SCD Research at Johns Hopkins

The Johns Hopkins Hospital has a long history in sudden cardiac death research. Dr. Michel Mirowski invented the implantable cardioverter-defibrillator (ICD) while working at Sinai Hospital in Baltimore which is an affiliate of Johns Hopkins. Many of his early papers were written with Dr. Helen Taussig, internationally known for her work with "blue babies" and Myron Weisfeldt who became the Chairman of Medicine at Johns Hopkins Hospital.

Prominent sudden cardiac death research continues to this day, particularly in the area of genetics. Dr. Dan Arking is a geneticist who has achieved wide recognition for his discovery of many genes involved in regulating electrical properties of the heart, including the PR, QRS, and QT intervals. Some of these genes also influence the risk of sudden cardiac death, and characterizing the biological role of these genes is under investigation. Dr. Arking is also using genome-wide association studies (GWAS) to identify specific genetic changes that make an individual more likely to die of sudden cardiac death.

Dr. Marc Halushka is a cardiovascular pathologist who has studied a variety of cardiovascular diseases ranging from aortic aneurysms to sudden cardiac death. Dr. Halushka has taken a technique commonly used in cancer research - the tissue microarray - and has adapted it to cardiovascular research questions. He is now focusing his efforts on using tissue microarrays for sudden cardiac death research.

Research Program of:


Marc Halushka Dr. Halushka has published extensively on many features of cardiovascular disease, particularly from a pathology perspective. He is also a world's expert on cardiovascular tissue microarrays. View a complete list of publications or visit The Halushka Research Lab site to learn more about his research.




TMA Studies +

TMA image The goal of this research project is to identify biomarkers for sudden cardiac death. Basically, we will establish which protein changes are found more frequently in people susceptible to sudden cardiac death. In doing this, we can use these changes to predict who would benefit the most from having an implantable cardioverter-defibrillator (ICD) device.

Dr. Marc Halushka is a pioneer in developing cardiovascular tissue microarrays and is the co-director of the Johns Hopkins Tissue Microarray Core Facility. Tissue microarrays are blocks of 99 to 400 separate tiny pieces of human or animal organs. Here, small punches of tissue, ranging in size from 0.4mm to 1.5mm, are taken from "donor" paraffin block of original heart tissues. These punches are placed (or "arrayed") together in an "acceptor" paraffin block. We can then use different laboratory methods such as immunohistochemistry or immunofluorescence to determine how much of certain proteins are present in the tissues. We are doing this experiment using human cardiac tissues taken from individuals who have passed away due to sudden cardiac death.

We intend to find protein differences in the heart tissues that can also be found in human serum. This will serve as the basis of a simple, non-invasive screening test for sudden cardiac death.

We are performing these studies in collaboration with Dr. Renu Virmani at CVPath, Inc, Dr. Heikki Huikuri at the University of Oulu and Dr. Joseph Maleszewski at the Mayo Clinic. This is being done due to the excellence of these institutions at collecting and preserving heart tissues. This study also speaks to the importance of collaboration and collegial activities to advance this important science.


Clinical Studies +

Clinical Studies Dr. Marc Halushka is one of two cardiovascular pathologists at Johns Hopkins Hospital. In this capacity he sees most heart and blood vessel materials that come to Johns Hopkins Hospital from either surgical specimens or autopsy specimens. Dr. Halushka has used this position to collect special specimens and collaborate extensively with cardiologists and geneticists at Johns Hopkins Hosptial on clinical and translational research projects.

Dr. Halushka has worked closely with Drs. Judge, Calkins and Tandri on projects relating to sudden cardiac death. Some of that work provided the impetus for the TMA project. He also has worked with Dr. Hal Dietz on projects related to genetic causes of aortic aneurysms with a risk of rupture and death.



Publications

  1. Stone JR, et al. Recommendations for processing cardiovascular surgical pathology specimens: a consensus statement from the Standards and Definitions Committee of the Society for Cardiovascular Pathology and the Association for European Cardiovascular Pathology. Cardiovasc Pathol. 2011 Feb 23.
  2. Jain D, et al. Causes and histopathology of ascending aortic disease in children and young adults. Cardiovasc Pathol. 2011 Jan-Feb;20(1):15-25.
  3. Tandri H, et al. Prolonged RV endocardial activation duration: a novel marker of arrhythmogenic right ventricular dysplasia/cardiomyopathy. Heart Rhythm. 2009.
  4. Asimaki A, et al. A new diagnostic test for arrhythmogenic right ventricular cardiomyopathy. N Engl J Med. 2009 Mar 12;360(11):1075-84.
  5. Halushka MK, et al. Use of human vascular tissue microarrays for measurement of advanced glycation endproducts. J Histochem Cytochem. 2009 Jun;57(6):559-66.
  6. Halushka MK, et al. Creation, validation, and quantitative analysis of protein expression in vascular tissue microarrays. Cardiovasc Pathol. 2010 May-Jun;19(3):136-46.
  7. Cornish TC and Halushka MK. Color deconvolution for the analysis of tissue microarrays. Anal Quant Cytol Histol. 2009 Oct;31(5):304-12.
  8. Tandri H, et al. Gap junction remodeling in a case of arrhythmogenic right ventricular dysplasia due to plakophilin-2 mutation. J Cardiovasc Electrophysiol. 2008 Nov;19(11):1212-4.
  9. Halushka MK, et al. Right ventricle-dominant cardiac sarcoidosis with sparing of the left ventricle. J Heart Lung Transplant. 2006 Apr;25(4):479-82.