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Dr. Marc A. Pfeffer, Brigham and Women’s Hospital, Division of Cardiovascular Medicine, 75 Francis Street, Boston, Massachusetts 02115-6110, USA.
I had the pleasure working with Drs. Jonathan Abrams, Howard A. Cohen, Sudhir S. Kushwaha, and Eric S. Williams to develop the specific contributions in the broad field of cardiac function and heart failure to be presented as original work at these Scientific Sessions. With the assistance of other highly respected reviewers, 1,143 abstracts were graded for selection for only 351 allotted slots on the overall program. As such, many highly ranked abstracts were not able to be accepted for presentation. The accepted abstracts were then assigned into thematically grouped sessions. Although it is impossible to cover the content of these original contributions, a brief overview of the titles of these sessions provides some insight into the active areas of investigation.
There were several sessions devoted to cardiomyopathies with specific sessions for hypertrophic, dilated, and restricted cardiomyopathies. The Program Committee also had one session termed miscellaneous cardiomyopathies. This does not indicate that the Program Committee identified a new form of cardiomyopathy, but does demonstrate that there were many highly ranked abstracts on the issue of cardiomyopathy that did not quite fall into one of the easily recognized clinical patterns. Myocarditis continues to be an important area of investigation.
Contributions concerning cardiac transplantation produced several high-quality sessions concentrating on clinical prognostic factors for both short-term rejection and allograft vasculopathy. It is noteworthy that two entire sessions were devoted to the left ventricular assist device, providing a flavor of the advances in this field in managing these highest risk patients.
A substantial proportion of the accepted presentations concentrated on the interface of cardiac function, heart failure, and the elderly. There were particular sessions devoted to physiologic alterations, coronary syndromes, and specific risk factors for failure in the elderly as well as the risk/benefits of pharmacologic therapy in this important segment of our population. My favorite session topic was entitled “Hazards of Being Elderly.” Although I did not attend the specific session, I was assured that an American Association of Retired Persons card was not required for admission.
The number of abstract submissions and acceptances concerning heart failure with preserved systolic function indicates that this is a clear investigative growth area. Exercise testing as well as exercise training continue to be important investigative and therapeutic areas. Contributions concerning ventricular remodeling continue to provide mechanistic underpinnings for a broad range of areas of cardiac function and heart failure. The prognostic importance of old standards, such as assessments of left ventricular as well as right ventricular ejection fractions, was emphasized in several sessions concerning outcomes of patients with heart failure.
The added prognostic value of a determination of B-type natriuretic peptide (BNP) levels was a clear theme across a strong group of accepted abstracts. Important contributions from Drs. McCullough and Maisel continue to lead the field by demonstrating the utility of “point of care” evaluations of BNP, particularly in the determination of whether dyspnea was a consequence of cardiac or pulmonary disease (1). B-type natriuretic peptide was also shown to be an additive prognostic factor for death in patients being considered for cardiac transplantation (2). However, we are also beginning to see the pendulum swing back a bit with an abstract indicating that in patients with severe heart failure, the correlation between wedge pressure and BNP was not ideal (3). In an interesting evaluation of clinical acumen versus the BNP analogous to the chess match between the IBM mega-computer versus the Russian master, the physician recognition of an S3 identified those with an elevated BNP (4). I personally chuckled when I noticed that the senior author on this abstract was Dr. Kanu Chatterjee, since with this leading clinical cardiologist performing the evaluation, one could anticipate that the BNP would be redundant!
This year’s contributions from basic investigations were particularly strong and covered an exciting range of novel concepts. Key studies probed the development of cardiomyopathies, demonstrating the signaling pathways involved in the development of hypertrophy and remodeling. Mechanisms of contractile dysfunction continue to be important fields, which enrich our understanding of pathophysiology of impaired pump function. Several sessions were devoted to studies of gene transfer where contractile abnormalities are already being selectively reversed by “genetic corrections” in animal models. An important new area of scientific contributions involves the use of novel cell therapies, which are already showing promise in both animal and preliminary clinical studies. Use of skeletal myoblasts, stem cells, as well as cytokines to stimulate natural repair processes to improve ventricular function were featured by several highly scored abstracts.
A definitive reminder of the progress in the care of patients with heart failure was provided by an analysis of a Swedish National Registry of admissions and discharges with the diagnosis of heart failure. Swedberg and co-workers demonstrated an impressive reduction in both in-hospital deaths and one-year mortality during and after an admission for heart failure during the interval between 1988 and 2000 (5). For patients between 55 and 64 years of age, one-year mortality decreased by over 50% during this period. Even in the elderly, those 75 to 84 years, the one-year mortality rate decreased by one-third during these 12 years. What is remarkable about these findings is that these were non-study patients, underscoring that the benefits observed in previous clinical trials have now been translated to real-world populations!
The cardiovascular community does not rest on past accomplishments, and at this Annual Scientific Session of the ACC, the new trials presented at the Late-Breaking Trial Sessions will undoubtedly favorably alter the practice of medicine. The Eplerenone Post-AMI Heart Failure Efficacy and Survival Study (EPHESUS) study, presented by Dr. Bertram Pitt, demonstrated that in high-risk myocardial infarction (MI) patients, those selected for pulmonary congestion, either permanent or transient, as well as reduced left ventricular ejection fraction showed a survival improvement with the use of a selective aldosterone inhibitor, eplerenone. In a well-conducted multicenter, randomized-controlled clinical trial involving over 6,000 patients, a 15% reduction in the risk of death with randomization to eplerenone was reported. Reductions in cardiovascular mortality and hospitalization were also observed, and an intriguing reduction in the risk of sudden death with the aldosterone antagonist was presented. Importantly, these benefits were observed on top of conventional therapy including beta-blocker and angiotensin-converting enzyme inhibitors, indicating that this use of eplerenone offers a true advance in the management of these high-risk patients. The public health implications of EPHESUS were underscored by another abstract presented at this meeting concerning a registry of over 5,000 non-trial acute MI patients (6). Eric Velazquez reported that patients having an MI complicated by left ventricular dysfunction and/or pulmonary congestion constitute approximately 40% of acute MI admissions and that this group has 80% of all hospital MI deaths. Therefore, the advance demonstrated by Dr. Pitt and his colleagues should have a substantial impact in reducing mortality and morbidity during and after MI.
Drs. Arthur Feldman and Michael Bristow presented the preliminary results of the Comparison of Medical Therapy, Pacing, and Defibrillation in Chronic Heart Failure (COMPANION) trial at one of the late-breaking sessions. Patients with advanced heart failure and QRS interval widening were randomized to either optimal pharmacologic therapy, biventricular cardiac resynchronization therapy (CRT), or CRT combined with the cardioverter-defibrillator (CRT-D). This trial was designed to address whether these device modalities would reduce the risk of death and hospitalizations. The preliminary results indicated that the one-year events of death or any hospitalization was reduced by approximately 20% with CRT and CRT-D. Similarly, death or cardiovascular hospitalization and death or heart failure hospitalization at one year were significantly reduced by approximately 30% to 40%. Although the results are preliminary, the COMPANION trial does indicate that in selected patients with severe heart failure (class III and IV) and wide QRS interval, this non-pharmacologic therapy can lead to clinical improvements over and above a currently optimal medical regimen.
Cardiac function and heart failure are now demonstrating a non-vicious cycle with positive interactions between basic and clinical investigators. It is really becoming difficult to ascertain whether the novel concepts are coming from the trials or more basic studies, or vice versa. The sessions were replete with high-quality studies, which both improved our understanding of pathophysiology and demonstrated the translation of previous research into better clinical outcomes.
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