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Heartline Winter 2008

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Heartline Winter 2008 HeArTLiNe Winter 2008 Beta-Blockade Therapy and Adrenergic Dr. Edmund H. Sonnenblick (1932 - 2007), receptor Polymorphisms in Heart Failure internationally renowned cardiologist by Ronald Zolty, MD (see page 4) he emerging fields of pharmacogenetics and pharma- cogenomics involve the search for genetic polymorphisms Tthat influence humoral response to drug therapy. These disciplines offer the promise of A subset, however, appear to have developing individualized, tailored drug functional consequences influencing the therapy on the basis of genotype, thus interplay of genetic and environmental increasing the likelihood of achieving factors on phenotype, including response treatment goals while limiting adverse to medications. effects from drug therapy. Heart failure (HF) represents a major Heterogeneity of clinical response to public health problem because of its high medical therapy, in terms of treatment prevalence, unfavorable outcome, and efficacy, may be explained by multiple economic burden. In HF, activation of variables including: the etiology and the adrenergic system has been shown by severity of the disease being treated, numerous studies to be deleterious to the drug interactions, patient factors such heart in the long term. Several large ran- Also in this issue: as age, nutritional status, renal and liver domized trials have confirmed the bene- 2 Cardiac Imaging with function, co-morbidities and compli- ficial role of ß-blockade in improving left ance with treatment regimens. Despite ventricular ejection fraction (LVEF) and Radiotracers: SPECT and PET the potential impact of these clinical mortality in HF patients. However, in 3 Cardiac Recovery at Montefiore variables on therapeutic efficacy, it is now spite of the clear benefits of ß-blockade, 4 In Memoriam: recognized that inherited genetic varia- clinical response to ß-blocker therapy Edmund H. Sonnenblick, MD tion in the metabolism and disposition of displays a high degree on inter-individual 5 The Peerless-HF Study drugs, and genetic variation of the targets and inter-ethnic variation. Underlying of drug therapy (such as receptors), play a genetic variation in adrenergic mecha- significant role in individual response to nisms is one potential explanation for Published by the Montefiore-Einstein Heart Center medical therapy. this variability in response. The ß1 and New York, New York 10467 α 2c adrenergic receptors (ARs) play a Co-Directors: Heartline Editors: Data from the Human Genome Project critical role for maintenance of homeo- Richard N. Kitsis, MD Chris Snyder found that small and even modest-sized stasis in the human heart. Certain ß1 Dorros Chair Melissa Crissman nucleotide deletions, insertions, and rear- Professor and Chief Joanne Choi (specifically at amino acid position 49 Division of Cardiology rangements contribute to diversity within α Correspondence: and 389) and 2c (deletion 322-325) the genome. These variations known as Robert E. Michler, MD AR polymorphisms have been shown to Marketing Department SNPs, or single nucleotide polymor- Belkin Chair 111 East 210th Street act as disease modifiers in HF. Thus, we Professor and Chairman phisms, represent the largest class of New York, NY hypothesized that the different inter- Department of 10467-2490 inter-individual genetic variation. The Cardiothoracic Surgery individual response to ß-blockers might tel. 718 920 7823 majority of these genetic polymorphisms fax 718 405 1938 are likely of little clinical importance. (Continued on back) 1 Cardiac imaging with radiotracers: SPeCT and PeT by Mark Travin, MD ardiovascular disease, mostly from coronary artery disease, is the leading cause of death in the United States, claiming the lives of close to 900,000 people annually, as many as the next Cfour leading causes combined.1 The good news is that over the past decade the death rate from cardiac disease has declined over 20%, in large part the result of improved therapies and greater public attention to cardiac risk factors. Cardiac imaging has also played a crucial role by providing accurate diagnoses of the presence, extent, and severity of coronary disease, thereby helping to better direct patient management. Among cardiac imaging techniques, stress radionuclide myocardial perfusion imaging (MPI) has become a standard for diagnosis, risk stratification, and coronary disease management. Stress MPI can separate low from high risk patients better than clinical data and other cardiac Hybrid PET/CT camera. imaging techniques. As opposed to alternative imaging methods, such as invasive cardiac catheterization and like SPECT, PET can effectively risk stratify patients. An newly developed noninvasive multidetector CT coronary important potential of cardiac PET is that it can quantify angiography that customarily look only at anatomy, MPI coronary blood flow. Development of PET quantitation assesses the functional significance of coronary disease, thus promises great improvement in diagnostic accuracy, often making this technique better at identifying patients at including the ability to identify every patient with high risk of an adverse cardiac event. risk disease, as well as allow detection of patients with New technologies promise to subclinical disease whose response to medical therapies enhance further the clinical can be monitored before a serious problem occurs. utility of MPI. For most of its The variety of imaging molecules that can be developed approximately 30 year history, with PET are numerous. Cardiac PET already has the MPI has used single photon ability to detect metabolically active regions in patients with emission computed tomographic severe congestive heart failure. PET radiotracers that can (SPECT) imaging techniques image the underlying molecular processes of coronary and and tracers, such as thallium-201 other cardiac diseases are under active investigation, thereby or Tc-99m sestamibi. Although making PET a promising tool that should make a dramatic cardiac SPECT MPI has served impact on the #1 cause of death in much of the world. patients well, it is impaired both by technical issues and the limited Dr. Mark I. Travin is the Director of Cardiovascular Nuclear cardiac imaging molecules that Medicine at Montefiore Medical Center and Professor of can be synthesized. A similar Clinical Nuclear Medicine and Clinical Medicine at Albert imaging technique, cardiac Einstein College of Medicine positron emitting tomography 1. Rosamond W, Flegal K, Friday G, Furie K, Go A, Greenlund K, et al. (PET), has for many years been Heart disease and stroke statistics — 2007 update. A report from the American Heart Association Statistics Committee and Stroke Statistics used mostly in research, but Subcommittee. Circulation 2007; 115: e69-e171. in part because of technologic developments, PET has been moving into the clinical mainstream. Recent studies have shown that with visual interpretation techniques, cardiac PET with N13-ammonia or rubidium-82 is more accurate Over the past decade the death rate from than SPECT for diagnosing coronary disease, and that cardiac disease has declined over 20%. 2 Cardiac recovery at montefiore little more than a year after CMS expanded the indications for cardiac rehabilitation more patients are being referred for cardiac rehabilitation from a variety of Aspecialties including internal medicine, family practice, and general practitioners. all aspects of secondary prevention. that, “The evidence is adequate to Dr. Prince has noted a shift in referral conclude that cardiac rehabilitation patterns following the CMS decision. is reasonable and necessary following “Primary care providers today are very acute myocardial infarction (AMI), proactive when it comes to preventive coronary artery bypass graft (CABG), medicine and they understand the stable angina pectoris, heart valve importance of exercise. Many of them repair/replacement, percutaneous are active exercisers themselves and transluminal coronary angioplasty they know patients will not initiate (PTCA), and heart or heart- or stick with an exercise program on lung transplant.” The diagnoses their own, especially when there is of PTCA, valve replacement, and fear or anxiety involved. The CMS heart or heart-lung transplant were decision has given increased emphasis new additions to the criteria to to the importance of these programs. meet medical necessity. “With this There is now abundant research that proposed coverage decision, CMS demonstrates the importance and cost seeks to expand coverage to a greater effectiveness of cardiac rehabilitation number of beneficiaries with cardiac programs and primary care providers illness,” said CMS Administrator want to practice evidence based Mark B. McClellan, MD, PhD. “But medicine.” just as importantly, we hope that our proposed decision will raise the The Montefiore-Einstein Heart public’s awareness regarding cardiac Center cardiac rehabilitation facility rehabilitation services in general.” Dr. David Prince, Director of the is located on the East campus close to Cardiac Recovery Program at Jack D. Weiler Hospital. “We accept Dr. David Prince is the Director of the Montefiore-Einstein Heart Center referrals from primary care providers Cardiac Recovery Program at Montefore explained this trend stating, “as as well as cardiologists. In the past Medical Center. For more information awareness of cardiac rehabilitation two years I have also seen more and please go to www.montefiore.org/Heart/ continues to grow the desire of more patients referring themselves Cardiac Rehabilitation.
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