Jama-Journal of the American Medical Association最新文献

Importance: Polycythemia vera (PV), a myeloproliferative neoplasm characterized by an increased red blood cell mass and increased risk of thrombosis, affects approximately 65 000 people in the US, with an annual incidence of 0.5 to 4.0 cases per 100 000 persons.

Observations: Erythrocytosis (hemoglobin >16.5 mg/dL in men or >16.0 mg/dL in women) is a required diagnostic criterion, although thrombocytosis (53%) and leukocytosis (49%) are common. Patients may have pruritus (33%), erythromelalgia (5.3%), transient visual changes (14%), and splenomegaly (36%) with abdominal discomfort. More than 95% of patients have a JAK2 gene variant, which helps distinguish PV from secondary causes of erythrocytosis, such as tobacco smoking or sleep apnea. Among 7 cohorts (1545 individuals), the median survival from diagnosis was 14.1 to 27.6 years. Prior to or at the time of PV diagnosis, arterial thrombosis occurred in 16% of patients and 7% had venous thrombotic events, which could involve unusual sites, such as splanchnic veins. PV is also associated with an increased bleeding risk, especially in patients with acquired von Willebrand disease, which can occur with extreme thrombocytosis (platelet count, ≥1000 × 109/L). All patients with PV should receive therapeutic phlebotomy (goal hematocrit, <45%) and low-dose aspirin (if no contraindications). Patients who are at higher risk of thrombosis include those aged 60 years or older or with a prior thrombosis. These patients and those with persistent PV symptoms may benefit from cytoreductive therapy with hydroxyurea or interferon to lower thrombosis risk and decrease symptoms. Ruxolitinib is a Janus kinase inhibitor that can alleviate pruritus and decrease splenomegaly in patients who are intolerant of or resistant to hydroxyurea. About 12.7% of patients with PV develop myelofibrosis and 6.8% develop acute myeloid leukemia.

Conclusions and relevance: PV is a myeloproliferative neoplasm characterized by erythrocytosis and is almost universally associated with a JAK2 gene variant. PV is associated with an increased risk of arterial and venous thrombosis, hemorrhage, myelofibrosis, and acute myeloid leukemia. To decrease the risk of thrombosis, all patients with PV should be treated with aspirin and therapeutic phlebotomy to maintain a hematocrit of less than 45%. Cytoreductive therapies, such as hydroxyurea or interferon, are recommended for patients at high risk of thrombosis.

Importance: Success rates of pulmonary vein isolation (PVI) are modest for persistent atrial fibrillation (AF). Additional linear ablation beyond PVI has not been proved superior to PVI alone in randomized trials. Ethanol infusion of the vein of Marshall (EIVOM) facilitates ablation at the mitral isthmus and may lead to improved effectiveness of a linear ablation strategy.

Objective: To determine whether linear ablation with radiofrequency energy combined with EIVOM added to PVI improves sinus rhythm maintenance compared with PVI alone in patients with persistent AF.

Design, setting, and participants: The PROMPT-AF trial is an investigator-initiated, multicenter, open-label, randomized trial involving 12 tertiary hospitals in China. A total of 498 patients aged 18 to 80 years, with AF persisting for more than 3 months, undergoing first-time AF ablation, were enrolled and randomized from August 27, 2021, to July 16, 2023.

Interventions: Patients were randomized to undergo PVI alone or PVI plus EIVOM and linear ablation (intervention). The latter group first underwent EIVOM, followed by PVI and linear ablation of the left atrial roof, mitral isthmus, and cavotricuspid isthmus.

Main outcomes and measures: The primary end point was freedom from any documented atrial arrhythmias lasting more than 30 seconds, without the use of antiarrhythmic drugs within 12 months. Secondary outcomes included freedom from atrial arrhythmia recurrence, AF, atrial arrhythmia recurrence after multiple procedures, and documented atrial tachycardia or atrial flutter with or without antiarrhythmic drugs; AF burden; and improvement in quality of life. Patients were monitored with wearable single-lead electrocardiographic (ECG) patches, worn for 24 hours a week, supplemented by symptom-triggered ECGs and Holter monitoring.

Results: Among 498 randomized patients, 495 (99.4%) were included in the primary analysis (mean age, 61.1 years [SD, 9.7] years, 361 male [72.9%]). After 12 months, 174 of 246 patients (70.7%) assigned to undergo PVI plus EIVOM and linear ablation and 153 of 249 patients (61.5%) assigned to undergo PVI alone remained free from atrial arrhythmias without taking antiarrhythmic drugs (hazard ratio, 0.73; 95% CI, 0.54-0.99, P = .045). The intervention effect was consistent across all prespecified subgroups. The comparison of secondary outcomes did not demonstrate significant results.

Conclusion: Among patients with persistent AF, linear ablation combined with EIVOM in addition to PVI significantly improved freedom from atrial arrhythmias within 12 months compared with PVI alone.

Trial registration: ClinicalTrials.gov Identifier: NCT04497376.

Importance: Polygenic risk scores (PRSs) for coronary heart disease (CHD) are a growing clinical and commercial reality. Whether existing scores provide similar individual-level assessments of disease susceptibility remains incompletely characterized.

Objective: To characterize the individual-level agreement of CHD PRSs that perform similarly at the population level.

Design, setting, and participants: Cross-sectional study of participants from diverse backgrounds enrolled in the All of Us Research Program (AOU), Penn Medicine BioBank (PMBB), and University of California, Los Angeles (UCLA) ATLAS Precision Health Biobank with electronic health record and genotyping data.

Exposures: Polygenic risk for CHD from published PRSs and new PRSs developed separately from testing samples.

Main outcomes and measures: PRSs that performed population-level prediction similarly were identified by comparing calibration and discrimination of models of prevalent CHD. Individual-level agreement was tested with intraclass correlation coefficient (ICC) and Light κ.

Results: A total of 48 PRSs were calculated for 171 095 AOU participants. The mean (SD) age was 56.4 (16.8) years. A total of 104 947 participants (61.3%) were female. A total of 35 590 participants (20.8%) were most genetically similar to an African reference population, 29 801 (17.4%) to an admixed American reference population, 100 493 (58.7%) to a European reference population, and the remaining to Central/South Asian, East Asian, and Middle Eastern reference populations. There were 17 589 participants (10.3%) with and 153 506 participants without (89.7%) CHD. When included in a model of prevalent CHD, 46 scores had practically equivalent Brier scores and area under the receiver operator curves (region of practical equivalence ±0.02). Twenty percent of participants had at least 1 score in both the top and bottom 5% of risk. Continuous agreement of individual predictions was poor (ICC, 0.373 [95% CI, 0.372-0.375]). Light κ, used to evaluate consistency of risk assignment, did not exceed 0.56. Analysis among 41 193 PMBB and 53 092 ATLAS participants yielded different sets of equivalent scores, which also lacked individual-level agreement.

Conclusions and relevance: CHD PRSs that performed similarly at the population level demonstrated highly variable individual-level estimates of risk. Recognizing that CHD PRSs may generate incongruent individual-level risk estimates, effective clinical implementation will require refined statistical methods to quantify uncertainty and new strategies to communicate this uncertainty to patients and clinicians.