Canine heart disease: progress and promise

Abstract

The great thing in the world is not so much where we stand, as in what direction we are moving - Oliver Wendell Holmes It is possible that naiveté is responsible for this sense I have that we are standing at the threshold of a great era in veterinary cardiology; and yet despite this possibility, I can’t quite shake the feeling that we are very close to major breakthroughs in our knowledge, approach, and treatment of heart disease in dogs. If I’m right, this new era of progress will almost assuredly stem from the tremendous growth of veterinary medicine in all its facets, namely the ongoing recognition of the societal value of companion animals, the availability of high quality general and specialty care, the unification of human and veterinary medical research under a “one medicine” approach, and the collaboration of a global and interconnected veterinary community. Strangely, my sense of optimism is not so much about what we know, but about what we don’t. Firstly, let’s look at what we (think we) know. The sum total of data from veterinary cardiology research indicates three important things. One, diuretics rescue dogs with congestive heart failure. Two, inhibition of the renin-angiotensin-aldosterone axis alleviates clinical signs and improves survival in dogs with heart failure. Three, the positive inotropic and vasodilator drug pimobendan substantially improves quality of life and longevity in dogs with heart failure. I believe it is safe to say that the “ideal” therapy of a dog with heart failure secondary to degenerative mitral valve disease or dilated cardiomyopathy includes all three of these agents. In addition to our confidence in this very practical information, our understanding regarding the underlying causes of disease has recently benefited from ever more sophisticated and elegant research. One has only to go to NCBI-PubMed (http://www.ncbi.nlm.nih.gov) or a similar searchable scientific manuscript database and enter in the search term “dog, heart disease, veterinary” to see the evolution of research over the past decade. For instance, we now understand that cardiomyopathy in the boxer dog is very homologous in phenotype and natural history to a similar human affliction, thus prompting the disease formally known as “boxer cardiomyopathy” to be renamed “boxer arrhythmogenic right ventricular cardiomyopathy” (ARVC). This represents more than just an empty exercise in nomenclature. The realisation that disease in boxer dogs shares many commonalities with that in man has prompted veterinarians to better define diagnostic criteria (Meurs 2004), systematically describe the morphologic features of disease (Basso and others 2004), and importantly, search for the aetiology of disease at a genetic and molecular level (Oxford and others 2007). While no causative genetic mutations have been reported, veterinary researchers are nipping at the heels of their medical counterparts and it is possible that the genetic cause(s) of this and other canine cardiac diseases will be found within the coming years. This obviously is cause for great optimism. Not only does each year bring a greater volume of research, but the nature of work being done increasingly has shifted from descriptive and retrospective studies to prospective hypothesis-driven studies that involve elegant methodology and powerful technology. In no way is this meant to condemn or belittle past research (after all, on the shoulders of giants…), but it is simply an honest recognition of our maturation as a veterinary specialty and our ambition to tackle problems in an increasingly sophisticated and collaborative way. I became a cardiologist in 1998 and, since that time, two major advances in the medical treatment of canine heart failure have occurred: the widespread use of ACE-inhibitors and the introduction of pimobendan. Efficacy of these drugs was most convincingly demonstrated by a series of prospective clinical trials, three trials in the 1990’s involving enalapril (COVE 1995, IMPROVE 1995, Ettinger 1998), the BENCH study of benazepril in 2004, and the QUEST study - a landmark trial regarding the efficacy of pimobendan (Haagstrom and others 2008). Recently, a colleague of mine encouraged me to reread the enalapril manuscripts and to examine their rigor and methodology in light of current standards. Let me state clearly; the enalapril trials remain without question, groundbreaking, and at the time of publication were truly remarkable for their scope and multicentred design; but as with all things, time has tended to dull their lustre. By “modern” standards, the enalapril trials wince slightly when compared to recent trials and methodology. Indeed, if my sense of the cardiology “zeitgeist” is correct the recent clinical trial regarding use of pimobendan (Haagstrom and others 2008) has set a new standard for study design, rigor, analysis, and reporting. The accomplishments of the past are not to be minimised; this is merely an observation (and a reassuring one at that) that we have become more sophisticated and ambitious in the questions we ask and the methods we use to seek the answers. We have now entered into an era where clinical studies in veterinary cardiology will be adequately powered, large-scale, multicentred, and deeply collaborative efforts that bring together the individual strengths of its participants to great collective promise. To know that we know what we know, and that we do not know what we do not know, that is true knowledge - Henry David Thoreau Which brings us to “what we don’t know”. With specific regards to canine cardiology, I believe that the cardiology community has begun to coalesce around several issues; firstly, uncovering a genetic cause of cardiomyopathy in great Danes, Doberman pinschers, and boxer dogs; secondly, gaining a deeper understanding the ultrastructural, molecular, and genetic causes of degenerative valve disease; thirdly, exploring the efficacy of novel pharmaceuticals using adequately powered multicentred trials; and finally, harnessing the potential of interventional devices and therapies such as mitral valve annuloplasty, valve repair, arrhythmia science, stem cell biology and gene therapy. I believe that by targeting these areas of “ignorance” the collective growth of our specialty in both numbers and expertise all but ensures significant achievement over the coming years. Now, I am not so naïve to expect that five years from now cardiologists will be sitting around at meetings poignantly reminiscing about all the cavalier King Charles spaniels or Doberman pinschers they used to see, but stranger things have happened in veterinary cardiology (remember taurine!). What has to happen to fulfil this promise of advancement—to launch this intellectual and practical assault on what we don’t yet know? The willingness of individuals to collaborate cannot be overemphasised. The veterinary profession has truly become a global community, and academic, state, and national boundaries are increasingly irrelevant. When planning clinical trials, gathering our best and brightest in a room somewhere (preferably on a tropical island…) to “make things happen” should be the new method de rigueur. Moreover, the traditional lines between veterinarians from academia and private practice are increasingly blurred as private referral hospitals push the envelope of diagnostics and treatments. Secondly, continued partnership with industry is essential for providing the petrol to fuel the engine. Veterinarians can find ways to enter into relationships with commercial organisations while still remaining independent, self-determining and without conflict of interest. Finally, we must be vigilant and proactive with regards to our mentoring and training programs. The integrity and quality of these programs is of utmost importance and requires our attention and oversight, such that the growth and future success of our specialty is inextricably linked to our trainees and residents. My musings may be dismissed as misguided optimism, but undoubtedly we have achieved a certain degree of clarity about what we know and what we don’t. As a profession and a specialty, we are well-placed to tackle these “unknowables” that have suddenly become much less intimidating. It is both our progress and promise that makes the current era of veterinary cardiology so remarkable. Go ahead and allow yourself to dream. It’s possible that we’re approaching some sort of critical mass and the roof is going to blow off of the whole joint (wouldn’t that be fun!). I, for one, am sure going to miss seeing those cavaliers. Dr Mark Oyama is an Associate Professor of cardiology at the School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA. He also serves as the president of the American College of Veterinary Internal Medicine, Specialty of Cardiology. His interests include the pathophysiology and treatment of mitral valve disease and cardiomyopathy in dogs, as well as in the field of cardiac biomarkers.