One of my brothers has adult onset bipolar disorder. As luck would have it, he also has type 2 diabetes mellitus. He struggles constantly with blood sugar control since he needs to take 2 psychotropic medications, both of which cause weight gain.

I mistakenly told a patient that her beta-blocker wasn't interfering with her weight loss.His situation has prompted me to think about the responsibility we have as we care, and advocate, for our patients with major mental illness who require these effective medications. At a minimum, we must be knowledgeable about the adverse metabolic effects of these drugs, avoid prescribing them when possible, and advocate for dose reductions when feasible. Knowing, for example, that these drugs fall on a spectrum, with haloperidol causing the least weight gain and olanzapine causing the most, is important.¹

An eye-opener. The article by Saunders in this issue provides advice on avoiding medications that commonly cause weight gain when prescribing for overweight or obese patients with diabetes, hypertension, and/or depression. I was unaware that some of the drugs on the list contribute to the problem. For example, I saw a new patient last week who has hypertension and is obese; she has been taking the beta-blocker metoprolol for the past 8 years. She has tried unsuccessfully to lose weight. She asked me if the metoprolol could be interfering with weight loss, and I mistakenly told her “No.” Thankfully, we decided to discontinue it anyway. I will admit to her my knowledge gap when I see her next month for follow-up. Errors are great teachers, especially when no harm is done.

The scope of the Saunders article is not meant to be comprehensive, since it focuses on medications for diabetes, hypertension, and depression. I think all of us are aware of the weight gain associated with other commonly prescribed drugs, such as systemic corticosteroids and long-acting progesterone for contraception. Thankfully, combination oral contraceptives do not appear to be associated with weight gain²—answering one of the more common questions I receive from patients about weight and medications.

The bottom line. Avoid prescribing medications that can cause weight gain in overweight and obese patients when possible, use the lowest effective dose when such agents are necessary, and warn patients of this adverse effect so that they can take precautions, such as walking an extra mile a day or giving up that high-calorie latte in the morning.

1. Leucht S, Cipriani A, Spineli L, et al. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet. 2013;382:951-962.

2. Gallo MF, Lopez LM, Grimes DA, et al. Combination contraceptives: effects on weight. Cochrane Database Syst Rev. 2011;CD003987.

One of my brothers has adult onset bipolar disorder. As luck would have it, he also has type 2 diabetes mellitus. He struggles constantly with blood sugar control since he needs to take 2 psychotropic medications, both of which cause weight gain.

I mistakenly told a patient that her beta-blocker wasn't interfering with her weight loss.His situation has prompted me to think about the responsibility we have as we care, and advocate, for our patients with major mental illness who require these effective medications. At a minimum, we must be knowledgeable about the adverse metabolic effects of these drugs, avoid prescribing them when possible, and advocate for dose reductions when feasible. Knowing, for example, that these drugs fall on a spectrum, with haloperidol causing the least weight gain and olanzapine causing the most, is important.¹

An eye-opener. The article by Saunders in this issue provides advice on avoiding medications that commonly cause weight gain when prescribing for overweight or obese patients with diabetes, hypertension, and/or depression. I was unaware that some of the drugs on the list contribute to the problem. For example, I saw a new patient last week who has hypertension and is obese; she has been taking the beta-blocker metoprolol for the past 8 years. She has tried unsuccessfully to lose weight. She asked me if the metoprolol could be interfering with weight loss, and I mistakenly told her “No.” Thankfully, we decided to discontinue it anyway. I will admit to her my knowledge gap when I see her next month for follow-up. Errors are great teachers, especially when no harm is done.

The scope of the Saunders article is not meant to be comprehensive, since it focuses on medications for diabetes, hypertension, and depression. I think all of us are aware of the weight gain associated with other commonly prescribed drugs, such as systemic corticosteroids and long-acting progesterone for contraception. Thankfully, combination oral contraceptives do not appear to be associated with weight gain²—answering one of the more common questions I receive from patients about weight and medications.

The bottom line. Avoid prescribing medications that can cause weight gain in overweight and obese patients when possible, use the lowest effective dose when such agents are necessary, and warn patients of this adverse effect so that they can take precautions, such as walking an extra mile a day or giving up that high-calorie latte in the morning.

1. Leucht S, Cipriani A, Spineli L, et al. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet. 2013;382:951-962.

2. Gallo MF, Lopez LM, Grimes DA, et al. Combination contraceptives: effects on weight. Cochrane Database Syst Rev. 2011;CD003987.

One of my brothers has adult onset bipolar disorder. As luck would have it, he also has type 2 diabetes mellitus. He struggles constantly with blood sugar control since he needs to take 2 psychotropic medications, both of which cause weight gain.

I mistakenly told a patient that her beta-blocker wasn't interfering with her weight loss.His situation has prompted me to think about the responsibility we have as we care, and advocate, for our patients with major mental illness who require these effective medications. At a minimum, we must be knowledgeable about the adverse metabolic effects of these drugs, avoid prescribing them when possible, and advocate for dose reductions when feasible. Knowing, for example, that these drugs fall on a spectrum, with haloperidol causing the least weight gain and olanzapine causing the most, is important.¹

An eye-opener. The article by Saunders in this issue provides advice on avoiding medications that commonly cause weight gain when prescribing for overweight or obese patients with diabetes, hypertension, and/or depression. I was unaware that some of the drugs on the list contribute to the problem. For example, I saw a new patient last week who has hypertension and is obese; she has been taking the beta-blocker metoprolol for the past 8 years. She has tried unsuccessfully to lose weight. She asked me if the metoprolol could be interfering with weight loss, and I mistakenly told her “No.” Thankfully, we decided to discontinue it anyway. I will admit to her my knowledge gap when I see her next month for follow-up. Errors are great teachers, especially when no harm is done.

The scope of the Saunders article is not meant to be comprehensive, since it focuses on medications for diabetes, hypertension, and depression. I think all of us are aware of the weight gain associated with other commonly prescribed drugs, such as systemic corticosteroids and long-acting progesterone for contraception. Thankfully, combination oral contraceptives do not appear to be associated with weight gain²—answering one of the more common questions I receive from patients about weight and medications.

The bottom line. Avoid prescribing medications that can cause weight gain in overweight and obese patients when possible, use the lowest effective dose when such agents are necessary, and warn patients of this adverse effect so that they can take precautions, such as walking an extra mile a day or giving up that high-calorie latte in the morning.

1. Leucht S, Cipriani A, Spineli L, et al. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet. 2013;382:951-962.

2. Gallo MF, Lopez LM, Grimes DA, et al. Combination contraceptives: effects on weight. Cochrane Database Syst Rev. 2011;CD003987.

Separate sampling of the duodenal bulb increased detection of celiac disease by only 0.1% when endoscopy patients had a low pretest probability of celiac disease, according to research published in the November issue of Clinical Gastroenterology and Hepatology.

Duodenal bulb histology did reveal other abnormal findings, such as chronic peptic duodenitis, gastric heterotopia, and Brunner gland hyperplasia, wrote Samantha Stoven, MD, of Mayo Clinic, Rochester, Minn., and her associates. These findings did not seem to impede the identification of celiac disease, but their clinical implications were unclear, the researchers noted.

©Monthian/Thinkstock

Most studies of the diagnostic yield of duodenal bulb specimens have been performed in patients with known celiac disease or positive serology. In past studies of these high-probability cohorts, duodenal bulb sampling increased the diagnostic yield of celiac disease anywhere from 1.8% to 18%, but whether and how that finding translates to low-probability cohorts is unclear, the researchers said. Therefore, they retrospectively analyzed data from 679 endoscopy patients who had both duodenal bulb and small bowel biopsies collected at three Mayo Clinic sites in 2011. These sites are “open access,” meaning that patients can be referred for endoscopy without the approval of a gastroenterologist.

The average age of the patients was 50 years, and 63% were female. They were most commonly referred for duodenal biopsy because of chronic dyspepsia (46% of patients), diarrhea (35%), or nausea (17%). Patients with either known celiac disease or positive serology were excluded from the study (Clin Gastroenterol Hepatol. 2016 Mar 7. doi: 10.1016/j.cgh.2016.02.026). A total of 265 patients (39%) had abnormal duodenal histology, which was most often diagnosed as chronic peptic duodenitis, the researchers said. Histologic abnormalities usually involved the duodenal bulb (36% of cases), not the distal duodenum (15%; P less than .0001). However, among the 16 patients (2%) found to have celiac disease, just one patient had disease only in the duodenal bulb. Thus, duodenal bulb sampling increased the diagnostic yield of celiac disease by only 0.1% when considering the overall cohort. The patient with celiac disease limited to the bulb was a 46-year-old female presenting with diarrhea and anemia who had normal serologies but a permissive human leukocyte antigen test. Her duodenal bulb had villous atrophy and more than 25 intraepithelial lymphocytes per 100 epithelial cells, while her distal duodenum was normal.

Among the 85% of patients who had normal distal duodenums, 28% had abnormal bulb histology, most often chronic peptic duodenitis, active chronic peptic duodenitis, or gastric heterotopia, the researchers said. Among the 59% of patients whose celiac serology before endoscopy was truly unknown, only two (0.5%) had histologic changes consistent with celiac disease, which in both cases were located in the distal duodenum.

SOURCE: American Gastroenterological Association

“Individual sampling of the duodenal bulb in patients with either negative or unknown celiac serologic status can be considered in practices where expert gastrointestinal pathologists are present and there is agreement that both samples can be submitted in the same bottle, or there is not a separate charge for the additional container. Further studies may be needed to assess the diagnostic yield of separate bulb biopsies for celiac detection in all comers.”

An American College of Gastroenterology Junior Faculty Development Award helped support the work. Senior author Joseph A. Murray, MD, disclosed ties to Alba Therapeutics, Alvine Pharmaceuticals, AMAG Pharmaceuticals, and several other corporate entities. The remaining authors had no disclosures.

Separate sampling of the duodenal bulb increased detection of celiac disease by only 0.1% when endoscopy patients had a low pretest probability of celiac disease, according to research published in the November issue of Clinical Gastroenterology and Hepatology.

Duodenal bulb histology did reveal other abnormal findings, such as chronic peptic duodenitis, gastric heterotopia, and Brunner gland hyperplasia, wrote Samantha Stoven, MD, of Mayo Clinic, Rochester, Minn., and her associates. These findings did not seem to impede the identification of celiac disease, but their clinical implications were unclear, the researchers noted.

©Monthian/Thinkstock

Most studies of the diagnostic yield of duodenal bulb specimens have been performed in patients with known celiac disease or positive serology. In past studies of these high-probability cohorts, duodenal bulb sampling increased the diagnostic yield of celiac disease anywhere from 1.8% to 18%, but whether and how that finding translates to low-probability cohorts is unclear, the researchers said. Therefore, they retrospectively analyzed data from 679 endoscopy patients who had both duodenal bulb and small bowel biopsies collected at three Mayo Clinic sites in 2011. These sites are “open access,” meaning that patients can be referred for endoscopy without the approval of a gastroenterologist.

The average age of the patients was 50 years, and 63% were female. They were most commonly referred for duodenal biopsy because of chronic dyspepsia (46% of patients), diarrhea (35%), or nausea (17%). Patients with either known celiac disease or positive serology were excluded from the study (Clin Gastroenterol Hepatol. 2016 Mar 7. doi: 10.1016/j.cgh.2016.02.026). A total of 265 patients (39%) had abnormal duodenal histology, which was most often diagnosed as chronic peptic duodenitis, the researchers said. Histologic abnormalities usually involved the duodenal bulb (36% of cases), not the distal duodenum (15%; P less than .0001). However, among the 16 patients (2%) found to have celiac disease, just one patient had disease only in the duodenal bulb. Thus, duodenal bulb sampling increased the diagnostic yield of celiac disease by only 0.1% when considering the overall cohort. The patient with celiac disease limited to the bulb was a 46-year-old female presenting with diarrhea and anemia who had normal serologies but a permissive human leukocyte antigen test. Her duodenal bulb had villous atrophy and more than 25 intraepithelial lymphocytes per 100 epithelial cells, while her distal duodenum was normal.

Among the 85% of patients who had normal distal duodenums, 28% had abnormal bulb histology, most often chronic peptic duodenitis, active chronic peptic duodenitis, or gastric heterotopia, the researchers said. Among the 59% of patients whose celiac serology before endoscopy was truly unknown, only two (0.5%) had histologic changes consistent with celiac disease, which in both cases were located in the distal duodenum.

SOURCE: American Gastroenterological Association

“Individual sampling of the duodenal bulb in patients with either negative or unknown celiac serologic status can be considered in practices where expert gastrointestinal pathologists are present and there is agreement that both samples can be submitted in the same bottle, or there is not a separate charge for the additional container. Further studies may be needed to assess the diagnostic yield of separate bulb biopsies for celiac detection in all comers.”

An American College of Gastroenterology Junior Faculty Development Award helped support the work. Senior author Joseph A. Murray, MD, disclosed ties to Alba Therapeutics, Alvine Pharmaceuticals, AMAG Pharmaceuticals, and several other corporate entities. The remaining authors had no disclosures.

Separate sampling of the duodenal bulb increased detection of celiac disease by only 0.1% when endoscopy patients had a low pretest probability of celiac disease, according to research published in the November issue of Clinical Gastroenterology and Hepatology.

Duodenal bulb histology did reveal other abnormal findings, such as chronic peptic duodenitis, gastric heterotopia, and Brunner gland hyperplasia, wrote Samantha Stoven, MD, of Mayo Clinic, Rochester, Minn., and her associates. These findings did not seem to impede the identification of celiac disease, but their clinical implications were unclear, the researchers noted.

©Monthian/Thinkstock

Most studies of the diagnostic yield of duodenal bulb specimens have been performed in patients with known celiac disease or positive serology. In past studies of these high-probability cohorts, duodenal bulb sampling increased the diagnostic yield of celiac disease anywhere from 1.8% to 18%, but whether and how that finding translates to low-probability cohorts is unclear, the researchers said. Therefore, they retrospectively analyzed data from 679 endoscopy patients who had both duodenal bulb and small bowel biopsies collected at three Mayo Clinic sites in 2011. These sites are “open access,” meaning that patients can be referred for endoscopy without the approval of a gastroenterologist.

The average age of the patients was 50 years, and 63% were female. They were most commonly referred for duodenal biopsy because of chronic dyspepsia (46% of patients), diarrhea (35%), or nausea (17%). Patients with either known celiac disease or positive serology were excluded from the study (Clin Gastroenterol Hepatol. 2016 Mar 7. doi: 10.1016/j.cgh.2016.02.026). A total of 265 patients (39%) had abnormal duodenal histology, which was most often diagnosed as chronic peptic duodenitis, the researchers said. Histologic abnormalities usually involved the duodenal bulb (36% of cases), not the distal duodenum (15%; P less than .0001). However, among the 16 patients (2%) found to have celiac disease, just one patient had disease only in the duodenal bulb. Thus, duodenal bulb sampling increased the diagnostic yield of celiac disease by only 0.1% when considering the overall cohort. The patient with celiac disease limited to the bulb was a 46-year-old female presenting with diarrhea and anemia who had normal serologies but a permissive human leukocyte antigen test. Her duodenal bulb had villous atrophy and more than 25 intraepithelial lymphocytes per 100 epithelial cells, while her distal duodenum was normal.

Among the 85% of patients who had normal distal duodenums, 28% had abnormal bulb histology, most often chronic peptic duodenitis, active chronic peptic duodenitis, or gastric heterotopia, the researchers said. Among the 59% of patients whose celiac serology before endoscopy was truly unknown, only two (0.5%) had histologic changes consistent with celiac disease, which in both cases were located in the distal duodenum.

SOURCE: American Gastroenterological Association

“Individual sampling of the duodenal bulb in patients with either negative or unknown celiac serologic status can be considered in practices where expert gastrointestinal pathologists are present and there is agreement that both samples can be submitted in the same bottle, or there is not a separate charge for the additional container. Further studies may be needed to assess the diagnostic yield of separate bulb biopsies for celiac detection in all comers.”

An American College of Gastroenterology Junior Faculty Development Award helped support the work. Senior author Joseph A. Murray, MD, disclosed ties to Alba Therapeutics, Alvine Pharmaceuticals, AMAG Pharmaceuticals, and several other corporate entities. The remaining authors had no disclosures.

A 62-year-old man with hypertension, type 2 diabetes mellitus, and hypercholesterolemia presented to the emergency department with substernal chest pain that started about 15 hours earlier while he was at rest watching television.

On examination, his pulse was 92 beats per minute and regular, his blood pressure was 160/88 mm Hg, and he had no evidence of jugular venous distention or pedal edema. Lung examination was positive for bibasilar crackles.

Electrocardiography revealed Q waves with ST elevation in leads I, aVL, V₄, V₅, and V₆ with reciprocal ST depression in leads II, III, and aVF.

His troponin T level on presentation was markedly elevated.

Image

He underwent heart catheterization and was found to have 100% occlusion of the proximal left anterior descending artery. He underwent successful percutaneous coronary intervention with placement of a drug-eluting stent, and afterward had grade 3 flow on the Thrombolysis in Myocardial Infarction (TIMI) scale.

Echocardiography the next day revealed a mobile echo-dense mass in the left ventricular apex (Figure 1) and a left ventricular ejection fraction of 35%.

THE INCIDENCE OF LEFT VENTRICULAR THROMBOSIS IN ACUTE MI

1. What is the incidence of left ventricular thrombosis after acute myocardial infarction (MI), now that primary percutaneous coronary intervention is common?

• 0.1%
• 2%
• 20%
• 40%

Left ventricular thrombosis is a serious complication of acute MI that can cause systemic thromboembolism, including stroke.¹ Before thrombolytic therapy was available, this complication occurred in 20% to 60% of patients with acute MI.^2,3 But early reperfusion strategies, anticoagulation for the first 48 hours, and dual antiplatelet therapy have reduced the incidence of this complication significantly.

In the thrombolytic era, the incidence of left ventricular thrombosis was 5.1% in the Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico (GISSI) 3 study, which had 8,326 patients. A subset of patients who had an anterior MI had almost double the incidence (11.5%).³

Image

The incidence has further declined with the advent of primary percutaneous coronary intervention, likely thanks to enhanced myocardial salvage, and now ranges from 2.5% to 15% (Table 1).^4–11 The largest observational study, with 2,911 patients undergoing percutaneous coronary intervention, reported an incidence of 2.5% within 3 to 5 days of the MI.⁷ At our center, the incidence was found to be even lower, 1.8% in 1,700 patients presenting with ST-elevation MI undergoing primary percutaneous coronary intervention. Hence, of the answers to the question above, 2% would be closest.

Large infarct size with a low left ventricular ejection fraction (< 40%), anterior wall MI, hypertension, and delay in time from symptom onset to intervention were independent predictors of left ventricular thrombus formation in most studies.^7,12 The risk is highest during the first 2 weeks after MI, and thrombosis almost never occurs more than 3 months after the index event.^5,13–16

WHAT IS THE PATHOGENESIS OF LEFT VENTRICULAR THROMBOSIS?

A large transmural infarct results in loss of contractile function, which causes stagnation and pooling of blood adjacent to the infarcted ventricular segment. In addition, endocardial injury exposes tissue factor, which then initiates the coagulation cascade. To make matters worse, MI results in a hypercoagulable state through unclear mechanisms, which completes the Virchow triad for thrombus formation. Elevations of D-dimer, fibrinogen, anticardiolipin antibodies (IgM and IgG), and tissue factor have also been reported after acute MI.¹⁷

Thrombus formation begins with platelet aggregation at the site of endocardial damage, forming a platelet plug, followed by activation of clotting factors. These thrombi are referred to as “mural,” as they adhere to the chamber wall (endocardium). They are composed of fibrin and entrapped red and white blood cells (Figure 2).

The natural course of thrombus evolution is established but variable. A left ventricular thrombus may dislodge and embolize, resulting in stroke or other thromboembolic complications. Alternately, it can dissolve over time, aided by intrinsic fibrinolytic mechanisms. On other occasions, the thrombus may organize, a process characterized by ingrowth of smooth muscle cells, fibroblasts, and endothelium.

HOW IS LEFT VENTRICULAR THROMBOSIS DIAGNOSED?

2. What is the best imaging test for detecting a thrombus?

• Transesophageal echocardiography
• Transthoracic echocardiography
• Cardiac magnetic resonance imaging (MRI) without gadolinium contrast
• Cardiac MRI with gadolinium contrast

Evaluation of left ventricular function after acute MI carries a class I indication (ie, it should be performed).¹⁸ 

Echocardiography is commonly used, and it has a 60% sensitivity to detect a thrombus.¹⁹ In patients with poorer transthoracic echocardiographic windows, contrast can be used to better delineate the left ventricular cavity and show the thrombus. Transesophageal echocardiography is seldom useful, as the left ventricular apex is foreshortened and in the far field.

A left ventricular thrombus is confirmed if an echo-dense mass with well-demarcated margins distinct from the endocardium is seen throughout the cardiac cycle. It should be evident in at least two different views (apical and short-axis) and should be adjacent to a hypokinetic or akinetic left ventricular wall. False-positive findings can occur due to misidentified false tendons, papillary muscles, and trabeculae.

Cardiac MRI with late gadolinium enhancement is now the gold standard for diagnostic imaging, as it accurately characterizes the shape, size, and location of the thrombus (Figure 3). Gadolinium contrast increases the enhancement of the ventricular cavity, thus allowing easy detection of thrombus, which appears dark. Cardiac MRI with delayed enhancement has 88% to 91% sensitivity and 99% specificity to detect left ventricular thrombosis.^20,21 However, compared with echocardiography, routine cardiac MRI is time-intensive, costly, and not routinely available. As a result, it should be performed only in patients with poor acoustic windows and a high clinical suspicion of left ventricular thrombosis.

Delayed-contrast cardiac computed tomography can be used to identify left ventricular thrombosis, using absence of contrast uptake. The need to use contrast is a disadvantage, but computed tomography can be an alternative in patients with contraindications to cardiac MRI.

WHAT COMPLICATIONS ARISE FROM LEFT VENTRICULAR THROMBOSIS?

The most feared complication of left ventricular thrombosis is thromboembolism. Cardioembolic stroke is generally severe, prone to early and long-term recurrence, and associated with a higher death rate than noncardioembolic ischemic stroke.^22,23 Thrombi associated with thromboembolism are often acute and mobile rather than organized and immobile.²⁴ They may embolize to the brain,  spleen, kidneys, and bowel.²⁵ In a meta-analysis of 11 studies, the pooled odds ratio for risk of embolization was 5.45 (95% confidence interval [CI] 3.02–9.83) with left ventricular thrombi vs without.²⁶ Before systemic thrombolysis and antiplatelet therapy became available, stroke rates ranged from 1.5% to 10%.^27–29

In a meta-analysis of 22 studies from 1978 to 2004, the incidence of ischemic stroke after MI during hospitalization was around 11.1 per 1,000 MIs.³⁰ This study found that anterior MI was associated with a higher risk of stroke, but reported no difference in the incidence of stroke with percutaneous coronary intervention, systemic thrombolysis, or no reperfusion.

In a large prospective cohort study of 2,160 patients,³¹ 259 (12%) had a stroke after MI. In multivariable analysis, age, diabetes, and previous stroke were predictors of stroke after MI. This study reported significantly fewer strokes in patients who underwent percutaneous coronary intervention than with other or no reperfusion therapies.³¹

ANTICOAGULATION TREATMENT

3. How would you treat a patient who has a drug-eluting stent in the left anterior descending artery and a new diagnosis of left ventricular thrombosis?

• Warfarin
• Aspirin and clopidogrel
• Aspirin, clopidogrel, and warfarin
• Aspirin and warfarin

The management of left ventricular thrombosis has been summarized in guidelines from the American College of Chest Physicians (ACCP) in 2012,³² and from the American College of Cardiology/American Heart Association in 2013,¹⁸ which recommend anticoagulation for at least 3 months, or indefinitely if bleeding risk is low, for all patients developing a left ventricular thrombus.

For patients with acute MI and left ventricular thrombosis, the ACCP guidelines recommend warfarin with a target international normalized ratio of 2.0 to 3.0 plus dual antiplatelet therapy (eg, aspirin plus clopidogrel)  for 3 months, after which warfarin is discontinued but dual antiplatelet therapy is continued for up to 12 months.³²

The European Society of Cardiology guidelines³³ recommend 6 months of anticoagulation. However, if the patient is receiving dual antiplatelet therapy, they recommend repeated imaging of the left ventricle after 3 months of anticoagulation, which may allow for earlier discontinuation of anticoagulation if the thrombus has resolved and apical wall motion has recovered. Therefore, most experts recommend 3 months of anticoagulation when used in combination with dual antiplatelet therapy and repeating echocardiography at 3 months to safely discontinue anticoagulation. The best answer to the question posed here is aspirin, clopidogrel, and warfarin.

Decisions about antithrombotic therapy may also depend on stent type and the patient’s bleeding risk. With bare-metal stents, dual antiplatelet therapy along with anticoagulation should be used for 1 month, after which anticoagulation should be used with a single antiplatelet agent for another 2 months; after this, the anticoagulant can be discontinued and dual antiplatelet therapy can be resumed for a total of 12 months. Newer anticoagulants such as rivaroxaban, dabigatran, edoxaban, and apixaban may also have a role, but they have not yet been studied for this indication.

Surgical thrombectomy is rarely considered now, given the known efficacy of anticoagulants in dissolving the thrombus. It was done in the past for large, mobile, or protruding left ventricular thrombi, which have a higher potential for embolization.³⁴ Currently, it can be done under very special circumstances, such as before placement of a left ventricular assist device or if the thrombus is large, to prevent embolism.^35,36

BLEEDING COMPLICATIONS WITH TRIPLE ANTITHROMBOTIC THERAPY

After stent placement, almost all patients need to be on dual antiplatelet therapy for a specified duration depending on the type and generation of stent used. Such patients end up on “triple” antithrombotic therapy (two antiplatelet drugs plus an anticoagulant), which poses a high risk of bleeding.³⁷ Consideration needs to be given to the risks of stroke, stent thrombosis, and major bleeding when selecting the antithrombotic regimen.³⁸ Triple antithrombotic therapy has been associated with a risk of fatal and nonfatal bleeding of 4% to 16% when used for indications such as atrial fibrillation.^39–41

Risks of triple antithrombotic therapy (aspirin 80–100 mg, clopidogrel 75 mg, and warfarin) were compared with those of clopidogrel plus warfarin in the What Is the Optimal Antiplatelet and Anticoagulant therapy in Patients With Oral Anticoagulation and Coronary Stenting Trial,³⁷ which reported a significantly lower risk of  major and minor bleeding with clopidogrel-plus-warfarin therapy than with triple antithrombotic therapy, 14.3% vs 31.7% (hazard ratio 0.40, 95% CI 0.28–0.58, P < .0001).

Additionally, the increased risk of major and minor bleeding associated with triple antithrombotic therapy has been confirmed in many observational studies; other studies found a trend toward lower risk with triple therapy, but this was not statistically significant (Table 2).^{38,40,42–55} A large multicenter European trial is being conducted to compare dual antiplatelet therapy vs triple antithrombotic therapy in patients with left ventricular thrombosis.

CASE FOLLOW-UP

Our patient was started on warfarin, clopidogrel 75 mg, and aspirin 75 mg at the time of discharge. He was continued on warfarin for 3 months, at which time a follow-up echocardiogram showed no thrombus in the left ventricle. Warfarin was discontinued, and he had no thromboembolic complications.

TAKE-HOME POINTS

Left ventricular thrombosis after an acute MI is very important to detect, as it can lead to serious complications through arterial embolism.

The incidence of left ventricular thrombosis has declined significantly with the use of percutaneous coronary intervention. However, it may still occur in a small number of patients with larger infarcts owing to delay in revascularization or proximal (left main or left anterior descending) occlusions with larger infarct size.

Echocardiography, which is routinely performed after acute MI to assess myocardial function, uncovers most left ventricular thrombi. In high-risk cases, MRI with late gadolinium enhancement can increase the diagnostic yield.

Anticoagulation with warfarin is recommended for at least 3 months. Post-MI patients undergoing stent implantation may need triple antithrombotic therapy, which, however, increases the bleeding risk significantly. Large randomized trials are needed to guide physicians in risk stratification of such patients.

A 62-year-old man with hypertension, type 2 diabetes mellitus, and hypercholesterolemia presented to the emergency department with substernal chest pain that started about 15 hours earlier while he was at rest watching television.

On examination, his pulse was 92 beats per minute and regular, his blood pressure was 160/88 mm Hg, and he had no evidence of jugular venous distention or pedal edema. Lung examination was positive for bibasilar crackles.

Electrocardiography revealed Q waves with ST elevation in leads I, aVL, V₄, V₅, and V₆ with reciprocal ST depression in leads II, III, and aVF.

His troponin T level on presentation was markedly elevated.

Image

He underwent heart catheterization and was found to have 100% occlusion of the proximal left anterior descending artery. He underwent successful percutaneous coronary intervention with placement of a drug-eluting stent, and afterward had grade 3 flow on the Thrombolysis in Myocardial Infarction (TIMI) scale.

Echocardiography the next day revealed a mobile echo-dense mass in the left ventricular apex (Figure 1) and a left ventricular ejection fraction of 35%.

THE INCIDENCE OF LEFT VENTRICULAR THROMBOSIS IN ACUTE MI

1. What is the incidence of left ventricular thrombosis after acute myocardial infarction (MI), now that primary percutaneous coronary intervention is common?

• 0.1%
• 2%
• 20%
• 40%

Left ventricular thrombosis is a serious complication of acute MI that can cause systemic thromboembolism, including stroke.¹ Before thrombolytic therapy was available, this complication occurred in 20% to 60% of patients with acute MI.^2,3 But early reperfusion strategies, anticoagulation for the first 48 hours, and dual antiplatelet therapy have reduced the incidence of this complication significantly.

In the thrombolytic era, the incidence of left ventricular thrombosis was 5.1% in the Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico (GISSI) 3 study, which had 8,326 patients. A subset of patients who had an anterior MI had almost double the incidence (11.5%).³

Image

The incidence has further declined with the advent of primary percutaneous coronary intervention, likely thanks to enhanced myocardial salvage, and now ranges from 2.5% to 15% (Table 1).^4–11 The largest observational study, with 2,911 patients undergoing percutaneous coronary intervention, reported an incidence of 2.5% within 3 to 5 days of the MI.⁷ At our center, the incidence was found to be even lower, 1.8% in 1,700 patients presenting with ST-elevation MI undergoing primary percutaneous coronary intervention. Hence, of the answers to the question above, 2% would be closest.

Large infarct size with a low left ventricular ejection fraction (< 40%), anterior wall MI, hypertension, and delay in time from symptom onset to intervention were independent predictors of left ventricular thrombus formation in most studies.^7,12 The risk is highest during the first 2 weeks after MI, and thrombosis almost never occurs more than 3 months after the index event.^5,13–16

WHAT IS THE PATHOGENESIS OF LEFT VENTRICULAR THROMBOSIS?

A large transmural infarct results in loss of contractile function, which causes stagnation and pooling of blood adjacent to the infarcted ventricular segment. In addition, endocardial injury exposes tissue factor, which then initiates the coagulation cascade. To make matters worse, MI results in a hypercoagulable state through unclear mechanisms, which completes the Virchow triad for thrombus formation. Elevations of D-dimer, fibrinogen, anticardiolipin antibodies (IgM and IgG), and tissue factor have also been reported after acute MI.¹⁷

Thrombus formation begins with platelet aggregation at the site of endocardial damage, forming a platelet plug, followed by activation of clotting factors. These thrombi are referred to as “mural,” as they adhere to the chamber wall (endocardium). They are composed of fibrin and entrapped red and white blood cells (Figure 2).

The natural course of thrombus evolution is established but variable. A left ventricular thrombus may dislodge and embolize, resulting in stroke or other thromboembolic complications. Alternately, it can dissolve over time, aided by intrinsic fibrinolytic mechanisms. On other occasions, the thrombus may organize, a process characterized by ingrowth of smooth muscle cells, fibroblasts, and endothelium.

HOW IS LEFT VENTRICULAR THROMBOSIS DIAGNOSED?

2. What is the best imaging test for detecting a thrombus?

• Transesophageal echocardiography
• Transthoracic echocardiography
• Cardiac magnetic resonance imaging (MRI) without gadolinium contrast
• Cardiac MRI with gadolinium contrast

Evaluation of left ventricular function after acute MI carries a class I indication (ie, it should be performed).¹⁸ 

Echocardiography is commonly used, and it has a 60% sensitivity to detect a thrombus.¹⁹ In patients with poorer transthoracic echocardiographic windows, contrast can be used to better delineate the left ventricular cavity and show the thrombus. Transesophageal echocardiography is seldom useful, as the left ventricular apex is foreshortened and in the far field.

A left ventricular thrombus is confirmed if an echo-dense mass with well-demarcated margins distinct from the endocardium is seen throughout the cardiac cycle. It should be evident in at least two different views (apical and short-axis) and should be adjacent to a hypokinetic or akinetic left ventricular wall. False-positive findings can occur due to misidentified false tendons, papillary muscles, and trabeculae.

Cardiac MRI with late gadolinium enhancement is now the gold standard for diagnostic imaging, as it accurately characterizes the shape, size, and location of the thrombus (Figure 3). Gadolinium contrast increases the enhancement of the ventricular cavity, thus allowing easy detection of thrombus, which appears dark. Cardiac MRI with delayed enhancement has 88% to 91% sensitivity and 99% specificity to detect left ventricular thrombosis.^20,21 However, compared with echocardiography, routine cardiac MRI is time-intensive, costly, and not routinely available. As a result, it should be performed only in patients with poor acoustic windows and a high clinical suspicion of left ventricular thrombosis.

Delayed-contrast cardiac computed tomography can be used to identify left ventricular thrombosis, using absence of contrast uptake. The need to use contrast is a disadvantage, but computed tomography can be an alternative in patients with contraindications to cardiac MRI.

WHAT COMPLICATIONS ARISE FROM LEFT VENTRICULAR THROMBOSIS?

The most feared complication of left ventricular thrombosis is thromboembolism. Cardioembolic stroke is generally severe, prone to early and long-term recurrence, and associated with a higher death rate than noncardioembolic ischemic stroke.^22,23 Thrombi associated with thromboembolism are often acute and mobile rather than organized and immobile.²⁴ They may embolize to the brain,  spleen, kidneys, and bowel.²⁵ In a meta-analysis of 11 studies, the pooled odds ratio for risk of embolization was 5.45 (95% confidence interval [CI] 3.02–9.83) with left ventricular thrombi vs without.²⁶ Before systemic thrombolysis and antiplatelet therapy became available, stroke rates ranged from 1.5% to 10%.^27–29

In a meta-analysis of 22 studies from 1978 to 2004, the incidence of ischemic stroke after MI during hospitalization was around 11.1 per 1,000 MIs.³⁰ This study found that anterior MI was associated with a higher risk of stroke, but reported no difference in the incidence of stroke with percutaneous coronary intervention, systemic thrombolysis, or no reperfusion.

In a large prospective cohort study of 2,160 patients,³¹ 259 (12%) had a stroke after MI. In multivariable analysis, age, diabetes, and previous stroke were predictors of stroke after MI. This study reported significantly fewer strokes in patients who underwent percutaneous coronary intervention than with other or no reperfusion therapies.³¹

ANTICOAGULATION TREATMENT

3. How would you treat a patient who has a drug-eluting stent in the left anterior descending artery and a new diagnosis of left ventricular thrombosis?

• Warfarin
• Aspirin and clopidogrel
• Aspirin, clopidogrel, and warfarin
• Aspirin and warfarin

The management of left ventricular thrombosis has been summarized in guidelines from the American College of Chest Physicians (ACCP) in 2012,³² and from the American College of Cardiology/American Heart Association in 2013,¹⁸ which recommend anticoagulation for at least 3 months, or indefinitely if bleeding risk is low, for all patients developing a left ventricular thrombus.

For patients with acute MI and left ventricular thrombosis, the ACCP guidelines recommend warfarin with a target international normalized ratio of 2.0 to 3.0 plus dual antiplatelet therapy (eg, aspirin plus clopidogrel)  for 3 months, after which warfarin is discontinued but dual antiplatelet therapy is continued for up to 12 months.³²

The European Society of Cardiology guidelines³³ recommend 6 months of anticoagulation. However, if the patient is receiving dual antiplatelet therapy, they recommend repeated imaging of the left ventricle after 3 months of anticoagulation, which may allow for earlier discontinuation of anticoagulation if the thrombus has resolved and apical wall motion has recovered. Therefore, most experts recommend 3 months of anticoagulation when used in combination with dual antiplatelet therapy and repeating echocardiography at 3 months to safely discontinue anticoagulation. The best answer to the question posed here is aspirin, clopidogrel, and warfarin.

Decisions about antithrombotic therapy may also depend on stent type and the patient’s bleeding risk. With bare-metal stents, dual antiplatelet therapy along with anticoagulation should be used for 1 month, after which anticoagulation should be used with a single antiplatelet agent for another 2 months; after this, the anticoagulant can be discontinued and dual antiplatelet therapy can be resumed for a total of 12 months. Newer anticoagulants such as rivaroxaban, dabigatran, edoxaban, and apixaban may also have a role, but they have not yet been studied for this indication.

Surgical thrombectomy is rarely considered now, given the known efficacy of anticoagulants in dissolving the thrombus. It was done in the past for large, mobile, or protruding left ventricular thrombi, which have a higher potential for embolization.³⁴ Currently, it can be done under very special circumstances, such as before placement of a left ventricular assist device or if the thrombus is large, to prevent embolism.^35,36

BLEEDING COMPLICATIONS WITH TRIPLE ANTITHROMBOTIC THERAPY

After stent placement, almost all patients need to be on dual antiplatelet therapy for a specified duration depending on the type and generation of stent used. Such patients end up on “triple” antithrombotic therapy (two antiplatelet drugs plus an anticoagulant), which poses a high risk of bleeding.³⁷ Consideration needs to be given to the risks of stroke, stent thrombosis, and major bleeding when selecting the antithrombotic regimen.³⁸ Triple antithrombotic therapy has been associated with a risk of fatal and nonfatal bleeding of 4% to 16% when used for indications such as atrial fibrillation.^39–41

Risks of triple antithrombotic therapy (aspirin 80–100 mg, clopidogrel 75 mg, and warfarin) were compared with those of clopidogrel plus warfarin in the What Is the Optimal Antiplatelet and Anticoagulant therapy in Patients With Oral Anticoagulation and Coronary Stenting Trial,³⁷ which reported a significantly lower risk of  major and minor bleeding with clopidogrel-plus-warfarin therapy than with triple antithrombotic therapy, 14.3% vs 31.7% (hazard ratio 0.40, 95% CI 0.28–0.58, P < .0001).

Additionally, the increased risk of major and minor bleeding associated with triple antithrombotic therapy has been confirmed in many observational studies; other studies found a trend toward lower risk with triple therapy, but this was not statistically significant (Table 2).^{38,40,42–55} A large multicenter European trial is being conducted to compare dual antiplatelet therapy vs triple antithrombotic therapy in patients with left ventricular thrombosis.

CASE FOLLOW-UP

Our patient was started on warfarin, clopidogrel 75 mg, and aspirin 75 mg at the time of discharge. He was continued on warfarin for 3 months, at which time a follow-up echocardiogram showed no thrombus in the left ventricle. Warfarin was discontinued, and he had no thromboembolic complications.

TAKE-HOME POINTS

Left ventricular thrombosis after an acute MI is very important to detect, as it can lead to serious complications through arterial embolism.

The incidence of left ventricular thrombosis has declined significantly with the use of percutaneous coronary intervention. However, it may still occur in a small number of patients with larger infarcts owing to delay in revascularization or proximal (left main or left anterior descending) occlusions with larger infarct size.

Echocardiography, which is routinely performed after acute MI to assess myocardial function, uncovers most left ventricular thrombi. In high-risk cases, MRI with late gadolinium enhancement can increase the diagnostic yield.

Anticoagulation with warfarin is recommended for at least 3 months. Post-MI patients undergoing stent implantation may need triple antithrombotic therapy, which, however, increases the bleeding risk significantly. Large randomized trials are needed to guide physicians in risk stratification of such patients.

A 62-year-old man with hypertension, type 2 diabetes mellitus, and hypercholesterolemia presented to the emergency department with substernal chest pain that started about 15 hours earlier while he was at rest watching television.

On examination, his pulse was 92 beats per minute and regular, his blood pressure was 160/88 mm Hg, and he had no evidence of jugular venous distention or pedal edema. Lung examination was positive for bibasilar crackles.

Electrocardiography revealed Q waves with ST elevation in leads I, aVL, V₄, V₅, and V₆ with reciprocal ST depression in leads II, III, and aVF.

His troponin T level on presentation was markedly elevated.

Image

He underwent heart catheterization and was found to have 100% occlusion of the proximal left anterior descending artery. He underwent successful percutaneous coronary intervention with placement of a drug-eluting stent, and afterward had grade 3 flow on the Thrombolysis in Myocardial Infarction (TIMI) scale.

Echocardiography the next day revealed a mobile echo-dense mass in the left ventricular apex (Figure 1) and a left ventricular ejection fraction of 35%.

THE INCIDENCE OF LEFT VENTRICULAR THROMBOSIS IN ACUTE MI

1. What is the incidence of left ventricular thrombosis after acute myocardial infarction (MI), now that primary percutaneous coronary intervention is common?

• 0.1%
• 2%
• 20%
• 40%

Left ventricular thrombosis is a serious complication of acute MI that can cause systemic thromboembolism, including stroke.¹ Before thrombolytic therapy was available, this complication occurred in 20% to 60% of patients with acute MI.^2,3 But early reperfusion strategies, anticoagulation for the first 48 hours, and dual antiplatelet therapy have reduced the incidence of this complication significantly.

In the thrombolytic era, the incidence of left ventricular thrombosis was 5.1% in the Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico (GISSI) 3 study, which had 8,326 patients. A subset of patients who had an anterior MI had almost double the incidence (11.5%).³

Image

The incidence has further declined with the advent of primary percutaneous coronary intervention, likely thanks to enhanced myocardial salvage, and now ranges from 2.5% to 15% (Table 1).^4–11 The largest observational study, with 2,911 patients undergoing percutaneous coronary intervention, reported an incidence of 2.5% within 3 to 5 days of the MI.⁷ At our center, the incidence was found to be even lower, 1.8% in 1,700 patients presenting with ST-elevation MI undergoing primary percutaneous coronary intervention. Hence, of the answers to the question above, 2% would be closest.

Large infarct size with a low left ventricular ejection fraction (< 40%), anterior wall MI, hypertension, and delay in time from symptom onset to intervention were independent predictors of left ventricular thrombus formation in most studies.^7,12 The risk is highest during the first 2 weeks after MI, and thrombosis almost never occurs more than 3 months after the index event.^5,13–16

WHAT IS THE PATHOGENESIS OF LEFT VENTRICULAR THROMBOSIS?

A large transmural infarct results in loss of contractile function, which causes stagnation and pooling of blood adjacent to the infarcted ventricular segment. In addition, endocardial injury exposes tissue factor, which then initiates the coagulation cascade. To make matters worse, MI results in a hypercoagulable state through unclear mechanisms, which completes the Virchow triad for thrombus formation. Elevations of D-dimer, fibrinogen, anticardiolipin antibodies (IgM and IgG), and tissue factor have also been reported after acute MI.¹⁷

Thrombus formation begins with platelet aggregation at the site of endocardial damage, forming a platelet plug, followed by activation of clotting factors. These thrombi are referred to as “mural,” as they adhere to the chamber wall (endocardium). They are composed of fibrin and entrapped red and white blood cells (Figure 2).

The natural course of thrombus evolution is established but variable. A left ventricular thrombus may dislodge and embolize, resulting in stroke or other thromboembolic complications. Alternately, it can dissolve over time, aided by intrinsic fibrinolytic mechanisms. On other occasions, the thrombus may organize, a process characterized by ingrowth of smooth muscle cells, fibroblasts, and endothelium.

HOW IS LEFT VENTRICULAR THROMBOSIS DIAGNOSED?

2. What is the best imaging test for detecting a thrombus?

• Transesophageal echocardiography
• Transthoracic echocardiography
• Cardiac magnetic resonance imaging (MRI) without gadolinium contrast
• Cardiac MRI with gadolinium contrast

Evaluation of left ventricular function after acute MI carries a class I indication (ie, it should be performed).¹⁸ 

Echocardiography is commonly used, and it has a 60% sensitivity to detect a thrombus.¹⁹ In patients with poorer transthoracic echocardiographic windows, contrast can be used to better delineate the left ventricular cavity and show the thrombus. Transesophageal echocardiography is seldom useful, as the left ventricular apex is foreshortened and in the far field.

A left ventricular thrombus is confirmed if an echo-dense mass with well-demarcated margins distinct from the endocardium is seen throughout the cardiac cycle. It should be evident in at least two different views (apical and short-axis) and should be adjacent to a hypokinetic or akinetic left ventricular wall. False-positive findings can occur due to misidentified false tendons, papillary muscles, and trabeculae.

Cardiac MRI with late gadolinium enhancement is now the gold standard for diagnostic imaging, as it accurately characterizes the shape, size, and location of the thrombus (Figure 3). Gadolinium contrast increases the enhancement of the ventricular cavity, thus allowing easy detection of thrombus, which appears dark. Cardiac MRI with delayed enhancement has 88% to 91% sensitivity and 99% specificity to detect left ventricular thrombosis.^20,21 However, compared with echocardiography, routine cardiac MRI is time-intensive, costly, and not routinely available. As a result, it should be performed only in patients with poor acoustic windows and a high clinical suspicion of left ventricular thrombosis.

Delayed-contrast cardiac computed tomography can be used to identify left ventricular thrombosis, using absence of contrast uptake. The need to use contrast is a disadvantage, but computed tomography can be an alternative in patients with contraindications to cardiac MRI.

WHAT COMPLICATIONS ARISE FROM LEFT VENTRICULAR THROMBOSIS?

The most feared complication of left ventricular thrombosis is thromboembolism. Cardioembolic stroke is generally severe, prone to early and long-term recurrence, and associated with a higher death rate than noncardioembolic ischemic stroke.^22,23 Thrombi associated with thromboembolism are often acute and mobile rather than organized and immobile.²⁴ They may embolize to the brain,  spleen, kidneys, and bowel.²⁵ In a meta-analysis of 11 studies, the pooled odds ratio for risk of embolization was 5.45 (95% confidence interval [CI] 3.02–9.83) with left ventricular thrombi vs without.²⁶ Before systemic thrombolysis and antiplatelet therapy became available, stroke rates ranged from 1.5% to 10%.^27–29

In a meta-analysis of 22 studies from 1978 to 2004, the incidence of ischemic stroke after MI during hospitalization was around 11.1 per 1,000 MIs.³⁰ This study found that anterior MI was associated with a higher risk of stroke, but reported no difference in the incidence of stroke with percutaneous coronary intervention, systemic thrombolysis, or no reperfusion.

In a large prospective cohort study of 2,160 patients,³¹ 259 (12%) had a stroke after MI. In multivariable analysis, age, diabetes, and previous stroke were predictors of stroke after MI. This study reported significantly fewer strokes in patients who underwent percutaneous coronary intervention than with other or no reperfusion therapies.³¹

ANTICOAGULATION TREATMENT

3. How would you treat a patient who has a drug-eluting stent in the left anterior descending artery and a new diagnosis of left ventricular thrombosis?

• Warfarin
• Aspirin and clopidogrel
• Aspirin, clopidogrel, and warfarin
• Aspirin and warfarin

The management of left ventricular thrombosis has been summarized in guidelines from the American College of Chest Physicians (ACCP) in 2012,³² and from the American College of Cardiology/American Heart Association in 2013,¹⁸ which recommend anticoagulation for at least 3 months, or indefinitely if bleeding risk is low, for all patients developing a left ventricular thrombus.

For patients with acute MI and left ventricular thrombosis, the ACCP guidelines recommend warfarin with a target international normalized ratio of 2.0 to 3.0 plus dual antiplatelet therapy (eg, aspirin plus clopidogrel)  for 3 months, after which warfarin is discontinued but dual antiplatelet therapy is continued for up to 12 months.³²

The European Society of Cardiology guidelines³³ recommend 6 months of anticoagulation. However, if the patient is receiving dual antiplatelet therapy, they recommend repeated imaging of the left ventricle after 3 months of anticoagulation, which may allow for earlier discontinuation of anticoagulation if the thrombus has resolved and apical wall motion has recovered. Therefore, most experts recommend 3 months of anticoagulation when used in combination with dual antiplatelet therapy and repeating echocardiography at 3 months to safely discontinue anticoagulation. The best answer to the question posed here is aspirin, clopidogrel, and warfarin.

Decisions about antithrombotic therapy may also depend on stent type and the patient’s bleeding risk. With bare-metal stents, dual antiplatelet therapy along with anticoagulation should be used for 1 month, after which anticoagulation should be used with a single antiplatelet agent for another 2 months; after this, the anticoagulant can be discontinued and dual antiplatelet therapy can be resumed for a total of 12 months. Newer anticoagulants such as rivaroxaban, dabigatran, edoxaban, and apixaban may also have a role, but they have not yet been studied for this indication.

Surgical thrombectomy is rarely considered now, given the known efficacy of anticoagulants in dissolving the thrombus. It was done in the past for large, mobile, or protruding left ventricular thrombi, which have a higher potential for embolization.³⁴ Currently, it can be done under very special circumstances, such as before placement of a left ventricular assist device or if the thrombus is large, to prevent embolism.^35,36

BLEEDING COMPLICATIONS WITH TRIPLE ANTITHROMBOTIC THERAPY

After stent placement, almost all patients need to be on dual antiplatelet therapy for a specified duration depending on the type and generation of stent used. Such patients end up on “triple” antithrombotic therapy (two antiplatelet drugs plus an anticoagulant), which poses a high risk of bleeding.³⁷ Consideration needs to be given to the risks of stroke, stent thrombosis, and major bleeding when selecting the antithrombotic regimen.³⁸ Triple antithrombotic therapy has been associated with a risk of fatal and nonfatal bleeding of 4% to 16% when used for indications such as atrial fibrillation.^39–41

Risks of triple antithrombotic therapy (aspirin 80–100 mg, clopidogrel 75 mg, and warfarin) were compared with those of clopidogrel plus warfarin in the What Is the Optimal Antiplatelet and Anticoagulant therapy in Patients With Oral Anticoagulation and Coronary Stenting Trial,³⁷ which reported a significantly lower risk of  major and minor bleeding with clopidogrel-plus-warfarin therapy than with triple antithrombotic therapy, 14.3% vs 31.7% (hazard ratio 0.40, 95% CI 0.28–0.58, P < .0001).

Additionally, the increased risk of major and minor bleeding associated with triple antithrombotic therapy has been confirmed in many observational studies; other studies found a trend toward lower risk with triple therapy, but this was not statistically significant (Table 2).^{38,40,42–55} A large multicenter European trial is being conducted to compare dual antiplatelet therapy vs triple antithrombotic therapy in patients with left ventricular thrombosis.

CASE FOLLOW-UP

Our patient was started on warfarin, clopidogrel 75 mg, and aspirin 75 mg at the time of discharge. He was continued on warfarin for 3 months, at which time a follow-up echocardiogram showed no thrombus in the left ventricle. Warfarin was discontinued, and he had no thromboembolic complications.

TAKE-HOME POINTS

Left ventricular thrombosis after an acute MI is very important to detect, as it can lead to serious complications through arterial embolism.

The incidence of left ventricular thrombosis has declined significantly with the use of percutaneous coronary intervention. However, it may still occur in a small number of patients with larger infarcts owing to delay in revascularization or proximal (left main or left anterior descending) occlusions with larger infarct size.

Echocardiography, which is routinely performed after acute MI to assess myocardial function, uncovers most left ventricular thrombi. In high-risk cases, MRI with late gadolinium enhancement can increase the diagnostic yield.

Anticoagulation with warfarin is recommended for at least 3 months. Post-MI patients undergoing stent implantation may need triple antithrombotic therapy, which, however, increases the bleeding risk significantly. Large randomized trials are needed to guide physicians in risk stratification of such patients.

Low-grade esophageal dysplasia must be confirmed by a GI pathologist with a special interest in Barrett’s esophagus, one who deals with the problem on a daily basis and whom peers recognize as an expert in the field, according to a new expert review from the American Gastroenterological Association (Gastroenterology. doi: http://dx.doi.org/10.1053/j.gastro.2016.09.040).

In the absence of reliable biomarkers, it’s the best guarantee that low-grade dysplasia (LGD) is truly present. Overdiagnosis of early dysplasia is common, and it leads to mistreatment and uncertainty about study results, the AGA said.

aotto@frontlinemedcom.com

Low-grade esophageal dysplasia must be confirmed by a GI pathologist with a special interest in Barrett’s esophagus, one who deals with the problem on a daily basis and whom peers recognize as an expert in the field, according to a new expert review from the American Gastroenterological Association (Gastroenterology. doi: http://dx.doi.org/10.1053/j.gastro.2016.09.040).

In the absence of reliable biomarkers, it’s the best guarantee that low-grade dysplasia (LGD) is truly present. Overdiagnosis of early dysplasia is common, and it leads to mistreatment and uncertainty about study results, the AGA said.

aotto@frontlinemedcom.com

Low-grade esophageal dysplasia must be confirmed by a GI pathologist with a special interest in Barrett’s esophagus, one who deals with the problem on a daily basis and whom peers recognize as an expert in the field, according to a new expert review from the American Gastroenterological Association (Gastroenterology. doi: http://dx.doi.org/10.1053/j.gastro.2016.09.040).

In the absence of reliable biomarkers, it’s the best guarantee that low-grade dysplasia (LGD) is truly present. Overdiagnosis of early dysplasia is common, and it leads to mistreatment and uncertainty about study results, the AGA said.

aotto@frontlinemedcom.com

New gout treatment guidelines support the use of urate-lowering therapy, but find no place for treating patients to achieve any specific serum urate target – a dichotomy that has some rheumatologists scratching their heads.

Created by the American College of Physicians, the gout diagnosis and treatment guideline doesn’t recommend monitoring physiologic response to urate-lowering therapy or treating to specific serum urate target (Ann Int Med. 2016 Nov 1. doi: 10.7326/M16-0570). Instead, it says patients should be treated according to their symptomatic response – a recommendation that flies in the face of accepted clinical practice.

• Corticosteroids, NSAIDs, and colchicine are effective treatments to reduce pain in patients with acute gout.

• Lower doses of colchicine (1.2 mg, followed by 0.6 mg 1 hour later) are as effective as higher doses (1.2 mg, followed by 0.6 mg/hour for 6 hours) at reducing pain and are associated with fewer gastrointestinal adverse effects.

• Do not initiate long-term uric acid–lowering therapy in most patients after a first gout attack or in patients with infrequent attacks.

• Although evidence supports the benefits of using uric acid–lowering therapy for shorter durations to reduce gout flares, the benefits of long-term use in patients with a single or infrequent gout attacks have not been studied.

• Clinicians should discuss benefits, harms, costs, and individual preferences with patients before initiating uric acid–lowering therapy, including concomitant prophylaxis, in patients with recurrent gout attacks. (Grade: strong recommendation, moderate-quality evidence).

• Febuxostat (40 mg/day) and allopurinol (300 mg/day) are equally effective at decreasing serum urate levels, and prophylactic therapy with low-dose colchicine or low-dose NSAIDs reduces the risk for acute gout attacks in patients initiating urate-lowering therapy.

Allopurinol dosage, however, is one key point upon which the ACP and ACR guidelines are sharply divided. The ACR guideline calls for starting at low doses – 100 mg/day, and even lower in patients with kidney disease – with very slow upward titration, only if necessary, to 300 mg/day or more. Allopurinol is not without risk and should be used with caution, Dr. Neogi wrote in her commentary.

“Continuing a management strategy of starting allopurinol at an inappropriately high dose will perpetuate the problem of unnecessarily increasing flare risk, because this risk in the early treatment phase is directly proportional to the potency of the urate-lowering therapy used.”

However, allopurinol doses of 300 mg/day or less leave more than half of all patients undertreated, she said. This dilemma points up the difficulty with symptomatic treatment. Without checking urate levels, clinicians may be shooting blind when trying to dose appropriately.

She refuted any suggestion that the ACR guidelines were based on a lesser degree of evidence than the ACP document.

“The ACR uses a rigorous evidence-based method to develop treatment guidelines. It is inaccurate to say that ACR relies on lower-class evidence or expert opinion ‘to a large extent.’ In the absence of randomized controlled data, other peer-reviewed, available published data are used to formulate guidance, supported by the known biology.”

Current practices outlined in the ACR document are based on a thorough understanding of the biology of gout and how it progresses. Hard data on uric acid targets would greatly impact current therapeutic thinking. But in the meantime, there are patients to be treated, Dr. Neogi said.

“Of course, it would be ideal if we had randomized trial data to definitively provide insights, but we don’t have that right now. So does that mean that patients should suffer unnecessarily because we can’t use the remaining existing body of scientific knowledge to guide rational treatment decisions? What if funding agencies never fund such a study – should gout patients remain poorly managed? Should we abandon all scientific knowledge that isn’t randomized trial data and just not treat at all while waiting to see if a randomized trial will ever be funded and conducted?”

Dr. McLean sees the flip side of that coin.

“I think the effect of our guideline will be to help push the need for more explicit evidence in treat to target being the right way to go. But right now there is not enough evidence now to endorse that approach.”

Dr. McLean reports personal fees from Takeda Pharmaceuticals speakers’ bureau before 2015. Dr. Neogi had no financial disclosures.

msullivan@frontlinemedcom.com

New gout treatment guidelines support the use of urate-lowering therapy, but find no place for treating patients to achieve any specific serum urate target – a dichotomy that has some rheumatologists scratching their heads.

Created by the American College of Physicians, the gout diagnosis and treatment guideline doesn’t recommend monitoring physiologic response to urate-lowering therapy or treating to specific serum urate target (Ann Int Med. 2016 Nov 1. doi: 10.7326/M16-0570). Instead, it says patients should be treated according to their symptomatic response – a recommendation that flies in the face of accepted clinical practice.

• Corticosteroids, NSAIDs, and colchicine are effective treatments to reduce pain in patients with acute gout.

• Lower doses of colchicine (1.2 mg, followed by 0.6 mg 1 hour later) are as effective as higher doses (1.2 mg, followed by 0.6 mg/hour for 6 hours) at reducing pain and are associated with fewer gastrointestinal adverse effects.

• Do not initiate long-term uric acid–lowering therapy in most patients after a first gout attack or in patients with infrequent attacks.

• Although evidence supports the benefits of using uric acid–lowering therapy for shorter durations to reduce gout flares, the benefits of long-term use in patients with a single or infrequent gout attacks have not been studied.

• Clinicians should discuss benefits, harms, costs, and individual preferences with patients before initiating uric acid–lowering therapy, including concomitant prophylaxis, in patients with recurrent gout attacks. (Grade: strong recommendation, moderate-quality evidence).

• Febuxostat (40 mg/day) and allopurinol (300 mg/day) are equally effective at decreasing serum urate levels, and prophylactic therapy with low-dose colchicine or low-dose NSAIDs reduces the risk for acute gout attacks in patients initiating urate-lowering therapy.

Allopurinol dosage, however, is one key point upon which the ACP and ACR guidelines are sharply divided. The ACR guideline calls for starting at low doses – 100 mg/day, and even lower in patients with kidney disease – with very slow upward titration, only if necessary, to 300 mg/day or more. Allopurinol is not without risk and should be used with caution, Dr. Neogi wrote in her commentary.

“Continuing a management strategy of starting allopurinol at an inappropriately high dose will perpetuate the problem of unnecessarily increasing flare risk, because this risk in the early treatment phase is directly proportional to the potency of the urate-lowering therapy used.”

However, allopurinol doses of 300 mg/day or less leave more than half of all patients undertreated, she said. This dilemma points up the difficulty with symptomatic treatment. Without checking urate levels, clinicians may be shooting blind when trying to dose appropriately.

She refuted any suggestion that the ACR guidelines were based on a lesser degree of evidence than the ACP document.

“The ACR uses a rigorous evidence-based method to develop treatment guidelines. It is inaccurate to say that ACR relies on lower-class evidence or expert opinion ‘to a large extent.’ In the absence of randomized controlled data, other peer-reviewed, available published data are used to formulate guidance, supported by the known biology.”

Current practices outlined in the ACR document are based on a thorough understanding of the biology of gout and how it progresses. Hard data on uric acid targets would greatly impact current therapeutic thinking. But in the meantime, there are patients to be treated, Dr. Neogi said.

“Of course, it would be ideal if we had randomized trial data to definitively provide insights, but we don’t have that right now. So does that mean that patients should suffer unnecessarily because we can’t use the remaining existing body of scientific knowledge to guide rational treatment decisions? What if funding agencies never fund such a study – should gout patients remain poorly managed? Should we abandon all scientific knowledge that isn’t randomized trial data and just not treat at all while waiting to see if a randomized trial will ever be funded and conducted?”

Dr. McLean sees the flip side of that coin.

“I think the effect of our guideline will be to help push the need for more explicit evidence in treat to target being the right way to go. But right now there is not enough evidence now to endorse that approach.”

Dr. McLean reports personal fees from Takeda Pharmaceuticals speakers’ bureau before 2015. Dr. Neogi had no financial disclosures.

msullivan@frontlinemedcom.com

New gout treatment guidelines support the use of urate-lowering therapy, but find no place for treating patients to achieve any specific serum urate target – a dichotomy that has some rheumatologists scratching their heads.

Created by the American College of Physicians, the gout diagnosis and treatment guideline doesn’t recommend monitoring physiologic response to urate-lowering therapy or treating to specific serum urate target (Ann Int Med. 2016 Nov 1. doi: 10.7326/M16-0570). Instead, it says patients should be treated according to their symptomatic response – a recommendation that flies in the face of accepted clinical practice.

• Corticosteroids, NSAIDs, and colchicine are effective treatments to reduce pain in patients with acute gout.

• Lower doses of colchicine (1.2 mg, followed by 0.6 mg 1 hour later) are as effective as higher doses (1.2 mg, followed by 0.6 mg/hour for 6 hours) at reducing pain and are associated with fewer gastrointestinal adverse effects.

• Do not initiate long-term uric acid–lowering therapy in most patients after a first gout attack or in patients with infrequent attacks.

• Although evidence supports the benefits of using uric acid–lowering therapy for shorter durations to reduce gout flares, the benefits of long-term use in patients with a single or infrequent gout attacks have not been studied.

• Clinicians should discuss benefits, harms, costs, and individual preferences with patients before initiating uric acid–lowering therapy, including concomitant prophylaxis, in patients with recurrent gout attacks. (Grade: strong recommendation, moderate-quality evidence).

• Febuxostat (40 mg/day) and allopurinol (300 mg/day) are equally effective at decreasing serum urate levels, and prophylactic therapy with low-dose colchicine or low-dose NSAIDs reduces the risk for acute gout attacks in patients initiating urate-lowering therapy.

Allopurinol dosage, however, is one key point upon which the ACP and ACR guidelines are sharply divided. The ACR guideline calls for starting at low doses – 100 mg/day, and even lower in patients with kidney disease – with very slow upward titration, only if necessary, to 300 mg/day or more. Allopurinol is not without risk and should be used with caution, Dr. Neogi wrote in her commentary.

“Continuing a management strategy of starting allopurinol at an inappropriately high dose will perpetuate the problem of unnecessarily increasing flare risk, because this risk in the early treatment phase is directly proportional to the potency of the urate-lowering therapy used.”

However, allopurinol doses of 300 mg/day or less leave more than half of all patients undertreated, she said. This dilemma points up the difficulty with symptomatic treatment. Without checking urate levels, clinicians may be shooting blind when trying to dose appropriately.

She refuted any suggestion that the ACR guidelines were based on a lesser degree of evidence than the ACP document.

“The ACR uses a rigorous evidence-based method to develop treatment guidelines. It is inaccurate to say that ACR relies on lower-class evidence or expert opinion ‘to a large extent.’ In the absence of randomized controlled data, other peer-reviewed, available published data are used to formulate guidance, supported by the known biology.”

Current practices outlined in the ACR document are based on a thorough understanding of the biology of gout and how it progresses. Hard data on uric acid targets would greatly impact current therapeutic thinking. But in the meantime, there are patients to be treated, Dr. Neogi said.

“Of course, it would be ideal if we had randomized trial data to definitively provide insights, but we don’t have that right now. So does that mean that patients should suffer unnecessarily because we can’t use the remaining existing body of scientific knowledge to guide rational treatment decisions? What if funding agencies never fund such a study – should gout patients remain poorly managed? Should we abandon all scientific knowledge that isn’t randomized trial data and just not treat at all while waiting to see if a randomized trial will ever be funded and conducted?”

Dr. McLean sees the flip side of that coin.

“I think the effect of our guideline will be to help push the need for more explicit evidence in treat to target being the right way to go. But right now there is not enough evidence now to endorse that approach.”

Dr. McLean reports personal fees from Takeda Pharmaceuticals speakers’ bureau before 2015. Dr. Neogi had no financial disclosures.

msullivan@frontlinemedcom.com

MONTREAL  – Three-fifths of pediatric liver-transplant recipients who were doing well enough to attempt weaning from their immunosuppression regimen succeeded in getting off immunosuppression and staying off for more than a year. In the process, they also significantly improved their health-related quality of life.

“Health-related quality of life domains associated with social interactions, worry, and medications improved” in pediatric liver recipients who had undergone immunosuppression withdrawal, Saeed Mohammad, MD, said at the World Congress of Pediatric Gastroenterology, Hepatology and Nutrition.

Patients who succeeded in staying off immunosuppressant drugs for at least 2 years after they first began ratcheting down their regimen showed better quality of life scores compared with their scores at baseline, and also compared with the scores of other pediatric liver transplant patients who unsuccessfully tried coming off immunosuppression.

Not every pediatric liver transplant patient should attempt withdrawing immunosuppression, cautioned Dr. Mohammad, a pediatric gastroenterologist at Northwestern University in Chicago. “To be successful withdrawal of immunosuppression needs to be in selected patients; not every patient is a good candidate.”

The Immunosuppression Withdrawal for Stable Pediatric Liver Transplant Recipients (iWITH) study ran at 11 U.S. center and one center in Toronto during October 2012 through June 2014. Pediatric liver transplant recipients were eligible to start a 9-10 month graduated withdrawal from their immunosuppression regimen if they met several criteria of stability including no rejection episode over at least the prior 12 months, normal laboratory-test results, no autoimmune disease and no problems detected in a liver biopsy. The prospective study enrolled 88 patients who averaged 10 years old. Patients underwent comprehensive examinations and laboratory testing at baseline and again  several times during the subsequent 2 years including assessment of several quality of life measures.

During follow-up, 35 of the 88 patients (40%) developed symptoms of rejection and had to go back on immunosuppression. Most of these patients developed their rejection symptoms early during immunosuppression weaning, but a few patients failed later including one patient who failed 22 months after starting immunosuppression withdrawal, Dr. Mohammad said. Researchers from the iWITH study first reported these results at the American Transplant Congress in June 2016.

The quality of life findings reported by Dr. Mohammad came from assessments at baseline, after 12 months, and after 24 months, and included 30 of the patients who resumed immunosuppression and 48 patients who remained off immunosuppression for 2 years. All of these 78 patients had relatively robust quality of life profiles at baseline. Their scores for both physical and social subscales as well as for total score were significantly superior to the average scores for a large number of primarily U.S. pediatric liver transplant patients in the SPLIT database. Dr. Mohammad called the patients who attempted immunosuppression discontinuation as the “creme de la creme” of pediatric liver transplant patients in terms of their clinical status.

Analysis of scores after 2 years compared with baseline showed statistically significant improvements among patients who stayed off immunosuppression for the domains of social function, treatment attitudes and compliance, communication, and worry. A comparison of changes in quality of life scores from baseline to 2 years showed that patients who stayed off immunosuppression had improvements in several of their scores while patients who went back onto immunosuppression had on average a small deterioration of their scores.
Dr. Mohammad had no disclosures.

mzoler@frontlinemedcom.com
On Twitter @mitchelzoler

MONTREAL  – Three-fifths of pediatric liver-transplant recipients who were doing well enough to attempt weaning from their immunosuppression regimen succeeded in getting off immunosuppression and staying off for more than a year. In the process, they also significantly improved their health-related quality of life.

“Health-related quality of life domains associated with social interactions, worry, and medications improved” in pediatric liver recipients who had undergone immunosuppression withdrawal, Saeed Mohammad, MD, said at the World Congress of Pediatric Gastroenterology, Hepatology and Nutrition.

Patients who succeeded in staying off immunosuppressant drugs for at least 2 years after they first began ratcheting down their regimen showed better quality of life scores compared with their scores at baseline, and also compared with the scores of other pediatric liver transplant patients who unsuccessfully tried coming off immunosuppression.

Not every pediatric liver transplant patient should attempt withdrawing immunosuppression, cautioned Dr. Mohammad, a pediatric gastroenterologist at Northwestern University in Chicago. “To be successful withdrawal of immunosuppression needs to be in selected patients; not every patient is a good candidate.”

The Immunosuppression Withdrawal for Stable Pediatric Liver Transplant Recipients (iWITH) study ran at 11 U.S. center and one center in Toronto during October 2012 through June 2014. Pediatric liver transplant recipients were eligible to start a 9-10 month graduated withdrawal from their immunosuppression regimen if they met several criteria of stability including no rejection episode over at least the prior 12 months, normal laboratory-test results, no autoimmune disease and no problems detected in a liver biopsy. The prospective study enrolled 88 patients who averaged 10 years old. Patients underwent comprehensive examinations and laboratory testing at baseline and again  several times during the subsequent 2 years including assessment of several quality of life measures.

During follow-up, 35 of the 88 patients (40%) developed symptoms of rejection and had to go back on immunosuppression. Most of these patients developed their rejection symptoms early during immunosuppression weaning, but a few patients failed later including one patient who failed 22 months after starting immunosuppression withdrawal, Dr. Mohammad said. Researchers from the iWITH study first reported these results at the American Transplant Congress in June 2016.

The quality of life findings reported by Dr. Mohammad came from assessments at baseline, after 12 months, and after 24 months, and included 30 of the patients who resumed immunosuppression and 48 patients who remained off immunosuppression for 2 years. All of these 78 patients had relatively robust quality of life profiles at baseline. Their scores for both physical and social subscales as well as for total score were significantly superior to the average scores for a large number of primarily U.S. pediatric liver transplant patients in the SPLIT database. Dr. Mohammad called the patients who attempted immunosuppression discontinuation as the “creme de la creme” of pediatric liver transplant patients in terms of their clinical status.

Analysis of scores after 2 years compared with baseline showed statistically significant improvements among patients who stayed off immunosuppression for the domains of social function, treatment attitudes and compliance, communication, and worry. A comparison of changes in quality of life scores from baseline to 2 years showed that patients who stayed off immunosuppression had improvements in several of their scores while patients who went back onto immunosuppression had on average a small deterioration of their scores.
Dr. Mohammad had no disclosures.

mzoler@frontlinemedcom.com
On Twitter @mitchelzoler

MONTREAL  – Three-fifths of pediatric liver-transplant recipients who were doing well enough to attempt weaning from their immunosuppression regimen succeeded in getting off immunosuppression and staying off for more than a year. In the process, they also significantly improved their health-related quality of life.

“Health-related quality of life domains associated with social interactions, worry, and medications improved” in pediatric liver recipients who had undergone immunosuppression withdrawal, Saeed Mohammad, MD, said at the World Congress of Pediatric Gastroenterology, Hepatology and Nutrition.

Patients who succeeded in staying off immunosuppressant drugs for at least 2 years after they first began ratcheting down their regimen showed better quality of life scores compared with their scores at baseline, and also compared with the scores of other pediatric liver transplant patients who unsuccessfully tried coming off immunosuppression.

Not every pediatric liver transplant patient should attempt withdrawing immunosuppression, cautioned Dr. Mohammad, a pediatric gastroenterologist at Northwestern University in Chicago. “To be successful withdrawal of immunosuppression needs to be in selected patients; not every patient is a good candidate.”

The Immunosuppression Withdrawal for Stable Pediatric Liver Transplant Recipients (iWITH) study ran at 11 U.S. center and one center in Toronto during October 2012 through June 2014. Pediatric liver transplant recipients were eligible to start a 9-10 month graduated withdrawal from their immunosuppression regimen if they met several criteria of stability including no rejection episode over at least the prior 12 months, normal laboratory-test results, no autoimmune disease and no problems detected in a liver biopsy. The prospective study enrolled 88 patients who averaged 10 years old. Patients underwent comprehensive examinations and laboratory testing at baseline and again  several times during the subsequent 2 years including assessment of several quality of life measures.

During follow-up, 35 of the 88 patients (40%) developed symptoms of rejection and had to go back on immunosuppression. Most of these patients developed their rejection symptoms early during immunosuppression weaning, but a few patients failed later including one patient who failed 22 months after starting immunosuppression withdrawal, Dr. Mohammad said. Researchers from the iWITH study first reported these results at the American Transplant Congress in June 2016.

The quality of life findings reported by Dr. Mohammad came from assessments at baseline, after 12 months, and after 24 months, and included 30 of the patients who resumed immunosuppression and 48 patients who remained off immunosuppression for 2 years. All of these 78 patients had relatively robust quality of life profiles at baseline. Their scores for both physical and social subscales as well as for total score were significantly superior to the average scores for a large number of primarily U.S. pediatric liver transplant patients in the SPLIT database. Dr. Mohammad called the patients who attempted immunosuppression discontinuation as the “creme de la creme” of pediatric liver transplant patients in terms of their clinical status.

Analysis of scores after 2 years compared with baseline showed statistically significant improvements among patients who stayed off immunosuppression for the domains of social function, treatment attitudes and compliance, communication, and worry. A comparison of changes in quality of life scores from baseline to 2 years showed that patients who stayed off immunosuppression had improvements in several of their scores while patients who went back onto immunosuppression had on average a small deterioration of their scores.
Dr. Mohammad had no disclosures.

mzoler@frontlinemedcom.com
On Twitter @mitchelzoler

An everolimus-eluting resorbable scaffold appeared to be safe and effective for percutaneous coronary intervention (PCI) in patients with diabetes and noncomplex coronary lesions, according to a study presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously in the Journal of the American College of Cardiology: Cardiovascular Interventions.

Patients with diabetes constitute an important and increasingly prevalent subgroup of PCI patients, who are at high risk of adverse clinical and angiographic outcomes such as MI, stent thrombosis, restenosis, and death. This is thought to be due to diabetic patients’ greater level of vascular inflammation and tendency toward a prothrombotic state and more complex angiographic features, said Dean J. Kereiakes, MD, of the Christ Hospital Heart and Vascular Center, Lindner Research Center, Cincinnati.

An everolimus-eluting resorbable scaffold appeared to be safe and effective for percutaneous coronary intervention (PCI) in patients with diabetes and noncomplex coronary lesions, according to a study presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously in the Journal of the American College of Cardiology: Cardiovascular Interventions.

Patients with diabetes constitute an important and increasingly prevalent subgroup of PCI patients, who are at high risk of adverse clinical and angiographic outcomes such as MI, stent thrombosis, restenosis, and death. This is thought to be due to diabetic patients’ greater level of vascular inflammation and tendency toward a prothrombotic state and more complex angiographic features, said Dean J. Kereiakes, MD, of the Christ Hospital Heart and Vascular Center, Lindner Research Center, Cincinnati.

An everolimus-eluting resorbable scaffold appeared to be safe and effective for percutaneous coronary intervention (PCI) in patients with diabetes and noncomplex coronary lesions, according to a study presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously in the Journal of the American College of Cardiology: Cardiovascular Interventions.

Patients with diabetes constitute an important and increasingly prevalent subgroup of PCI patients, who are at high risk of adverse clinical and angiographic outcomes such as MI, stent thrombosis, restenosis, and death. This is thought to be due to diabetic patients’ greater level of vascular inflammation and tendency toward a prothrombotic state and more complex angiographic features, said Dean J. Kereiakes, MD, of the Christ Hospital Heart and Vascular Center, Lindner Research Center, Cincinnati.

Intravitreal sirolimus 440 mcg or 880 mcg administered on days 1, 60, and 120, was shown to significantly improve ocular inflammation with preservation of best-corrected visual acuity in patients with noninfectious uveitis of the posterior segment, a phase III study has shown.

In the multinational SAKURA (Study Assessing Double-masked Uveitis Treatment) study, 346 study eyes were analyzed in this randomly assigned, double-masked, actively controlled study. In the study arm given intravitreal sirolimus 440 mcg, 22.8% (P = .025) met the primary endpoint of no vitreous haze (VH) at month 5 in the study eye without the aid of rescue therapy. In the group given intravitreal sirolimus 880 mcg, 16.4% (P = .182) met the primary endpoint, compared with 10.3% of active controls who were given 44 mcg intravitreal sirolimus.

For the secondary outcome, 52.6% (P = .008) of the intravitreal sirolimus 440 mcg arm had VH scores of 0 or a 0.5+ response rate at month 5. In the intravitreal sirolimus 880 mcg, 43.1% (P = .228) achieved a VH score of 0 or a 0.5+ response rate, compared with 35% of the 44 mcg active control group. Mean best-corrected visual acuity was maintained throughout the study in each study arm, with 76.9% of those who received corticosteroids at baseline in the 440 mcg study arm successfully tapering them to 5 mg per day or less by month 5, and 66.7% of those receiving corticosteroids in the 880 mcg group doing so. This was in comparison with 63.6% of those using corticosteroids in the active control group. Adverse events were similar across the study, and all doses were well tolerated. The study was funded by Santen.

Read the full study in Ophthalmology (2016;23[11]:2413-23).
 

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

Intravitreal sirolimus 440 mcg or 880 mcg administered on days 1, 60, and 120, was shown to significantly improve ocular inflammation with preservation of best-corrected visual acuity in patients with noninfectious uveitis of the posterior segment, a phase III study has shown.

In the multinational SAKURA (Study Assessing Double-masked Uveitis Treatment) study, 346 study eyes were analyzed in this randomly assigned, double-masked, actively controlled study. In the study arm given intravitreal sirolimus 440 mcg, 22.8% (P = .025) met the primary endpoint of no vitreous haze (VH) at month 5 in the study eye without the aid of rescue therapy. In the group given intravitreal sirolimus 880 mcg, 16.4% (P = .182) met the primary endpoint, compared with 10.3% of active controls who were given 44 mcg intravitreal sirolimus.

For the secondary outcome, 52.6% (P = .008) of the intravitreal sirolimus 440 mcg arm had VH scores of 0 or a 0.5+ response rate at month 5. In the intravitreal sirolimus 880 mcg, 43.1% (P = .228) achieved a VH score of 0 or a 0.5+ response rate, compared with 35% of the 44 mcg active control group. Mean best-corrected visual acuity was maintained throughout the study in each study arm, with 76.9% of those who received corticosteroids at baseline in the 440 mcg study arm successfully tapering them to 5 mg per day or less by month 5, and 66.7% of those receiving corticosteroids in the 880 mcg group doing so. This was in comparison with 63.6% of those using corticosteroids in the active control group. Adverse events were similar across the study, and all doses were well tolerated. The study was funded by Santen.

Read the full study in Ophthalmology (2016;23[11]:2413-23).
 

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

Intravitreal sirolimus 440 mcg or 880 mcg administered on days 1, 60, and 120, was shown to significantly improve ocular inflammation with preservation of best-corrected visual acuity in patients with noninfectious uveitis of the posterior segment, a phase III study has shown.

In the multinational SAKURA (Study Assessing Double-masked Uveitis Treatment) study, 346 study eyes were analyzed in this randomly assigned, double-masked, actively controlled study. In the study arm given intravitreal sirolimus 440 mcg, 22.8% (P = .025) met the primary endpoint of no vitreous haze (VH) at month 5 in the study eye without the aid of rescue therapy. In the group given intravitreal sirolimus 880 mcg, 16.4% (P = .182) met the primary endpoint, compared with 10.3% of active controls who were given 44 mcg intravitreal sirolimus.

For the secondary outcome, 52.6% (P = .008) of the intravitreal sirolimus 440 mcg arm had VH scores of 0 or a 0.5+ response rate at month 5. In the intravitreal sirolimus 880 mcg, 43.1% (P = .228) achieved a VH score of 0 or a 0.5+ response rate, compared with 35% of the 44 mcg active control group. Mean best-corrected visual acuity was maintained throughout the study in each study arm, with 76.9% of those who received corticosteroids at baseline in the 440 mcg study arm successfully tapering them to 5 mg per day or less by month 5, and 66.7% of those receiving corticosteroids in the 880 mcg group doing so. This was in comparison with 63.6% of those using corticosteroids in the active control group. Adverse events were similar across the study, and all doses were well tolerated. The study was funded by Santen.

Read the full study in Ophthalmology (2016;23[11]:2413-23).
 

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

Amyloid PET scans can affect diagnostic thinking and patient management when used alongside routine diagnostic work up in adults suspected of having Alzheimer’s disease, results from the multicenter, open-label Assessment of the Incremental Diagnostic Value of Florbetapir ¹⁸F Imaging in Patients with Cognitive Impairment (INDIA-FBP) study reveal.

The investigators, led by Marina Boccardi, PhD, of the LANVIE-Laboratory of Neuroimaging of Aging at the University of Geneva, conducted the study to provide evidence of whether amyloid PET imaging has diagnostic utility in patients suspected of having Alzheimer’s disease because amyloid PET scanning in its current state has debatable clinical value because of a lack of disease-modifying drugs available to treat Alzheimer’s and the expense of the scans.

The trial was published in this week’s edition of JAMA Neurology and Dr. Boccardi and her colleagues found that amyloid PET scans in 228 cognitively impaired Italian adults improved diagnostic confidence and led to a change in diagnosis in 28% of patients whose prescan diagnosis was Alzheimer’s disease and in 25% (P = .02) of patients who had a non–Alzheimer’s disease–related dementia diagnosis. A positive scan resulted in a change in diagnosis to Alzheimer’s disease 72% of the time in patients with a prescan diagnosis of frontotemporal lobar degeneration (FTLD). Cognition-specific medications were initiated in 66% of previously untreated patients and were withdrawn in 33% of previously treated patients, results from the study showed (JAMA Neurol. 2016 Oct 31. doi: 10.1001/jamaneurol.2016.3751).

The scans’ ability to provide additional information to change a diagnosis justifies their use, especially when considering “reports of adverse events in patients with FTLD treated with cholinesterase inhibitors and of ineffectiveness for cognitive impairment of vascular etiology,” the investigators wrote.

The use of amyloid PET scans to change a diagnosis to Alzheimer’s disease or confirm its diagnosis also allowed for earlier detection and intervention, gave patients an opportunity to be included in clinical trials, and allowed patients to make residential and financial arrangements at a time when they were still able to express their preference.

Anticipated results from the Imaging Dementia—Evidence for Amyloid Scanning (IDEAS) and Amyloid Imaging to Prevent Alzheimer’s Disease (AMYPAD) studies will expand on the current observations on a larger scale as well as help to quantify the cost-effectiveness of amyloid PET in clinical routine practice, they said.

In the current study, a prescan diagnosis was made by clinicians who, at the time of the work-up, estimated diagnostic confidence and provided drug treatment. At the same time, an amyloid PET/CT scan was performed and the result was communicated to the clinicians upon work-up completion. Clinicians relied on the scan results for their final clinical diagnoses and identification of the most-appropriate treatment.

Amyloid PET scans are currently not reimbursed by the Centers for Medicare & Medicaid Services outside of their use in clinical trials.

This study was sponsored by Istituto di Ricovero e Cura a Carattere Scientifico Centro San Giovanni di Dio Fatebenefratelli in Brescia, Italy, and Avid Radiopharmaceuticals. Several of the authors reported serving on the scientific advisory boards of pharmaceutical companies.

Amyloid PET scans can affect diagnostic thinking and patient management when used alongside routine diagnostic work up in adults suspected of having Alzheimer’s disease, results from the multicenter, open-label Assessment of the Incremental Diagnostic Value of Florbetapir ¹⁸F Imaging in Patients with Cognitive Impairment (INDIA-FBP) study reveal.

The investigators, led by Marina Boccardi, PhD, of the LANVIE-Laboratory of Neuroimaging of Aging at the University of Geneva, conducted the study to provide evidence of whether amyloid PET imaging has diagnostic utility in patients suspected of having Alzheimer’s disease because amyloid PET scanning in its current state has debatable clinical value because of a lack of disease-modifying drugs available to treat Alzheimer’s and the expense of the scans.

The trial was published in this week’s edition of JAMA Neurology and Dr. Boccardi and her colleagues found that amyloid PET scans in 228 cognitively impaired Italian adults improved diagnostic confidence and led to a change in diagnosis in 28% of patients whose prescan diagnosis was Alzheimer’s disease and in 25% (P = .02) of patients who had a non–Alzheimer’s disease–related dementia diagnosis. A positive scan resulted in a change in diagnosis to Alzheimer’s disease 72% of the time in patients with a prescan diagnosis of frontotemporal lobar degeneration (FTLD). Cognition-specific medications were initiated in 66% of previously untreated patients and were withdrawn in 33% of previously treated patients, results from the study showed (JAMA Neurol. 2016 Oct 31. doi: 10.1001/jamaneurol.2016.3751).

The scans’ ability to provide additional information to change a diagnosis justifies their use, especially when considering “reports of adverse events in patients with FTLD treated with cholinesterase inhibitors and of ineffectiveness for cognitive impairment of vascular etiology,” the investigators wrote.

The use of amyloid PET scans to change a diagnosis to Alzheimer’s disease or confirm its diagnosis also allowed for earlier detection and intervention, gave patients an opportunity to be included in clinical trials, and allowed patients to make residential and financial arrangements at a time when they were still able to express their preference.

Anticipated results from the Imaging Dementia—Evidence for Amyloid Scanning (IDEAS) and Amyloid Imaging to Prevent Alzheimer’s Disease (AMYPAD) studies will expand on the current observations on a larger scale as well as help to quantify the cost-effectiveness of amyloid PET in clinical routine practice, they said.

In the current study, a prescan diagnosis was made by clinicians who, at the time of the work-up, estimated diagnostic confidence and provided drug treatment. At the same time, an amyloid PET/CT scan was performed and the result was communicated to the clinicians upon work-up completion. Clinicians relied on the scan results for their final clinical diagnoses and identification of the most-appropriate treatment.

Amyloid PET scans are currently not reimbursed by the Centers for Medicare & Medicaid Services outside of their use in clinical trials.

This study was sponsored by Istituto di Ricovero e Cura a Carattere Scientifico Centro San Giovanni di Dio Fatebenefratelli in Brescia, Italy, and Avid Radiopharmaceuticals. Several of the authors reported serving on the scientific advisory boards of pharmaceutical companies.

Amyloid PET scans can affect diagnostic thinking and patient management when used alongside routine diagnostic work up in adults suspected of having Alzheimer’s disease, results from the multicenter, open-label Assessment of the Incremental Diagnostic Value of Florbetapir ¹⁸F Imaging in Patients with Cognitive Impairment (INDIA-FBP) study reveal.

The investigators, led by Marina Boccardi, PhD, of the LANVIE-Laboratory of Neuroimaging of Aging at the University of Geneva, conducted the study to provide evidence of whether amyloid PET imaging has diagnostic utility in patients suspected of having Alzheimer’s disease because amyloid PET scanning in its current state has debatable clinical value because of a lack of disease-modifying drugs available to treat Alzheimer’s and the expense of the scans.

The trial was published in this week’s edition of JAMA Neurology and Dr. Boccardi and her colleagues found that amyloid PET scans in 228 cognitively impaired Italian adults improved diagnostic confidence and led to a change in diagnosis in 28% of patients whose prescan diagnosis was Alzheimer’s disease and in 25% (P = .02) of patients who had a non–Alzheimer’s disease–related dementia diagnosis. A positive scan resulted in a change in diagnosis to Alzheimer’s disease 72% of the time in patients with a prescan diagnosis of frontotemporal lobar degeneration (FTLD). Cognition-specific medications were initiated in 66% of previously untreated patients and were withdrawn in 33% of previously treated patients, results from the study showed (JAMA Neurol. 2016 Oct 31. doi: 10.1001/jamaneurol.2016.3751).

The scans’ ability to provide additional information to change a diagnosis justifies their use, especially when considering “reports of adverse events in patients with FTLD treated with cholinesterase inhibitors and of ineffectiveness for cognitive impairment of vascular etiology,” the investigators wrote.

The use of amyloid PET scans to change a diagnosis to Alzheimer’s disease or confirm its diagnosis also allowed for earlier detection and intervention, gave patients an opportunity to be included in clinical trials, and allowed patients to make residential and financial arrangements at a time when they were still able to express their preference.

Anticipated results from the Imaging Dementia—Evidence for Amyloid Scanning (IDEAS) and Amyloid Imaging to Prevent Alzheimer’s Disease (AMYPAD) studies will expand on the current observations on a larger scale as well as help to quantify the cost-effectiveness of amyloid PET in clinical routine practice, they said.

In the current study, a prescan diagnosis was made by clinicians who, at the time of the work-up, estimated diagnostic confidence and provided drug treatment. At the same time, an amyloid PET/CT scan was performed and the result was communicated to the clinicians upon work-up completion. Clinicians relied on the scan results for their final clinical diagnoses and identification of the most-appropriate treatment.

Amyloid PET scans are currently not reimbursed by the Centers for Medicare & Medicaid Services outside of their use in clinical trials.

This study was sponsored by Istituto di Ricovero e Cura a Carattere Scientifico Centro San Giovanni di Dio Fatebenefratelli in Brescia, Italy, and Avid Radiopharmaceuticals. Several of the authors reported serving on the scientific advisory boards of pharmaceutical companies.