July 16th, 2012
Selections from Richard Lehman’s Literature Review: July 16th
Richard Lehman, BM, BCh, MRCGP
CardioExchange is pleased to reprint selections from Dr. Richard Lehman’s weekly journal review blog at BMJ.com. Selected summaries are relevant to our audience, but we encourage members to engage with the entire blog.
Arch Intern Med 9 July 2012 Vol 172
Rhythm vs. Rate Control in AF (pg. 992): Two trials in the last decade have stopped cardiovascular medicine in its tracks: AFFIRM and COURAGE. In both cases, a widespread presumption about the superiority of more invasive treatment was proved wrong in a large randomized trial. AFFIRM in 2002 showed that rhythm control is not superior to rate control in atrial fibrillation, and this was later confirmed in the heart failure population (AF-CHF). But some cardiologists have been reluctant to abandon their gut feeling that rhythm control must be intrinsically superior; and this Canadian population study will give them a glimmer of support. There is a tiny difference in favour of rhythm control in observed survival at 9 years; nothing significant at 4 years. Informed patient choice should guide treatment here, as in all areas where there is virtual equipoise.
Diabetes Drugs and Specific Harms and Benefits (pg. 1005): Most oral drugs for type 2 diabetes lower sugar by about the same amount: so does that mean they all have similar effects on end-points? Oddly enough, even very intelligent diabetologists often act on the assumption that they do. Trying to explain choices to patients, they rely on aggregated data showing that for such and such a lowering of HbA1c you will get such and such a lowering of, say, heart attacks or blindness. But convenient though this approach may be, it simply won’t do: everything depends on the agents you use to lower sugar, and we know far too little about them. GlaxoSmithKline has just been fined a billion dollars for concealing data about the cardiovascular risks of its thiazolidinedione drug rosiglitazone (Avandia), and another billion apiece for two unrelated drugs. But you could still argue—from very unconvincing aggregated data—that for patients wishing to avoid eye damage, there might still be a case for using any drug which lowers glucose. This study shows that is not true: both thiazolidinediones (pioglitazone as well as rosiglitazone) are associated with an increased risk of macular oedema in this study using the British primary care THIN database. Both harms and benefits in the treatment of type 2 diabetes are class and agent-specific.
JAMA 11 July 2012 Vol 308
Acadesine and CABG (pg. 157): Last week, I expressed the hope that JAMA Boring might progress to JAMA Slightly Interesting, but this has not happened. Instead, it has turned into JAMA Negative, no doubt for the worthiest of reasons: Effect of Adenosine-Regulating Agent Acadesine on Morbidity and Mortality Associated With Coronary Artery Bypass Grafting: The RED-CABG Randomized Controlled Trial. Red Cabbage! That is so funny. Result: acadesine had no effect.
July 13th, 2012
Meta-Analysis: ACE Inhibitors Associated with Lower Pneumonia Risk
Angiotensin-converting–enzyme inhibitors may offer some protection against pneumonia, according to a BMJ meta-analysis. An editorialist isn’t so sure.
Researchers looked at almost 40 studies — including cohort studies, case-control studies, and randomized trials — that reported pneumonia outcomes after use of ACE inhibitors, angiotensin-receptor blockers, and control treatments. The data revealed that ACE inhibitors conferred a roughly 30% decrease in risk for pneumonia, when compared with ARBs or control treatments. The effect was particularly pronounced in Asian patients.
The authors speculate that the cough often associated with ACE inhibitors may actually play a part in the protective effect by clearing respiratory tract secretions.
An editorialist finds it “difficult to agree” with the authors’ enthusiasm. She calls for more studies “before we advise patients to put up with their cough because it may prevent them from getting pneumonia.”
July 12th, 2012
Selections from Richard Lehman’s Literature Review: July 12th
Richard Lehman, BM, BCh, MRCGP
CardioExchange is pleased to reprint selections from Dr. Richard Lehman’s weekly journal review blog at BMJ.com. Selected summaries are relevant to our audience, but we encourage members to engage with the entire blog.
Arch Intern Med 25 June 2012 Vol 172
Sex Differences in the Protective Effect of Statins (pg. 909): The Archives are about to mutate into JAMA Internal Medicine, but I generally find them a better read than JAMA proper. One reason is the abundance of lively comment—and in the case of this paper on sex differences in the protective effect of statins, I find the comment more believable than the paper. This is a meta-analysis of eleven double-blinded RCTs of statin therapy for the prevention of recurrent cardiovascular events, and purports to show that although statins are as good at preventing recurrent cardiac events in women as in men, they do not prevent stroke or reduce all-cause mortality in women. Two British luminaries contest this, arguing that the literature search was incomplete and that the meta-analysis does not include a number of key studies which show that the protective effect of statins in women and men is remarkably similar in every category.
Action Measure to Lower BP Among Diabetics (pg. 938): Pay for performance diverts effort from high risk patients who need it towards low risk patients who don’t need it, and can even be harmed by it. This was demonstrated a couple of years ago with glycaemic control among British diabetics, and it’s now demonstrated again in Americans with diabetes—this time in respect of blood pressure control. Over 700,000 diabetic patients were subject to an “action measure” by the Veterans’ Administration that encouraged lowering of the systolic BP below 140 mm Hg. “While 94% of diabetic veterans met the action measure, rates of potential overtreatment are currently approaching the rate of undertreatment, and high rates of achieving current threshold measures are directly associated with overtreatment.” In other words, when “action measures” are imposed, low risk patients suffer the adverse effects of treatment to target. And these targets are generally derived from studies where the vast majority of the effect was derived from treating the patients at highest risk, as demonstrated by Timbie, Hayward and Vijan two years ago.
Prediction Tool for Initial Survivors of In-Hospital Cardiac Arrest (pg. 947): A group of notable US outcomes researchers derive a beautifully predictive prediction tool for initial survivors of in-hospital cardiac arrest, based on the outcomes of 43,000 resuscitated patients. Its eleven points lie on a straight downward line. This time the invited commentary is merely curmudgeonly, arguing that you’re either dead or you aren’t, so you mustn’t give up on any group, even the ones with a 2.8% chance of surviving without neurological damage.
Diagnosis and Treatment of Pulmonary Embolism (pg. 955): Now here’s a lively, must-read paper that you probably wouldn’t find in any other main journal: not a review, not original research, not just an opinion piece—but an intelligent examination of what we mean by pulmonary embolism and how this sheds light on the phenomena of diagnostic drift, overtreatment, and futile therapeutic innovation. “Trials of newer anticoagulants and longer durations of anticoagulation have not yielded real improvements over heparin, inviting doubts regarding its efficacy. Thus, PE is the quintessential diagnosis of medicine not because it represents our greatest success, but because it captures all the complexity of medicine in the evidence-based era. It may serve as a metaphor for many other conditions in medicine, including coronary artery disease. New trials in the field continue to test trivialities, whereas fundamental questions are unanswered.” Do try and get hold of it.
Ann Intern Med 3 July 2012 Vol 157
Intervention to Prevent Medication Errors After Hospital Discharge (pg. 1): A trial to make you pause. It was carried out in two leading academic hospitals in the USA using a highly labour-intensive intervention to prevent medication errors in the month following admission for an acute coronary event or acute heart failure. “Among 851 participants, 432 (50.8%) had 1 or more clinically important medication errors; 22.9% of such errors were judged to be serious and 1.8% life-threatening. Adverse drug events occurred in 258 patients (30.3%) and potential ADEs in 253 patients (29.7%).” But the point is that the intervention made no difference at all, even though it was intelligently thought out and well executed, as far as one can tell. Moral: half of patients who are of above average “health literacy” will suffer some kind of “preventable” adverse drug event after a cardiac admission, and there is nothing we know of that will make any difference.
Rehospitalization After Acute MI (pg. 11): So what does “preventable” really mean in contexts like this? Many rehospitalizations following myocardial infarction are also deemed “preventable” and preventing them is a quality of care indicator in several health systems. Here is an observational study from little Olmsted county which went through the charts of 3,010 patients who were discharged following MI between 1987 and 2010. Just over 40% of the 643 readmissions were definitely MI-related: the rest were either definitely not or uncertainly related. Co-morbidity played a large role, and complications of revascularization were relatively common too. How truly preventable these readmissions were is not at all clear.
July 12th, 2012
FDA Issues Class I Recall of Cardiovascular Diagnostic Tests
Kristin J. Kelley, CardioExchange Staff
The FDA announced on Wednesday a Class I recall of several lots of cardiovascular diagnostic tests aiding in the triage of heart failure, MI, and pulmonary embolism. According to the agency, the affected products do not provide the precision described in the package insert, which could lead to potentially fatal false-positive and false-negative test results.
The manufacturer specifically warned about an increased frequency of troponin I results >0.05 ng/mL that, on retesting, are actually below that level. Over 98,000 test kits could be defective, says the FDA.
The manufacturer is advising consumers to stop using the tests immediately and discard them. See this recall notice for the full list of affected products.
July 12th, 2012
Clopidogrel–PPI Interaction Deemed ‘Clinically Unimportant’
Nicholas Downing, MD
The interaction between clopidogrel and proton-pump inhibitors is “clinically unimportant,” researchers conclude in BMJ.
The researchers used U.K. registries to study some 24,000 acute coronary syndrome patients who were prescribed both aspirin and clopidogrel; half the patients also received a PPI at some point during the study.
After nearly a year’s follow-up, incident MI or all-cause mortality had occurred significantly more often during PPI use than nonuse (11% vs. 8% of patients). However, a self-controlled case series analysis — performed to eliminate confounding from differences between patients — showed no significant association between PPI use and MI (rate ratio, 0.75).
These findings suggest that the PPI–clopidogrel interaction “does not result in clinical harm,” the researchers write. They add that concomitant use of PPIs with clopidogrel and aspirin “is well proved to prevent harm through gastrointestinal bleeding, and we should continue to consider proton-pump inhibitors as important prophylactic drugs in patients at high risk.”
Click here to read the editorial that accompanied the study.
July 11th, 2012
Panel: How to Develop the Best Fellowship Application — Part II
Andrew M. Kates, MD, James De Lemos, MD and John Ryan, MD
Cardiology fellowship applications are due during the next few weeks. We sat down with moderators of our Fellowship Training blog to ask for their advice regarding the application process and how residents can best prepare for it.
We are joined by Dr. James de Lemos, past Cardiology Fellowship Program Director at UT Southwestern, Dr. Andrew Kates, Cardiology Fellowship Program Director at Washington University, St. Louis, and Dr. John Ryan, Cardiology Fellow at University of Chicago.
This is Part II of a two-part series. Part I concerns the personal statement and choosing who will write your letters of recommendation.
CardioExchange: For residents who have not published research, will that affect their ability to be competitive for academic programs?
de Lemos: The short answer is yes, it definitely will. We’re in the business of repopulating our ranks with future academic cardiologists. Even programs that are not hard-core academic also look carefully at research as it may be an indirect barometer of drive and organization/multitasking skills. Still, it is not an absolute must; most of us still rank highly the best purely clinical applicants. Research is an important piece, but only a piece, of the puzzle. Just putting in time for research isn’t enough. “Closing” projects is also important, as is being able to articulately describe your research in your personal statement and interview. Too often, residents are not really committed and are just filling in the blanks with research. We try to see through this in the evaluation process. For this reason, it is important that a research mentor write one of your letters. The absence of a letter from the research mentor is a sign that the applicant either didn’t do good research work or didn’t do much of anything at all.
Kates: Not necessarily. What we are looking most for is intellectual curiosity. Some residents may have undertaken research but not accumulated adequate data to publish, or the data obtained may have not been accepted for publication. I do want to hear about the research the applicant is involved in and, especially, his or her role in the research. Above all we are looking for cardiologists who want to be leaders — be it in research, education, or patient care.
Ryan: Applicants can still be competitive without published research, but the research performed during residency does help, albeit it does not need to be ground-breaking or bench research. It can be an audit, for example, or a comprehensive review paper. What distinguishes applicants is their ability to start a research project, get a poster accepted at a meeting, and follow it all the way through to a publication. The research does not need to be what the resident is going to concentrate on for the rest of his or her career — it is the process, the acquired skills, and the demonstrated diligence to create a finished product that academic programs are looking for.
CardioExchange: Do applicants need to differentiate themselves by knowing what field of cardiology they want to go into, namely imaging, interventional, etc.?
de Lemos: Not necessarily, but it does help to list the areas that are highest on the list. The key is to show direction and focus, like you have really thought this all through. Listing your likely career trajectory helps to demonstrate this.
Kates: Applicants do not need to be differentiated in this way. It is ok to be sincere in your desire “to be a cardiologist” while still undecided about your ultimate goal. However if you have a specific person with whom you would like to meet based on your ultimate goals, I encourage you to notify the program so that an interview can be arranged.
Ryan: I do not think so. It is almost impossible for a resident to say that he or she wants to be an interventional cardiologist when the most advanced procedure they have done is a lumbar puncture. Similarly, it is only during fellowship that one begins to appreciate the daily life of a heart failure doctor or an echocardiologist. Of course, some applicants have been extensively trained in science or engineering or have already completed advanced training overseas. These more mature applicants might have a more definite idea about their career path. But in reality there is a benefit to being undifferentiated and then allowing your experience during fellowship to mold your career path, which is exactly what happened to me.
CardioExchange: The fellowship application cycle begins earlier this year by several months. Are fellowship programs prepared for this change, and are they ready to start reviewing applications in the next month?
de Lemos: Yes and no. We’ll all be figuring out timelines as we go, but the process of evaluation and interviews won’t change. It will be trickier to do all the application reviewing and interview scheduling over the summer during vacation times, but once interviews start, the change won’t be a big deal. I like the idea of the applicants being more mature with more “skins on the wall” when they apply.
Kates: Yes. We expect an outstanding pool of talented applicants. The challenge may be that there will be more applicants than in the last few years due to the change. We will see.
Ryan: I think that the programs are ready. Many people need to be reminded to review applications regardless of the time of year. In reality so much is going on later in the year, such as AHA Scientific Sessions and the holidays, that bringing everything forward a few months will actually alleviate some of the excess work load that commonly occurs towards the end of the year. The main issue for applicants is to be ready.
July 10th, 2012
Intensive Insulin Therapies Similarly Efficacious in Diabetes
Nicholas Downing, MD
Multiple daily insulin injections and continuous subcutaneous insulin analogue infusion are similarly effective in lowering hemoglobin A1c levels while limiting episodes of severe hypoglycemia in type 2 diabetes, according to a systematic review published in the Annals of Internal Medicine.
The analysis included 33 randomized controlled trials among children and adults with type 1 or type 2 diabetes. Among the other findings:
- The two intensive therapies also performed similarly well in children with type 1 diabetes; in adults with type 1 diabetes, however, continuous subcutaneous infusion led to greater HbA1c reductions than did multiple daily injections (this latter outcome was heavily influenced by one trial).
- Real-time continuous blood glucose monitoring, assessed in type 1 diabetes, generally produced better outcomes than self-monitoring of blood glucose with fingersticks.
The authors caution that most of the studies in their analysis were of fair to poor quality — with the largest having 322 participants.
July 9th, 2012
AHA and ADA Cautiously Endorse Non-Nutritive Sweeteners
Larry Husten, PHD
In a newly released scientific statement, the American Heart Association and the American Diabetes Association offer a cautious endorsement of the use of non-nutritive sweeteners in the diet. But the statement notes that the products are not “magic bullets” and that there is no strong evidence demonstrating their beneficial effects.
Sugar in the diet has been linked repeatedly to obesity, type 2 diabetes, and cardiovascular disease, leading to recommendations that sugar intake be limited. However, the evidence to date is “inconclusive” that non-nutritive sweeteners (including aspartame, acesulfame-K, neotame, saccharin, sucralose, and stevia) can reduce caloric intake, lower body weight, or help prevent diabetes or cardiovascular disease.
“Determining the potential benefits from non-nutritive sweeteners is complicated and depends on where foods or drinks containing them fit within the context of everything you eat during the day,” sad Christopher Gardner, one of the authors of the report, in an AHA press release. “For example, if you choose a beverage sweetened with non-nutritive sweeteners instead of a 150-calorie soft drink, but then reward yourself with a 300-calorie slice of cake or cookies later in the day, non-nutritive sweeteners are not going to help you control your weight because you added more calories to your day than you subtracted.”
“However, if you substitute the beverage with non-nutritive sweeteners for a 150-calorie sugar-sweetened soft drink, and don’t compensate with additional calories, that substitution could help you manage your weight because you would be eating fewer calories,” said Gardner.
The following text is taken from the summary and recommendations of the report:
At this time, there are insufficient data to determine conclusively whether the use of NNS [non-nutritive sweeteners] to displace caloric sweeteners in beverages and foods reduces added sugars or carbohydrate intakes, or benefits appetite, energy balance, body weight, or cardiometabolic risk factors…. There are some data to suggest that NNS may be used in a structured diet to replace sources of added sugars and that this substitution may result in modest energy intake reductions and weight loss. Successful reduction in energy intake requires that there is incomplete compensation of energy reduction from the use of NNS containing beverages and/or foods. The impact of incorporating NNS and NNS-containing beverages and foods on overall diet quality should be included in assessing the overall balance of benefits and risks.
Addressing the negative perception of non-nutritive sweeteners that many people have developed, weight loss expert and blogger Yoni Freedhoff sent the following comment to CardioBrief:
Likely consequent to the natural fallacy many readily assume that the consumption of NNS carries risk, included among them a risk towards increased consumption and weight gain. It’s refreshing then to see the analysis of actual evidence on the use of NNS in people rather than animal models concludes that if anything there’s a suggestion of benefit to weight management, rather than risk, with the consumption of NNS. Given the complexity of weight regulation and human behavior, no intervention will work in a vacuum and my clinical experience definitely suggests a synergy between their use and true caloric literacy and may help to explain the lackluster results. Hopefully future studies will shine more conclusive light on the situation.”
July 7th, 2012
New Algorithm for Patients with LBBB and Suspected MI
John W McEvoy, MB BCh BAO, Ian Neeland, MD, James De Lemos, MD and John Ryan, MD
CardioExchange editor John Ryan interviews John W. McEvoy, cardiology fellow at Johns Hopkins, about an algorithm — newly proposed by Ian Neeland and colleagues in JACC — for selecting patients with left bundle-branch block and suspected MI for primary PCI. Neeland and coauthor James de Lemos respond to each of McEvoy’s comments.
The Algorithm
In their JACC Viewpoint article, Neeland and his colleagues highlight that ACCF/AHA guidelines, which recommend patients with new or presumed-new LBBB undergo early reperfusion therapy (fibrinolysis or PCI), are based on studies from more than 20 years ago. Citing newer research, the authors observe that a substantial proportion of patients who present with LBBB are not actually experiencing a STEMI-equivalent MI: For example, in 2007 Larson and colleagues reported that among patients with LBBB at presentation, the rate of false activation of the catheterization laboratory was 44%, compared with a baseline of 14%. For patients with presumed-new LBBB and suspected MI, Neeland and coauthors propose a new algorithm involving Sgarbossa criteria on ECG, bedside echocardiography, and serial echocardiogram, as shown here.
CLICK TO EXPAND
The Interview
Ryan: Do you often get called by the ED or house staff about a “new” LBBB?
McEvoy: Yes, this is a fairly common clinical dilemma at our institution. Previous registry studies would suggest that only about 2% of acute coronary syndrome patients present with LBBB. However, such studies did not include patients who were catheterized for LBBB but did not actually have ACS. Indeed, up to 40% of patients who undergo cardiac catheterization for LBBB are not found to have occlusive coronary artery disease. This has been my personal experience as well. Therefore, some catheterization-lab activations may be unnecessarily triggered by new LBBB and “concern for ACS.” Anecdotally, at least as many of these calls come from our general inpatient floors as from our ED. That’s presumably because such patients are often transferred from outside hospitals or directly admitted without prior EKGs recorded in our electronic medical record.
Neeland & de Lemos:We agree with Dr. McEvoy. Only a small minority of patients presenting with a suspected ACS have LBBB, but this group is over-represented among patients who prompt a false activation of the catheterization lab. In a recent study by McCabe et al., of the 146 patients with false STEMI lab activations, over 10% had LBBB. Notably, these figures reflect only patients who make it all the way to cardiac catheterization. In our institution and probably many others, it’s not uncommon to “deactivate” for a patient with LBBB whose clinical scenario is not consistent with STEMI.
Ryan: What do you normally do? And how has your practice evolved from when you were a resident, to junior fellow, and now a more-senior fellow at Hopkins?
McEvoy: My threshold to act on any suspicion for ACS has been—and remains—very low. However, my approach has become more nuanced. As a resident, I learned that although “time is muscle,” one needs to “treat the patient and not the EKG.” Of course, the EKG is more than enough to proceed to catheterization if the patient is unstable or has elevated cardiac enzymes. However, we are not currently considering such a straightforward scenario.
In cases (not uncommon) where the story is atypical, the vital signs and exam are stable, and the enzymes are initially negative, my approach has changed. I have found it helpful to get aggressive about chasing down old ECG reports in such cases. Primary care providers and outside hospital records can often establish that the LBBB is old, even when the actual ECGs are not obtained. If the LBBB is old, the management can change drastically. Similarly, if the LBBB is definitively new, I think the threshold to perform cardiac catheterization should be extremely low. However, a management dilemma often arises when the LBBB is not proven to be old or new in this type of intermediate-risk patient. I have come to see in these cases that the ECG, on its own, is not a helpful bedside triage test.
Thankfully, these are the very cases when you may have some time to consider everything before activating the catheterization lab. Of course, such a strategy may jeopardize the door-to-needle or door-to-balloon time if the presentation is, in fact, a real ACS. If such a patient presents very early, it is often interesting to obtain a STAT myoglobin level (although I suspect such a maneuver will be superseded by highly sensitive troponin assays and circulation endothelial cells). However, my usual strategy is to bring an echocardiography machine directly to the bedside. We know that ACS-induced LBBB is caused by a large anterior infarct. Therefore, a normal echocardiogram would reassure me in the right clinical scenario.
As a fellow, I also like to discuss all intermediate-risk patients who present with possible-new LBBB with the on-call interventionalist. It is important to acquire as much information as possible (including echocardiographic data) within the required time window, to facilitate a complete discussion of the case with interventionalist colleagues.
Neeland & de Lemos: We agree that the decision threshold to activate the catheterization lab should be low, given the clear benefits of timely PCI and the relatively less important consequences of false cath-lab activation versus lytic administration. It may also differ a bit depending on whether the cath-lab personnel are present or must be called in from home.
At our institution, we’ve created a rapid fellow/faculty consult pathway for ED cases where STEMI is ambiguous or the indications for emergent cath are not clear. This represents a “stop and take a breath” approach for cases where primary PCI is not obviously indicated. LBBB patients make up a sizable proportion of this pathway. Bedside echocardiography, a class IIa indication in this setting, can be very helpful to differentiate an acute ischemic syndrome from chronic disease in a patient with LBBB.
We think it’s important to emphasize that even “new” LBBB may not necessarily translate to an occluded coronary artery/STEMI equivalent. In our experience, truly new LBBB from complete coronary artery occlusion is very rare, given the size and extent of infarcted myocardium necessary to cause a new LBBB; so most of the cases of even new LBBB are not concordant with an occluded coronary artery. In fact, from 4 contemporary angiographic studies of patients presenting with ACS and LBBB, the prevalence of a STEMI-equivalent MI ranged only from 7% to 61% among those with a new LBBB. In Dr. de Lemos’s experience, the prevalence is much closer to 7% than 61%! We’ve seen very few true acute LBBB “STEMI equivalents” in our entire careers. We’d be very interested to hear from other experienced cardiologists about how often they see “the big one” in the LBBB population in contemporary practice.
Ryan: Some people argue that it’s better to err on the side of caution by taking the “new” LBBB to the lab. Do you agree?
McEvoy: We should never allow a truly ischemic LBBB to go without rapid revascularization. Again, I have a very high threshold to not catheterize a proven-new LBBB. So I tend to agree with the above sentiment. However, such a strategy may be somewhat outdated in the modern era, particularly in those “grey zone” cases when the previous EKG is not available and the LBBB cannot be proven as either old or new. Specifically, we now have additional diagnostic tests, complementary to the EKG, which can be brought to bear in a timely manner. Echocardiography can be rapidly performed in most institutions (usually on a 24-hour basis). Whether CT coronary angiography will also find a role in the work-up of such cases is another interesting research question. I do realize that this may not be realistic in all medical facilities. However, any such patient presenting to a facility with limited resources must be transferred to a facility with a catheterization lab. Those facilities also have the ability to do an echocardiogram on arrival.
Neeland & de Lemos: It’s easy for those of us who don’t take interventional calls to say we should have a very low threshold! However, these false activations do put patients at some risk — and are demoralizing for the interventionalists and cath lab staff. That said, we agree that the downside risks of delayed reperfusion and missed diagnoses may matter even more. The challenge is to weigh these opposing risks and make the right decision for the patient. Additional information — ECG, biomarker, or echo-based — can be helpful in these situations, which is where our proposed algorithm should be applied.
Ryan: Neeland and colleagues suggest that because patients with LBBB have an overall higher risk for bleeding, they should, if possible, be preferentially transferred for primary PCI. In areas without cath lab access, what are your thoughts on fibrinolysis in patients with presumed new LBBB? And what was your approach to this issue in Ireland, where you worked as a cardiology registrar/fellow before coming to the U.S.?
McEvoy: For me, the fundamental question is not one of geography, but simply whether a patient presenting with LBBB needs to be rapidly considered for revascularization or not. Again, if the patient presents with clearly new LBBB, a good ACS story, or positive enzymes, revascularization must be prompt. However, if the LBBB duration is unknown, the story is atypical, and the enzymes are negative, a decision about the benefit of rapid triage for revascularization still needs to be made. If such a patient is deemed likely to benefit from revascularization (possibly with echocardiographic guidance) and the door-in/door-out (DIDO) time prior to transfer is <30 minutes (or the difference in door-to-needle time versus door-to-balloon time is <60minutes), the patient should be transferred for primary PCI. In addition to the bleeding risk with thrombolysis in LBBB, I would also suspect that the anterior and massive distribution of ischemia required to cause LBBB inherently means that the patient would derive probabilistic benefit from PCI. Unfortunately, in Ireland these temporal targets were often not realistic and thrombolysis would need to be performed.
Neeland & de Lemos: Given that the risks of bleeding are higher in patients with LBBB (because of a greater likelihood of comorbidities) and the chance of an occluded artery is lower, fibrinolysis is a riskier endeavor in these situations. Data from Pinto et al. suggest that longer PCI-related delay (up to about 2 hours) may still have a favorable risk/benefit ratio than fibrinolytic therapy. In older patients, such as those who present with LBBB, the risk/benefit tradeoff may occur even later. We feel that LBBB patients should be preferentially transferred to centers capable of primary PCI for these reasons and that fibrinolysis should be discouraged unless PCI really cannot be performed within a reasonable time frame. Another issue is that positive enzymes in the absence of a suggestive clinical history, even in the setting of a new LBBB, should not automatically be considered an ACS. Chronic elevations in troponin are common in these patients, related to concomitant structural heart and renal disease, and the trend of the enzymes can be very helpful to differentiate ACS from non-ACS causes of elevations.
Ryan: What do you think of this new proposed algorithm?
McEvoy: My biggest concern about this well-thought-out algorithm is the complete exclusion of the clinical history. I think a convincing and concerning history for ACS in the setting of LBBB should prompt rapid consideration for revascularization. I worry that not including the history and also the pretest probability for ACS (Diamond and Forrester, Duke clinical score, Genders score, etc.) in the algorithm may potentially lead to delays in unstable patients while echocardiography or serial enzymes are being performed. Multiple studies have also now demonstrated the value of CT coronary angiography in triaging patients presenting to the ED with intermediate probability of ACS. Interestingly, recent research also suggests that coronary artery calcium testing (with noncontrast CT) may also be useful in this situation. I would suggest that such tests could also be effectively incorporated into this algorithm in many cases.
Neeland & de Lemos: We completely agree with Dr. McEvoy’s point that the clinical history is a cornerstone of correct diagnosis and management. The first box of our proposed algorithm begins with LBBB and a clinical scenario consistent with ACS (“suspected ACS”), and it should not be extrapolated to situations where the pretest probability of ACS is low. The points about CT angiography are interesting, but it may be challenging to use in patients with LBBB, given their usually older age and greater probability of coronary calcification (which can create technical challenges), as well as a higher likelihood of diffuse coronary disease. We hope that our Viewpoint article will prompt more research into new approaches for rapid differential diagnosis of the patient with LBBB and possible ACS, because we are not satisfied with our current diagnostic and management approach.
Share your views on the new algorithm proposed by Neeland and colleagues.
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