MEETING HIGHLIGHTS
Highlights of the 2008 Scientific Sessions of the Heart Failure Society of AmericaToronto, Ontario, Canada, September 20–23, 2008
Mandeep R. Mehra, MD*,*,
Howard A. Rockman, MD and
Barry H. Greenberg, MD
* University of Maryland School of Medicine, Baltimore, Maryland
Duke University, Durham, North Carolina
University of California at San Diego, San Diego, California
Manuscript received October 24, 2008;
accepted November 3, 2008.
* Reprint requests and correspondence: Dr. Mandeep R. Mehra, 22 South Greene Street, S3B06, Baltimore, Maryland 21201 (Email: mmehra{at}medicine.umaryland.edu).
Key Words: HFSA • highlights • heart failure • guidelines
The Heart Failure Society of America (HFSA) is the leading professional society that provides a multidisciplinary forum for a diverse group of health care professionals involved in basic, clinical, and translational research, patient care, and public policy about heart failure. The HFSA actively promotes and facilitates education and training efforts through the development of comprehensive and continuously updated patient care guidelines, a program for young trainee physicians pursuing careers in academic medicine, patient education materials, and public awareness. Through the development of position reports and participation in collaborative working groups, the HFSA serves as a resource for government, providers, and industry on issues of mutual interest including the design of clinical trials for drugs and devices for heart failure.
Most recently, on September 22, 2008, the American Board of Medical Specialties approved the American Board of Internal Medicine proposal to establish a secondary subspecialty certification in Advanced Heart Failure and Transplant Cardiology. The certification will establish standards and competencies for cardiologists with the experience necessary to treat patients with advanced or complex presentations of heart failure syndrome.
The 12th Annual Scientific Meeting, cochaired by Drs. Mandeep R. Mehra and Howard A. Rockman was attended by approximately 2,300 health care professionals including cardiologists, surgeons, nurses, pharmacists, and other allied health professionals representing academia, government, and industry. Presentations covered topics in basic, translational, and clinical research, as well as clinical care and public policy. Topics were addressed in a variety of formats, including symposia, award competitions, oral abstract sessions, how-to sessions, debates, and moderated posters. This article provides a brief overview of some of the new, innovative and interesting topics covered.
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Excellence in Basic Science
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Dr. Louis J. Ignarro, corecipient of the 1998 Nobel Prize in Physiology and Medicine, delivered the second Distinguished Lecture in Basic Science entitled "Nitric Oxide as a Unique Signaling Molecule in Physiology." In his lecture he provided a historical perspective of the discovery of nitric oxide and discussed the effects on cardiovascular disease when nitric oxide signaling is dysregulated. Dr. Ingarro's lecture was followed by other presentations describing new research on the basic molecular mechanisms of heart failure.
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Opening Session: Aerobiology, the Environment, and Cardiovascular Health
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In a departure from tradition, the opening plenary session focused on global public health to prevent heart failure with speakers addressing environmental aspects of cardiovascular disease. Salim Yusuf (McMaster University, Hamilton, Ontario, Canada) addressed heart disease from a global perspective with a particular focus on the role of urbanization in his talk on "Metabolic Syndrome: A Detriment to Societal Evolution." Urbanization is associated with automation, decreased physical activity, and increased energy consumption especially of fats in addition to increased levels of psycho-social stress. The result is an increase in the prevalence of obesity, dyslipidemia, dysglycemia, hypertension, and other markers of heart disease. The major differentiating risk factor for cardiovascular disease is not ethnicity but how and where you live, said Dr. Yusuf who underscored that the world is urbanizing quickly. In 1970, one-third of the world's population lived in urban settings. By 2025, it is expected to increase to 60%. "Therefore, the root cause of heart disease is not biology but is sociology." "We need to understand both the benefits and adverse effects on health of urbanization," Dr. Yusuf said.
To reduce the global risk of heart disease in high-risk populations, he advocated increased efforts to reduce tobacco use and more widespread use of a polypill containing 4 simple, cost-effective drugs: aspirin, a beta-blocker, a lipid-lowering drug, and an angiotensin-converting enzyme inhibitor. Implementation of these measures is suboptimal in the U.S. let alone in other parts of the world.
Richard J. Jackson, visiting professor of environmental health sciences at the School of Public Health at the University of California at Los Angeles, Los Angeles, California, discussed a related consequence of urbanization in his talk, "Tackling the Obesity Epidemic through Urban Planning." "A failed environment equals failed health," said Dr. Jackson, a pediatrician who formerly served as Director of the National Center for Environmental Health for the Centers for Disease Control, Atlanta, Georgia, and as the California State Public Health Officer. The way we have constructed our homes and environment is the leading cause of these problems, he said. "The environment is rigged against people."
We supersize schools and site them way out of town, so children have to sit on school buses instead of walking or biking to school. We give patients pedometers, and they do work somewhat. But you have to give people a place to walk. "It's time for doctors to speak up more aggressively against this rigging of the environment. We need to create environments that allow people to be healthy," said Dr. Jackson who cited examples in California where health care professionals have worked actively with government officials to facilitate land use that supports increased physical activity.
Joel D. Kaufman (University of Washington, Seattle, Washington) addressed a different aspect of environmental health in his talk "Particulate Matter Air Pollution and Heart Health." Particulate matter air pollution, which is currently a main research target, not only has respiratory toxicity but is clearly related to premature mortality and in particular cardiovascular mortality. Particulate matter, commonly referred to as soot, is emitted either directly by vehicles or from products of combustion or indirectly from atmospheric chemical reactions. The fact that air pollution can kill has been established by historical episodes such as the London smog that occurred in December 1952 during which particle levels reached 3,000 µg/m3 and which has been linked to 12,000 excess deaths. Since then, large cohort and time-series studies have consistently established increased mortality related to particulate matter. Increased mortality has been shown with the kind of exposures people in the U.S. experience everyday and not just the elevated exposures associated with the most polluted cities, Dr. Kaufman said. Additionally, several studies show increased heart failure hospitalizations related to short-term increases in air pollution. The exact mechanism of action remains an open question and potentially includes remote mediators of inflammation and oxidative stress leading either directly or indirectly to endothelial dysfunction and myocardial effects.
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Late-Breaking Trials
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Because of the number and quality of submissions, 2 late-breaking trial sessions were held for the first time at the 2008 Annual Scientific Meeting. Four of the 8 trials that were presented are summarized here.
3,5 diiothyropropionic acid (DITPA): a thyroid hormone analog to treat heart failure: phase II trial Veterans' Administration Cooperative Study.
Steven Goldman (Southern Arizona Veterans' Administration Health Care System, Tucson, Arizona) presented the results of the DITPA trial, which studied the ability of the thyroid hormone analog DITPA to improve clinical outcomes in patients with heart failure (1). It has been known for approximately 30 years that thyroid hormone can switch myosin heavy chain V1 and V3. In animal studies and a small 19-patient trial, DITPA increased cardiac output and decreased vascular resistance and left ventricular end-diastolic pressure as well as increased angiogenesis with no change in myocardial oxygen consumption or heart rate.
The phase II DITPA trial was a multicenter, randomized, placebo-controlled, escalating dose study with a primary composite end point that included heart failure morbidity and mortality, change in New York Heart Association (NYHA) functional class, and the change in global patient assessment. Secondary end points included a variety of cardiac and biochemical measures. A total of 86 patients with NYHA functional class II to IV heart failure were randomized 2:1 to receive an escalating dose of DITPA (90 to 360 mg/day) over 8 weeks until thyroid-stimulating hormone dropped to <0.02 mµ/l or placebo. Patients were studied at 2, 4, 6, 8, 16, and 24 weeks and at 28 weeks, 4 weeks after the drug had been stopped.
The study was prematurely stopped in October 2006, because of slow recruitment, adverse effects (44% discontinued study drug), and futility. The composite primary end point showed a tendency toward worsening heart failure with DITPA, primarily driven by patient global assessment scores. However, there were no differences in heart failure morbidity and mortality and in tachyarrhythmia between the 2 study groups. Both total cholesterol and low-density lipoprotein cholesterol dropped in the DITPA group. Additionally, patients in the DITPA group lost an average of 11 lbs while the placebo group experienced no weight loss.
Predictors of clinical success to continuous aortic flow augmentation in heart failure exacerbation refractory to pharmacological therapy: analysis of the multicenter MOMENTUM (Orqis Medical Cancion System for the Enhanced Treatment of Heart Failure Unresponsive to Medical Therapy) trial.
Mandeep Mehra (University of Maryland, Baltimore, Maryland) presented the results of this study assessing aortic flow therapy involving a percutaneously placed device attached to an extracorporeal centrifugal pump that delivers a flow of approximately 1.5 l/min to the descending aorta (2). The device, which is not a left ventricular assist device (LVAD) in the traditional sense, is designed to correct abnormal flow within the aorta, Dr. Mehra said. The MOMENTUM study was a multicenter, randomized study. This post-hoc analysis of the MOMENTUM data evaluated baseline clinical, laboratory, and hemodynamic predictors that correlated with post-discharge success with medical therapy versus aortic flow therapy. Success was defined as hospital discharge with no readmission for heart failure, alternative mechanical support, or death within 35 days.
The MOMENTUM trial enrolled a total of 168 patients with chronic heart failure who were hospitalized for decompensation and who were not responding adequately to therapy with intravenous inotropes, vasodilators, and diuretics and who had a pulmonary capillary wedge pressure  20 mm Hg; a cardiac index <2.4 l/min/m2 and creatinine >1.2 mg/dl; or were receiving 120 mg/day of intravenous furosemide. Patients were randomized to aortic flow therapy and background medications or medications alone for 4 days with 109 patients in the device therapy and 59 in the control group. The patient population was one of the sickest populations ever enrolled in a decompensated heart failure trial, said Dr. Mehra. Most were on at least 1 inotrope, and 30% of patients had died within 2 months.
Results of the study found that the device improved left ventricular performance in the aortic-flow device group as demonstrated by an increase in the cardiac index and reduction in left-sided filling pressures. Multivariate subgroup analysis found that a combination of nonischemic etiology, blood-urea-nitrogen levels <32 mg/dl, and N-terminal pro-B-type natriuretic peptide levels <5,200 pg/ml identify patients in the MOMENTUM study population in whom aortic-flow therapy demonstrated an incremental clinically significant benefit of 23% when compared with the control group. Dr. Mehra noted that 21% of the patient population in the MOMENTUM study population met these criteria. These data pointed out that patients with the more severe hemodynamic perturbations but less advanced heart failure comorbidity may derive the most benefit from aortic-flow therapy. Dr. Clyde Yancy, Baylor Medical Center, Dallas, Texas, commented that these data were post hoc and thus could represent a play of chance and should be proven in further trial populations.
Results of the COMPARE (Multicenter, Randomized, Double-Blind, Double-Dummy, Parallel Group Study to Compare Effects of Coreg CR and Coreg IR on Left Ventricular and Systolic Volume Index in Subjects With Stable Chronic Heart Failure) trial.
Barry H. Greenberg (University of California at San Diego, San Diego, California) presented the results of the COMPARE trial, a prospective, multicenter, double-blind, double-dummy, noninferiority study in which the immediate release (IR) formulation of carvedilol was compared with a controlled release (CR) formulation (3). Randomized controlled trials have demonstrated that carvedilol IR has beneficial effects to reverse maladaptive left ventricular remodeling and improve outcomes in patients with chronic heart failure. The initial primary end point of change in left ventricular ejection fraction (LVEF) was revised to evaluation of change in the left ventricular end-systolic volume index as measured with 2-dimensional echocardiography due to considerations regarding measurement variability and patient dropout rate. Secondary end points included the change in LVEF, change in left ventricular structure, change in serum B-type natriuretic peptide, and hospitalizations for heart failure and all other causes, all-cause death, drug dose tolerability, and compliance.
A total of 318 patients with chronic, mild-to-severe heart failure who were on stable, optimal therapy, naïve to beta-blockers and had an LVEF  0.40 were randomized to either carvedilol IR or carvedilol CR. Carvedilol IR was started at 3.125 mg twice daily and titrated to a dose of 25 mg twice daily. Coreg CR was started at 10 mg daily and titrated to a maximum daily dose of 80 mg. In the double-dummy design, patients were instructed to take 1 capsule out of bottles labeled A and B in the morning and 1 capsule out of bottles labeled C and D in the afternoon. Patients were followed for 24 weeks on blinded therapy after titration. Analysis was based on 253 patients as there was an 18.9% drop-out rate providing >80% power to establish noninferiority of carvedilol CR. Results of the study found there was no significant difference between the 2 groups for the primary end point of left ventricular end-systolic volume index. Similarly, there were comparable changes for important secondary end points including LVEF, the left ventricular end systolic volume index, left ventricular wall thickness, biomarkers, and morbidity and mortality measures for both preparations. Additionally, there were no significant differences in adverse events. A continuous release preparation with once-daily administration may beneficially affect compliance and further improve outcomes, but this assertion was contested by members who raised concerns about the increased price tag of such therapy compared with that of cheap generic carvedilol.
SADHART-CHF (Safety and Efficacy of Sertaline for Depression in Patients With Congestive Heart Failure) trial.
Christopher M. O'Connor (Duke University, Durham, North Carolina) presented the results of the SADHART-CHF trial, which studied the efficacy of sertaline, a selective serotonin reuptake inhibitor antidepressant, on depressive symptoms in heart failure (4). Depression is a common comorbidity and associated with higher mortality in heart failure patients with a step-wise increase in risk based on the gradation of depression. The SADHART-CHF study was a multicenter, randomized, double-blind, placebo-controlled study designed to determine whether sertaline plus nurse-facilitated intervention improves symptoms of depression and/or reduces cardiac events to a greater extent than nursing intervention alone. The primary end points were a change in severity of depressive symptoms during acute treatment, and the occurrence of worsening cardiovascular status at the end of acute treatment using a composite end point. Secondary end points included scores on a number of rating scales and rehospitalization. The study is the largest trial of an intervention for depression in heart failure.
A total of 469 patients with chronic systolic heart failure who were 45 years old with NYHA functional class II to IV heart failure and an LVEF 45% who had symptoms of major depression were randomized to receive a dosage of 50 mg/day of sertaline plus nurse-facilitated supported intervention or placebo and nurse-facilitated intervention. Patients were followed for 12 weeks in the acute phase of the trial. The long-term phase with follow-up of up to 5 years is still ongoing. Patients received telephone calls during weeks 1, 2, 4, 8, and 10 from nurses with psychiatric training and participated in face-to-face meetings at the clinic or in the home during weeks 6 and 12. Women and minority patients were well represented, and there was a high rate of diabetes and renal disease. Baseline depression scores were among the highest seen in a heart failure trial. Results of the study found no significant differences in depression scale ratings between the 2 groups. There were improvements in both groups, but over 50% of patients remained depressed at 12 weeks. Similarly, scores on the composite cardiovascular end point were equivalent for both groups. In conclusion, the SADHART-CHF study found that sertaline appears to be safe in high-risk patients with heart failure. Although there were no significant differences between the 2 treatment methods, a nurse-facilitated intervention that occurred with both groups may have contributed to the placebo effect and diminished the ability to observe differences between the groups, emphasizing the importance of a nurse-based intervention in heart failure.
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Debates
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Is the heart failure continuum (prevention to destination) best managed in the U.S.?.
Harlan M. Krumholz (Yale University, New Haven, Connecticut) and Paul W. Armstrong (University of Alberta, Edmonton, Alberta, Canada) faced off in a debate over which country provides the best patient care for heart failure. Dr. Krumholz acknowledged that, although free and universal health coverage in Canada is a remarkable accomplishment, this approach did not result in better care for heart failure patients. Waiting for care is an issue in Canada compared with that in the U.S. The median waiting time for catheterization outpatients in Hamilton, Ontario, is 60 days, noting that the city is close to the U.S. border, but wait times can be longer in more remote areas. Waiting can have consequences, he asserted. Furthermore, in Canada <15% of patients are seen by a cardiologist, while in the U.S. more than 25% receive care from a cardiologist. Additionally, Canada has a slow adoption of technology compared with the U.S., citing implantable cardioverter-defibrillator usage by example. Dr. Krumholz also noted the risk/treatment paradox in Canada, whereby the highest-risk patients are least likely to be treated with lifesaving heart failure drugs. In a review of mortality data, the U.S. held an advantage at 30 days, while 1-year results were about the same. Better short-term survival, shorter wait times, and more access to specialists and technology favor heart failure patients in the U.S., he concluded.
Dr. Armstrong argued superior performance on prevention and public health initiatives supports heart failure patient care in Canada. Cost and access to health care are issues in the U.S. with 42% of Americans either uninsured or underinsured. In terms of meeting guideline-recommended care for heart failure such as control of hypertension, Dr. Armstrong pointed out the poor compliance in the U.S. where treatment and control is <40%. The record is not only better in Canada but also in Cuba, a country with far fewer resources than in the U.S. In another measure of cardiac risk factors, obesity is prolific in the U.S. Similarly, he cited poor results in quality performance measures such as percentage of hospitalized heart failure patients given explanations for their medications or provided with discharge instructions. Primary and secondary prevention provides the best return on investment. Although the U.S. is faster on the uptake of new technologies, in the end the overall advantage goes to Canada, Dr. Armstrong concluded.
Should an endomyocardial biopsy be performed in most heart failure patients?.
In presenting the case for endomyocardial biopsy in heart failure patients, James B. Young (Cleveland Clinic, Cleveland, Ohio) reframed the question to exclude ischemic etiology for which a biopsy would not add much information. Those patients aside, Dr. Young said a biopsy can provide valuable information about pathology that can then be addressed appropriately. Additionally, the causes of nonischemic heart failure are heterogeneous, and we must know the diagnosis before talking to the patient about their etiology. A biopsy can also provide information on hypertrophy, fibrosis, and immunohistological changes important to prognosis. It is a safe, well-tolerated, and easy-to-perform procedure. It helps plan treatment, Dr. Young concluded.
In contrast, Stephen S. Gottlieb (University of Maryland, Baltimore, Maryland) argued that endomyocardial biopsy should only be used in selected cases since only 1% of patients have a biopsy that provides useful information. Dr. Gottlieb also pointed out that although the risk is small, there is still a risk in performing the procedure and it is not negligible. Risks include perforation, tricuspid valve regurgitation, and death among others. Biopsies are unreliable, and even if a biopsy demonstrates prognosis, it will have minimal impact on the treatment plan. Most biopsies will provide information that you will not do anything about. The facts are not there now, he concluded.
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Leading Clinical Research
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Promoting research related to all aspects of heart failure is critical to the mission of the HFSA. Leading clinical research abstracts were divided into 2 oral abstract sessions. The sessions provided a forum for investigators to present research on leading-edge topics. In the first session, Gregory R. Hartlage (University of South Florida, Tampa, Florida) presented data on discontinuation of the chemotherapeutic agent trastuzumab due to cardiotoxic effects.
Dr. Hartlage's talk was followed by 3 others: Amrut V. Ambardekar (University of Colorado, Denver, Colorado) presented data from the Get With the Guidelines–Heart Failure registry on outcomes for nonadherent patients; Greg Fonarow (University of California at Los Angeles, Los Angeles, California) presented on whether quality of care and outcomes differed for patients hospitalized on the weekend; and Wayne C. Levy (University of Washington, Seattle, Washington) presented the Seattle Heart Failure Model and how it is used to identify risk stratification of patients for an LVAD. In the second session Michael Bristow (University of Colorado, Denver, Colorado) presented on the agonist binding exhibited by human myocardial preparations with differing genotypes and their selective inactivation by bucindolol; Christian Zellner (University of California at San Francisco, San Francisco, California), recipient of a 2007 to 2008 HFSA Research Fellowship, presented the results of his research on the gene variants caveolin-1 and caveolin-2 in patients with idiopathic pulmonary arterial hypertension; Gautam G. Lalani (University of California at San Diego, San Diego, California) presented on action potential dynamics and arrhythmic susceptibility in systolic heart failure; and Lisa C. Costello-Boerrigter (Mayo Clinic, Rochester, Minnesota) concluded the session with a presentation on a polymorphism of the B-type natriuretic peptide associated with a higher prevalence of type 2 diabetes and atrial fibrillation.
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Novel Interventions in Heart Failure: A New Age?
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Novel techniques reflecting new approaches to the treatment of heart failure were addressed in a session that examined applications of gene therapy, nitric oxide scavenge, and device therapy.
Roger J. Hajjar (Mount Sinai School of Medicine, New York, New York) discussed gene therapy targeting sarcoplasmic reticulum Ca2+ ATPase (SERCA2a), which is important in maintaining calcium homeostasis in cardiomyocytes. SERCA2a activity is decreased in failing human hearts. Pharmacological targeting of SERCA2a has failed, and multiple large-scale efforts have been abandoned. Rescuing SERCA2a via gene transfer has been shown to improve cardiac contractility and calcium handling in cardiac myocytes in patients with heart failure. In a rodent model, overexpression of SERCA2a was associated with further favorable cardiovascular effects including a decrease in ventricular arrhythmias and cardiac hypertrophy, an improved energetic profile, and an increase in coronary flow. A number of clinical trials have been developed to study dose escalation of SERCA2a in heart failure patients, as well as studies researching new vectors and targets.
Frank W. Smart (Gagnon Cardiovascular Institute, Morrison, New Jersey) presented on the role of nitric oxygen scavengers in the treatment of cardiogenic shock of ischemic etiology. Current treatment involves stabilizing blood pressure, reperfusing tissue, and supporting the patient through the use of inotropes, pressors, and mechanical circulation and ventilation. Despite these measures, cardiogenic shock after acute myocardial infarction (MI) continues to be a major cause of mortality. There is evidence that there are similarities between the pathophysiology of cardiogenic shock and other types of shock such as septic and anaphylactic shock and that an excessive systemic inflammatory response including an increase in nitric oxide is involved. Dr. Smart, however, noted that nitric oxide is a double-edged sword with both positive and negative impacts on cardiovascular function. Recent studies examining the affect of nitric oxide inhibition in patients with cardiovascular dysfunction have demonstrated this dual function. Nonselective nitric oxide inhibition was found to increase blood pressure but did not reduce 30-day mortality in a large clinical trial. He surmised the results were due to the helpful and harmful aspects of nitric acid. Animal data indicate that nitric oxide scavengers may prove more advantageous than completely blocking nitric acid production. However, he concluded, human data are needed to determine whether this approach results in a mortality benefit.
Philip B. Adamson (Oklahoma Heart Hospital, Oklahoma City, Oklahoma) opened his presentation on implantable pressure sensors and their application in the management of heart failure by asking participants to first consider whether hemodynamic monitors were even needed (5). Even in the best of hands, physical examination is specific but not very sensitive. Hemodynamic monitoring may, therefore, provide needed information. Dr. Adamson went on to review 3 types of implantable hemodynamic monitors in advanced clinical development: those that provide continuous assessment, noncontinuous assessment, and hemodynamic monitors that are integrated into other devices such as an implantable cardioverter-defibrillator or biventricular pacemaker. Although there is no definitive clinical study confirming the value of such hemodynamic monitors, there have been signals as to which types of patient would benefit the most. In the COMPASS-HF (Chronicle Offers Management to Patients With Advanced Signs and Symptoms of Heart Failure) trial, there were indications that monitoring would be better suited in nonstage D refractory heart failure patients. Conversely, hemodynamic monitoring is of little value in trying to manage volume in patients with advanced renal disease. We are still learning how to work with these devices. Michael R. Zile (Medical University of South Carolina, Charleston, South Carolina) concluded the session with a presentation on investigational devices for heart failure with a preserved ejection fraction (50%). Dr. Zile discussed 4 devices: an implantable hemodynamic monitor, baroreceptor stimulation, a device designed to augment diastolic recoil, and chronotropic incompetence pacing. He also reviewed ongoing clinical studies of these devices regarding application to diastolic heart failure. He concluded that these devices and studies present the possibility of device therapy for diastolic heart failure or will at least generate testable hypotheses.
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Valvular Disease in Heart Failure
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Current thinking in regard to the treatment of valve dysfunction in heart failure patients was addressed in this session that touched upon mitral regurgitation (MR), aortic valve disease, and the possibilities of less invasive intervention.
Todd M. Koelling (University of Michigan, Ann Arbor, Michigan) discussed MR in heart failure and various assessment methods. The severity of MR has strong prognostic value in terms of survival of patients with systolic heart failure. Transthoracic echocardiography is the preferred imaging method of determining the severity of MR. The convergence zone on the proximal side of the mitral valve, the vena contracta, and the jet can all be visualized with color flow Doppler and used to assess MR severity. Dr. Koelling noted that eccentricity, the Nyquist limit, and spectral consistency are among the factors that must be taken into account when using echocardiography to assess MR severity. Additionally, pulmonary vein inflow, reverberation, excessive gain, and reverse timing of the signal among others can result in echocardiography images that can confuse assessment when using echocardiography. Broad-beam spectral Doppler, which allows for both narrow and broad beam assessment and provides velocities for the entire regurgitant orifice area, may be used in the future for more refined assessment of MR. For patients that do not have good echocardiography windows, catheterization and magnetic resonance imaging provide alternative assessment tools. With all of the focus on imaging MR, Dr. Koelling underscored the need to ensure that the patient is receiving optimal medical therapy as medications can change the degree of MR with time.
Robert C. Gorman (University of Pennsylvania, Philadelphia, Pennsylvania) focused on the surgical treatment of "ischemic" MR, defined as a mitral valve with normal leaflets and chordae tendinae that is rendered incompetent due to left ventricular remodeling after an MI. Approximately 19% of patients have some MR early after an MI, and 15% of heart failure patients have severe MR. Any degree of MR after an MI has negative prognostic implications with longevity decreasing as the degree of MR increases. The favored surgical approach involves placement of an undersized annuloplasty ring, usually concomitant with a coronary artery bypass procedure. Dr. Gorman, however, noted the limited clinical data assessing the effect of surgery on longevity in patients with ischemic MR. Available studies have not demonstrated a survival benefit from valve surgery for ischemic MR. The suboptimal results may be due to recurrent MR, which is a common problem and which may also confound the clinical results. More importantly, the remodeling stimulus due to ischemic MR may be relatively small compared with the MI.
Peter C. Block (Emory University, Atlanta, Georgia) overviewed transcatheter approaches to MR therapy. Percutaneous options include a clip that creates a tissue bridge in mitral valve orifice. A nonrandomized trial has demonstrated that the device works and is most useful in patients with degenerative MR. Four other investigational devices have targeted the coronary sinus as a route to repair the posterior mitral annulus. Preliminary clinical results have been disappointing. Other percutaneous devices under investigation include 2 devices designed to change the coaptation line in the mitral valve. In discussing device therapy for MR in heart failure, Dr. Block pointed out that it is important to recognize that MR in heart failure is not due to valvular disease but due to left ventricular remodeling. Therefore, another device that can be placed either surgically or percutaneously, that decreases the size of the ventricle and causes the mitral leaflets to coapt again by pushing the posterior portions of the myocardium and mitral annulus forward is of particular interest. Remaining to be seen is whether these devices can provide long-term benefit and whether eventually percutaneous mitral valve replacement can become a possibility.
Blase A. Carabello (Baylor University, Houston, Texas) concluded the session with a presentation addressing various aspects of aortic valve disease in heart failure. Symptoms of aortic valve disease should be taken very seriously and treated at the earliest onset with a valve replacement. Aortic regurgitation and aortic stenosis are both predictors of poor prognosis. With aortic regurgitation, an ejection fraction of 50% is too low, and intervention should take place before an end-systolic dimension of 50 mm to protect the ventricles. One of the challenging situations is low-gradient aortic stenosis in patients with a low ejection fraction. These patients have severe left ventricular dysfunction, and pose a high operative risk—26% mortality in 1 series. However, some of these patients return to completely normal ejection fraction. Inotropic challenge may help in the selection of patients who will most benefit from surgery and experience less surgical risk, but additional patient selection tools are needed. With aortic insufficiency, as with other types of aortic valve dysfunction, earlier treatment is preferred. However, even patients with a large ventricle may do well and should be considered for surgery. Finally, Dr. Carabello explained that the availability of percutaneous aortic valve replacement may change the treatment paradigm for aortic valve disease.
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Advanced Heart Failure: Prognosis-Guided Clinical Decision Making
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The use of prognostic tools in the treatment of advanced heart failure was discussed in the context of ventricular assist devices (VADs), transplantation, and palliative care in a session on the treatment of advanced heart failure. Douglas S. Lee (University of Toronto, Toronto, Ontario, Canada) discussed the role of predictive modeling from a population-based point of view and reviewed available prognostic tools. Prognostic models are needed to guide clinical decision making and to tailor therapeutic care. The HFSA guidelines, for example, include recommendations for implantable cardioverter-defibrillator therapy based on a patient's predicted survival, so determining prognosis is needed to provide guideline-based care. He reviewed a wide array of markers that have been used in prognostic models for heart failure including comorbidities, left ventricular systolic function, troponin and B-type natriuretic peptide among a large and growing number of biomarkers and heart failure hospitalizations, as well as multivariable models. New predictors should demonstrate incremental value beyond routine clinical models.
Randall C. Starling (Cleveland Clinic, Cleveland, Ohio) discussed the use of risk stratification models to decide when a VAD should be implanted. In the past, VADs have not provided the outcomes that patients and clinicians desire. More recent data show a 1-year survival of 56%, which drops to approximately 31% at 2 years and approximately 17% at 3 years. However, if patients are stratified into low-, moderate-, and very high-risk groups, outcomes vary significantly by risk group. The NYHA functional class, the presence of inotropic support, the level of cardiogenic shock, and a right ventricular risk score have been used as stratification criteria. The challenges are to define a patient population that can benefit most from a VAD and deciding when to refer a patient for implantation. Dr. Starling said the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profiles should be used in deciding whether to implant a VAD in a patient waiting for a transplant and should be avoided in INTERMACS Level 1. Similarly, in the case of an inotrope-dependent patient who is a candidate for a destination LVAD, the device should be implanted before INTERMACS level 1. Right ventricular function should also be assessed. A randomized trial should be performed to determine the benefit of an LVAD versus medical therapy in inotrope-dependent patients.
Mariell L. Jessup (University of Pennsylvania, Philadelphia, Pennsylvania) spoke on risk stratification in heart failure patients waiting for transplantation. In the U.S., the sickest patients get hearts earlier, so Status 2 patients wait a long time before transplantation. It is hard to tell patients that they have to get really sick before they can be transplanted, but the approach seems to work in terms of outcomes. No single criterion should be used to decide whether to transplant a patient. Rather, the entire picture should be taken into account, said Jessup who went on to explain the use of various criteria to triage patients for transplant including exercise assessment, response to medical therapy, body size, hemodynamics, and the patient's blood group. Clinical assessment and INTERMACS score are also important. She said there was almost a bewildering array of available predictors and recommended that clinicians pick 1 or 2 and strategize how to use them in practice. However, she cautioned that there can be a disconnect between the patient's score and their actual status, and that the patient who is very sick despite their score should be followed closely.
Sarah J. Goodlin (Patient-Centered Education and Research, Salt Lake City, Utah) addressed the role of palliative care in the in the context of providing hope in a hopeless situation. Research shows that people make decisions regarding treatment depending on the likelihood of a certain outcome. However, physicians are not very comfortable in discussing end of life with heart failure patients. Dr. Goodlin discussed skills needed for having "bad news" conversations with patients. We need to ask what patients and their significant others hope for and to address their concerns or fears. We also have to change the way we talk to people about heart failure and redefine heart failure care. We need to talk about managing heart failure rather than about curing the problem. People die after a fight with cancer, but they "succumb" to heart failure. We have to encourage patients to take ownership of their illness and to actively engage in optimizing their function, she concluded.
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Integrating Care for Decompensated Heart Failure: The Emergency Department, Hospitalist, and Cardiologist
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The role of the hospitalist and the integration of care for patients hospitalized for decompensated heart failure were discussed in a session that also discussed the evolving roles of the emergency department and cardiologist. Alpesh N. Amin (University of California at Irvine, Irvine, California) discussed patient care from the perspective of the hospitalist. Research has demonstrated that hospitalists reduce hospital costs and length of stay, and decrease readmissions and mortality while preserving patient satisfaction. There is a great opportunity for collaboration between hospitalists, emergency medicine doctors, and cardiologists working with heart failure patients. There are opportunities to collaborate on quality improvement measures, patient care, and education. We need to develop a nimble system with effective teams using evidence-based processes for patient care. If we stay in our silos, we will have trouble meeting the demand for heart failure management, he concluded.
Uri Elkayam (University of Southern California, Los Angeles, California) maintained that cardiologists should play a central role in the management of patients hospitalized for acute decompensated heart failure. Acute decompensated heart failure is a complicated and malignant disease. Patients hospitalized with acute decompensated heart failure are among the sickest patients physicians will see. The majority of patients will come in with volume overload, and the management of these patients can be very challenging. He reviewed treatment modalities and clinical evidence regarding their use noting that it takes a special expertise to administer certain treatments citing the example of managing diuretic resistance. Additionally, he said that ultrafiltration is an effective treatment, but it cannot be performed by just anyone in the hospital. Similarly, inotropes and vasodilators should be used only in selected patients. It requires a special expertise to select appropriate patients and deliver them properly.
Sean Collins (University of Cincinnati, Cincinnati, Ohio) recommended that the emergency rooms should be the starting point for clinical trials on acute decompensated heart failure. We should study acute heart failure when it is acute. The first 6 to 12 h after hospitalization is an important time. Citing the example of dyspnea, Dr. Collins said the majority of heart failure patients show early improvement in dyspnea after traditional treatment. Therefore, if dyspnea is used as an end point in a clinical trial, it should be measured early. If measured late, it may represent a unique subset of nonresponders. Additionally, a wide range of heart failure patients present to the emergency department. It is important to target the heterogeneity early. In regard to obstacles to enrolling patients in the emergency department, Dr. Collins cited the following reasons: chaos in the emergency department, misdiagnosis, and the problem of enrolling acutely ill patients. He went on to cite the work of the Emergency Research Group in Acute Heart Failure, a group of academic health centers where emergency medicine physicians and cardiologists have worked together to overcome these obstacles.
Mihai Gheorghiade (Northwestern University, Chicago, Illinois) concluded the session with a presentation on unmet needs and areas for research and collaboration on acute heart failure syndrome. No matter how well heart failure patients respond to therapy during hospitalization, within 3 to 6 months as many as 50% of the patients will be either rehospitalized or dead. Though controversial, Dr. Gheorghiade supports the hypothesis that heart failure resulting in hospitalization is a distinct entity from chronic heart failure, and that the poor prognosis may be due to renal injury that occurs before, during, and after hospitalization that contributes to the progression of heart failure. To improve post-discharge morbidity and mortality, we need identify patient profiles that stratify risk, study the downstream effects of early therapy, and develop a road map for post-emergency department patient care in collaboration with the hospitalist and cardiologist, he concluded.
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Heart Failure Guidelines: Updates and Applications
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Since publishing their Comprehensive Heart Failure Practice Guidelines in 2006, the HFSA established an ongoing process to update the guidelines and increase accessibility via a dedicated website among other initiatives. JoAnn Lindenfeld (University of Colorado, Denver, Colorado), HFSA Guideline Committee chair, outlined how the guidelines undergo a systematic review process with the goal of updating recommendations based on new evidence, and how new areas are vetted for inclusion in the guidelines. Two areas nearing completion are genetic evaluation of cardiomyopathy, and prevention and treatment of heart failure in patients receiving chemotherapy. Both are expected to be published in 2009. Four new topics are under consideration: palliative care for heart failure patients, referral for and care of patients with VADs, telemonitoring, and risk stratification. The issue of patient self-care will be addressed in these guidelines as well. This year's session was case-based and focused on evaluation admission criteria for acute heart failure, genetic evaluation of cardiomyopathy, heart failure patients receiving anticancer therapy, and disease management.
Ray E. Hershberger (University of Miami, Miami, Florida) discussed the genetic evaluation of cardiomyopathy. He noted that the field of genetics differs from other cardiovascular disease, and that the guidelines committee recognizes that the standard of evidence differs as well. The guidelines are designed to be practical to use and are organized by disease phenotype. Another major focus of the guidelines is about family screening and management. Recommendations include taking a careful family history for 3 or more generations for all patients with cardiomyopathy. Additionally, genetic screening is recommended for 1 clearly affected person to facilitate family screening and management.
Daniel J. Lenihan (M.D. Anderson Cancer Center, Houston, Texas) presented on the evaluation of heart failure patients receiving anticancer therapy. This new guideline will include recommendations for the prevention of heart failure in survivors of anticancer therapy and for optimal identification, prevention, and management of cardiac disease and heart failure during anticancer therapy. He also noted that therapy for both cancer and heart failure are intricately intertwined at the molecular level.
Debra K. Moser (University of Kentucky, Lexington, Kentucky) discussed new factors to consider in disease management. While there has not been a lot of change in the guidelines for disease management, there is an increased emphasis on self-care. Self-care is a way of doing disease management in the absence of a formal disease management program. In discussing self-care, it is important to recognize the complexities involved in patient self-care and factors that should be considered to ensure success. Very few people are experts at self-care. Knowledge is necessary, but patients also need skills in self-care. Clinicians should also suspect misconceptions about basic concepts and look for factors that interfere with learning. Clinicians can also work to overcome barriers to self-care by addressing treatable causes and engaging family members and other informal caregivers.
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Acknowledgments
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The authors wish to thank Harriet Guthertz for help with the composition of the manuscript, Cheryl Yano and Bart Galle for their assistance with editing of the report, as well as for organization of the 12th Annual Scientific Meeting of the HFSA.
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Footnotes
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Dr. Mehra has received research grants from the NIH, Maryland Industrial Partnerships Agency, State of Maryland Other Tobacco Related Diseases fund, and Orqis, and is a consultant to Orqis, Roche, Astellas, Celladon, GlaxoSmithKline, Geron, Debio Pharma, Solvay, Novartis, Medtronic, Scios, Boston Scientific, and St. Jude. Dr. Rockman is a consultant and co-scientific founder of Trevena, Inc. Dr. Greenberg has served as a consultant to AstraZeneca, Celladon, GlaxoSmithKline, NitroMed, Otsuka, ARCA Biopharma, and Orqis Medical; and derived honoraria from AstraZeneca, GlaxoSmithKline, Medtronic, Merck, NitroMed, Novartis, and Scios.
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References
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1. Goldman S, McCarren M, Morkin E, et al. DITPA, a thyroid hormone analog to treat heart failure: phase II trial VA cooperative study (abstr) J Card Fail 2008;14:796.2. Mehra MR, Zile MR, Colombo P, Brown S, Greenberg BH, Konstam MA, MOMENTUM Investigators Baseline predictors of clinical success during randomized assessment of aortic flow therapy in heart failure exacerbation refractory to pharmacological therapy: analysis of the multi-center MOMENTUM trial (abstr) J Card Fail 2008;14:796. 3. Greenberg BH, Mehra MR, Teerlink JR, Gilbert EM, Lukas MA, COMPARE Investigators Results of a multicenter, randomized, double blind, double dummy, parallel group study to compare effects of Coreg CR and Coreg IR on left ventricular end systolic volume index in subjects with stable chronic heart failure (the COMPARE trial) (abstr) J Card Fail 2008;14:796-797. 4. O'Connor CM, Jiang W, Silva SG, et al. SADHART-CHF Investigators Safety and efficacy of sertraline plus nurse facilitated supportive intervention (NFSI) versus placebo plus nurse facilitated supportive intervention for depression in patients with CHF (SADHART-CHF) (abstr) J Card Fail 2008;14:797. 5. Bourge RC, Abraham WT, Adamson PB, et al. COMPASS-HF Study Group Randomized controlled trial of an implantable continuous hemodynamic monitor in patients with advanced heart failure: the COMPASS-HF study J Am Coll Cardiol 2008;51:1073-1079.[Abstract/Free Full Text]
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