September 2010 Vol. 16 No.

9
From the publishers of The New England Journal of Medicine

CA RDI OLOGY
Bystander CPR: Chest Compression Alone or with Rescue Breathing?
A randomized trial shows no difference in adult patient outcomes with the two approaches.

years at the three sites, 1941 patients were enrolled. No significant differences were noted between the chest-compressiononly and conventional CPR groups in rates of survival to hospital discharge the primary outcome (12.5% and 11.0%) or favorable neurological status at discharge (14.4% and 11.5%). Prespecified subgroup analysis of patients with cardiac causes of arrest showed no significant difference in overall survival rate between the chestcompressiononly and conventional CPR groups (15.5% and 12.3%) but a significant improvement in the rate of neurologically favorable survival in the chest-compressiononly CPR group (18.9% vs. 13.5%).
COMMENT

from the subgroup analysis should prompt research in targeted application of type-specific CPR. J. Stephen Bohan, MD, MS,
FACP, FACEP, Journal Watch Emergency Medicine
Rea TD et al. CPR with chest compression alone or with rescue breathing. N Engl J Med 2010 Jul 29; 363:423.

A previous nonrandomized study showed improved outcomes from adult cardiac arrest with compression-only cardiopulmonary resuscitation (CPR) compared with conventional CPR (JW Cardiol May 2007, p. 44, and Lancet 2007; 369:920). Now, researchers compared outcomes with the two methods in a randomized study of consecutive 911 calls for cardiac arrest to three emergency medical services systems (2 in Washington State and 1 in London). After determining patient eligibility (unconscious, not breathing normally, bystander CPR not already under way), dispatchers randomly assigned patients to chest compression only or conventional CPR and provided instructions to bystanders about how to perform the assigned method. Patients who were younger than 18 years or who had arrest because of trauma, drowning, or asphyxiation were excluded. During the study period, which ranged from 3 to 5

CPR: Conventional or Compressions Only?

Survival rates at 30 days are similar in patients with out-of-hospital cardiac arrest who receive either type.

The finding that chest compression alone is not inferior to chest compression plus rescue breathing is important, because doing away with breathing might increase the prevalence of bystander CPR. This simpler technique should be adopted for both bystanders and basic-level prehospital providers. The authors note that the finding

A growing body of evidence indicates that chest compressions alone are as effective as conventional cardiopulmonary resuscitation (CPR) for out-of-hospital cardia arrest in adults (see previous article, N Engl J Med 2010; 363:423; JW Cardiol May 2007, p. 44; and Lancet 2007; 369:920). In a prospective national study, researchers in Sweden compared outcomes in patients older than 8 years who experienced witnessed out-of-hospital primary cardiac arrest (not from trauma, airway obstruction, drowning, or intoxication) and underwent chest compressiononly CPR or traditional CPR by bystanders. Dispatchers randomly assigned patients to one of the two methods and instructed bystanders about how to perform the assigned method. Of 3809 calls to dispatchers from 2005 to 2009 for patients with suspected cardiac arrest, 1828 met inclusion criteria and 1276 with complete data were included in the primary analysis. The standard-CPR and chest compressiononly groups did not differ significantly in the rate of survival at 30 days (the primary endpoint; 7.0% and 8.7%) or rate of survival at 24 hours. Subgroup analysis by age, sex, location of arrest, time

CONTENTS
SUMMARY & COMMENT

Bystander CPR: Chest Compression Alone or with Rescue Breathing? ......................... 69 CPR: Conventional or Compressions Only? ............ 69 Improving Outcomes of Cardiac Arrest: Dont Forget About CPR! ......................................... 70 Microvascular Outcomes in the ACCORD Trial ..... 70 Retinopathy in the ACCORD Trial.............................. 71 Blood Pressure Control in Patients with Diabetes and CAD ........................................... 71 Self-Management of Hypertension Outperforms Usual Care ......................................... 72 A New, but Not Yet Approved, Weight Loss Drug ..................................................... 72 HDL and Cardiovascular Risk in the Presence of Very Low LDL...................................... 72

Adherence to Cardiovascular Performance Measures in Outpatients ............... 74 Allopurinol for Chronic Stable Angina?................... 74 Antibiotic-Induced Hyperkalemia and Renin-AngiotensinSystem Inhibitors................. 74 Treating Heart Failure in Hospitalized Patients: How Are We Doing? ................................................ 75 Is Exercise Testing Necessary to Assess ........................................ 75 Degenerative MR? Multivessel Interventions for Stable STEMI: Still a No-Go! ............................................................. 75 Why Dont ICDs Prevent SCD After Recent MI? ...................................................... 76
FEATURE

Diagnosing Acute Coronary Syndromes: The Troponin Conundrum........................................ 73

JOURNAL WATCH (AND ITS DESIGN) IS A REGISTERED TRADEMARK OF THE MASSACHUSETTS MEDICAL SOCIETY. AN EDITORIALLY INDEPENDENT LITERATURE-SURVEILLANCE NEWSLETTER SUMMARIZING ARTICLES FROM MAJOR MEDICAL JOURNALS. 2010 MASSACHUSETTS MEDICAL SOCIETY. ALL RIGHTS RESERVED. DISCLOSURE INFORMATION ABOUT OUR AUTHORS CAN BE FOUND AT http://cardiology.jwatch.org/misc/board_disclosures.dtl

70
EDITOR-IN-CHIEF Harlan M. Krumholz, MD, SM, Harold H. Hines, Jr., Professor of Medicine, Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven EXECUTIVE EDITOR Kristin L. Odmark Massachusetts Medical Society DEPUTY EDITOR Howard C. Herrmann, MD, Professor of Medicine, Director, Interventional Cardiology and Cardiac Catheterization Laboratories, University of Pennsylvania Medical Center, Philadelphia ASSOCIATE EDITORS JoAnne M. Foody, MD, Director, Cardiovascular Wellness Center, Brigham and Womens Hospital, Boston Joel M. Gore, MD, Edward Budnitz Professor of Cardiovascular Medicine, University of Massachusetts, Worcester Mark S. Link, MD, Associate Professor of Medicine, New England Medical Center and Tufts University School of Medicine, Boston Frederick A. Masoudi, MD, MSPH, Division of Cardiology, Denver Health Medical Center and Associate Professor of Medicine, University of Colorado at Denver Beat J. Meyer, MD, Associate Professor of Cardiology, University of Bern; Chief, Division of Cardiology, Lindenhofspital, Bern, Switzerland CONTRIBUTING EDITORS William T. Abraham, MD, Professor of Medicine, Chief, Division of Cardiovascular Medicine, The Ohio State University Heart Center, Columbus Hugh Calkins, MD, Professor of Medicine and Director of Electrophysiology, The Johns Hopkins Hospital, Baltimore FOUNDING EDITOR Kim A. Eagle, MD, Albion Walter Hewlett Professor of Internal Medicine and Chief of Clinical Cardiology, Division of Cardiology, University of Michigan Medical Center, Ann Arbor MASSACHUSETTS MEDICAL SOCIETY Christopher R. Lynch, Vice President for Publishing; Alberta L. Fitzpatrick, Publisher Betty Barrer, Christine Sadlowski, Sharon S. Salinger, Staff Editors; Kara OHalloran, Copy Editor; Misty Horten, Layout; Matthew ORourke, Director, Editorial and Product Development; Robert Dall, Editorial Director; Art Wilschek, Christine Miller, Lew Wetzel, Advertising Sales; William Paige, Publishing Services; Bette Clancy, Customer Service Published 12 times a year. Subscription rates per year: $119 (U.S.), C$166.67 (Canada), US$165 (Intl); Residents/Students/Nurses/PAs: $69 (U.S.), C$96.19 (Canada), US$80 (Intl); Institutions: $219 (U.S.), C$256.19 (Canada), US$230 (Intl); individual print only: $89 (U.S.). Prices do not include GST, HST, or VAT. In Canada remit to: Massachusetts Medical Society C/O #B9162, P.O. Box 9100, Postal Station F, Toronto, Ontario, M4Y 3A5. All others remit to: Journal Watch Cardiology, P.O. Box 9085, Waltham, MA 02454-9085 or call 1-800-843-6356. E-mail inquiries or comments via the Contact Us page at JWatch.org. Information on our conflict-of-interest policy can be found at JWatch.org/misc/conflict.dtl

CARDIOLOGY

Vol. 16

No. 9

to EMS response, and initial rhythm similarly revealed no differences in outcome.

COMMENT

proved in survivors treated according to 2005 protocols, compared with controls.

COMMENT

Rescue breathing in out-of-hospital bystander CPR does not seem to improve survival compared to chest compressions alone, and, given its drawbacks difficult to perform and potential transmission of infection it should be abandoned.
J. Stephen Bohan, MD, MS, FACP, FACEP, Journal Watch Emergency Medicine
Svensson L et al. Compression-only CPR or standard CPR in out-of-hospital cardiac arrest. N Engl J Med 2010 Jul 29; 363:434.

Increased emphasis on cardiopulmonary circulation has improved outcomes of cardiac arrest. Yet further improvement is likely to be possible, not only in survival but in survival with good neurological function. The path to improvement will be multifactorial, including higher rates and quality of bystander CPR and improved postarrest treatment. Mark S. Link, MD
Aufderheide TP et al. Implementing the 2005 American Heart Association Guidelines improves outcomes after out-of-hospital cardiac arrest. Heart Rhythm 2010 Apr 24; [e-pub ahead of print]. (http://dx.doi.org/10.1016/j.hrthm .2010.04.022)

Improving Outcomes of Cardiac Arrest: Dont Forget About CPR!

The 2005 AHA resuscitation guidelines, which emphasize high-quality CPR, have had a positive effect.

Microvascular Outcomes in the ACCORD Trial

Intensive glycemic control did not lower the incidence of microvascular adverse outcomes.

In the late 1990s and early 2000s, many predicted that automated external defibrillators would markedly improve cardiac arrest outcomes; unfortunately, these hopes were not realized. In 2005, the American Heart Association published resuscitation guidelines reemphasizing the importance of circulatory support with properly performed chest compressions in addition to defibrillation. Changes from previous recommendations included a compression-to-ventilation ratio of 30:2, ventilation at 10 breaths per minute, and a more-vigorous compression technique. To evaluate the effects of the new guidelines, investigators compared outcomes in 1605 cardiac arrest patients treated according to the 2005 guidelines and 1641 controls treated before guideline implementation in five U.S. emergency medical services (EMS) systems. Age, sex, rates of bystander cardiopulmonary resuscitation (CPR), and time from 911 call to arrival of EMS personnel did not differ significantly between the two groups. The rate of survival to hospital discharge was significantly higher in patients treated after guideline implementation than in controls (13.1% vs. 10.1%). In patients with ventricular tachycardia or fibrillation, the rate of survival to discharge was 32.3% and 20.0%, respectively. Neurological function was also significantly im-

In the ACCORD trial, 10,000 patients with type 2 diabetes (mean age, 62; average duration of diabetes, 10 years) were randomized to receive intensive or standard glycemic control; choice of antidiabetic agents was individualized. The main purpose of ACCORD was to determine whether intensive treatment (target glycosylated hemoglobin [HbA1c] level, 6%) improved cardiovascular outcomes. The trial was halted after an average follow-up of 3.5 years, when overall and cardiovascular mortality were significantly higher with intensive than with standard treatment (JW Cardiol Jul 2008, p. 53, and N Engl J Med 2008; 358:2545). Now, the researchers present microvascular outcomes. The principal composite microvascular outcome was end-stage renal disease, rise of serum creatinine to >3.3 mg/dL, or need for photocoagulation or vitrectomy to treat retinopathy. This outcome occurred in similar proportions of patients in the intensive and standard treatment groups, both during the study itself (9%) and after 1.5 additional years of follow-up (11%). Although intensive treatment appeared to slow the progression of neuropathy, the incidence of a composite endpoint that included neuropathy (along with nephropathy and retinopathy) remained similar between groups. Some secondary endpoints (e.g., incident albu-

September 2010

JWatch.org

71

minuria) occurred less often with intensive than with standard therapy.
COMMENT

In ACCORD, intensive glycemic control did not lower the incidence of a composite endpoint of advanced microvascular adverse outcomes. When this finding is considered against the background of excess mortality noted in the intensively treated group, a target HbA1c level of 6% clearly is not appropriate for patients like those enrolled in ACCORD. Allan S. Brett, MD,
Journal Watch General Medicine
Ismail-Beigi F et al. Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: An analysis of the ACCORD randomised trial. Lancet 2010 Aug 7; 376:419.

Intensive antihypertensive therapy (vs. standard therapy) did not lower the incidence of either progressive retinopathy or vision loss.

COMMENT

Retinopathy in the ACCORD Trial

Findings from the ACCORD Eye Study are not straightforward.

In the ACCORD study of patients with type 2 diabetes (mean age, 62; average duration of diabetes, 10 years), intensive glycemic control led to excess mortality and did not lower the incidence of adverse cardiovascular events (JW Cardiol Jul 2008, p. 53, and N Engl J Med 2008; 358:2545). Moreover, in the ACCORD Lipid and Blood Pressure substudies, neither fenofibrate nor intensive antihypertensive therapy resulted in fewer adverse cardiovascular outcomes (JW Cardiol Apr 2010, p. 29, and N Engl J Med 2010; 362:1563 and 1575). Now, ACCORD researchers present retinopathy outcomes in 2856 patients. The primary endpoint was a 3-step change on a 17-step retinopathy scale (determined from serial retinal photographs) or development of proliferative retinopathy requiring photocoagulation or vitrectomy. A secondary outcome was moderate vision loss on a visual acuity chart. Findings at 4 years were as follows: Intensive glycemic therapy (vs. standard therapy) significantly lowered the incidence of progressive retinopathy (7.3% vs. 10.4%) but not vision loss (16.3% vs. 16.7%). Fenofibrate plus simvastatin (vs. simvastatin alone) significantly lowered the incidence of progressive retinopathy (6.5% vs. 10.2%) but not vision loss (16.0% vs. 15.2%).

Intensive glycemic control and fenofibrate lowered the incidence of progressive retinopathy but not moderate vision loss during 4 years of follow-up. However, ACCORDs intensive glycemic target (glycosylated hemoglobin [HbA1c], 6%) cannot be recommended to prevent progressive retinopathy, because it also resulted in excess mortality. The effect of intensive glycemic control on all microvascular outcomes in ACCORD retinopathy, nephropathy, and neuropathy also was published recently (see previous article and Lancet 2010; 376:419). As for fenofibrate, it did not prevent adverse cardiovascular events in ACCORD; using it solely to limit retinopathy is premature until we know that it will prevent vision loss, with an acceptable number needed to treat and without adverse effects during long-term administration.
Allan S. Brett, MD, Journal Watch General Medicine
The ACCORD Study Group and ACCORD Eye Study Group. Effects of medical therapies on retinopathy progression in type 2 diabetes. N Engl J Med 2010 Jul 15; 363:233.

Patients were divided into three groups according to their average systolic BP during the trial: tight control (<130 mm Hg), usual control (130139 mm Hg), or uncontrolled (>139 mm Hg). During median follow-up of 3 years, the primary outcome (all-cause mortality or nonfatal myocardial infarction or stroke) occurred in 12.7% of the tight-control group, in 12.6% of the usual-control group, and in 19.8% of the uncontrolled group. In adjusted analyses that included secondary outcomes, researchers found no difference between tight and usual control. After an additional 5-year follow-up, all-cause mortality was higher in the tight-control group than in the usual-control group (22.8% vs. 21.8%; P=0.04).
COMMENT

Blood Pressure Control in Patients with Diabetes and CAD

No benefit for lowering BP to <130/80 mm Hg

Because this was a post hoc analysis of observational data from patients who werent randomized to different BP targets, confounding factors could have influenced the findings. However, in the recently published ACCORD BP trial, high-risk patients with diabetes were randomized to one of two systolic BP targets (120 mm Hg or 140 mm Hg), and researchers found no difference in adverse cardiovascular events between the groups (JW Cardiol Apr 2010, p. 29, and N Engl J Med 2010; 362:1575). Taken together, INVEST and ACCORD suggest that a systolic BP goal in the 130s is reasonable for hypertensive diabetic patients with CAD or multiple cardiovascular risk factors.
Thomas L. Schwenk, MD, Journal Watch General Medicine
Cooper-DeHoff RM et al. Tight blood pressure control and cardiovascular outcomes among hypertensive patients with diabetes and coronary artery disease. JAMA 2010 Jul 7; 304:61.

Several organizations recommend a blood pressure (BP) goal of <130/80 mm Hg for patients with diabetes. To determine whether this goal is appropriate for patients with diabetes and known coronary artery disease (CAD), researchers conducted a secondary analysis of data from the INVEST study, a randomized trial in which hypertensive patients with CAD received -blockerbased or calciumchannel blockerbased regimens (JAMA 2003; 290:2805). Researchers reported previously that overly aggressive BP lowering in these patients was associated with excess risk for adverse cardiovascular events (JW Cardiol Aug 2006, p. 67, and Ann Intern Med 2006; 144:884); now, they focus on subset of 6400 INVEST patients with diabetes.

JOURNAL WATCH ONLINE

Is internship depressing? Read about a study that shows increased depressive symptoms in interns. Listen to our latest podcasts, including Survivors of childhood cancer face manageable reproductive risks.

JWatch.org/online

72

CARDIOLOGY
McManus RJ et al. Telemonitoring and selfmanagement in the control of hypertension (TASMINH2): A randomised controlled trial. Lancet 2010 Jul 17; 376:163.

Vol. 16

No. 9

Self-Management of Hypertension Outperforms Usual Care

The intervention involved self-measured blood pressure readings and a predetermined drug-titration plan.

HDL and Cardiovascular Risk in the Presence of Very Low LDL

HDL levels were not associated with residual cardiovascular risk in patients treated with potent statin therapy.

As many as half of patients who receive treatment for hypertension still have uncontrolled high blood pressure (BP). Patient self-monitoring and self-titration of treatment are effective in anticoagulation control and management of diabetes and asthma but have not been well studied for hypertension management. British investigators randomized 480 adults with uncontrolled hypertension (BP >140/90 mm Hg, despite treatment with one or two antihypertensive medications) to self-management or usual care. Patients in the self-management group measured their BPs with automated sphygmomanometers twice each morning for 1 week during each month; patients whose average BP was above target level (130/85 mm Hg, or 130/75 mm Hg for people with diabetes) for 2 consecutive months contacted their personal physicians for new prescriptions that were dispensed according to individually predetermined guideline-based titration algorithms. Patients adherence to the protocol was observed by their personal physicians via telemonitoring. BP was measured at office visits at baseline and at 6 and 12 months. Mean office BP at baseline was 152/85 mm Hg in both groups. After 6 months, mean office BPs in the usual care and intervention groups were 143/80 mm Hg and 139/80 mm Hg, respectively; after 12 months, they were 140/80 mm Hg and 135/77 mm Hg, respectively. Betweengroup differences in mean systolic and diastolic BPs were significant at 12 months. Additional hypertensive medications were prescribed significantly more often for self-management patients than for control patients.
COMMENT

A New, but Not Yet Approved, Weight Loss Drug

A new serotonergic drug appeared to be safe in this study.

The weight loss drugs fenfluramine and dexfenfluramine were removed from the U.S. market in 1997. These drugs were agonists of serotonin receptors located not only in the central nervous system (CNS; where the drugs suppressed appetite), but also in heart valves and pulmonary arteries (where the drugs caused valvulopathy and pulmonary hypertension). In contrast, a new serotonin receptor agonist, lorcaserin, is highly selective for CNS receptors. In an industry-sponsored randomized trial, 3182 obese or overweight adults received lorcaserin or placebo, along with dietary and exercise counseling. People with diabetes or psychiatric disease were excluded. Only half the patients completed 1 full year in the study. At 1 year, mean weight loss was significantly greater in the lorcaserin group than in the placebo group (5.8% vs. 2.2% decrease from baseline weight); the proportion of patients with >5% weight loss was also higher with lorcaserin than with placebo (48% vs. 20%). After 1 year, patients in the lorcaserin group were re-randomized to further active drug therapy or to placebo; at 2 years, those who received continuous lorcaserin were more likely to maintain weight loss than those who were switched to placebo. Serial echocardiography showed no evidence of cardiac valvulopathy.
COMMENT

Population-based studies show that HDL levels <40 mg/dL (<1.03 mmol/L) are a risk factor for cardiovascular disease. To find out whether this association remains when LDL levels are effectively reduced with high-dose statin treatment, researchers conducted a post hoc study of data from the manufacturer-sponsored JUPITER trial (JW Cardiol Dec 2008, p. 93, and N Engl J Med 2008; 359:2195). A total of 17,802 patients with elevated highsensitivity C-reactive protein levels and baseline LDL levels <130 mg/dL (<3.37 mmol/L) and without cardiovascular disease or diabetes were randomized to receive rosuvastatin (20 mg daily) or placebo. The composite endpoint of myocardial infarction, stroke, hospitalization for unstable angina, arterial revascularization, and cardiovascular death was analyzed by quartiles of HDL and apolipoprotein A1 levels. At 2 years, the composite event rate was 44% lower (P<0.0001) in the rosuvastatin group than in the placebo group. In the placebo group, the median on-treatment LDL level was 108 mg/dL (2.8 mmol/L), and lower HDL levels were significantly associated with increased cardiovascular risk (P=0.0047). However, in the rosuvastatin group, the median on-treatment LDL level was 54 mg/dL (1.4 mmol/L), and neither baseline nor on-treatment HDL level was associated with cardiovascular risk. Likewise, low apolipoprotein A1 levels were associated with a significant increase in the composite event rate in the placebo group but not in the rosuvastatin group.
COMMENT

Socially challenged patients were underrepresented in this study and appeared to benefit less from the intervention, so the generalizability of these encouraging findings requires further exploration. Costeffectiveness of the intervention will be reported separately. Bruce Soloway, MD,
Journal Watch General Medicine

Lorcaserin has been submitted for FDA approval. Although it seemed to be safe and moderately effective in this study, the high dropout rate is an important caveat. If lorcaserin is approved, careful postmarketing surveillance will be essential, given the checkered history of serotonergic weight loss drugs. Allan S. Brett, MD,
Journal Watch General Medicine
Smith SR et al. Multicenter, placebo-controlled trial of lorcaserin for weight management. N Engl J Med 2010 Jul 15; 363:245.

These findings suggest that HDL levels do not predict cardiovascular events in patients who attain very low LDL levels with potent statin therapy for primary prevention. As editorialists note, these results should not distract from the fact that raising HDL cholesterol with lifestyle changes and drugs such as niacin might provide additional cardiovascular benefit in the majority of patients on statin therapy who do not
continued on page 74

September 2010

JWatch.org

73

FEATURE

Diagnosing Acute Coronary Syndromes: The Troponin Conundrum

As the sensitivity of Tn assays rises, electrocardiographic and clinical evidence of ACS become more not less important in treatment decisions.

The diagnostic criteria for myocardial infarction (MI) are obtained from the triad of clinical presentation, electrocardiogram (ECG) changes, and serial cardiac enzyme or biomarker measurements. In recent years, the emphasis on biomarkers specifically, troponin (Tn) has increased, while ECG findings and clinical symptoms have received relatively little attention. Nonetheless, a detectable Tn level alone does not equal a diagnosis of MI.
TROPONIN AND MYOCARDIAL DAMAGE

induced Tn release. Researchers have now determined that hsTn can be detected in healthy populations and that elevated levels are associated with increased cardiovascular risk.5 The goal of diagnosing any medical condition is to classify patients by prognosis, pathophysiology, and response to specific therapies. An elevated Tn level in a patient with sepsis, hypertensive emergency, pulmonary embolism, hypotension, renal failure, or any of several other conditions indicates that myocardial damage or even nonthrombotic MI (the extreme end of the spectrum of demand ischemia) has occurred, producing leakage of low levels of Tn and likely indicating a poor prognosis. However, an elevated Tn level does not mean that the patient has ACS, and therefore should not necessarily lead to ACS-directed care. To distinguish ACS from nonocclusive conditions, a compatible clinical syndrome must be accompanied by a change in Tn levels rising, falling, or both.
CONCLUSION

Acute coronary syndromes (ACS) is a general term used when clinical symptoms and signs of myocardial ischemia are caused by obstruction of flow through the coronary arteries, and it typically has included both MI and unstable angina. A European Society of Cardiology and American College of Cardiology joint consensus document1 (published in 2000, updated in 2007) explicitly defines MI as myocardial necrosis secondary to ischemia, which can also occur in ACS without MI. Cardiac Tn is an extremely specific marker of cardiac injury; however, myocardial damage is not specific to either MI or ACS. Several new high-sensitivity Tn (hsTn) assays are able to detect levels of Tn that would register as zero with older, conventional assays. The advantages of the hsTn assays greater sensitivity in identifying myocardial injury and potential for earlier detection of MI come at the cost of a reduction in specificity for the diagnosis of ACS. Indeed, in a recent report 2, investigators used cardiac computed tomography to confirm a mechanistic association between elevated hsTn levels and myocardial damage, not only in patients with ACS but also in those without ACS. Even with conventional Tn assays, patients can have detectable Tn levels because of etiologies other than ACS; the use of hsTn is likely to increase such false-positive findings. We need to reassess the currently held belief that Tn is released only from irreversibly injured myocardial cells. In a recent study3, marathon runners had significant elevations in Tn levels after a race. The authors postulated two alternative mechanisms for increased Tn values after heavy exertion: true myocardial injury resulting from the breakdown of myocytes, and cytosolic release of the biomarker. In the marathon study, delayed-enhancement cardiac magnetic resonance imaging supported a cytosolic release, and the authors of a recent review4 concluded that increased membrane permeability is a likelier mechanism than myocardial necrosis for exercise-

High-sensitivity assays will enable physicians to both confirm and exclude MI sooner than is now possible, but serial testing at 0, 4, and 8 hours remains necessary. Moreover, the tests are useful for diagnosing (ruling in) certain high-risk conditions (demand ischemia and MI) but not for excluding (ruling out) the diagnosis of unstable angina also a high-risk situation for the patient but one in which troponin leak might not occur. Overreliance on Tn and failure to consider ECG findings and clinical presentation appropriately can lead to both over- and underdiagnosis of MI, each of which carries its own set of hazards.
J. Stephen Bohan, MD, MS, FACP, FACEP, Journal Watch Emergency Medicine; and Joel M. Gore, MD
1. Thygesen K et al. Universal definition of myocardial infarction. J Am Coll Cardiol 2007 Nov 27; 50:2173. 2. Januzzi JL Jr et al. High-sensitivity troponin T concentrations in acute chest pain patients evaluated with cardiac computed tomography. Circulation 2010 Mar 16; 121:1227. 3. Mousavi N et al. Relation of biomarkers and cardiac magnetic resonance imaging after marathon running. Am J Cardiol 2009 May 15; 103:1467. 4. Shave R et al. Exercise-induced cardiac troponin elevation: Evidence, mechanisms, and implications. J Am Coll Cardiol 2010 Jul 13; 56:169. 5. Otsuka T et al. Association between high-sensitivity cardiac troponin T levels and the predicted cardiovascular risk in middle-aged men without overt cardiovascular disease. Am Heart J 2010 Jun; 159:972.

74
continued from page 72 COMMENT

CARDIOLOGY

Vol. 16

No. 9

attain very low LDL cholesterol levels. However, we dont yet know whether such strategies or novel HDL-raising agents will improve outcomes in these patients.
Beat J. Meyer, MD
Ridker PM et al. for the JUPITER Trial Study Group. HDL cholesterol and residual risk of first cardiovascular events after treatment with potent statin therapy: An analysis from the JUPITER trial. Lancet 2010 Jul 31; 376:333. Hausenloy DJ et al. Dissociating HDL cholesterol from cardiovascular risk. Lancet 2010 Jul 31; 376:305.

In this registry, adherence to most performance measures was moderate to high for common cardiovascular diagnoses with notable exceptions. An editorialist highlights some limitations of self-reported registry data: Participating providers may be more motivated than nonparticipants, leading to overestimated adherence, and data may be less complete and less detailed than data routinely collected in clinical trials. Nonetheless, this snapshot of outpatient practice is helpful in highlighting areas for discussion and quality improvement.
Kirsten E. Fleischmann, MD, MPH, Journal Watch General Medicine
Chan PS et al. Cardiac performance measure compliance in outpatients: The American College of Cardiology and National Cardiovascular Data Registrys PINNACLE (Practice Innovation And Clinical Excellence) program. J Am Coll Cardiol 2010 Jun 29; 56:8. Rao SV. Scaling new heights in quality improvement: The PINNACLE (Practice Innovation And Clinical Excellence) program. J Am Coll Cardiol 2010 Jun 29; 56:15.

rable to that of other drugs such as amlodipine and nitrates, but its mechanism remains obscure. The authors speculate that allopurinol might reduce oxidative stress, thereby making more molecular oxygen available to ischemic myocardium and improving endothelial function. Although allopurinol generally is tolerated well, serious adverse effects occur occasionally. Thus, in future trials, researchers should compare allopurinol to other anti-anginal agents and include more patients and clinical outcomes. Bruce Soloway, MD,
Journal Watch General Medicine
Noman A et al. Effect of high-dose allopurinol on exercise in patients with chronic stable angina: A randomised, placebo controlled crossover trial. Lancet 2010 Jun 19; 375:2161.

Adherence to Cardiovascular Performance Measures in Outpatients

Adherence to most performance measures was moderate to high.

The PINNACLE project is a self-report provider registry sponsored by the American College of Cardiology to track the quality of outpatient cardiovascular care. In this report from the registry, researchers assessed adherence by providers in cardiology practices to a variety of performance measures for 14,464 outpatients with common cardiac diagnoses such as coronary artery disease (CAD; 56%), heart failure (35%), and atrial fibrillation (19%). Adherence ranged from very low (for example, only 18% of CAD patients received a referral for cardiac rehabilitation) to very high (94% of CAD patients and 97% of heart failure patients had blood pressure measured at their last visit). Adherence to most measures ranged from 70% to 90%. Differences in adherence by patient sex and race were generally small. However, among CAD patients with ejection fractions 40%, men were more likely than women to receive angiotensinconvertingenzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs; 72.1% vs. 71.7%), and warfarin was more commonly prescribed to treat atrial fibrillation (CHADS2 score 2) in men than women (80.7% vs. 75.7%). Interestingly, among heart failure patients (ejection fraction 40%), blacks were marginally less likely than whites to receive ACE inhibitors or ARBs (relative risk, 0.93; P=0.05).

Antibiotic-Induced Hyperkalemia and Renin-Angiotensin System Inhibitors

Among older patients receiving RAS inhibitors, trimethoprim-sulfamethoxazole increased hyperkalemia risk.

Allopurinol for Chronic Stable Angina?

In a small study, allopurinol improved exercise tolerance in patients with CAD.

Recent years have seen greatly increased use of renin-angiotensin system inhibitors, including angiotensin-convertingenzyme inhibitors and angiotensin-receptor blockers. With this increase, we should expect a rise in novel drug interactions. Knowing that hyperkalemia has been associated both with renin-angiotensin system inhibitors and with trimethoprim, investigators in Toronto performed a population-based, nested case-control study among older patients (aged 66) who were receiving continuous treatment with one of these blockers and had also been prescribed trimethoprim-sulfamethoxazole (TMP-SMX), ciprofloxacin, norfloxacin, nitrofurantoin, or amoxicillin. Cases (371 patients who were hospitalized between 1994 and 2008 for treatment of hyperkalemia 14 days after receiving an antibiotic of interest) were each matched with one to four controls (similar patients without such hospitalization before the index date). The risk for hyperkalemia-associated hospitalization within 14 days of antibiotic prescription was nearly sevenfold higher with TMP-SMX than with amoxicillin (adjusted odds ratio, 6.7; 95% confidence interval, 4.510.0). Findings were similar when the index hospitalization occurred within 7 days of antibiotic prescription.

Experimental evidence suggests that allopurinol lowers myocardial oxygen consumption. To assess whether this effect might benefit patients with cardiac ischemia, U.K. investigators randomized 60 patients with chronic stable exertion-induced angina, angiographically proven coronary artery disease, and positive exercise stress tests to add daily allopurinol (600 mg) or placebo to their baseline angina medications for 6 weeks; patients then crossed over to the opposite treatment for 6 weeks. Exercise stress testing was performed after randomization and at the end of each treatment period. Compared with placebo recipients, allopurinol recipients exhibited significantly longer mean total exercise time (393 vs. 307 seconds), mean time to ST depression (298 vs. 249 seconds), and mean time to symptoms (304 vs. 272 seconds). No adverse treatment effects were noted.
COMMENT

The anti-ischemic effect of allopurinol that was demonstrated in this study is compa-

September 2010

JWatch.org

75

No association was seen between use of any of the other study antibiotics and development of hyperkalemia.
COMMENT

These findings should prompt us to consider using an alternative to TMP-SMX, if feasible, among older patients who are receiving renin-angiotensinsystem inhibitors. Larry M. Baddour, MD,
Journal Watch Infectious Diseases
Antoniou T et al. Trimethoprim-sulfamethoxazole induced hyperkalemia in patients receiving inhibitors of the renin-angiotensin system: A population-based study. Arch Intern Med 2010 Jun 28; 170:1045.

beneficiaries has been documented previously [N Engl J Med 2009; 360:1418]). The best treatment model for older patients with heart failure is still a work in progress and will require more emphasis on the transition of care from hospital to home.
Neil H. Winawer, MD, FHM, Journal Watch Hospital Medicine
Bueno H et al. Trends in length of stay and shortterm outcomes among Medicare patients hospitalized for heart failure, 1993-2006. JAMA 2010 Jun 2; 303:2141.

and, potentially, treated more aggressively than current guidelines recommend.

Howard C. Herrmann, MD
Magne J et al. Exercise-induced changes in degenerative mitral regurgitation. J Am Coll Cardiol 2010 Jul 20; 56:300. Flachskampf FA. Mitral regurgitation is incompletely characterized at rest. J Am Coll Cardiol 2010 Jul 20; 56:310.

Multivessel Interventions for Stable STEMI: Still a No-Go!

Revascularizing noninfarct-related arteries during primary PCI significantly increases 90-day mortality.

Is Exercise Testing Necessary to Assess Degenerative MR?

Exercise-induced echocardiographic changes can provide valuable functional and prognostic information.

Treating Heart Failure in Hospitalized Patients: How Are We Doing?

A review of Medicare data reveals significant trends toward shorter length of stay and lower 30-day mortality, but more readmissions.

During the past decade, we have witnessed substantial shortening in hospital length of stay for patients with heart failure. Although better medical therapy and new cardiac devices have resulted in improved longterm outcomes in these patients, whether shorter length of stay puts patients at risk for short-term adverse events is unclear. Researchers performed a retrospective observational study on data from almost 7 million fee-for-service Medicare patients (age, 65) who were hospitalized with heart failure from 1993 to 2006. During the study, mean length of stay decreased by 2.5 days (from 8.8 days in 1993 to 6.3 days in 2006), and in-hospital and 30-day mortality rates decreased from 8.5% to 4.3% and from 12.8% to 10.7%, respectively. Discharges to home or home-care services decreased from 74% to 67%, and discharges to skilled nursing facilities increased from 13% to 20%. The 30-day readmission rate increased from 17% to 20%.
COMMENT

The value of exercise testing in characterizing functional mitral regurgitation (MR) is well established, but less is known about the importance of dynamic measures in degenerative MR. In this study, 61 patients with degenerative, asymptomatic MR (moderate or severe) underwent bicycle exercise echocardiographic evaluation. Mean exercise duration was 8.9 minutes, and maximal heart rate achieved was 125 beats per minute. In the cohort as a whole, regurgitant volume (6870 mL, as calculated with the proximal isovelocity surface area method) did not differ from baseline to peak exercise, although effective regurgitant orifice area increased slightly from 42 mm2 to 45 mm2. However, in 18 patients, mean regurgitant volume increased by 15 mL at peak exercise, whereas in 15 patients mean regurgitant volume decreased with exercise. In 25% of patients with moderate MR at rest, MR became severe with exercise. During a mean followup of 22 months, symptom-free survival was reduced in patients with marked exercise-induced increases in MR (26% at 2 years vs. 54% for the entire cohort).
COMMENT

Current guidelines discourage revascularization of noninfarct-related arteries (IRAs) during primary or rescue percutaneous coronary intervention (PCI) in patients with stable ST-segment-elevation myocardial infarction (STEMI). However, these recommendations are based on evidence derived from clinical trials with limited power and from the era before routine stenting, platelet glycoprotein inhibition, and clopidogrel pretreatment. In a retrospective analysis of data from the manufacturer-sponsored APEX-AMI trial, investigators identified 5373 STEMI patients undergoing primary PCI and examined the rate of, propensity for, and associated 90-day outcomes of revascularization of non-IRAs during primary PCI. Of 2201 patients with multivessel disease, 217 underwent non-IRA interventions. At 90 days, rates of death and the composite endpoint of death, heart failure, and cardiogenic shock were significantly higher in the non-IRA group compared with patients who received IRA-only interventions (12.5% vs. 5.6% and 17.4 vs. 12.0%, respectively). After adjustment for patient and procedural characteristics as well as propensity for performing non-IRA PCI, additional interventions remained independently associated with an increased 90-day mortality risk (P<0.001).
COMMENT

At first glance, quality of care seems to have improved for Medicare patients with heart failure, because in-hospital and 30-day mortality were lower by 2006. However, the shorter hospital length of stay during the 14-year study came at the cost of more admissions to nursing home facilities and a higher percentage of patients who required hospital readmission. (The high rate of readmissions among Medicare

These findings demonstrate that degenerative MR can be dynamic, and that asymptomatic patients with exercise-induced increases in severity of MR are more likely than those without such increases to become symptomatic during follow-up. Incorporating echocardiographic exercise testing into the work-up of patients with degenerative MR could allow us to identify some who should be followed more closely

These findings from the largest contemporary cohort to date show that non-IRA interventions were performed in 10% of patients with multivessel disease during primary PCI and were significantly associated with increased 90-day mortality. Despite the nonrandomized nature of the analysis, these findings strongly support

JW ONLINE CME
JOURNAL WATCH SUBSCRIBERS HAVE 10 FREE CREDITS! This is one of four questions in a recent Journal Watch Online CME exam. from Is Exercise Testing Necessary to Assess Degenerative MR? (p. 75) In a study of exercise testing in patients with degenerative mitral valve regurgitation (MR), what percentage of those with moderate MR at rest developed severe MR with exercise? A. 18% B. 25% C. 54% D. 70% Category: Cardiovascular Diseases Exam Title: Mitral Valve Disease Posted Date: Aug 24 2010 View this exam and others at http://cme.jwatch.org User name and password are required. CME FACULTY Kelly Anne Spratt, DO, FACC, Section Editor, Cardiology

No part of this newsletter may be reproduced or otherwise incorporated into any information retrieval system without the written permission of the Massachusetts Medical Society. Printed in the USA. ISSN 1521-5822.

Massachusetts Medical Society 860 Winter Street Waltham, MA 02451-1413 JWatch.org

76

CARDIOLOGY

Vol. 16

No. 9

current guideline recommendations discouraging non-IRA PCI procedures in hemodynamically stable STEMI patients.
Beat J. Meyer, MD
Toma M et al. for the APEX-AMI Investigators. Non-culprit coronary artery percutaneous coronary intervention during acute ST-segment elevation myocardial infarction: Insights from the APEX-AMI trial. Eur Heart J 2010 Jul; 31:1701.

2009; 361:1427), in contrast to results of other ICD trials. To examine this lack of benefit more closely, investigators studied data from VALIANT, an international trial of valsartan in MI survivors. Of 14,703 participants with left ventricular dysfunction, clinical heart failure, or both, 2878 died during a median of 25 months of follow-up, and autopsy results were available for 398. Of these, the cause of death was clinically judged to be SCD in 105; autopsy revealed recurrent MI or cardiac rupture in 44; pump failure in 4; and stroke, pulmonary embolism, and drug overdose in 1 each. The proportion of clinically adjudicated SCDs that were nonarrhythmic on autopsy was even more dramatic during the first post-MI month (24 of 30 deaths).
COMMENT

and 80% of SCDs within the first month were nonarrhythmic. If confirmed in other populations, this finding would explain the failure of ICDs to prevent SCD in previous trials. This study appears to validate current guidelines that call for a 40-day delay in ICD placement after an acute MI.
Mark S. Link, MD
Pouleur A-C et al. Pathogenesis of sudden unexpected death in a clinical trial of patients with myocardial infarction and left ventricular dysfunction, heart failure, or both. Circulation 2010 Aug; 122:597.

Why Dont ICDs Prevent SCD After Recent MI?

Recurrent MI and mechanical factors such as cardiac rupture may account for nearly 50% of SCD early after MI.

FREE online access to

The risk for sudden cardiac death (SCD) is particularly high in the early months after a myocardial infarction (MI). However, two trials of prophylactic implantable cardioverter-defibrillator (ICD) placement after MI failed to show a survival benefit in ICD recipients (JW Cardiol Mar 2005, p. 25; N Engl J Med 2004; 351:2481; JW Cardiol Nov 2009, p. 85; and N Engl J Med

Journal Watch Cardiology

for print subscribers!
Journal Watch Cardiology publishes summaries on the web even before they appear in print.

This unique analysis of the causes of SCD early after MI yielded a surprising result: Nearly 50% of SCDs in the first 2 years

Visit us at cardiology.jwatch.org