Heart Failure: Molecules, Mechanisms and Therapeutic Targets
Gregory Bock, Jamie Goode, eds
291 pages. Chichester, UK: John Wiley & Sons Ltd; 2006. $145.00. ISBN: 0–470–01597–7.
The statistics of the staggering and ever-increasing burden of heart failure worldwide do not need to be fully repeated. Suffice it to say that in the United States alone, there are 5 million patients with congestive heart failure and another 500 000 new cases every year. Despite this, progress in treatment of the complex collection of disorders leading to congestive heart failure has been slow and generally incremental since the landmark trials of the last decades established angiotensin converting enzyme inhibitors and β-adrenergic receptor antagonists as standard therapies. Even with these therapies, prognosis is poor, and it has become increasingly clear that novel approaches to treatment are desperately needed.
Heart Failure: Molecules, Mechanisms and Therapeutic Targets consists of the proceedings of a Novartis Foundation symposium held in April 2005 in England. It was organized by Eric Olson and chaired by Seigo Izumo, and the participants consisted of 25 thought leaders in the study of cardiac hypertrophy and heart failure. The stated purpose was to identify novel therapeutic targets in heart failure. There were 15 formal presentations, each followed by a lengthy question and answer session, and 2 discussion groups. All of these are faithfully captured in the book.
The vast majority of the formal presentations either were published before the meeting or subsequently have been published in expanded forms in various journals. Thus, I found the introduction and the question and answer sessions most interesting. In the introduction, Dr Olson lays out several basic questions for the field that, although not answered during the course of the meeting, should serve as a guide to all who work in this area. Such basic questions as, “Is pathological cardiac hypertrophy a reasonable therapeutic target?” and “Are there final common pathways and nodal points in cardiac disease signaling, or do multiple parallel pathways lead to disease?” are asked. In the question and answer sessions, many questions highlighting the unknowns in this field are clearly stated and debated by the participants. Information exchange is extensive, and unpublished data are freely discussed. At many scientific meetings, presenters tend to focus on 1 specific area (their area of expertise), with minimal attempts to view the work in a larger context, often avoiding areas of uncertainty in the formal presentations. This was not the case at the 2005 meeting. In many ways, the exchanges remind me of the idealistic, but rarely achieved, stated goals of the Gordon conferences related to free information exchange. Although the discussions sometimes wander off target, they provide insights into the thinking of some of the true leaders in the field.
Another positive element of the meeting was the presence of participants well versed in clinical medicine and clinical trials, as well as individuals involved in drug development. Their insights provide essential backdrops and greatly contribute to the “translational” tone of the question and answer sessions, even when they follow very basic science presentations.
One discussion that is particularly interesting is generally carried by Dr Izumo and Dr Arnold Katz. It concerns the difficulty of bringing new drugs to market in the heart failure arena, in contrast to the relative ease with which new cancer therapeutics achieve US Food and Drug Administration approval. The issues of a need for superior safety data, and whether mortality should be required as an end point, are discussed.
Although most of the formal presentations are now somewhat dated because of the lag time between the meeting and publication of the book, these presentations could be an excellent source for someone who wants to be quickly brought up to speed in the field, and they also may provide an understanding of future directions. As to the latter, Loren Field’s discussion of the cardiomyocyte cell cycle and Ken Chien’s discussion of manipulation of the SERCA2a/phospholamban system with adeno-associated viral vectors, at least 1 of which (SERCA2a) seems headed for approval by the US Food and Drug Administration for a phase I clinical trial, certainly provide glimpses into the future.
Finally, and appropriately, the meeting is closed by Arnold Katz, probably the field’s preeminent historian. Dr Katz beautifully reviews the history of cardiology and heart failure, dating back to Galen’s theories that held the field back for 1000 years. Thankfully, none of the “theories” proposed in this book will do that, even if they are wrong.
In summary, although few if any of the initial questions posed by Dr Olson are answered, the discussion of such questions in this kind of forum should serve as a model for future attempts to answer them.
Dr Force will be serving as a consultant for Novartis on an upcoming clinical trial not related to the subject of the book.