February 16th, 2015
Case: Rising Coronary Artery Calcium in a Patient Who Has a Normal Stress Echo with an Abnormal ECG
Ethan J Weiss, M.D.
A 74-year-old physically active man exercises daily, takes a statin for hyperlipidemia, and has no other risk factors aside from a mildly elevated hemoglobin A1c. His most recent lipid profile, in January 2015, was:
- Total-c: 144 mg/dL
- LDL-c: 84 mg/dL
- HDL-c: 48 mg/dL
- Triglycerides: 59 mg/dL
His coronary artery calcium scores were 109.5 in the year 2000 and 400.4 in 2008.
Stress tests in 2002 and 2006 were normal with good exercise tolerance, but the ECG portion of both stress tests was abnormal. The nuclear perfusion scans were normal both times. His cardiologist at the time told him to continue his medical therapy, which included aspirin 81 mg and atorvastatin 10 mg.
In 2014, a new cardiologist repeats the stress test and again finds discordant results: The echo is normal, but the ECG is abnormal. An exercise nuclear perfusion scan is ordered. Again the perfusion is normal, but the ECG is abnormal. The new cardiologist increases the atorvastatin to 40 mg. The patient continues to exercise and remains asymptomatic.
The patient is sent for a CT angiogram, but the test is not done because the patient has a calcium score of 756, which is felt to be too high to exclude CAD by CT angiography.
Questions:
1. Do you agree that nuclear perfusion imaging and treadmill echo are more specific than treadmill ECG alone without imaging? Does an abnormal exercise ECG with normal imaging raise a concern?
2. Should an increasing calcium score in an asymptomatic individual raise concerns?
3. Would this patient have met the enrollment criteria for the COURAGE trial? Should the data from COURAGE help guide decision making for this patient?
4. What would you do next to care for this patient?
February 16th, 2015
Selections from Richard Lehman’s Literature Review: February 16th
Richard Lehman, BM, BCh, MRCGP
CardioExchange is pleased to reprint this selection 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.
JAMA 10 Feb 2015 Vol 313
Blood Pressure Lowering in Type 2 Diabetes (pg. 603): A new systematic review of blood pressure lowering in type 2 diabetes raises deep questions about the purpose and direction of medical intervention in chronic risk states. I haven’t space even to list them here, but I would just like to propose two common scenarios. A Bangladeshi woman of 34 is found to have high blood sugar and raised BP in her third pregnancy: these persist and within two years she is on six different medications including increasing doses of insulin. Her BMI is 41, she does not speak English and usually attends the practice nurse with a family member. Secondly, a 73 year old white male was found to have a BP of 164/96 ten years ago and has been on two antihypertensive drugs since. He has also been taking metformin for 5 years and his HbA1c runs at about 8 and his BMI is 32. Now I just want you to ask yourself: what are the absolute risks of cardiovascular disease, blindness, amputation and renal failure and the absolute benefits of each element of management (including surgery and lifestyle change) in either of these people? How are you going to communicate them and achieve the goals that your patient would most like? Do these people in fact have anything in common except a pair of labels (“hypertension” and “type 2 diabetes”)? What real-life questions would you like to see answered by new forms of what we now call meta-analysis? This particular one concludes that: “Among patients with type 2 diabetes, BP lowering was associated with improved mortality and other clinical outcomes with lower RRs observed among those with baseline BP of 140 mm Hg and greater. These findings support the use of medications for BP lowering in these patients.”
The BMJ 14 Feb 2015 Vol 350
Trajectories of Risk After Hospitalization for HF, Acute MI, or Pneumonia: My happy week continues with cracker of a BMJ paper from another young doctor I’ve tried to encourage—the phenomenally able Kumar Dharmarajan from the Harlan Krumholz circle at Yale. These guys—Joe Ross, Kumar, Kasia Lipska, Erica Spaatz, Leora Horwitz, Behnood Bikdeli, Nicholas Downing—are going to change the face of medicine long after I have left the fray. We have reached a futility point in the way we deliver acute medical care. In they come and out they go: home if lucky, or to institutional care, or the morgue. And then the cycle continues: “Within one year of hospital discharge, readmission to hospital and death, respectively, occurred following 67.4% and 35.8% of hospitalizations for heart failure, 49.9% and 25.1% for acute myocardial infarction, and 55.6% and 31.1% for pneumonia.”
February 13th, 2015
Can Clopidogrel Get Along with Proton Pump Inhibitors?
CardioExchange Editors, Staff
The debate rages on about whether the FDA’s warning against the administration of a proton pump inhibitor (PPI) with clopidogrel is appropriate. This was recently addressed in a study by Duke cardiologists, who noted that most registries suggest an interaction and all randomized trials indicate no such interaction. The issue was further addressed in an accompanying editorial by Dr. Peter Berger.
Sorry, there are no polls available at the moment.
February 12th, 2015
Discontinuing Aspirin for Primary Prevention: What Do You Say to Your Patient?
Harlan M. Krumholz, MD, SM
This post continues our series “What Do You Say to Your Patient?” In this series, we ask members to share how they interpret a complex or controversial issue for patients. To review earlier posts, click
The following scenario stems from a recent Japanese Primary Prevention Project study, published in JAMA, which found that once-daily, low-dose aspirin did not significantly reduce the risk for cardiovascular events among patients age 60 older with atherosclerotic risk factors.
A 60-year-old man walks into your office. He has mild hypertension treated by diet and exercise and his LDL is 120 mg/dl. He has no personal or family history of heart disease and does not have diabetes. Physically active, he is keen to find ways to reduce his cardiovascular risk.
Having taken an aspirin a day since he turned 50, your patient says he’s learned of several recent studies that indicate he should not be taking it.
He does not know what to do, and wonders if another study will be published next year that says he should take aspirin. He asks you for guidance – and for help understanding what he is reading in the news.
What do you say?
Do you advise him to stop taking aspirin?
How do you put the news media coverage in perspective for him?
February 12th, 2015
Three Trials Show Benefits of Thrombectomy in Stroke Patients
Larry Husten, PHD
Three new studies offer important additional evidence that early treatment with current thrombectomy devices that extract clots from blood vessels in the brain can lead to improved outcomes in carefully selected stroke patients. The trials were stopped early based on efficacy following positive findings last year from another trial, MR CLEAN. The three new trials were presented today at the AHA/ASA International Stroke Conference in Nashville; two of the trials were published simultaneously in the New England Journal of Medicine.
In the ESCAPE trial, 316 patients were randomized within 12 hours of the onset of symptoms to standard care or standard care plus the use of a thrombectomy device. Patients enrolled in the trial were carefully selected. They all had a proximal vessel occlusion, a small infarct core, and moderate-to-good collateral circulation.
At 90 days 53% of patients in the intervention group versus 29.3% in the standard care group were considered functionally independent (modified Rankin score of 0-2) (p<0.001). There was also a significant reduction in mortality, from 19% in the control group to 10.4% in the treatment group (p=0.04). Symptomatic intracerebral hemorrhage occurred in 3.6% of the treatment group and 2.7% of the standard care group (p=0.75).
“The trial confirms the benefit of endovascular treatment reported recently in the MR CLEAN trial,” the investigators wrote.
The smaller EXTEND-IA trial was stopped after only 70 patients were enrolled. These patients had a blockage of the internal carotid or middle cerebral artery with evidence of reversible ischemic range and a small infarct. They were randomized to thrombolysis alone or thrombolysis plus thrombectomy. All patients were treated within 4.5 hours of the onset of symptoms.
Reperfusion at 24 hours and early neurologic improvement — the coprimary outcomes — were both significantly better in the treatment group. The percentage of ischemic territory that had undergone reperfusion was 100% in the treatment group versus only 37% in the control group (p<0.001). At three days early neurologic improvement was seen in 80% of the treatment group versus 37% of controls (p=0.002). At 90 days 71% of patients in the treatment group had achieved functional independence, compared with 40% in the control group (p=0.01).
The investigators noted that “a unique feature” of their study “was the use of standardized, universal CT perfusion-imaging selection to exclude patients with large ischemic cores and without evidence of clinically significant salvageable ischemic brain.”
The SWIFT PRIME trial studied 196 patients receiving thrombolysis for confirmed large vessel anterior circulation occlusions within six hours of the onset of symptoms. Following randomization half received additional endovascular therapy with the Solitaire device. Functional independence, defined as a score under two on the modified Rankin scale, was achieved in 60.2% in the treatment group and 35.5% in the control group (p=0.0008). There was no significant difference in mortality at 90 days (9.2% versus 12.4%, p=0.50).
The authors calculated that “for every two and half patients treated, one more patient has a better disability outcome” and that “for every four patients treated, one more patient is independent at long time follow-up.”
Medtronic/Covidien was the sole sponsor of EXTEND-IA and SWIFT PRIME, and a partial sponsor of ESCAPE.
February 12th, 2015
Insights About the Use of IV Fluids in Patients Hospitalized for Heart Failure
Behnood Bikdeli, M.D. and Larry Allen, MD, MHS
The CardioExchange Editors interview Behnood Bikdeli, lead author of a retrospective cohort study of the use of intravenous fluids, within 2 days after admission, among patients hospitalized with acute decompensated heart failure and treated with loop diuretics at 346 hospitals in 2009 and 2010. Larry A. Allen, who wrote the editorial about the study, answers the same questions. Both articles are published in JACC: Heart Failure.
MAIN FINDINGS
Of more than 130,000 patients hospitalized for heart failure, 11% were treated with IV fluids during the first 2 days after admission. Patients who received IV fluids had significantly higher rates of subsequent critical care admission (5.7% vs. 3.8%;), intubation (1.4% vs. 1.0%), renal replacement therapy (0.6% vs. 0.3%), and in-hospital death (3.3% vs. 1.8%) than patients who received only diuretics. Hospitals varied widely in the proportion of hospitalized HF patients who received IV fluids (range: 0% to 71%; median: 12.5%).
THE INTERVIEW
CardioExchange Editors: How do you think administration of IV fluids affects outcomes among patients hospitalized with congestive heart failure?
Bikdeli: This is an excellent question. There are multiple potential explanations. First, let me take a step back. We studied the early phase after admission (the first 48 hours of the inpatient stay). So it is less likely that patients in our study received IV fluids in response to excessive diuresis, although we cannot exclude that possibility. Another possibility is that — despite our exclusion criteria (people with sepsis, bleeding, or anaphylaxis, and those undergoing cardiac procedures) — some of these patients did require IV fluids for legitimate medical conditions and that use of IV fluids is a marker (rather than a cause) of higher risk and worse outcomes. Yet another possibility is that IV fluids were used inadvertently for some patients, and this might have contributed to worse outcomes. The wide variations in the risk-standardized utilization of IV fluids make me wonder whether this third hypothesis is important. I should clarify again, though, that our findings should not be interpreted as demonstrating causation at this stage.
Allen: Certainly administration of IV fluids to patients who actually need decongestion is counter to therapeutic goals. This may directly worsen a patient’s status or at least slow improvement, thereby unnecessarily prolonging symptoms and the hospital stay. Perhaps more important, simultaneous administration of IV fluids and IV diuretics may be a marker of poorly defined therapeutic goals or inadequately coordinated care.
Note that the use of both IV fluids and IV diuretics within the first 48 hours after hospitalization for heart failure may occur for a variety of reasons: reflexive connection of IV fluids in the emergency setting, carrier fluid for other IV medications, confusion over hemodynamic status, development of worsening renal function or hypotension with diuresis, development of sepsis physiology on top of heart failure, and so on. Administrative data have limits in elucidating the actual clinical decision-making rationale (or the lack of it). However, the significant variation among hospitals in IV fluid administration for these patients suggests that the reasons are not necessarily standard responses to physiology or accepted guidelines.
CardioExchange Editors: How should physicians and health care systems address this problem?
Bikdeli: There are multiple implications. At the patient level, we need to better identify the people who receive both diuretics and fluids within a short time span. Using more granular data, we also must determine whether or not the use of IV fluids is the main cause of these patients’ worse outcomes.
At the level of health-system pharmacists, it might be prudent to help promote initiatives that aim to minimize the amounts of IV fluids required for administration of other necessary medications (e.g., antibiotics) in patients with heart failure.
At the policy-making level, it might be helpful for hospital administrators to promote strategies that would reduce the chances of inadvertent IV fluid use in patients with decompensated heart failure. These might include (1) reminders/ alerts when a provider tries to add IV fluids for someone with HF, with the flexibility to override the alert if the patient’s clinical profile warrants it; (2) EMR-related strategies that would minimize routine use of IV fluids when patients present to the emergency department; and (3) better hand-offs when the level of care changes.
Allen: For clinicians treating individual patients, this study raises many questions. Most important, what are the reasons behind IV fluid administration? How can we improve rapid, accurate assessment of volume status and then implement care consistent with optimizing hemodynamics? In the face of worsening renal function during heart failure hospitalization, how can we know better when cardiorenal syndrome is due to persistent venous congestion, overdiuresis, or something else?
Health systems also need to understand the reasons behind IV fluid administration. With that knowledge, systems can then work to ensure that automated responses are consistent with clinical realities and that all ordered therapies reflect individualized, high-quality care.
JOIN THE DISCUSSION
Should these insights from Drs. Bikdeli and Allen influence how your institution approaches the use of IV fluids in hospitalized patients with heart failure?
February 11th, 2015
New US Guidelines Will Lift Limits on Dietary Cholesterol
Larry Husten, PHD
The influential Dietary Guidelines Advisory Committee has recommended that limitations on dietary cholesterol be removed from the upcoming 2015 edition of Dietary Guidelines for Americans. Recommendations to reduce dietary cholesterol have been a mainstay of the USDA and other guidelines for many years, starting with guidance from the American Heart Association in the 1960s.
The proposed change reflects a major shift in the scientific view of cholesterol in recent years. Although serum cholesterol is still considered an important risk factor, cholesterol consumed in food is now thought to play a relatively insignificant role in determining blood levels of cholesterol. In previous guidelines, excess dietary cholesterol was considered to be a public health concern. The draft of the new report [PDF] states:
“Cholesterol is not considered a nutrient of concern for overconsumption.”
The proposed change was first reported on Tuesday by Peter Whoriskey in the Washington Post. He reports that “a person with direct knowledge of the proceedings said the cholesterol finding would make it to the group’s final report, which is due within weeks.” The final guideline will be published later this year by HHS and the USDA. Whoriskey writes that the guidance”has broad effects on the American diet, helping to determine the content of school lunches, affecting how food manufacturers advertise their wares, and serving as the foundation for reams of diet advice.”
“It’s the right decision,” Steve Nissen told USA Today. “We got the dietary guidelines wrong. They’ve been wrong for decades.” Nissen also said that advice about reducing saturated fat and salt may be wrong, but no major change in these areas is expected in the new guidelines.
February 10th, 2015
Study Examines Blood Pressure Thresholds in Hypertensive Diabetics
Larry Husten, PHD
Although the general benefits of lowering high blood pressure are widely accepted, there has been intense debate over specific goals for treatment and the threshold at which therapy should be initiated. A large new meta-analsysis published in JAMA helps shed lights on this important controversy.
U.K. and Australian researchers analyzed the effect of lowering blood pressure in type 2 diabetes using data from more than 100,000 people who participated in 40 trials. They found that lowering blood pressure was beneficial: for each 10-mm Hg drop in systolic blood pressure, there were statistically significant reductions in mortality, cardiovascular events, coronary heart disease, stroke, albuminuria, and retinopathy. For instance, each 10-mm Hg drop was associated with a 13% reduction in mortality and a 27% reduction in stroke — translating into absolute risk reductions of 3.16 and 4.06 events per 1,000 patient-years, respectively.
However, when the trials were stratified according to whether systolic blood pressure at baseline was above or below 140 mm Hg, relative risks for outcomes other than stroke, retinopathy, and albuminuria were lower for those with initial blood pressures of 140 or higher. Similarly, when the trials were compared according to the blood pressure levels reached during the trial, relative risks for most outcomes were lower in patients achieving a systolic blood pressure of 130 mm Hg or higher versus those reaching lower levels, with the exception of stroke and albuminuria.
The authors take issue with the recent JNC 8 guideline which raised the threshold for treatment in diabetics to 140 mm Hg. They recommend that therapy should be considered at the lower level in people at high risk for stroke, retinopathy, and progression of albuminuria.
In an accompanying editorial, Bryan Williams writes that the findings “are timely, clear, and important and lend support to current guideline recommendations to consider offering patients with type 2 diabetes antihypertensive therapy when their systolic BP is 140 mm Hg or greater, aiming for a target systolic BP toward 130 mm Hg but not usually lower than this.” But, he continues, “for some patients, these treatment thresholds and targets might be too conservative, especially for optimally reducing the risk of stroke and the development or progression of albuminuria.”
February 10th, 2015
Risk for Sudden Death in Spironolactone Users Who Take Trimethoprim-Sulfamethoxazole
Tony Antoniou, PharmD, PhD
The CardioExchange Editors interview Tony Antoniou, lead author of a population-based case-control study of elderly residents of Ontario who were users of spironolactone and died suddenly within 14 days after receiving an antibiotic prescription (for trimethoprim– sulfamethoxazole, amoxicillin, ciprofloxacin, norfloxacin, or nitrofurantoin). The article is published in CMAJ.
THE STUDY
Main finding: In patients age 66 or older who were treated with spironolactone from April 1994 through December 2011, trimethoprim-sulfamethoxazole (TMP-SMX) was associated with a more than twofold higher risk for sudden death, compared with amoxicillin (adjusted odds ratio, 2.46; 95% CI, 1.55–3.90).
Conclusion: When patients receiving spironolactone require an antibiotic, clinicians should either select one that does not contain trimethoprim or limit the dose and duration of trimethoprim-based therapies, while closely monitoring the patient’s serum potassium concentration.
THE INTERVIEW
CardioExchange Editors: What made you think to pursue this research question?
Antoniou: Initially, my background in pharmacy prompted me to suspect an interaction. We also did a study that found that the combination of TMP-SMX and spironolactone increased the risk of hospitalization for hyperkalemia.
Editors: Should anyone be treated with this combination?
Antoniou: It would probably be most prudent to avoid the combination, given that there are few indications for which TMP-SMX is the only antibiotic option.
Editors: Should there be regulatory action?
Antoniou: Given how commonly the two drugs are used, the likelihood of co-prescription could be high. Safety alerts to physicians, pharmacists, and other prescribers may be warranted.
Editors: What you are doing at your institution to teach doctors about this interaction?
Antoniou: No specific action has been undertaken yet, apart from highlighting the interaction in a daily bulletin received by all staff. We are considering several initiatives, such as preparing an alert in our electronic medical record system that would flag the interaction.
JOIN THE DISCUSSION
How will the findings from Dr. Antoniou’s study change your antibiotic prescription practices for users of spironolactone?
February 9th, 2015
Selections from Richard Lehman’s Literature Review: February 9th
Richard Lehman, BM, BCh, MRCGP
CardioExchange is pleased to reprint this selection 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.
NEJM 5 Feb 2015 Vol 372
Efficacy of a Device to Narrow the Coronary Sinus in Refractory Angina (pg. 519): Refractory angina seems to be common in cardiac clinics but not in primary care. When all the drugs have failed, and revascularization is not an option, device makers like to get inventive. The latest gizmo is an hour-glass shaped expandable metal object which sits at the portal of the coronary arteries and “creates a focal narrowing and increases pressure in the coronary sinus, thus redistributing blood into ischemic myocardium.” My inclination is to say “Yeah, right,” but these things do seem to work, somehow or other. “The device was also associated with improvement of at least one Canadian Cardiovascular Society angina class in 71% of the patients in the treatment group (37 of 52 patients), as compared with 42% of those in the control group (22 of 52) (P=0.003).” The control was a sham procedure.
Lancet 7 Feb 2015 Vol 385
Optimum and Stepped Care Standardized Antihypertensive Treatment With or Without Renal Denervation for Resistant Hypertension (OL): In the course of my clinical working life, I had as little to do with drug companies as possible, and nothing whatever to do with device manufacturers. It came as a jaw-dropping surprise to me when Medtronic decided to let its full data on a commercial product be analysed by two independent teams. I was at Yale University when it happened and I got some trickle-down money from that project, so I must declare an interest. The other thing that impressed me about Medtronic was that it performed a sham-controlled trial on the Symplicity renal denervation device which it had bought from another company on the back of a massively successful open-label trial in so-called resistant hypertension. The Symplicity-2 trial, using a sham procedure as control, failed to meet its prespecified end-point, and rather than make excuses, Medtronic accepted that it should not be promoted thereafter. Now along comes another open-label trial comparing the Symplicity device with stepped drug treatment, paid for by the French government: and Symplicity wins by 6mm Hg.
Bizarrely, the accompanying editorial in effect criticizes Medtronic for not pushing its own product, pointing out various flaws in the Symplicity-2 trial and alleging “an important question is whether a sham procedure is ethical and practical in patients with resistant hypertension often accompanied by other comorbidities, leaving these patients at high risk of cardiovascular and renal disease progression and potentially adding to treatment costs.” What nonsense. We have no idea what these devices do for long term outcomes and sham-controlled trials are the only ethical way to find out.
NEJM Journal Watch — Recent Cardiology Articles- To Lower Stroke Risk in Patients Undergoing Atrial Fibrillation Ablation, Is a Device or a Medication Better?
- Intensive vs. Standard Blood Pressure Lowering in Patients with Diabetes
- Anticoagulation in Patients with Cancer-Associated Pulmonary Embolism: How Long is Long Enough?
- Spironolactone Use After Percutaneous Intervention for Acute Myocardial Infarction
- CRISPR/Cas9 Gene Editing for Transthyretin Cardiomyopathy