The clinical application of molecular diagnostics (MDx) has grown in recent years and shows much promise for delivering a broad range of important socioeconomic benefits. Progress in this area depends on substantial high-risk investments in innovation made by both public- and private- entities. At the same time, business models in MDx and personalized medicine are rapidly evolving and effectively leveraging IP in this area to support investment and innovation is particularly challenging. Adding to this challenge, the U.S. patent office has made a series of changes to its evaluation process for MDx inventions. While the ‘gene patent’ concept has gained the attention of a broad range of stakeholders, it is ill defined and there is a lack of shared understanding of the concept across different types of stakeholders, e.g. patent practitioners vs. academic researchers. To address this issue and gain insights into the development of MDx for use in Cardiology, we have completed a systematic and in-depth analysis of U.S. patents and patent applications using the Thompson Innovation database since 2000. We have extracted and analysed more than 6,000 claims to methods or compositions for use in MDx for Cardiology. Claims were classified according to: use (diagnostic, prognostic, for treatment selection), type of method (gene expression, protein level, genotyping), type of composition (nucleotide, primer, probe, antibody), type of invention (natural product, algorithm, multiplex test) and clinical indication. We have assessed trends and changes over time in the number of applications filed and patents granted with respect to claim properties. This work documents IP trends related to MDx applications in cardiology over time and with respect to changes in U.S. patent office practice over the last 15 years. The study results provide important insights into MDx innovation in Cardiology, as well as improved approaches and measures for tracking trends in MDx IP going forward.