Different Impact of Immunosuppressive Therapy on Cardiac Outcomes in Systemic Versus Isolated Cardiac Sarcoidosis.

Isolated cardiac sarcoidosis (iCS) is increasingly recognized; however, its prognosis and the efficacy of immunosuppressive therapy remain undetermined. We aimed to compare the prognosis of iCS and systemic sarcoidosis including cardiac involvement (sCS) under immunosuppressive therapy.We retrospectively reviewed the clinical data of 42 patients with sCS and 30 patients with iCS diagnosed at Kyushu University Hospital from 2004 through 2022. We compared the characteristics and the rate of adverse cardiac events including cardiac death, fatal ventricular tachyarrhythmia, and heart failure hospitalization between the 2 groups. The median follow-up time was 1535 [interquartile range, 630-2555] days, without a significant difference between the groups. There were no significant differences in gender, NYHA class, or left ventricular ejection fraction. Immunosuppressive agents were administered in 86% of sCS and in 73% of iCS patients (P = 0.191). When analyzed only with patients receiving immunosuppressive therapy (sCS, n = 36; iCS, n = 21), the cardiac event-free survival was significantly lower in iCS than sCS (37% versus 79%, P = 0.002). Myocardial LGE content at the initial diagnosis was comparable in both groups. The disease activity was serially evaluated in 26 sCS and 16 iCS patients by quantitative measures of FDG-PET including cardiac metabolic volume and total lesion glycolysis, representing 3-dimensional distribution and intensity of inflammation in the entire heart. Although iCS patients had lower baseline disease activity than sCS patients, immunosuppressive therapy did not attenuate disease activity in iCS in contrast to sCS.iCS showed a poorer response to immunosuppressive therapy and a worse cardiac prognosis compared to sCS despite lower baseline disease activity.

Succinyl-CoA-based energy metabolism dysfunction in chronic heart failure.

Heart failure (HF) is a leading cause of death and repeated hospitalizations and often involves cardiac mitochondrial dysfunction. However, the underlying mechanisms largely remain elusive. Here, using a mouse model in which myocardial infarction (MI) was induced by coronary artery ligation, we show the metabolic basis of mitochondrial dysfunction in chronic HF. Four weeks after ligation, MI mice showed a significant decrease in myocardial succinyl-CoA levels, and this decrease impaired the mitochondrial oxidative phosphorylation (OXPHOS) capacity. Heme synthesis and ketolysis, and protein levels of several enzymes consuming succinyl-CoA in these events, were increased in MI mice, while enzymes synthesizing succinyl-CoA from α-ketoglutarate and glutamate were also increased. Furthermore, the ADP-specific subunit of succinyl-CoA synthase was reduced, while its GDP-specific subunit was almost unchanged. Administration of 5-aminolevulinic acid, an intermediate in the pathway from succinyl-CoA to heme synthesis, appreciably restored succinyl-CoA levels and OXPHOS capacity and prevented HF progression in MI mice. Previous reports also suggested the presence of succinyl-CoA metabolism abnormalities in cardiac muscles of HF patients. Our results identified that changes in succinyl-CoA usage in different metabolisms of the mitochondrial energy production system is characteristic to chronic HF, and although similar alterations are known to occur in healthy conditions, such as during strenuous exercise, they may often occur irreversibly in chronic HF leading to a decrease in succinyl-CoA. Consequently, nutritional interventions compensating the succinyl-CoA consumption are expected to be promising strategies to treat HF.

Management of Airway Obstruction due to Diffuse Idiopathic Skeletal Hyperostosis in the Cervical Spine: A Case Report and Literature Review.

Diffuse idiopathic skeletal hyperostosis (DISH) is a relatively common progressive noninflammatory entheses disease. Patients are often asymptomatic or are undiagnosed due to minor chronic symptoms. We herein report a rare case in which the primary symptom was sudden-onset upper airway obstruction due to exuberant osteophytosis in the cervical spine. Treatment was successful with careful airway management and surgical osteophyectomy. Most DISH cases in the literature with airway obstruction have been managed with tracheotomy. However, the safety and necessity of this approach remain questionable. We herein discuss the possibility of conservative management as a choice of airway control. Airway obstruction due to DISH may be underrecognized. This highlights the importance of including DISH in the differential diagnosis of airway obstruction. In addition, a detailed evaluation and personalized care for each individual case is essential.