Matthew Lytwyn

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.

Delayed contrast enhancement cardiac magnetic resonance imaging in trastuzumab induced cardiomyopathy

BackgroundTrastuzumab (Herceptin), an antagonist to the human epidermal growth factor 2 (HER2) receptor significantly decreases the rates of breast cancer recurrence and mortality by 50%. Despite therapeutic benefits, the risk of cardiotoxicity with trastuzumab ranges from 10–15% when administered sequentially following anthraycline chemotherapy. Little is known about the utility of cardiac magnetic resonance (CMR) in the assessment of trastuzumab mediated cardiomyopathy.Methods and resultsBetween 2005–2006 inclusive, 160 breast cancer patients were identified at a single tertiary care oncology centre. Of the total population, 10 patients (mean age 40 ± 8 years) were identified with trastuzumab induced cardiomyopathy, based on a LVEF less than 40% on serial MUGA or echocardiography. CMR was performed in all patients to determine LV volumes, systolic function and evidence of late gadolinium enhancement (LGE). At the time of diagnosis of trastuzumab induced cardiomyopathy, the mean LVEF was 29 ± 4%. Subepicardial linear LGE was present in the lateral portion of the left ventricles in all 10 patients.ConclusionLGE-CMR is a novel way of detecting early changes in the myocardium due to trastuzumab induced cardiotoxicity.

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.

A cardioprotective preservation strategy employing ex vivo heart perfusion facilitates successful transplant of donor hearts after cardiocirculatory death

BACKGROUND Ex vivo heart perfusion (EVHP) has been proposed as a means to facilitate the resuscitation of donor hearts after cardiocirculatory death (DCD) and increase the donor pool. However, the current approach to clinical EVHP may exacerbate myocardial injury and impair function after transplant. Therefore, we sought to determine if a cardioprotective EVHP strategy that eliminates myocardial exposure to hypothermic hyperkalemia cardioplegia and minimizes cold ischemia could facilitate successful DCD heart transplantation. METHODS Anesthetized pigs sustained a hypoxic cardiac arrest and a 15-minute warm ischemic standoff period. Strategy 1 hearts (S1, n = 9) underwent initial reperfusion with a cold hyperkalemic cardioplegia, normothermic EVHP, and transplantation after a cold hyperkalemic cardioplegic arrest (current EVHP strategy). Strategy 2 hearts (S2, n = 8) underwent initial reperfusion with a tepid adenosine-lidocaine cardioplegia, normothermic EVHP, and transplantation with continuous myocardial perfusion (cardioprotective EVHP strategy). RESULTS At completion of EVHP, S2 hearts exhibited less weight gain (9.7 ± 6.7 [S2] vs 21.2 ± 6.7 [S1] g/hour, p = 0.008) and less troponin-I release into the coronary sinus effluent (4.2 ± 1.3 [S2] vs 6.3 ± 1.5 [S1] ng/ml; p = 0.014). Mass spectrometry analysis of oxidized pleural in post-transplant myocardium revealed less oxidative stress in S2 hearts. At 30 minutes after wean from cardiopulmonary bypass, post-transplant systolic (pre-load recruitable stroke work: 33.5 ± 1.3 [S2] vs 19.7 ± 10.9 [S1], p = 0.043) and diastolic (isovolumic relaxation constant: 42.9 ± 6.7 [S2] vs 65.2 ± 21.1 [S1], p = 0.020) function were superior in S2 hearts. CONCLUSION In this experimental model of DCD, an EVHP strategy using initial reperfusion with a tepid adenosine-lidocaine cardioplegia and continuous myocardial perfusion minimizes myocardial injury and improves short-term post-transplant function compared with the current EVHP strategy using cold hyperkalemic cardioplegia before organ procurement and transplantation.

The impact of repeated marathon running on cardiovascular function in the aging population

BackgroundSeveral studies have correlated elevations in cardiac biomarkers of injury post marathon with transient and reversible right ventricular (RV) systolic dysfunction as assessed by both transthoracic echocardiography (TTE) and cardiovascular magnetic resonance (CMR). Whether or not permanent myocardial injury occurs due to repeated marathon running in the aging population remains controversial.ObjectivesTo assess the extent and severity of cardiac dysfunction after the completion of full marathon running in individuals greater than 50 years of age using cardiac biomarkers, TTE, cardiac computed tomography (CCT), and CMR.MethodsA total of 25 healthy volunteers (21 males, 55 ± 4 years old) from the 2010 and 2011 Manitoba Full Marathons (26.2 miles) were included in the study. Cardiac biomarkers and TTE were performed one week prior to the marathon, immediately after completing the race and at one-week follow-up. CMR was performed at baseline and within 24 hours of completion of the marathon, followed by CCT within 3 months of the marathon.ResultsAll participants demonstrated an elevated cTnT post marathon. Right atrial and ventricular volumes increased, while RV systolic function decreased significantly immediately post marathon, returning to baseline values one week later. Of the entire study population, only two individuals demonstrated late gadolinium enhancement of the subendocardium in the anterior wall of the left ventricle, with evidence of stenosis of the left anterior descending artery on CCT.ConclusionsMarathon running in individuals over the age of 50 is associated with a transient, yet reversible increase in cardiac biomarkers and RV systolic dysfunction. The presence of myocardial fibrosis in older marathon athletes is infrequent, but when present, may be due to underlying occult coronary artery disease.

The utility of tissue Doppler imaging for the noninvasive determination of left ventricular filling pressures in patients with septic shock.

Background: Pulmonary artery wedge pressure (PAWP) is an important indicator of volume status in septic patients. Although it requires invasive pulmonary artery catheterization (PAC), a noninvasive method to assess PAWP would be clinically useful in this select patient population. Diastolic indices using transthoracic echocardiography (TTE) may provide an accurate estimate of PAWP. Objective: To determine whether echocardiographic Doppler assessment is accurate in estimating PAWP in patients with septic shock. Methods: A retrospective chart review was performed of 320 patients admitted with a diagnosis of septic shock from 2007-2008. Of the total patient population, 40 patients fulfilled the inclusion criteria, having undergone both TTE and PAC within 4 hours. Spectral Doppler indices including peak early (E) and late (A) transmitral velocities, E/A ratio, and E-wave deceleration time were measured. Tissue Doppler indices including S’, E’ and A’ velocities were determined. Pulmonary artery wedge pressure values measured invasively were compared to the dimensionless index of E/E’ in each patient. Results: The mean age was 68 ± 12 years with 28 males (70%). On echo assessment, 28% of patients had evidence of mild left ventricular diastolic dysfunction while 17% of patients had moderate diastolic dysfunction. Pulmonary artery wedge pressures ranged from 7 to 31 mm Hg with a mean of 18 ± 5 mm Hg. The mean E/E’ was 11 ± 8. Linear regression analysis between PAWP and E/E7apos; demonstrated a strong correlation (r = .84, P < .05). Conclusion: Tissue Doppler indices using TTE is a feasible and strong predictor of PAWP in patients with septic shock.

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.