Jama-Journal of the American Medical Association最新文献

Importance: Correction of tricuspid regurgitation using tricuspid transcatheter edge-to-edge repair (T-TEER) in addition to guideline-directed optimized medical therapy (OMT) may improve clinical outcomes.

Objective: To evaluate the efficacy of T-TEER + OMT vs OMT alone in patients with severe, symptomatic tricuspid regurgitation.

Design, setting, and participants: Investigator-initiated, prospective, randomized (1:1) trial evaluating T-TEER + OMT vs OMT alone in adult patients with severe, symptomatic tricuspid regurgitation. The trial was conducted at 24 centers in France and Belgium (March 2021 to March 2023; latest follow-up in April 2024).

Intervention: Patients were randomized to T-TEER + OMT or OMT alone.

Main outcomes and measures: The primary outcome was a composite clinical end point at 1 year comprising change in New York Heart Association class, change in patient global assessment, or occurrence of major cardiovascular events. Tricuspid regurgitation severity was the first of 6 secondary outcomes analyzed in a hierarchical closed-testing procedure, including Kansas City Cardiomyopathy Questionnaire (KCCQ) score, patient global assessment, and a composite outcome of all-cause death, tricuspid valve surgery, KCCQ score improvement, or time to hospitalization for heart failure.

Results: Of 300 enrolled patients (mean age, 78 [SD, 6] years, 63.7% women), 152 were allocated to T-TEER + OMT and 148 to OMT alone. At 1 year, 109 patients (74.1%) in the T-TEER + OMT group had an improved composite score compared with 58 patients (40.6%) in the OMT-alone group. Massive or torrential tricuspid regurgitation was found in 6.8% of patients in the T-TEER + OMT group and in 53.5% of those in the OMT-alone group (P < .001). Mean overall KCCQ summary score at 1 year was 69.9 (SD, 25.5) for the T-TEER + OMT group and 55.4 (SD, 28.8) for the OMT-alone group (P < .001). The win ratio for the composite secondary outcome was 2.06 (95% CI, 1.38-3.08) (P < .001).

Conclusions and relevance: T-TEER reduces tricuspid regurgitation severity and improves a composite score driven by improved patient-reported outcome measures in patients with severe, symptomatic tricuspid regurgitation.

Trial registration: ClinicalTrials.gov Identifier: NCT04646811.

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.