structural differentiation of atrial fibrillation TR and left heart TR while demonstrating how 3-dimensional (3D) echocardiography can be used to model the tricuspid valve. They were …

Jill (or Jack) of All Trades, Master of None?

Competency-basedevaluationand training are the latestwatchwords from the Accreditation Council for Graduate Medical Education, now mandated in theNextAccreditation System and arriving on cardiology fellowships’ doorsteps in July 2014. We now have clinical competency committees meeting regularly to evaluate fellows’ advancement along the milestone rubric. COCATS 4—the American College of Cardiology’s 2015Core Cardiovascular Training Statement—is themost recent revision of the document since 2008. It incorporates those competencies andmilestones and announces ‘‘A New Era in Cardiovascular Training.’’ The committee for the new COCATS faced the Herculean task of fitting ever more content into the standard 3-year cardiovascular fellowship, while incorporating the fundamentals of the Next Accreditation System. COCATS has maintained the previously defined levels of competence. Level 1 is ‘‘the basic training required of trainees to become competent consultants.’’ Level 2 encompasses the training that ‘‘enables some cardiovascular specialists to perform or interpret specific diagnostic tests and procedures. This level of training is recognized for those areas in which an accepted instrument or benchmark, such as a qualifying exam, is available to measure specific knowledge, skills or competence.’’ Finally, level 3 is achieved when a fellow ‘‘acquires specialized knowledge and competencies in performing, interpreting and training others to perform specific procedures or render advanced, specialized care at a high level of skill and is defined by competency components and outcome metrics.’’ Published elsewhere in this issue of JASE is the report of COCATS 4 Task Force 5 on training in echocardiography. A future document is promised outlining the additional exposure and requirement for level 3 training, but this document contains some guidance, and the goal numbers of studies to be performed and interpreted has not been changed from COCATS 3. Along with the Accreditation Council for Graduate Medical Education, COCATS moves to addressing competency by way of milestones and observable behaviors. This is a welcome move away from purely prescriptive numbers of studies and procedures to ensure competence. The change makes sense. It is intuitively obvious that completing 300 cursory transthoracic studies, without adequate supervision or feedback, would not constitute the experience necessary to meet the level 3 requirements. Certainly, faculty members are not promoted for simple time in rank but are expected to meet a set of (hopefully) well-defined criteria to advance. Thus, the procedure targets outlined in Table 2 of the document are now more guidelines than strict requirements. The outline of curricular milestones is well thought out and will be helpful to training programs.