Jonathan R. Walker

Role of Three-Dimensional Echocardiography in Breast Cancer: Comparison With Two-Dimensional Echocardiography, Multiple-Gated Acquisition Scans, and Cardiac Magnetic Resonance Imaging

PURPOSE In patients with breast cancer, the administration of doxorubicin and trastuzumab is associated with an increased risk of cardiotoxicity. Although multiple-gated acquisition (MUGA) scans and two-dimensional transthoracic echocardiography (TTE) are conventional methods for baseline and serial assessment of left ventricular ejection fraction (LVEF) in these patients, little is known about the use of real-time three-dimensional TTE (RT3D TTE) in this clinical setting. The aim of this study was to assess the accuracy of MUGA, 2D TTE, and RT3D TTE for determining LVEF in comparison to cardiac magnetic resonance imaging (CMR). METHODS Between 2007 and 2009 inclusive, 50 female patients with human epidermal growth factor receptor 2-positive breast cancer received adjuvant trastuzumab after doxorubicin. Serial MUGA, 2D TTE, RT3D TTE, and CMR were performed at baseline, 6, and 12 months after the initiation of trastuzumab. RESULTS A comparison of left ventricular end diastolic volume (LVEDV) demonstrated a modest correlation between 2D TTE and CMR (r = 0.64 at baseline; r = 0.69 at 12 months, respectively). A comparison of LVEDV between RT3D TTE and CMR demonstrated a stronger correlation (r = 0.87 at baseline; r = 0.95 at 12 months, respectively). Although 2D TTE demonstrated a weak correlation with CMR for LVEF assessment (r = 0.31 at baseline, r = 0.42 at 12 months, respectively), both RT3D TTE and MUGA showed a strong correlation when compared with CMR (r = 0.91 at baseline; r = 0.90 at 12 months, respectively). CONCLUSION As compared with conventional MUGA, RT3D TTE is a feasible, accurate, and reproducible alternate imaging modality for the serial monitoring of LVEF in patients with breast cancer.

Obstructive Sleep Apnea : Effects of Continuous Positive Airway Pressure on Cardiac Remodeling as Assessed by Cardiac Biomarkers, Echocardiography, and Cardiac MRI

BACKGROUND Obstructive sleep apnea (OSA) is associated with an increased risk of cardiovascular morbidity and mortality. Although previous echocardiographic studies have demonstrated short-term improvement in cardiovascular remodeling in patients with OSA receiving continuous positive airway pressure (CPAP) therapy, a long-term study incorporating cardiac biomarkers, echocardiography, and cardiac MRI (CMR) has not been performed to date. METHODS A prospective study of 47 patients with OSA was performed between 2007 and 2010. Cardiac biomarkers, including C-reactive protein (CRP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and troponin T (TnT), were measured at baseline and serially over 1 year. All patients underwent baseline and serial transthoracic echocardiography (TTE) and CMR to assess cardiac remodeling. RESULTS Following 12 months of CPAP therapy, levels of CRP, NT-proBNP, and TnT did not change significantly from normal baseline values. As early as 3 months after initiation of CPAP, TTE revealed an improvement in right ventricular end-diastolic diameter, left atrial volume index, right atrial volume index, and degree of pulmonary hypertension, which continued to improve over 1 year of follow-up. Finally, left ventricular mass, as determined by CMR, decreased from 159 ± 12 g/m(2) to 141 ± 8 g/m(2) as early as 6 months into CPAP therapy and continued to improve until completion of the study at 1 year. CONCLUSION Both systolic and diastolic abnormalities in patients with OSA can be reversed as early as 3 months into CPAP therapy, with progressive improvement in cardiovascular remodeling over 1 year as assessed by both TTE and CMR.

Utility of Tissue Doppler and Strain Rate Imaging in the Early Detection of Trastuzumab and Anthracycline Mediated Cardiomyopathy

BACKGROUND Trastuzumab provides considerable therapeutic benefits in the adjuvant setting of breast cancer. However, its use is limited by an elevated incidence of cardiotoxicity when used in combination with doxorubicin. Although Myocet (liposomal encapsulated doxorubicin) is less cardiotoxic, its cardiac safety profile with trastuzumab is not well known. The aim of this study was to determine if sensitive indices of left ventricular (LV) dysfunction, specifically Doppler tissue imaging (DTI), would be useful for addressing the early detection of trastuzumab and anthracycline-mediated cardiotoxicity. METHODS In an acute murine model, wild-type C57Bl/6 mice (n = 60) received one of the following drug regimens: (1) control, (2) doxorubicin, (3) Myocet, (4) trastuzumab, (5) doxorubicin plus trastuzumab, or (6) Myocet plus trastuzumab. DTI-derived peak endocardial systolic velocity, strain rate, and LV ejection fraction were measured serially for 5 days. On day 5, the hearts, lungs, and livers were removed for histopathologic and Western blot analyses. RESULTS Mice treated with Myocet plus trastuzumab demonstrated minimal cardiotoxicity compared with those treated with doxorubicin plus trastuzumab. Progressive LV dilatation and LV systolic dysfunction were observed by day 4 of treatment with doxorubicin plus trastuzumab, compared with preserved LV ejection fraction in the remaining groups. DTI parameters decreased within 24 hours in the doxorubicin alone and doxorubicin plus trastuzumab groups and predicted early mortality. The survival rate was only 20% at day 5 of the experiment in the doxorubicin plus trastuzumab group, whereas 100% of mice receiving trastuzumab, Myocet, or Myocet plus trastuzumab survived the 5 days. CONCLUSION DTI can detect early LV dysfunction prior to alterations in conventional echocardiographic indices and predicts early mortality in mice receiving doxorubicin plus trastuzumab.

The Cardioprotective Role of Probucol Against Anthracycline and Trastuzumab-Mediated Cardiotoxicity

OBJECTIVE Although the combination of doxorubicin (Dox) and trastuzumab (Trz) reduces breast cancer progression and recurrence, it is limited by significant cardiotoxic side effects. Little is known about the utility of antioxidants in the prevention of this drug-induced cardiomyopathy. The aim of the study was to determine whether the antioxidant probucol (Prob) would be useful in attenuating Dox and Trz-mediated cardiotoxicity. METHODS A total of 114 mice were randomized to treatment with Trz, Dox, or Dox+Trz. Within each arm, mice received prophylactic treatment with placebo or Prob. Serial murine echocardiography with tissue Doppler imaging was performed daily for 10 days. At 10 days posttreatment, the hearts were removed for histopathologic and Western blot analyses. RESULTS Left ventricular cavity dimensions and systolic parameters were preserved in mice prophylactically treated with Prob after the administration of Dox+Trz. Although the combination of Dox+Trz demonstrated >80% mortality at day 5, prophylactic treatment with Prob reduced mortality to 40% at day 10. There was decreased histologic evidence of cardiac damage and reduced apoptosis due to Dox+Trz in mice pretreated with Prob. CONCLUSION The cardiotoxic effects of Dox+Trz are partially attenuated by the prophylactic administration of the antioxidant Prob.

Multimodality Imaging of Aortic Dimensions: Comparison of Transthoracic Echocardiography with Multidetector Row Computed Tomography

Background: With recent advances in multimodality cardiac imaging, a number of methods exist for the noninvasive assessment of aortic disease. Although multidetector row computed tomography (MDCT) remains the gold standard for aortic measurements, there are a number of limitations including radiation and contrast‐induced nephropathy. Transthoracic echocardiography (TTE) is an alternative to MDCT for providing accurate anatomic assessment of aortic root and ascending aorta dimensions. Objectives and Methods: To determine the accuracy of two‐dimensional (2D) TTE for determining aortic measurements in comparison to MDCT, a retrospective study of individuals with varying aortic root and ascending aorta dimensions was performed. Results: There were 116 patients (77 males, mean age 49 ± 12 years) in total. The maximum aortic diameters by 2D TTE were 26.1 ± 4.3 mm (annulus), 32.4 ± 5.6 mm (sinuses), 30.1 ± 5.9 mm (sinotubular [ST] junction), and 33.4 ± 7.3 mm (ascending aorta). The maximum aortic diameters by MDCT were 30.1 ± 4.1 mm (annulus), 35.8 ± 5.8 mm (sinuses), 33.2 ± 5.9 mm (ST junction), and 37.4 ± 7.6 mm (ascending aorta). There was good to excellent correlation between 2D TTE and MDCT at all four levels of the aorta (annulus: r = 0.84; sinuses: r = 0.93; ST junction: r = 0.93; ascending aorta: r = 0.88). There was a consistent underestimation of aortic measurements obtained by 2D TTE when compared to MDCT. Conclusion: 2DTTE is a feasible, accurate, and reproducible method for the noninvasive assessment of thoracic aortic diameters as compared to MDCT. (Echocardiography 2012;29:735‐741)

The Role of Three-Dimensional Echocardiography in the Assessment of Right Ventricular Dysfunction after a Half Marathon: Comparison with Cardiac Magnetic Resonance Imaging

BACKGROUND Although marathon running is associated with transient right ventricular (RV) systolic dysfunction as detected by two-dimensional transthoracic echocardiography, quantitative assessment of the right ventricle is difficult because of its complex geometry. Little is known about the use of real-time three-dimensional echocardiography (RT3DE) in the detection of cardiac dysfunction after a half marathon. The aim of this study was to assess the extent of RV dysfunction after the completion of a half marathon using cardiac biomarkers, RT3DE, and cardiac magnetic resonance imaging (CMR). METHODS A prospective study was performed in 15 individuals in 2009 participating in the Manitoba Half Marathon. Cardiac biomarkers (myoglobin, creatine kinase-MB and cardiac troponin T) were assessed and RT3DE and CMR were performed 1 week before, immediately after, and 1 week after the race. RESULTS At baseline, cardiac biomarkers and ventricular function were within normal limits. Immediately following the half marathon, all patients demonstrated elevated cardiac troponin T levels, with a median value of 0.37 ng/mL. RV ejection fraction, as assessed by RT3DE, decreased from 59 ± 4% at baseline to 45 ± 5% immediately following the race (P < .05). On CMR, RV end-diastolic volume increased after the half marathon, and the RV ejection fraction was reduced, at 47 ± 5% compared with 60 ± 2% at baseline (P < .05). There were strong linear correlations between RV ejection fraction assessed by RT3DE and CMR at baseline and after the half marathon (r = 0.69 and r = 0.87, P < .01, respectively). CONCLUSIONS Compared with CMR, RT3DE is a feasible and reproducible method of assessing transient RV dysfunction in athletes completing a half marathon.

Left ventricular pseudoaneurysm: The role of multimodality cardiac imaging

A 71-year-old man presented with an inferior ST elevation myocardial infarction. Coronary angiography demonstrated 99% occlusion of the proximal right coronary artery. A posterior wall pseudoaneurysm was incidentally observed on left ventriculography (arrows; Figure 1A). Transthoracic echocardiography revealed a site of rupture in the posterior left ventricular (LV) wall measuring 36 mm in width, communicating with a large, thrombus-free pseudoaneurysm (asterisks; Figure 1B). Cardiac magnetic resonance imaging (MRI) confirmed the presence of an aneurysmal dilation along the basal inferolateral wall with a mouth orifice of 36 mm in diameter and 36 mm deep (arrows; Figure 1C). A rim of delayed enhancement around the aneurysm could have represented either a full-thickness myocardial scar or an enhancing pericardium containing a false aneurysm, although the location was of concern for the latter (arrows; Figure 1D). At surgery, following resection of the aneurysmal sac (Figure 1E), an examination of the interior of the LV wall revealed a zone of transition from healthy-appearing myocardium to thinned scarred myocardium, followed by a thinner fibrous edge, which was compatible with the diagnosis of a pseudoaneurysm. Pathological examination demonstrated organizing fibrous tissue (Figure 1F). The lack of LV wall was consistent with the diagnosis of a pseudoaneurysm. Figure 1) Ao Aorta; LA Left atrium; LV Left ventricle; RV Right ventricle LV pseudoaneurysms develop when myocardial rupture is contained by pericardial adhesions or scar tissue (1). In contrast, true LV aneurysms form following myocardial infarction as a result of scar formation and thinning of the myocardial wall. Echocardiography, left ventriculography and cardiac MRI are complementary imaging modalities used to distinguish theses two entities. Cardiac MRI, with its higher spatial resolution, is more sensitive and specific for the diagnosis of a pseudoaneurysm than transthoracic echocardiography (2). The absence of delayed enhancement findings of myocardial elements within the sac of the aneurysm on cardiac MRI, and the presence of delayed enhancement of the pericardium, is highly suggestive of a pseudoaneurysm (2). In some cases, however, such as in the present patient, differentiation of a delayed enhancement of the myocardium from an adjacent pericardium may be challenging, leading to an incorrect diagnosis because an enhancing pericardium containing a pseudoaneurysm can mimic an infarcted myocardium (2). Hence, surgical assessment and pathological evaluation is occasionally imperative to make a definitive diagnosis.

A High-Lipid Diet Potentiates Left Ventricular Dysfunction in Nitric Oxide Synthase 3-Deficient Mice after Chronic Pressure Overload

A high-lipid diet (HLD) may lead to adverse left ventricular (LV) remodeling and endothelial dysfunction in conditions of hemodynamic stress. Although congenital absence of nitric oxide synthase 3 (NOS3) leads to adverse LV remodeling after transverse aortic constriction (TAC), the effects of a HLD in this state remains unknown. Wild-type (WT) and NOS3 knockout mice (NOS3(-/-)) were randomized into the following 4 groups: 1) WT + low-lipid diet (LLD) (10% of energy); 2) WT + HLD (60% of energy); 3) NOS3(-/-) + LLD; and 4) NOS3(-/-) + HLD for a total of 12 wk. After 1 wk of randomization, TAC was performed on all groups. Serial echocardiography revealed a decrease in LV ejection fraction (LVEF) in WT and NOS3(-/-) mice fed the HLD compared with those fed the LLD diet at 12 wk post-TAC. Mice fed the NOS3(-/-) + HLD diet had a lower LVEF compared with mice in the other 3 groups (P < 0.05). There was greater myocyte hypertrophy, interstitial fibrosis, and percentage change in plasma cholesterol concentrations in the NOS3(-/-) + HLD group 12 wk post-TAC compared with the other 3 groups. Although high molecular weight fibroblast growth factor-2, a marker of cardiac hypertrophy, was more upregulated in the NOS3(-/-) + HLD group than in the other groups, markers of the renin-angiotensin system did not differ among them. A HLD potentiates LV dysfunction in NOS3(-/-) mice in a chronic pressure overload state.

Tricuspid Valvular Papillary Muscle Rupture With Intractable Hypoxia: A Rare Complication Post MI

Acute inferior ST-elevation myocardial infarction (STEMI) alone contributes to approximately 10% of in-hospital mortality due to ischemic heart disease. Right ventricular involvement occurs in 50% of patients who present with inferior STEMIs, increasing in-hospital mortality to 31%. In the setting of concomitant severe tricuspid regurgitation, acute rupture of the papillary muscles within the right ventricle should be considered in the differential diagnosis. The authors present the case of a patient with intractable hypoxia in the setting of an acute inferior STEMI complicated by rupture of the posterior tricuspid valve papillary muscle.

The role of cardiac MRI for serial assessment of left ventricular ejection fraction in breast cancer patients

Background Breast cancer and cardiovascular disease are major public health concerns worldwide. The two diseases are intricately involved as treatment of one disease may lead to detrimental effects in the other. Although the current combination of surgical resection, radiotherapy, and chemotherapy may lead to remission in breast cancer patients, the administration of chemotherapeutic based agents, in particular Doxorubicin, are associated with an increased risk of cardiotoxicity. The introduction of novel monoclonal antibodies in breast cancer therapy, including Trastuzumab (Herceptin), which target growth factor receptors, further compounds this issue of drug induced cardiac dysfunction. Although serial multi gated acquisition scans (MUGA) are the conventional method for baseline and serial assessment of left ventricular ejection fraction (LVEF), little is known about the use of cardiac MRI (CMR) in this clinical setting.