|
Dr. Davinder S. Jassal
Principal Investigator, Cardiovascular Imaging
Institute of Cardiovascular Sciences
Research Focus
Dr. Jassal’s research focuses on the complementary use of multimodality cardiovascular imaging in the noninvasive assessment of heart failure syndromes. Using a combination of echocardiography (ultrasound of the heart), cardiac CT (computed tomography) and CMR (cardiac MRI), the Cardiovascular Imaging Laboratory at St. Boniface General Hospital and Research Centre is dedicated to translational research focusing on four heart failure models:
1. Trastuzumab (Herceptin) and Heart failure: A Tale of Two Cities
Cardiovascular disease and breast cancer are major public health concerns in Canada. 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 which target growth factor receptors further compounds this issue of drug induced cardiac dysfunction.
Trastuzumab (Herceptin), a humanized monoclonal antibody against the extracellular domain of the HER-2 protein, is used in both the adjuvant and metastatic settings of breast cancer. Despite its clear therapeutic benefits, cardiotoxicity is a major concern, especially when trastuzumab is used in combination with anthracyclines. Although clinical trials have demonstrated that the risk of developing LV systolic dysfunction after receiving trastuzumab is up to 10%, recent studies have shown an even higher risk of nearly 1 in 4 women developing this drug induced cardiomyopathy. An understanding of the potential mechanisms for the deleterious cardiac effects of HER-2 blockade may be beneficial in improving breast cancer therapy.
2. Obstuctive Sleep Apnea and Heart Failure
Obstructive sleeping apnea (OSA) is a sleeping disorder characterized by periodic reduction of breathing. It has direct adverse cardiovascular effects, where OSA patients can develop biventricular failure. Continuous positive airway pressure (CPAP) is used to treat OSA, yet the long term effects of this treatment on cardiovascular remodeling is ill defined. We are currently evaluating the effects of CPAP on a heterogeneous population of individuals with OSA by assessing cardiac remodeling using cardiac biomarkers, echo and CMR over a one year followup.
3. Metabolic Syndrome and Heart Failure
The metabolic syndrome is an increasing public health concern in Canada due to the growing incidence and prevalence of obesity nationwide. It is estimated that 1 in 4 Canadians will be afflicted with the metabolic syndrome by 2010. The metabolic syndrome is characterized by a cluster of risk factors including impaired glucose tolerance, hypertension, dyslipidemia, and obesity. Individuals afflicted with the metabolic syndrome are at an increased risk of developing premature cardiovascular disease and diabetes. The development of safe and inexpensive ways of preventing and treating the metabolic syndrome is fundamental in reducing the increasing diabetic and cardiovascular complications of this disease. We are exploring whether nutraceuticals and pharmaceuticals can prevent the adverse diabetic and cardiovascular effects of the metabolic syndrome.
4. Marathon Running and Heart Failure
Can too much exercise be detrimental to your health? Physical fitness has been shown to be an independent, long-term predictor of reduced morbidity and mortality from cardiovascular causes. Although the cardiovascular benefits of moderate exercise are well established, the cardiovascular effects of prolonged exertion, including marathon running, are less clear. Even though the risk of sudden death associated with participation in marathons is small, participation in such events is consistently associated with biochemical evidence of heart damage and dysfunction. Using cardiac biomarkers, echocardiography, cardiac CT and cardiac MRI, Dr. Jassal is evaluating the effects of marathon running on cardiac function through our participation with the 2006-2010 Manitoba Marathons.
Why is this work important?
Diagnostic medical imaging has undergone a dramatic evolution over the past decade, owing to rapid technological advancement and innovative clinical applications. Today's diagnostic imaging technologies, in particular echocardiography and cardiac MRI, are rapidly being adopted in Canada as new tools for understanding mechanisms of disease including Herceptin induced cardiomyopathy, obstructive sleep apnea and the metabolic syndrome.
Although Herceptin has demonstrated considerable therapeutic benefits in decreasing the rates of disease recurrence and death in the setting of breast cancer, it is associated with a 5-10% risk of cardiotoxicity. Early detection of cardiac dysfunction using echocardiography and cardiac MRI may allow one to adjust treatment with Herceptin prior to the development of irreversible heart failure.
With the increasing epidemic of obesity in Canada, the prevalence of OSA will continue to rise. A composite of mechanisms including mechanical, neurohormonal, inflammatory, endothelial and oxidative stress are involved in the increasing cardiovascular disturbances observed in OSA patients. The anticipated outcome of the current research proposal is that Dr. Jassal will demonstrate for the first time that CPAP will favorably improve biventricular remodeling in a heterogeneous population of OSA patients, as assessed noninvasively by echocardiography, cardiac MRI, and biomarkers over a one year followup.
There is increasing evidence that obesity and the metabolic syndrome plays a major role in cardiovascular disease. By studying the effects of a high fat diet on adverse cardiac remodeling, and understanding the various mechanisms involved, the insights gained will help with the development of novel dietary and pharmaceutical strategies to limit heart failure and its associated morbidity and mortality.
What techniques and equipment are used in this laboratory?
Dr. Jassal’s small animal cardiovascular imaging laboratory provides expertise in murine echocardiography. A dedicated GE Vivid 7 echocardiography machine with probes for small animal imaging (13 MHz) is housed in the animal facility at St. Boniface Research Centre. Five dedicated postprocessing work stations are located in Dr. Jassal’s laboratory, Rm 4010 for analysis of the images using standard M-Mode, 2D echocardiography, color Doppler and Tissue Doppler imaging. The work stations are also used for postprocessing of cardiac MRI images.
To delineate mechanistic pathways involved in the cardiovascular remodeling assessed by murine echocardiography, the lab is also equipped with histological and immunohistochemistry techniques.
About Dr. Davinder S. Jassal
Dr. Jassal was born in Thompson, Manitoba, obtained an International Baccalaureate Degree at Sisler High School in Winnipeg, and graduated from the University of Manitoba with an MD in 1998. He completed a residency in Internal Medicine at the University of Manitoba from 1998-2001 and a residency in Cardiology at Dalhousie University in Halifax, Nova Scotia, Canada. Subsequently, he completed a clinical and research fellowship in Cardiac Imaging specializing in echocardiography, computed tomography, and MRI at Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Dr. Jassal recently rejoined the Cardiac Sciences division as an Academic Clinician Scientist, where half of his time is devoted to patient care in CCU and cardiac imaging and the other half devoted to translational research. He is currently Assistant Professor of Cardiology and Radiology, Affiliated Scientist of the Institute of Biodiagnostics at National Research Council of Canada, Principal Investigator of the Cardiovascular Imaging Laboratory as a member of the Institute of Cardiovascular Sciences, and holds the F.W. DuVal Clinical Research Professorship.
For more information, please contact:
Dr. Davinder S. Jassal
Rm. 4010, St. Boinface Research Center, 351 Tache, R2H 2A6
Lab Phone: (204) 237-2599
Lab Office: (204) 235-3056
Hospital Office: (204) 237-2023
Fax: (204) 233-2157
Email:
This e-mail address is being protected from spam bots, you need JavaScript enabled to view it
Sheena Bohonis
Research Technician
Rm. 4010, St. Boinface Research Center, 351 Tache, R2H 2A6
Lab Phone: (204) 237-2599, (204) 235-3741
Fax: (204) 233-6723
Email:
This e-mail address is being protected from spam bots, you need JavaScript enabled to view it
In Detail
INSIGHTS INTO CHEMOTHERAPY INDUCED CARDIOMYOPATHY
In women who have been diagnosed with HER-2 positive breast cancer, studies have shown that when treated with a drug called Herceptin (Trastuzumab), the rate of recurrence and death decreases substantially. Despite these positive effects, Herceptin also increases the change of developing heart failure in 10% of women. At the basic science level, Dr. Jassal has evaluated the use of Tissue Doppler imaging in murine echocardiography to predict a decrease in overall left ventricular ejection fraction and apoptosis (programmed cell death) in a chemotherapy induced model of heart failure in mice. Translating this to the clinical bedside, his research will focus on the early detection of heart failure using cardiac imaging including echocardiography and MRI in patients with breast cancer, such that alterations in treatment with Herceptin can be made prior to irreversible heart damage.
|
