Casale graduated from Cornell University Medical College prior to completing an internal medicine residency at The New York Hospital-Cornell University Medical Center. Following residency, he completed a clinical and research fellowship in Cardiology at Massachusetts General Hospital and Harvard Medical School. He earned a master of public health at the Harvard School of Public Health. He is an interventional cardiologist and chief of the Division of Cardiology at Lancaster General Hospital in Lancaster, PA and serves as medical director of quality for Lancaster General Health. He is active in clinical research and medical education and is a clinical professor of medicine at Temple University School of Medicine. Casale is chair of the ACC Partners in Quality Committee and the PINNACLE Registry Steering Committee.