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Conference Calendar

Conference Calendar 2012

has a long and rich history, and we are proud to bring it back with a fresh look and new ways to help physicians keep current in their practice. In this 24/7 world, physicians realize that a multitude of information is at their fingertips on the Internet, and in fact, they can find countless online resources to help them in their profession. But with physicians’ always pressing need to stay current in their field, ultimately the most useful information revolves around the very latest published research and studies. That’s where 

comes in—bringing together the most valuable content directly to the physician&mdash;or, as we say, “What you need, when you need it most!”

This journal will prove to be one of your “must-reads” right away, as we will continue our mission to bring you the most relevant, timely, and thought-provoking content in your field. Under this new roof you’ll find Reviews of key articles from the literature that examine the thrust of the material and explain them in detail. Next, our expert authors provide an informative Commentary to kick off the discussion, bring out salient points, and raise questions. Finally, these Review articles form the basis for the CME lesson in this issue of 

—and provide you with the opportunities to test your new knowledge right away. Each upcoming issue will gather together current research and offer this unique chance to learn again.

Additionally, we offer timely congress and convention coverage in “Meeting Report” as well as a look down the road at important conferences and meetings. “News & Trends” brings significant news from the world of cardiology and will help you stay up-to-date. Finally, your patients are not shy about telling you what they know about their medical condition, so the “What Your Patients Are Reading” column will tip you off and provide insight.

We offer you the opportunity to take the CME activity online at www.cardiologyreview. com each and every issue. Part of HCPlive.com, this Web site will enhance your practice, offer new ways to look at important topics, and perhaps most importantly, keep you current and on top of what you need to know. Look for additional online resources and watch for an iPad launch for this distinguished journal.

Keeping patients healthy and utilizing best practices—and keeping an open mind as to how best to accomplish these worthy goals&mdash;is the reason 

President, Chairman, Chief Executive Officer 

Letter from the Publisher

Keeping Current for Your Practice 

(September 2011), “No” may be the word patients should use more frequently— as in, “No, I don’t want to have that diagnostic test.” 

quotes several prominent physicians who themselves have chosen to forgo screening tests like mammograms, PSA, and EKGs in the belief that, most of the time, they lead to a “dangerous odyssey of tests and procedures” that can result in a cascade of events creating unnecessary anxiety, procedures, and expense. “Less is more,” say these doctors.

Cardiology was singled out as having the most “disturbing”—and expensive&mdash; overuse of interventions that don’t improve survival rates or quality of life any more than making lifestyle changes. An analysis of at least five large, randomized controlled studies of stable heart patients with mild chest pain found that angioplasty, stenting, and bypass surgery did not improve survival rates or quality of life more than noninvasive procedures such as medications, exercise, and a healthy diet.

Cleveland Clinic cardiologist Steven Nissen, MD, points out that we spend almost twice as much per capita on health care [as other developed countries] but can show no gain in health or longevity. While many medical advances have saved lives and prevented suffering for millions, some of the same health care that helps certain patients can be useless or even harmful when offered on a huge scale.

Angioplasty comes in for particular criticism. “Many of the 500,000 elective angioplasties performed each year are done on patients who could benefit more from drugs, exercise, and healthy eating,” writes 

Cardiac CT angiography, introduced a decade ago to screen for cardiovascular disease, provides such detailed images that doctors are seeing things that were previously hidden and feeling as if they should do something. But NIH cardiologist Michael Lauer, MD, cautions that being able to see vivid detail doesn’t mean that doctors know whether or not they need to intervene.

goes even further, asserting that “cardiac care is a moneymaking machine that too often favors profit over science.” There’s no argument that when performed within hours of an MI to clear a blockage, emergency PCI and stenting is a lifesaver. But in nonemergency situations, it doesn’t prolong life better than medical therapy, and it triggers heart attack in 1% to 2% of patients. And rates of the procedure have increased 300% in the last decade.

With millions of Baby Boomers hitting their 60s and heart disease still the number-one killer of US adults, direct-to-consumer advertisements are appearing around the country, encouraging people to worry about their hearts—and get CTs and heart scans, which aren’t covered by most insurers. Kimberly Lovett, MD, of Kaiser Permanente and the University of California, San Diego School of Medicine, suggested that inappropriate testing can lead to inappropriate treatments. “Direct to consumer cardiac testing may pose more harm than benefit,” she says.

investigation concluded that angioplasty is overused; that patients often get the wrong cardiac tests and have too little information and understanding about the tests they’re signing on for; and that doctors often do not follow the latest practice guidelines. Finally, the report criticizes the “tendency to tackle heart disease with a $10,000 procedure before running a simple test or prescribing an inexpensive generic medication.” 

What Your Patients Are Reading

Just Say No? 

he 1984 case of Libby Zion, an 18-year-old college freshman who died in a New York hospital while being treated by overworked and tired medical residents, was a key event behind changes in rules guiding residents’ work hours that have been developed over the past 25 years.

In those days, residency was brutal. There was no cap on admissions or duty-hour restrictions, and many residents were overworked, stressed, and sleep deprived, a combination of factors that could create a dangerous situation. But it was a scenario that was considered part of “normal,” necessary medical training. The Zion case brought public attention to the issue of residents’ work hours and how it affects patient care.

In the last decade, two important regulations have been instituted: in 2003 the Accreditation Council for Graduate Medical Education (ACGME) issued a set of guidelines limiting time for residents to 80 hours per week.

 Recently, in April 2010, ACGME adopted new federal regulations further limiting work hours for resident physicians. There were several changes that became effective July 1, 2011: constant supervision of PGY1, duty hours that are now down from 24 hours per shift to no longer than 16 hours, and frequency of call no more than every third day, or a maximum of six nights in a row.

Nationwide surveys have been conducted to evaluate the opinion of both residents and program directors about the new work-hour regulations.

Expectations and perceptions about the new regulations are divided. While concerned about achieving a good balance between preventing exhaustion among the residents and thus enhancing their patients’ safety and wellbeing, directors of residency programs are concerned that the reduced hours would have a negative effect on resident training because less time in the hospital means less “hands-on” experience with patients and procedures. Concerns were raised that with fewer hours on call there would be less exposure to a wider amount of clinical encounters, and in this way the resident would have less practical learning. Others noted the financial costs of reducing resident work hours, and the need to imprint responsibility and professionalism and place patient care as the uppermost aim.

It is my belief that the new rules regarding a change in work hours will be shown to benefit both the patients and residents. Patient care will be improved because well-rested residents are better equipped to perform critical patient care, with rapid decisions and more lucid management at 3 a.m. Residents will have fewer episodes of depression and accidents inside and outside of the hospital, and take better care of their health and personal lives. I believe that when residents have more free time to study at home, they can improve their body of theoretical knowledge. Spending more time with family and being able to deal with personal concerns also gives us a sense of personal fulfillment that carries over to our professional lives and makes us better practitioners.

It makes sense to have more work-hour restrictions for interns, because they are not only the most inexperienced practitioners, but are writing orders under the most stressful conditions—not only because they are just starting to know the system but also because that is an important part of their training. Constant supervision during those critical moments of making a tough decision will benefit the patient, and getting validation of one’s clinical decision by supervisors will build better clinicians for the future. I believe that patients will be able to perceive that physicians are more rested and committed and have a better attitude, which will enhance their confidence and well-being.

On the other hand, time to acquire practical skills will be reduced, and residents will need to take advantage of every single clinical encounter with patients. We are also expected to be ready when the moment comes, after finishing our training and becoming real doctors, that we no longer require a teacher, are able to work in the current healthcare system—very often in less-than-ideal circumstances&mdash;and are independent enough to deliver optimal patient care.

A problem that arises with work-hour restrictions will be optimal hand-off of patients’ care. Fatigue-related errors might drop with the new system but the errors related to hand-offs could potentially increase.

 There is also the potential drawback that interns are not going to be prepared to be senior residents due to a lack of exposure to increased amounts of work and challenging situations that will greet them as they advance. Another potential issue would be to have to see the same number of patient in fewer hours, which can compromise quality of care, with potential harm to patients and decreased insight to problems in care.

In summary, the new work-hour regulations have benefits for the physical and intellectual well-being of the resident, but may have disadvantages with respect to the learning process. As has been said, learning about a disease from a book is like reading about a voyage without being in the ship at all. We need to see patients to learn the true nuances of disease and patient care.

The current regulations are not perfect; new studies are needed to objectively assess patients’ benefits derived from having more willing, alert, and enthusiastic residents to devote their attention to the Holy Grail of excellent patient care. I believe each doctor must make the most out of his or her new-found free time, and make a personal commitment to harness this opportunity to enhance themselves as clinicians.

It is my belief that in general the new ACGME regulations are in the best interest of our patients, and that we as residents can make our training a success. If we use our time wisely, we will learn to practice medicine as well as was the case with the previous work-hour standards.

1. Lerner BH. A life-changing case for doctors in training. New York Times. August 14, 2011. http://www.nytimes.com/2009/03/03/ health/03zion.html. Accessed September 1, 2011.

2. Philibert I, Friedmann P, Williams WT. New requirements for resident duty hours. 

3. Nasca TJ, Day SH, Amis ES Jr. The new recommendations on duty hours from the ACGME Task Force. 

4. Drolet BC, Spalluto LB, Fischer SA. Residents’ perspectives on ACGME regulation of supervision and duty hours — a national survey. 

5. Antiel RM, Thompson SM, Reed DA, et al. ACGME duty-hour recommendations — a national survey of residency program directors. 

6. Joint Commission International Center for Patient Safety. Strategies to Improve Hand-Off Communication: Implementing a Process to Answer Questions. 

Joint Commission Perspectives on Patient Safety

7. Arora VM, Georgitis E, Siddique J, et al. Association of workload of on-call medical interns with on-call sleep duration, shift duration, and participation in educational activities. 

8. Gaba DM, Howard SK. Fatigue among clinicians and the safety of patients. 

Resident's Corner

New Resident Work-Hour Restrictions: Good or Bad for Training?

he passage of the Affordable Care Act (ACA) in March 2010 created the potential for millions of uninsured Americans to access quality health care. At the same time, the ACA contains unclear provisions that have created challenges for the health care industry to reduce costs without compromising quality of care.

Over the course of the past 18 months, a partnership evolved between The American College of Cardiology (ACC) and 

The American Journal of Managed Care (AJMC) 

that resulted in the recent launch of the Community on Payment Innovations. This new online venue is dedicated to advancing the payment reform debate in order to foster an environment where patients can access high-quality care for the most affordable cost.

Led by Editor-in-Chief Len Nichols, PhD, the site encourages key stakeholders—cardiologists, pharmacists, hospital executives, government officials, and payers, including health plans and employers&mdash;to share best practices and innovative payment models that move away from the traditional fee-forservice system and instead reward high quality, cost-effective care and improved outcomes.

“Managed care is continuing to evolve under health care reform,” said Brian Haug, president of Intellisphere, publishers of 

. “Given the shared goals and vision of the ACC and 

, it was a natural decision to work together to develop an online environment that further cultivates and promotes best practices in care delivery and payment reform.”

The ACC has a rich history that began in 1949 with a group of 14 cardiovascular physicians who discovered they had a common mission—to continually advance the quality of cardiovascular care through the furtherance of science, education, and emerging initiatives. In recent years, the ACC has been a leader in the health care reform debate, launching Quality First, a major campaign to establish a new standard for health care reform centered on patient value and quality care.

“The ACC has long argued that payment reform is crucial to the success of real health care reform,” said Jack Lewin, MD, Chief Executive Officer of the ACC. “To date there is no one payment model that stands above the crowd. Partnering with 

on this Community opens up a much-needed forum for the health care community and other stakeholders to engage around this important topic and find a solution that meets the needs of patients, providers, and the government.”

To learn more about the Community on Payment Innovations, visit 

http://paymentinnovations.cardiosource.org

is an independent, peer-reviewed publication dedicated to publishing original research in health care outcomes and creating a forum for scientific communication in the ever-evolving field of health care delivery. Please visit www.ajmc.com to review original research and other editorial content.

About the American College of Cardiology 

The American College of Cardiology is transforming cardiovascular care and improving heart health through continuous quality improvement, patient-centered care, payment innovation and professionalism. The College is a 39,000-member nonprofit medical society comprised of physicians, surgeons, nurses, physician assistants, pharmacists, and practice managers, and bestows credentials upon cardiovascular specialists who meet its stringent qualifications. The College is a leader in the formulation of health policy, standards, and guidelines, and is a staunch supporter of cardiovascular research. The ACC provides professional education and operates national registries for the measurement and improvement of quality care. More information about the association is available online at 

AJMC/ACC

Roadmap to Payment Innovation

The Continuing Challenge of Effectively Managing Type 2 Diabetes: An Expert Discussion in Two Parts 

The risk for death among people with diabetes is about twice that of people of similar age but without diabetes. Primary care practitioners treat more than 75% of patients with T2DM. Despite all the work that clinicians put into managing T2DM, statistics reflect that many patients with the condition are not achieving their glycemic goals. Yehuda Handelsman, Vivian Fonseca, and Harold Lebovitz shared some of their biggest challenges to improving outcomes for these patients, as well as the ways in which primary care practitioners can most effectively treat their patients.

Prescription for Pot - A Debate on the Merits of Medical Marijuana 

Are there any patients with particular conditions for whom medical marijuana is appropriate? If you don’t necessarily believe that’s true, what do the believers in medical marijuana say? Joel W. Hay, PhD, and Joseph I. Sirven, MD, sat down with us and discussed the potential of medical marijuana for treating a variety of different conditions and their symptoms. But they agreed that there are many unanswered questions regarding the use of medical marijuana.

New Health Risk of Smoking Cessation Drug 

Since its approval in May 2006, varenicline has offered hope to the 70% of the estimated 45 million smokers in the US hoping to quit. In July, the authors of a meta-analysis published in the 

Canadian Medical Association Journal (CMAJ) 

concluded that healthy, middle-aged smokers taking varenicline had a 72% higher risk of heart attack or stroke compared with those taking placebo. So what’s a clinician to do? Do the benefits of varenicline outweigh its risks? We interviewed Sonal Singh, MD, the lead author of the study, for his perspective.

Seeking Doctors Who Work Well With Others 

Can medical schools select and produce doctors with better people skills? As a means of selecting potential doctors who have the people skills, ability, and inclination to work well with others, a number of medical schools have done away with the traditional personal interview in their application process and replaced it with the multiple mini interview (MMI).

Coming in October: Contemporary Management Issues in Hypertension: An Expert Discussion with Jan Basile, Keith Ferdinand, and Karol Watson 

will feature an expert panel discussion on managing hypertension for primary care practitioners. Among the issues that will be discussed are: effective screening of patients to identify those who have pre-hypertension and help prevent their progression to HTN; measures to increase the portion of patients with HTN who are well controlled; and how guidelines for treating HTN are likely to change in the near future. 

MD Peers & Perspectives

Join the Conversation!

Atzema CL, Austin PC, Huynh T, et al. Effect of marriage on duration of chest pain associated with myocardial infarction before seeking care. 

arriage certainly has some benefits. A recent article published in the 

1 provides interesting insight that may help explain the observed lower cardiovascular mortality rates among married people compared with their single counterparts.

This retrospective analysis evaluated 4,403 patients who presented to 82 hospitals in Ontario, Canada, during a 1-year period between April 2004 and March 2005 with symptoms of chest discomfort due to acute myocardial infarction (MI). The investigators hypothesized that being married is associated with less time delay from symptom onset to hospital arrival, and that this effect would be more pronounced in married men compared with married women. All data were abstracted from hospital records by trained nursing personnel and MIs were verified by positive cardiac enzymes.

The primary analysis compared patients who presented more than 6 hours after onset of chest pain with those who presented after less than 6 hours, consistent with previous literature and the significant incremental myocardial salvage obtained through urgent revascularization within this time period. Marital status was characterized as single, married, divorced or separated, or widowed. Attempts were made to assess for potential confounders including age, clinical features, living arrangement, ethnic origin, socioeconomic status, mode of transportation, arrival time, and arrival day. Multivariable logistic regression modeling was used to determine an independent effect of marital status on delayed presentation.

The mean age of patients was 67 years; 34% were women. The overall 30-day mortality rate was 6.9%. Discrete times from chest pain onset to hospital arrival were available for 87% of patients. The adjusted odds ratio (OR) of a delayed presentation greater than 6 hours after chest pain onset were lower for married patients compared with single patients (OR, 0.46; 95% CI, 0.30-0.71, 

<0.001). A separate analysis of men and women concluded that there is a significant relationship between being married and early presentation for men (OR, 0.35; 95% CI, 0.21-0.59, 

<0.001) but not for married women (OR, 1.36; 95% CI, 0.49- 3.73, 

Several other factors were determined to be associated with a reduced likelihood of delay in presentation. For men these included nighttime presentation (midnight to 8 a.m.), South Asian ethnicity, being separated or divorced, and calling an ambulance. For women, calling an ambulance and higher income level were associated with a reduced likelihood of delay, but being divorced (as opposed to single) and having a documented history of depression were associated with an increased likelihood of delay in presentation. Older age was associated with an increased likelihood of delay in presentation in both men and women. Of all the factors evaluated, calling an ambulance had the greatest effect on the primary outcome.

For all patients the reduced likelihood of presenting late when married compared with being single was significant at all time periods assessed (>2, >6, or >12 hours of delay), but this relationship was not significant when the analysis was restricted to women only. Interestingly, of the subgroup of patients in whom discrete time duration between symptom onset and presentation was known, only a trend toward shorter time to presentation among married people was identified (30 minutes less; CI, 63 minutes less to 2 minutes more). Of equal interest is that “living with someone” was associated with a significant increase in delay to presentation (OR, 1.47; CI, 1.06-2.04, 

= 0.02) that was not present in the subgroup analysis of patients who had a discrete time from pain onset to presentation.

he authors conclude that in the setting of acute chest discomfort due to MI, earlier presentation is seen in married people and that effect is more pronounced in married men compared with married women. They also conclude that earlier presentation in married men is one explanation for the observed lower risk of cardiovascular death in this group compared with single men. The authors further conjecture that women may be more likely than men to be caregivers because they advise their husbands to seek early medical assessment. Study limitations inherent in a retrospective design were acknowledged.

1. Atzema CL, Austin PC, Huynh T, et al. Effect of marriage on duration of chest pain associated with myocardial infarction before seeking care. 

2. Canto JG, Goldberg RJ, Hand MM, et al. Symptom presentation of women with acute coronary syndromes: myth vs reality. 

3. McSweeney JC, Cody M, O’Sullivan P, Elberson K, Moser DK, Garvin BJ. Women’s early warning symptoms of acute myocardial infarction. 

4. Macleod U, Mitchell ED, Burgess C, Macdonald S, Ramirez AJ. Risk factors for delayed presentation and referral of symptomatic cancer: evidence for common cancers. 

5. Ting HH, Bradley EH, Wang Y, et al. Factors associated with longer time from symptom onset to hospital presentation for patients with ST-elevation myocardial infarction. 

6. King KB, Reis HT. Marriage and longterm survival after coronary artery bypass grafting 

. [published online ahead of print August 22,2011]

7. Burgoa M, Regidor E, Rodriguez C, Gutierrez- Fisac JL, et. al. Mortality by cause of death and marital status in Spain. 

hile this study demonstrates a statistically significant earlier presentation during chest discomfort due to MI among married people (primarily married men) compared with single people, these results should be interpreted with caution. First, the authors reason that time delays due to atypical presentations in women have been minimized by including only patients presenting with chest discomfort. However, the character of chest discomfort was not evaluated in this study and is often the very essence of what defines an atypical presentation. Women present with higher percentages of indigestion symptoms, neck discomfort, and jaw discomfort compared with their male counterparts.

Any of these symptoms may be generalized and loosely referred to as “chest” discomfort in a medical record being retrospectively reviewed.

Second, the ability to document and control for potential confounders was limited. For example, ethnicity may have a strong association with delay to presentation but was not consistently recorded and was only analyzed for two overlapping ethnic backgrounds (Chinese and South Asian). Ethnicity has been shown to be a strong predictor in delayed presentation of other conditions such as cancer.

 In one recent study, being black and/or Hispanic (both groups have a significant presence in Ontario, Canada) were strongly associated with delay to presentation with ST elevation MI.

A diagnosis of depression, another potential confounder, was based only on its appearance in the medical record reviewed. The authors acknowledge that distance required to travel to a hospital, another potential confounder, was not evaluable in this retrospective analysis. Time of day was determined to be significantly associated with time delay of presentation, so other potential related confounders such as weather or traffic that could not be assessed may have also had an effect.

Third, the results are statistically significant only when compared with patients who are single and not to patients who have been divorced, separated, or widowed. If a caretaker effect were responsible for the decrease in time to presentation among married men compared with those who are single, as the authors conjecture, then why wouldn’t there be a difference between married men and other groups evaluated? These results raise the possibility that satisfaction within a status (happily divorced, unhappily married, as examples) may be important influences. Indeed, separated or divorced men had a statistically significant earlier presentation in this study.

One recent study demonstrated significantly improved cardiac outcomes in happily married patients compared with those who reported low marital satisfaction.

 Other studies have shown that divorced and separated persons have a lower mortality from cardiovascular and cerebrovascular disease compared with married persons, implying a more complex relationship between marital status and health effects than is stated in this article.

Finally, the results show some inconsistencies. On one hand, married men have an earlier presentation compared with single people, but opposite results were demonstrated for those living with someone—where a longer time to presentation was found compared with living alone (

= 0.023). Certainly most married men would also be correctly categorized as living with someone. Also, in analyzing the large subgroup (3,967 patients) with a known discrete time between symptom onset and presentation, the association between marital status and earlier time of presentation no longer reached statistical significance. One would expect that if an association existed, it would have been strengthened by a group with more accurate determination of time between symptom onset and presentation as compared with a cohort that included estimates of that same interval.

In summary, this analysis by Atzema et al adds some information to the relationship between marriage and delay in presentation with chest discomfort due to MI, but lack of symptom characterization and lack of ability to adequately control for potential confounders inherent in a retrospective study design likely contributes to inconsistencies in the results and limits the applicability of the findings. Information from this study underscores the complexity of properly evaluating the effects of marriage on any health condition. Furthermore, to surmise that we may understand the reason behind the shaky marital differences identified, such as a “spouse encouraging earlier pursuit of medical care” or “wives more likely than husbands to assume the caregiver role” is a wild guess at best and approaching discrimination at worse.

James P. Eichelberger, MD, FACC, is Associate Professor of Medicine, Cardiology Division, at the University of Rochester Medical Center, Rochester, NY, Program Director of the Adult Cardiovascular Fellowship, a member of the Medical Student Admission Committee, Co-Director of the Adult Congenital Heart Disease Program, Director of Outpatient Cardiology, Clinton Crossings, and an attending physician at Strong Memorial Hospital. Dr Eichelberger received his MD from the University of Rochester School of Medicine and completed his Residency at University of Vermont Medical Center and Fellowship at the University of Rochester Medical Center.

Features

Effect of Marriage on Duration of Chest Pain Before Seeking Care

Dangas GD, Caixeta A, Mehran R, et al. Frequency and predictors of stent thrombosis after percutaneous coronary intervention in acute myocardial infarction. 

rug eluting stents (DES) have in general substantially ameliorated restenosis, the previous Achilles’ heel of percutaneous coronary intervention (PCI). However, their use has been largely limited due to concerns about stent thrombosis (ST). Although the prevalence of ST is much lower than that of restenosis, the clinical sequella of ST appear to be much more consequential and include death and myocardial infarction. The concern about ST is even greater among patients with STEMI given its higher prevalence (4.4% in the current study) compared with that of NSTEMI (~1.5%) or elective PCI (0.1-0.6%).

A number of mechanisms may explain why individuals with STEMI experience higher rates of ST. These include noncompliance, technical errors such as undersizing, and issues related to plaque morphology, inflammation, and late acquired stent malapposition (LASM). For these reasons—despite evidence from nine STEMI trials showing lower restenosis rates with DES compared with bare metal stents (BMS)&mdash;use of DES in the setting of STEMI remains lower than that of elective PCI.

To address some of these concerns, Dangas et al conducted a post hoc analysis of Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONSAMI) to determine the incidence and predictors of definite or probable ST within 2 years.

Of the 3,202 patients enrolled in HORIZONS- AMI, 2,261 (71%) received only a DES and 861 (27%) only a BMS. The rate of definite or probable ST, which was adjudicated by an independent committee, was 4.4% at 2 years, with 50% of the events occurring in the acute (0.9%) and subacute (1.6%) setting, while others occurred either late (1%) or very late (1.1%). It is important to note that cumulative risk of ST was similar with both DES and BMS, as well as in patients receiving bivalirudin monotherapy or heparin plus glycoprotein IIb/IIIa inhibitors.

Acute ST occurred more frequently in the bivalirudin monotherapy group (1.4% versus 0.3%; 

<0.001). Subacute, late, and very late ST was more common among those receiving heparin plus glycoprotein IIb/IIIa inhibitors. Predictors of cumulative 2-year ST include insulin dependent diabetes mellitus, angiographic aneurysm, history of PCI, current smoking, baseline Thrombolysis In Myocardial Infarction (TIMI) flow rate and platelet count, and prerandomization heparin therapy. However, the most important modifiable predictor for subacute ST was preloading with 600 mg of clopidogrel.

1. Brar SS, Leon MB, Stone GW, et al. Use of drug-eluting stents in acute myocardial infarction: a systematic review and meta-analysis. 

2. Laarman GJ, Suttorp MJ, Dirksen MT, et al. Paclitaxel-eluting versus uncoated stents in primary percutaneous coronary intervention. 

3. Valgimigli M, Campo G, Percoco G, et al. Comparison of angioplasty with infusion of tirofiban or abciximab and with implantation of sirolimus-eluting or uncoated stents for acute myocardial infarction: the MULTISTRATEGY randomized trial. 

4. Raber L, Windecker S. Data presented at China Interventional Therapeutics 2011. March 16-19, 2011, Beijing, China.

5. Guagliumi G, Costa MA, Sirbu V, et al. Strut coverage and late malapposition with paclitaxel-eluting stents compared with bare metal stents in acute myocardial infarction: optical coherence tomography substudy of the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) Trial. 

6. Raber L, Windecker S. Primary percutaneous coronary intervention and risk of stent thrombosis: a look beyond the HORIZON. 

2011;123:1709-1712. 7. Stone GW, Rizvi A, Newman W, et al. Everolimus-eluting versus paclitaxel-eluting stents in coronary artery disease. 

angas and colleagues have raised important unanswered questions in their analysis. First, the rate of ST at two years is substantial, and consistent with previous randomized trials such as Paclitaxel-Eluting Versus Conventional Stent in Myocardial Infarction With ST-Segment Elevation (PASSION) and Multicenter Evaluation of Single High-Dose Bolus Tirofiban versus Abciximab Sirolimus-Eluting Stent or Bare-Metal stent in Acute Myocardial Infarction Study (MULTI STRATEGY).

 Observational data have raised concerns about very late ST with DESs compared with BMS, and this has been collaborated by autopsy specimens showing more inflammation, fibrin deposition, and uncovered stent struts among patients with STEMI receiving DES.

Furthermore, intravascular ultrasound (IVUS) and optical coherence tomography (OCT) data from HORIZONS- AMI also confirmed the presence of LASM and higher rates of uncovered struts with DESs compared with BMS at 13 months.

 However, despite such evidence, the current study and nine other randomized trials to date have consistently shown similar rates of ST for DESs and BMS among patients presenting with STEMI.

 The results are reassuring, but given the duration of follow-up in these trials, concerns about very late ST remains and longer-term ST data in this setting of STEMI are needed. Luckily, the majority of the trials in STEMI patients, including this study by Dangas et al, evaluated first-generation DESs, which are known to be inferior to the current 3rd-generation devices and possibly more pro-inflammatory. This is supported by the results of SPIRIT III and IV, showing a lower cumulative incidence of ST with everolimus as compared with paclitaxel-eluting stents.

 The ongoing Clinical Evaluation of Everolimus Eluting Coronary Stents in the Treatment of Patients With ST-segment Elevation Myocardial Infarction (EXAMINATION) should provide further safety and efficacy data for newer DESs.

The role of pharmacotherapy in preventing ST is the second important finding from this study. As noted, the higher rate of acute ST with bivalirudin is of concern, given the shift toward using this drug for STEMI to prevent bleeding. While potent antiplatelet agents such as clopidogrel may potentially ameliorate the risk, this is not supported by the current study. Clopidogrel loading did, however, reduce the risk of subacute ST. As has been shown previously, timing of the loading dose is important. 

 Newer agents, such as prasugrel and ticagrelor, may have added benefit in those receiving bivalirudin, but without 600 mg clopidogrel preloading.

 Longer infusion of bivalirudin—up to 4 to 6 hours after primary PCI&mdash;is another alternative, but the safety and efficacy of this approach has not been tested.

As noted above, the findings from this study are important but have one major limitation: lack of data on the technical aspects of all STs. Given the inflammatory nature of STEMI and the known risk of stent undersizing in this setting, supplemental imaging with IVUS or OCT are even more important. Clopidogrel preloading, if possible, is extremely important, but when not achievable, alternative agents such as prasugrel or ticagrelor should be considered, especially if bivalirudin will be the anticoagulation of choice. While difficult to achieve in an acute setting, patient compliance and ability to obtain long-term antiplatelet agents should be assessed. A comprehensive approach using 3rd-generation DESs supplemented by IVUS or OCT guidance and newer antiplatelet agents should help reduce the risk of ST in the setting of STEMI.

Mehdi H. Shishehbor, DO, MPH, is a specialist in interventional cardiology and endovascular interventions in the Robert and Suzanne Tomsich Department of Cardiovascular Medicine at the Cleveland Clinic. He received his DO from Nova Southeastern University in Florida and a Master’s degree in public health at Cleveland State University. He is presently working on a doctorate in epidemiology at Case Western Reserve University. He is widely published on cardiovascular epidemiology, interventional cardiology outcomes, and techniques, and is co-author of a book on coronary intensive care.

CME Reviews

Frequency and Predictors of Stent Thrombosis After Percutaneous Coronary Intervention in Acute Myocardial Infarction

Liu Y-W, Su C-T, Yang C-S, et al. Left ventricular systolic strain in chronic kidney disease and hemodialysis patients. 

his cross-sectional study provides an insight into the usefulness of 2-dimensional speckle tracking echocardiography (2D-STE) in the cardiac evaluation of chronic kidney disease (CKD) and end-stage renal disease (ESRD).

The authors compared 37 CKD and 60 ESRD patients with 56 randomly selected controls who did not have any kidney problems and who were having an echocardiogram for other medical reasons. ESRD patients had an echocardiogram halfway through the hemodialysis session (the 2nd or 3rd hour of each session). Authors measured the end expiratory inferior vena cava (IVC) diameter to assess the volume status in ESRD patients. In order to compare volume status between CKD and ESRD patients, the authors also measured the left ventricular diastolic volume index (LV EDVi), the left atrial volume index (LAVI), and the stroke volume (SV) in all three groups of patients.

The 2D-STE analysis was performed by cardiologists without knowledge of the clinical information. The average of the three apical peak longitudinal strain values is considered the global peak systolic longitudinal strain (GS1). Circumferential strain (Sc) and strain rates (SRc) were the average of the six mid-papillary left ventricular (LV) segmental strain values measured during the parasternal views.

Even though CKD, ESRD, and controls had similar left ventricular ejection fractions (LVEF), the average LV mass index and diastolic dysfunction were higher in the CKD and ESRD groups. LV mass index was higher in the ESRD group compared with the CKD group. CKD and ESRD patients had more global ventricular strain compared with controls in order to maintain similar ejection fraction (EF). CKD patients had more negative GS1 values when compared with the ESRD group, indicating that CKD patients have more diastolic dysfunction compared with the ESRD group. Volume status of the patients will not explain this difference, as both groups had similar LV EDVi, LAVI, and SV. There was no significant difference in the GS1 values between dialysis or interdialytic days. However, the size of the study population for this finding was very limited.

The major limitation of the study is its cross-sectional design. It identified the differences between the three groups of patients but did not explain the progression of LV dysfunction from normal renal function to CKD and to ED. It is also limited by sample size, particularly with respect to the CKD group.

1. Hayashi SY, Brodin LA, Alvestrand A, et al. Improvement of cardiac function after haemodialysis. Quantitative evaluation by colour tissue velocity imaging. 

2. Yan P, Li H, Hao C, et al. 2D-speckle tracking echocardiography contributes to early identification of impaired left ventricular myocardial function in patients with chronic kidney disease. 

3. Gulel O, Soylu K, Yuksel S, et al. Evidence of left ventricular systolic and diastolic dysfunction by color tissue Doppler imaging despite normal ejection fraction in patients on chronic hemodialysis program. 

4. Edwards NC, Hirth A, Ferro CJ, Townend JN, Steeds RP. Subclinical abnormalities of left ventricular myocardial deformation in early-stage chronic kidney disease: the precursor of uremic cardiomyopathy? 

5. Aljaroudi W, Koneru J, Iqbal F, Aggarwal H, Heo J, Iskandrian AE. Left ventricular mechanical dyssynchrony by phase analysis of gated single photon emission computed tomography in end-stage renal disease. 

6. Rudhani ID, Bajraktari G, et al. Left and right ventricular diastolic function in hemodialysis patients. 

7. Dandel M, Lehmkuhl H, Knosalla C, Suramelashvili N, Hetzer R. Strain and strain rate imaging by echocardiography - basic concepts and clinical applicability. 

8. Liu YW, Su CT, Huang YY, et al. Left ventricular systolic strain in chronic kidney disease and hemodialysis patients. 

9. Choi JO, Shin DH, Cho SW, et al. Effect of preload on left ventricular longitudinal strain by 2D speckle tracking. 

10. McAlister FA, Ezekowitz J, Tonelli M, Armstrong PW. Renal insufficiency and heart failure: prognostic and therapeutic implications from a prospective cohort study. 

he prevalence of chronic kidney diseases and ESRD has gradually increased over the last several years. Cardiovascular diseases account for more than half of the deaths in CKD and ESRD patients. The pathophysiological mechanisms contributing to these deaths are not clearly understood.

 Conventional echocardiogram is a reliable method for estimating EF and LV mass index. EF provides an estimation of the global myocyte contractions but will not provide a significant insight into the regional systolic function.2 Moreover, studies have shown that there have been significant changes in cardiac function that will occur much earlier than the EF change.

 ESRD patients could have mechanical dyssynchrony even without electrical dyssynchrony and normal EF.

 ESRD patients could have both right and left ventricular dysfunction and still have normal EF.

 With advances in tissue Doppler imaging (TDI), it is possible to identify diastolic and systolic dysfunctions.

There are significant numbers of studies that have shown the usefulness of TDI in identifying diastolic dysfunction in CKD and ESRD patients.

 With TDI one can not only diagnose diastolic dysfunction but also can estimate the longitudinal strain early in the disease course.

 Unfortunately, TDI is an angle-dependent study and the angle of the study should be below 20 degrees. Moreover, it is a time-intensive study that has a high inter- observer variation and requires expert interpretation. 2D-STE is a novel method of calculating the ventricular strain pattern that provides a reliable estimation of ventricular strain analysis in a shorter duration of time than TDI. It provides an angle-independent assessment and has less inter-observer variability.

 The accuracy of 2DSTE is well established in estimating ventricular strain.

There are very few studies of ventricular strain evaluation with 2D-STE in CKD and ESRD patients.

The study by Liu et al is the first published study that provides insight into the role of 2D-STE in the evaluation of the CKD and ESRD patients, and confirms that ESRD and CKD patients have more diastolic dysfunction than controls that were well assessed previously with TDI. CKD and ESRD patients have more ventricular strain (more negative value) than controls. Yan et al conducted a similar study, and were able to reproduce similar results.

 They identified an inverse relation not only between Nterminal pro-B-type natriuretic peptide (BNP) and radial peak systolic strain but also between calcium phosphorus product and mid-wall peak systolic strain.

The study by Liu et al is the first to use 2D-STE to evaluate strain difference between dialysis day and interdialytic day—and they were unable to show any significant difference between those days. In their study, Choi et al identified a statistically significant difference in the ventricular strain before and after dialysis. The differences in the results reported in these studies could be because in Liu et al’s study, the strain pattern was evaluated 2 to 3 hours after the initiation of dialysis during the dialysis day and during the interdialytic day. There was no significant difference in the volume status between the dialysis and interdialytic day. These studies provide insight into the ventricular strain pattern, but we need a much larger cohort of studies to identify the progression of the ventricular dysfunction over the course of CKD progression to ESRD. Heart failure patients with CKD have a high mortality rate.

 Identifying high-risk patients and optimizing their medical management early in the disease course will help to improve their longevity.

Srikanth Seethala, MD, MPH, is an Assistant Professor in the Department of Internal Medicine at the Paul L Foster School of Medicine, Texas Tech University Health Sciences Center in El Paso, TX. Dr Seethala received his MD from Andhra Medical College in Visakhapatnam, India, and received his Master’s in Public Health from Northern Illinois University in DeKalb. His residency in internal medicine was at the University of Pittsburgh Medical Center-Mercy Hospital of Pittsburgh. He plans to pursue electrophysiology as a career.

Left Ventricular Systolic Strain in Chronic Kidney Disease and Hemodialysis Patients

Boussageon R, Bejan-Angoulvant T, Saadatian-Elahi M, et al. Effect of intensive glucose lowering treatment on all cause mortality, cardiovascular death, and microvascular events in type 2 diabetes: meta-analysis of randomised controlled trials. 

. 2011;343:d4169. doi: 10.1136/bmj.d4169.

 has important implications for the treatment of diabetic patients in developing a strategy to minimize cardiovascular, as well as macro- and microvascular risk. Intensive blood glucose control is often a preferred strategy to minimize macro- and microvascular events, especially in type 2 diabetics,

 despite the accumulation of data and meta-analyses suggesting its limited benefits in reduction of events.

However, prior meta-analyses focused on macrovascular events only, while the study by Boussageon and colleagues included microvascular event rates, contributing to its novelty.

The methodology was sound, following standard protocols for a meta-analysis to examine event rates for intensive control of blood glucose in adults with type 2 diabetes using both insulin and oral hypoglycemics. The authors used the Jadad score to analyze the quality of studies used, which has been criticized as overly simplistic and inaccurate for the purpose of classification of study quality.

Primary end points were all-cause mortality and death from cardiovascular causes. Secondary end points were myocardial infarction, non-fatal myocardial infarction, stroke (fatal and non-fatal), congestive heart failure, photocoagulation, retinopathy (new or worsening), visual deterioration or blindness, neuropathy (new or worsening), microalbuminuria (new or worsening), renal failure (occurrence of renal failure or doubling of serum creatinine level), peripheral vascular events (leg revascularization, peripheral arterial disease, or intermittent claudication), amputation, and severe hypoglycemia corresponding to those reported in the originally published papers.

The authors used the more stringent 99% confidence interval (CI) instead of the commonly used 95% level; they also altered the usual order of tests assessing statistical heterogeneity across trials— using random effects models for studies with unknown heterogeneity and then using a fixed-effects model once heterogeneity was assessed and found to be low. Another addition made to enhance the quality of the study was inclusion of calculation of absolute risk reduction and number needed to treat (NNT). The authors provided information about the excluded studies and the reasons for their exclusion. In total, 18,315 patients were randomized to the intensive treatment group and 16,218 to the standard treatment group. The mean duration of follow-up was 5.0 years (range, 1-10 years). Intensive treatment did not significantly affect all-cause mortality (risk ratio [RR], 1.04; 99% CI, 0.91-1.19) or death from cardiovascular causes (RR, 1.11; CI, 0.86-1.43), even when analysis was restricted to highquality trials. Intensive treatment also did not reduce microvascular complications.

The risk of severe hypoglycemia was more than twice as high in the intensive treatment group (RR, 2.33; CI, 1.62- 3.36). Absolute 5-year risk increases in severe hypoglycemia ranged from 1.9% to 6.6%, making the number of patients who needed to be treated to provoke an event between 52 and 15. There was no significant reduction in myocardial infarctions; there was actually an increase in the risk of congestive heart failure. Neither was there any benefit noted with the incidence of microvascular complications. This meta-analysis found that intensive glucose lowering was not associated with improvement in hard clinical outcomes—neither macronor microvascular.

1. Boussageon R, Bejan-Angoulvant T, Saadatian-Elahi M, et al. Effect of intensive glucose lowering treatment on all cause mortality, cardiovascular death, and microvascular events in type 2 diabetes: meta-analysis of randomised controlled trials. 

2. Nathan DM, Buse JB, Davidson MB, et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. 

3. Action to Control Cardiovascular Risk in Diabetes Study Group; Gerstein HC, Miller ME, Byington RP, et al. Effects of intensive glucose lowering in type 2 diabetes. 

4. Ray KK, Seshasai SR, Wijesuriya S, et al. Effect of intensive control of glucose on cardiovascular outcomes and death in patients with diabetes mellitus: a meta-analysis of randomised controlled trials. 

5. Berger VW. Is the Jadad score the proper evaluation of trials? 

6. Clark HD, Wells GA, Huet C, McAlister FA. Assessing the quality of randomized trials: reliability of the Jadad scale. 

7. Shukla VK, Bai A, Milne S, Wells G. Systematic review of quality assessment instruments for randomized control trials: selection of SIGN50 methodological checklist. The Cochrane Collaboration. http://www. imbi.uni-freiburg.de/OJS/cca/index.php/cca/ article/viewArticle/5053. Accessed September 19, 2011.

8. Dormandy JA, Charbonnel B, Eckland DJ, et al; PROactive Investigators. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. 

9. Tzoulaki I, Molokhia M, Curcin V, et al. Risk of cardiovascular disease and all cause mortality among patients with type 2 diabetes prescribed oral antidiabetes drugs: retrospective cohort study using UK general practice research database. 

10. Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. 

11. Gamble JM, Simpson SH, Eurich DT, Majumdar SR, Johnson JA. Insulin use and increased risk of mortality in type 2 diabetes: a cohort study. 

12. Cooper-DeHoff RM, Egelund EF, Pepine CJ. Blood pressure lowering in patients with diabetes--one level might not fit all. 

. [published online ahead of print November 16, 2011] 2011;8:42-49.

oussageon et al present us with a well-conducted meta-analysis of clinical trials assessing the effects of intensive glucose lowering with macro- and microvascular clinical end points, showing no significant benefits resulted with the strategy. However, a few interesting points merit consideration.

The authors used the Jadad score to assess and evaluate quality of trials instead of the more prevalent and accepted Cochrane metrics.

 It remains open to conjecture whether a reclassification of trial quality might have affected the outcomes. In addition, the authors performed assessment of risk ratios using 99% confidence intervals instead of the traditional 95%, which might have negatively influenced outcomes that might have been statistically borderline.

The authors focused on the strategy of intensive glucose reduction and did not stratify the analysis according to the medications used for achieving the same. It may well be a case of comparing apples with oranges when the authors themselves mention that using metformin as first-line therapy yields vastly different outcomes compared with sulfonylureas. Additionally, the risk of thiazolidinediones have been well documented in causing exacerbation of heart failure,

 and intensive glucose lowering with insulin has often been implicated in causing increased mortality by increasing risk of hypoglycemia.

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Frequency and Predictors of Stent Thrombosis After Percutaneous Coronary Intervention in Acute Myocardial Infarction

Left Ventricular Systolic Strain in Chronic Kidney Disease and Hemodialysis Patients

Effect of Intensive Glucose Lowering on All-Cause Mortality, Cardiovascular Death, and Microvascular Events in Type 2 Diabetes

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