2024 NEJM Journal Watch Audio General Medicine: May Week 2

Educational Objectives

After hearing and assimilating this program, the listener will be better able to:

1. Increase his/her/their basic knowledge of important advances in medicine;
2. Identify a broad range of clinical research reported in the medical literature;
3. Synthesize research findings through one-on-one interviews with authors, editorialists, or experts in the field;
4. Integrate new treatments reviewed in the summaries into current practice;
5. Challenge oneself with thoughtful, clinically relevant questions.

Summary

Guideline Watch: Managing Acute Pancreatitis

Early management of acute pancreatitis (AP) is critical to prevent complications that occur in as many as 20% of hospitalized patients with AP. Experts from the American College of Gastroenterology (ACG) completed a systematic review of the literature and developed the following guidelines for managing AP. Details appear in The American Journal of Gastroenterology (https://doi.org/10.14309/ajg.0000000000002645).

Key Recommendations

All recommendations are conditional with very low or low quality of evidence unless otherwise stated.

• All patients with AP should undergo transabdominal ultrasound for evaluation of biliary pancreatitis. When the cause of AP is unclear after initial laboratory testing and imaging, patients eventually should undergo additional diagnostic evaluation, which might include repeat ultrasound, magnetic resonance imaging, or endoscopic ultrasound.

• Moderately aggressive fluid resuscitation with lactated Ringer’s solution should be started (https://www.jwatch.org/na56421 and Am J Gastroenterol 2023; 118:2258), defined as a bolus of 10 mL/kg followed by infusion of 1.5 mL/kg/hour (https://www.jwatch.org/na55331 and N Engl J Med 2022; 387:989), and additional boluses can be given if a patient has evidence of hypovolemia.

• Medical therapy is preferred over endoscopic retrograde cholangiopancreatography (ERCP) within the first 72 hours for patients who have AP without cholangitis.

• Rectal indomethacin should be given to individuals at high risk for post-ERCP pancreatitis (strong recommendation with moderate-quality evidence).

• Pancreatic duct stents should be used in patients at high risk for post-ERCP pancreatitis who are receiving rectal indomethacin.

• Although antibiotics are critical for patients with infected pancreatic necrosis, fine-needle aspiration should not be performed, and prophylactic antibiotics should not be given to all patients with severe AP.

• Early oral feeding (within 24-48 hours) should begin with a low-fat solid diet (as opposed to liquid) for patients with mild AP.

Our understanding of the optimal management of acute pancreatitis has changed during the past decade. These evidence-based, practical recommendations support evolving trends in treating this patient population.

Andrew S. Parsons, MD, MPH

Long-Term Follow-Up Confirms That Delaying Drainage of Infected Necrotizing Pancreatitis Is Safe

The best timing for intervention in patients with necrotizing pancreatitis has been debated extensively. In a trial published in 2021, Dutch investigators randomized 104 patients with infected necrotizing pancreatitis to either immediate or delayed drainage. All patients received antibiotics. At 6 months, immediate catheter drainage was not superior to postponed drainage, and 39% of patients in the delayed-intervention group never required drainage (https://www.jwatch.org/na54133 and N Engl J Med 2021; 385:1372). Now, the researchers have examined longer-term outcomes. Details appear in the Annals of Surgery (https://doi.org/10.1097/SLA.0000000000006001).

Twelve patients died in the first 6 months of the trial, and 4 additional patients in each group died during prolonged follow-up of 51 months. Two deaths in the immediate-intervention group and no deaths in the delayed-intervention group were attributed to pancreatitis. Major complications and recurrent pancreatitis were similar in both groups. About one third of patients in the delayed-intervention group never underwent drainage.

These findings support the recommendation to prescribe antibiotics for patients with infected necrotizing pancreatitis and to delay intervention. During prolonged follow-up, similar outcomes occurred with or without immediate drainage. Additionally, avoiding invasive intervention entirely in a substantial minority of patients has real benefits and no obvious downside based on these data.

Patricia Kritek, MD

Guideline Watch: The Role of Imaging in Managing Patients with Gastrointestinal Bleeding

Existing guidelines for managing gastrointestinal (GI) bleeding vary in their recommendations for when to use radiologic studies for evaluation. Furthermore, no thorough evaluation of the advantages and limitations of endoscopic and radiologic studies has been done previously. A guideline in The American Journal of Gastroenterology (https://doi.org/10.14309/ajg.0000000000002631), sponsored by the American College of Gastroenterology and the Society of Abdominal Radiology, fills that void.

Key Points

• Evaluating nonvariceal upper GI bleeding (esophagus, stomach, and duodenum):
  
  — Unless contraindicated, begin with esophagogastroduodenoscopy (EGD).
  
  — Catheter angiography is indicated when EGD is unsuccessful in achieving hemostasis.
  
  — Computed tomographic angiography (CTA), followed by catheter angiography if CTA is positive, can be considered in actively bleeding patients when the site of bleeding cannot be identified by EGD (unusual).

• Evaluating small bowel bleeding (between the ligament of Treitz and ileocecal valve):
  
  — Capsule endoscopy is the test of choice if EGD and colonoscopy do not reveal a source in patients who present with GI bleeding.
  
  — CT enterography, which utilizes oral and intravenous contrast, should be performed instead of CTA in hemodynamically stable patients with suspected ongoing small bowel bleeding after negative colonoscopy, EGD, and capsule endoscopy.
  
  — If ongoing bleeding is brisk with hemodynamic instability, CTA should be performed instead of CT enterography.
  
  — CT enterography should be the first-line imaging test in patients at excess risk for video capsule retention (e.g., strictures, radiation) or with suspected small bowel neoplasm.

• Evaluating lower GI bleeding (distal to the ileocecal valve):
  
  — CTA should be performed as the first diagnostic study in hemodynamically unstable patients.
  
  — In unstable patients with active extravasation seen on CTA, catheter angiography with embolization should be performed, ideally within 90 minutes.
  
  — Colonoscopy should be performed in hemodynamically stable patients after adequate colon cleansing.

This collaborative guideline, based primarily on expert opinion, is an excellent review for clinicians taking care of patients with GI bleeds. In general, EGD or colonoscopy still is the preferred initial diagnostic step for most patients. However, CTA should be used more frequently in hemodynamically unstable patients with lower GI bleeds when time to diagnosis is crucial and there is no window for a colonic cleanse. Supplementary material for these guidelines is available online (https://cdn-links.lww.com/permalink/ajg/d/ajg_2024_01_31_fidler_3_sdc1.pdf).

Aaron J. Calderon, MD, FACP, SFHM

Diagnosing Heparin-Induced Thrombocytopenia: How Accurate Is the Recommended Algorithm?

Heparin-induced thrombocytopenia (HIT) is a high-risk condition that requires immediate therapy with high-risk medications; thus, accurate diagnosis is critical. Because HIT-antibody testing has a relatively high false-positive rate, guidelines direct clinicians to use an algorithm that starts with the 4Ts score (https://www.mdcalc.com/calc/1787/4ts-score-heparin-induced-thrombocytopenia) and then recommend antibody testing in patients whose 4Ts scores indicate intermediate or high risk for HIT. In a prospective study of 1300 patients with possible HIT, investigators assessed the accuracy of the 4Ts score and the guideline-recommended diagnostic algorithm. The reference-standard test for comparison was a heparin-induced platelet activation assay; prevalence of HIT was 8.4% by reference-standard testing. Findings appear in JAMA Network Open (https://doi.org/10.1001/jamanetworkopen.2024.3786).

Positive predictive values of 4Ts score and the recommended diagnostic algorithm were expectedly low (15% and 66%, respectively). However, nearly half of patients were low risk using 4Ts score and would not have warranted antibody testing by the recommended diagnostic algorithm. That algorithm had high sensitivity (87%) and specificity (96%) and a very high negative predictive value (99%).

Because clinicians order reference-standard testing (i.e., serotonin release assay or heparin-induced platelet activation assay) to confirm positive HIT-antibody testing, false positives by the recommended algorithm eventually get resolved. However, 9% of patients with confirmed HIT (10 of 111) had false-negative (i.e., “low-risk”) 4Ts scores in this study. Additional testing still should be considered if suspicion for HIT remains despite a low-risk 4Ts score; for example, a score of 3 points is technically “low risk” but might warrant further testing based on clinical gestalt.

Daniel D. Dressler, MD, MSc, MHM, FACP

Transcatheter vs Surgical Aortic Valve Replacement for Low-Risk Patients

Transcatheter aortic valve replacement (TAVR) has demonstrated similar short-term and intermediate-term outcomes as surgical aortic valve replacement (SAVR) across the spectrum of surgical risk. TAVR thus carries a class I recommendation for most older patients with severe, symptomatic aortic stenosis. Nonetheless, concerns remain regarding the interpretation of previous trials, which were industry-funded, required use of specific TAVR valves, and allowed for concomitant coronary-artery bypass grafting in the SAVR group (which confers short-term risk).

To address these issues, investigators in Germany performed a manufacturer-independent, randomized trial to compare TAVR and SAVR in 1414 patients (mean age, 74) with severe, symptomatic trileaflet aortic stenosis who were at low or intermediate surgical risk and who did not require concomitant coronary revascularization. Details appear in the New England Journal of Medicine (https://doi.org/10.1056/NEJMoa2400685).

The primary endpoint — a composite of all-cause death or stroke by 1 year — occurred significantly less often in the TAVR group (5.4% vs 10.0%); TAVR also appeared to result in lower mortality (2.6% vs 6.2%) and fewer disabling strokes (1.3% vs 3.1%).

This is the fourth randomized clinical trial to demonstrate noninferiority (and, in this case, probable superiority) of TAVR vs SAVR with respect to 1-year clinical outcomes in low-to-intermediate-risk patients with severe aortic stenosis. Coupled with recent data showing similar or superior outcomes with TAVR at 4- to 5-year follow-up, these data reinforce my current practice of offering TAVR to most patients with severe aortic stenosis and trileaflet valves. The main exceptions are patients with unfavorable valve anatomy (often a bicuspid aortic valve) and those who are younger than 65 (for whom at least 2 additional aortic valve procedures might be necessary).

David J. Cohen, MD, MSc

No Benefit of β-Blockers in Revascularized Patients with Normal Ejection Fraction After MI

β-blockers, a long-established cornerstone of medical therapy after acute myocardial infarction (MI), have strong recommendations in treatment guidelines. The supporting evidence, however, predates advances in MI care such as primary percutaneous coronary intervention and intensive antiplatelet regimens.

To update the evidence, researchers conducted a randomized trial to compare long-term β-blocker therapy (metoprolol or bisoprolol) with no β-blockers in 5020 patients (median age, 65; most from Sweden) who had normal left-ventricular ejection fraction after MI (35% with ST-segment elevation) for which they had undergone angiography and coronary revascularization. β-blockers were first initiated during the MI hospital stay; most patients were discharged on aspirin (97%), a P2Y12-receptor blocker, a statin, and an angiotensin-converting–enzyme inhibitor or angiotensin-receptor blocker. Patients in the no–β-blocker group who had been taking β-blockers were weaned off over several weeks. Findings appear in the New England Journal of Medicine (https://doi.org/10.1056/NEJMoa2401479).

At median follow-up of 3.5 years, the primary composite endpoint — all-cause death or recurrent MI — did not differ significantly in the β-blocker and no–β-blocker groups (7.9% and 8.3%). Incidences of secondary endpoints (i.e., all-cause death, cardiovascular-related death, new MI, hospitalization for atrial fibrillation or heart failure) also were similar in the two groups.

These findings suggest that β-blockers are not beneficial in relatively low-risk patients with MI who have normal left ventricular ejection fraction after revascularization and who receive other evidence-based therapies. Although ongoing trials will offer further clarity, the era of “β-blockers for all” after MI probably is ending. (https://doi.org/10.1056/NEJMe2402731)

Frederick A. Masoudi, MD, MSPH, MACC, FAHA

Can Routine Chest X-Ray Predict Risk for Adverse Cardiac Events?

Recent advancements in artificial intelligence have enabled the use of “deep learning,” which involves processing complex patterns in pictures, text, and other data, to predict patient outcomes based on plain-film chest x-rays — likely by identifying coronary calcium deposits that go unrecognized by the human eye (https://doi.org/10.1148/ryct.2021200486). Harvard investigators developed a deep-learning computer model using routine chest x-rays from ≈40,000 participants in a longitudinal cancer screening trial and evaluated its ability to predict 10-year risk for major adverse cardiac events (MACEs) in a separate group of 11,000 patients. Twenty percent of patients had both routine chest x-rays and sufficient electronic medical record data to estimate risk with a traditional cardiovascular disease risk score (ASCVD calculator; https://www.mdcalc.com/calc/3398/ascvd-atherosclerotic-cardiovascular-disease-2013-risk-calculator-aha-acc). Details appear in the Annals of Internal Medicine (https://doi.org/10.7326/M23-1898).

Statin eligibility (i.e., 10-year risk for MACE ≥7.5%) was predicted similarly by the chest x-ray–based model and the traditional risk score (37% of patients were statin-eligible under each model). Moreover, adjustment for traditional risk score indicated that the chest x-ray–based model added substantial predictive ability, such that the 10-year incidence of MACE was 88% higher in statin-eligible patients than in statin-ineligible patients, independent of traditional risk score.

Although deep-learning models might not be actionable immediately by individual clinicians, healthcare systems might consider using existing chest x-rays to identify patients at elevated risk for MACE when other clinical factors are not available electronically. Such information then could be routed to physicians and patients for discussion or risk reduction. The authors do not recommend ordering screening chest x-rays to assess cardiovascular disease risk.

Daniel D. Dressler, MD, MSc, MHM, FACP

Accuracy of Wearable Monitors for Assessment of Heart Rate During Rest and Exercise

Wearable monitors have become ubiquitous, but their accuracy at assessing heart rate has been unclear. In an analysis in the Journal of the American College of Cardiology (https://doi.org/10.1016/j.jacc.2024.01.024), researchers compared the accuracy of six common wearable monitors during exercise testing in 61 patients with normal sinus rhythm and in 20 patients in atrial fibrillation (AF). They measured heart rates at rest and then during treadmill tests using both wearable monitors and electrocardiogram (ECG) monitors as the reference standard.

At rest, wearable devices showed reasonable accuracy; the mean absolute difference between ECG and wearable devices was 4.6±8.4 beats per minute (bpm) in normal sinus rhythm and 7.0±11.8 bpm in AF. At peak exercise, the difference was substantially larger: 13.8±18.9 bpm in sinus rhythm and 28.7±23.7 bpm in AF. The device underestimated the true heart rate in 62% of cases and overestimated it in 25%.

As we learn more about wearable devices, it is clear that they are imperfect. In many studies, researchers have examined wearable devices’ ability to detect AF, which is their most important clinical use. Those analyses, like this one, show that not all devices perform well. The current study specifically focused on how well wearable devices capture maximal heart rate during exercise and showed a very large variability. We must thus be cautious about the readings of these devices, particularly during exercise, and follow up with confirmatory diagnostic testing, especially for AF.

Mark S. Link, MD

Semaglutide Improves Outcomes in Patients with Obesity, HFpEF, and Type 2 Diabetes

Obesity and type 2 diabetes are common comorbidities in patients with heart failure with preserved ejection fraction (HFpEF). Currently, no therapy is U.S. FDA approved to manage all three conditions at once; but the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide has the potential to do so.

In an industry-funded randomized trial in the New England Journal of Medicine (https://doi.org/10.1056/NEJMoa2313917), 616 adults with HFpEF (left ventricular ejection fraction, ≥45%), body-mass index >30 kg/m², and type 2 diabetes received semaglutide (2.4 mg) or placebo once weekly for 52 weeks. Mean improvement in heart failure symptoms, according to the Kansas City Cardiomyopathy Questionnaire clinical summary score, was significantly greater with semaglutide than with placebo (13.7 points vs 6.4 points on a 100-point scale). And as expected, mean change in body weight was greater with semaglutide than with placebo (−9.8% vs −3.4%). Several secondary end points also favored semaglutide. Incidence of serious adverse events leading to discontinuation of semaglutide or placebo was similar in the two groups.

Once again, semaglutide shows clinical benefit. Prior research has shown improved outcomes in patients with diabetes and high cardiovascular risk, overweight or obesity and high cardiovascular risk (https://www.jwatch.org/na56763 and N Engl J Med 2023; 389:2221), and HFpEF and obesity but no diabetes (https://www.jwatch.org/na56490 and N Engl J Med 2023; 389:1069). Now, this study shows efficacy in patients with HFpEF, obesity, and type 2 diabetes. These findings make me very likely to recommend semaglutide to appropriate patients for improving symptoms and lowering cardiovascular risk.

Karol E. Watson, MD, PhD, FACC

Why Do Some People Develop Obesity Despite High Levels of Physical Activity?

We know that exercise levels alone don’t fully explain a person’s tendency to obesity. To explore the potential genetic basis for at least some of this variability, investigators used step count and genetic data from an existing U.S. population-based data set for a study in JAMA Network Open (https://doi.org/10.1001/jamanetworkopen.2024.3821). Genetic risk for obesity was determined by using known loci from a prior genome-wide association study to create quartiles of polygenic risk score (PRS) for 3100 adults (median age, 53) of European ancestry who were not obese at baseline (median body-mass index, ≈24.5 kg/m²).

Participants walked a median 8300 steps daily at baseline and were followed for a median 5.4 years, during which obesity developed in 13% of those in the lowest PRS quartile and 43% in the highest quartile. Both step count and PRS quartile were correlated with risk for developing obesity. For example, participants at the 75th percentile of PRS risk needed to walk 2280 more steps daily than participants at the 50th percentile to have the same relative risk reduction. Conversely, participants at the 25th percentile needed to walk 3660 fewer steps daily than those at the 50th percentile for the same relative risk reduction.

The authors acknowledge that dietary intake is an important contributor to obesity that this analysis does not address. The analysis was strengthened by excluding participants whose obesity developed within 6 months of study entry, which reduced, but did not eliminate the possibility for reverse causality as an explanation. The fact that these results apply only to patients of European ancestry also is a limitation. Despite these caveats, these results can help clinicians explain to patients why not all steps are equal. A patient whose weight increases despite following the usual recommendation of 8000 to 10,000 steps daily (and therefore might have a high PRS) might need to increase activity by 3000 to 4000 additional steps daily.

Thomas L. Schwenk, MD

These summaries are presented to facilitate your understanding of ongoing medical research. They aren’t intended for use as the sole basis for clinical treatment nor as a substitute for reading the original research. Journal Watch is a registered trademark of the Massachusetts Medical Society, publishers of the New England Journal of Medicine.

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Disclosures

In adherence to the ACCME Standards for Commercial Support, Audio Digest requires all faculty and members of the planning committee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. The planning committee members reported that they had nothing to disclose.

Acknowledgements

CME/CE INFO

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The Audio- Digest Foundation designates this enduring material for a maximum of 1.00 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

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To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

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Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.

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