肺動脈性肺高血圧症

BACKGROUND: Aging is associated with increases in pulmonary pressure related to concomitant age-associated left ventricular remodeling, diastolic dysfunction, and declines in pulmonary function. Little is known regarding morphological changes in the pulmonary arterial vasculature underlying these associations. Our aim was to determine the associations between pulmonary vascular arterial remodeling, reflected in distal pruning and proximal dilation, and cardiac structure and function, pulmonary pressure, and functional outcomes. METHODS: Among 2275 participants in the community-based Atherosclerosis Risk in Communities study (ARIC) who underwent echocardiography and noncontrast cardiac computed tomography at study visit 7 (2018-2019), we quantified the fraction of total pulmonary vascular area comprised of arterial vessels with cross-sectional area <5 mm2 (aBV5/aTBV) and arterial vessels with cross-sectional area >10 mm2 (aBVg10/aTBV) using a validated image processing approach. We assessed the associations of aBV5/aTBV and aBVg10/aTBV with echocardiographic measures of cardiac structure and function and pulmonary artery systolic pressure using multivariable linear regression models adjusted for demographics and cardiovascular risk factors. We also evaluated associations of pulmonary vascular arterial remodeling metrics with circulating NT-proBNP (N-terminal pro-B-type natriuretic peptide), self-reported dyspnea, and incident heart failure. RESULTS: Mean age was 80±4 years, 61% were women, 22% reported Black race, and mean left ventricular ejection fraction was 64±7%. Mean aBV5/aTBV was 0.30±0.08, and aBVg10/aTBV was 0.45±0.09. Lower aBV5/aTBV, reflecting greater distal pruning, and higher aBVg10/aTBV, reflecting greater proximal dilation, were both associated with greater left ventricular remodeling, worse diastolic function, and worse systolic function. Lower aBV5/aTBV and higher aBVg10/aTBV demonstrated nonlinear associations with greater pulmonary artery systolic pressure. Both lower aBV5/aTBV and higher aBVg10/aTBV were associated with higher circulating NT-proBNP and greater odds of moderate to severe dyspnea. Higher aBVg10/aTBV, in particular, was associated with greater risk of incident heart failure over a 4-year follow-up with a hazard ratio of 1.25 (95% CI, 1.03-1.51) per one SD in aBVg10/TBV. CONCLUSIONS: Among older adults, pulmonary vascular arterial remodeling is associated with greater left ventricular remodeling, worse diastolic and systolic dysfunction, greater pulmonary artery systolic pressure, greater odds of significant dyspnea, and greater risk of heart failure development. Our findings clarify the morphologic changes in the pulmonary vasculature that link cardiac dysfunction to higher pulmonary pressure in late life and may appear before symptomatology.

Multicentric reticulohistiocytosis (MRH) is a rare non-Langerhans cell histiocytosis characterized by destructive polyarthritis and papulonodular cutaneous lesions. We describe a woman who developed erythroderma 20 years after MRH diagnosis-to our knowledge, a previously unreported manifestation of this disease. The patient initially presented at age 50 with arthralgia, and MRH was diagnosed one year later based on distal interphalangeal (DIP) joint deformities, erythematous papules on the lower legs, and a skin biopsy showing dermal infiltration of CD68-positive, S-100- and CD1a-negative histiocyte-like cells with ground-glass eosinophilic cytoplasm. Despite long-term treatment with methotrexate (MTX), prednisolone (PSL), infliximab (year 11), and bone-modifying agents (alendronate, later denosumab), the disease progressed, with development of pulmonary arterial hypertension (PAH) attributable to lesions around the upper pulmonary veins. At age 71, twenty years after diagnosis, pruritic erythema appeared on the back and evolved into erythroderma despite topical corticosteroids. Biopsies from erythematous areas demonstrated CD68-positive histiocytic infiltrate identical to that of the original MRH lesions, whereas biopsies from clinically uninvolved skin showed no such infiltration, supporting a direct association with the MRH disease process. Comprehensive evaluation excluded eczematous/atopic erythroderma (normal eosinophils and IgE), drug-induced erythroderma (no new medications; infliximab discontinued 9 years previously), dermatophytosis (negative PAS staining), granulomatous mycosis fungoides (absent characteristic histological features), sarcoidosis (normal sIL-2R; no granulomas on biopsy), dermatomyositis (absent characteristic features; normal creatine kinase), and internal malignancy (contrast-enhanced CT and 2-year follow-up). MTX was discontinued because of MTX-induced interstitial pneumonia, and oral PSL was increased to 30 mg/day, with rapid improvement; the patient is currently maintained on PSL 10 mg/day without relapse. The cumulative inflammatory burden of long-standing MRH may have culminated in this erythrodermic phenotype.

RATIONALE: Pulmonary arterial hypertension (PAH) leads to heart failure and impaired exercise capacity. Rehabilitation may improve exercise tolerance, but most previous trials were short-term and open-label. OBJECTIVES: To assess the 12-month efficacy and safety of a 3-month supervised rehabilitation program in PAH. MEASUREMENTS AND MAIN RESULTS: Stable patients from nine French PAH centers were enrolled in a prospective cohort without mention of rehabilitation, and thereafter randomized using a Zelen design either to usual follow-up or to a supervised 3-month rehabilitation program, following a second consent for the latter group. The primary endpoint was endurance time at 75% of maximal workload during cardiopulmonary exercise testing at 12 months (NCT02579954).Between 2015 and 2022, 49 patients were enrolled and 47 randomized (mean age 54.7 years; 27 females; 35 idiopathic PAH; mean mPAP 37.1 mmHg; PVR 5.7 UW; CI 3.0 L/min/m2). Twenty-one patients were assigned to rehabilitation. At baseline, 32 were at low risk, with preserved functional capacity (31 had 6-min walk distance >440 m). Mean (SD) endurance time was 8.7 (8.0) min in the rehabilitation group and 8.1 (4.8) min in controls. At 12 months, mean endurance time was 16.8 ± 20.0 minutes in the rehabilitation arm versus 8.0 ± 7.2 minutes in the control arm (adjusted p = 0.047). Clinical worsening risk tended lower with rehabilitation (RR 0.17, 95%CI 0.02-1.27; p = 0.055). No deaths occurred. CONCLUSIONS: In this multicenter trial using a design limiting performance bias, a 3-month supervised rehabilitation program significantly improved exercise endurance at 12 months and may reduce clinical worsening.

BACKGROUND: Congenital diaphragmatic hernia (CDH) remains a challenging neonatal surgical condition associated with significant morbidity and mortality. Thoracoscopic repair has emerged as a minimally invasive alternative to conventional open repair in selected patients. AIM: The aim of this study is to share our experience in the surgical management of CDH and to compare postoperative outcomes between thoracoscopic repair and open laparotomy. MATERIALS AND METHODS: A retrospective analysis of six patients with CDH managed surgically at a tertiary care center was performed. Demographic data, antenatal diagnosis, pulmonary arterial hypertension (PAH), surgical approach, ventilator requirement, initiation of enteral feeding, duration of analgesia, hospital stay, and follow-up outcomes were evaluated. RESULTS: All patients had left-sided Bochdalek hernias. Three patients underwent thoracoscopic repair, and three underwent open laparotomy. Thoracoscopic repair was associated with a reduced ventilator requirement, earlier initiation of enteral feeds, shorter duration of intravenous analgesia, and reduced hospital stay. One mortality occurred in the laparotomy group. No patient required extracorporeal membrane oxygenation (ECMO) or patch repair. Conclusion: Thoracoscopic repair of CDH, when performed in carefully selected patients, is safe and associated with improved short-term postoperative outcomes compared to open repair.