Ultrasound-Accelerated, Catheter-Directed Thrombolysis for Submassive Pulmonary Embolism: Single-Center Retrospective Review with Intermediate-Term Outcomes.

PURPOSE: To evaluate ultrasound-accelerated, catheter-directed thrombolysis (CDT) for treatment of acute submassive pulmonary embolism (PE). MATERIALS AND METHODS: This single-center, retrospective study included patients who underwent CDT for acute submassive PE (N = 113, 52% men/48% women) from 2013 to 2017. Baseline characteristics included history of deep venous thrombosis (12%), history of PE (6%), and history of cancer (18%). Of cohort patients, 88% (n=99) had a simplified PE severity index score of ≥ 1 indicating a high risk of mortality. RESULTS: A technical success rate of 100% was achieved with 84% of patients having bilateral catheter placements. Average tissue plasminogen activator (tPA) therapy duration was 20.7 hours ± 1.5, and median tPA dose was 21.5 mg. Three patients (2.6%) experienced minor hemorrhagic complications. Mean hospital length of stay was 6 days. Mean pulmonary arterial pressure decreased from 55 mm Hg on presentation to 37 mm Hg (P < .01) 1 day following initiation of thrombolytic therapy. All-cause mortality rate of 4% (n = 4) was noted on discharge, which increased to 6% (n = 7) at 6 months. At 6-month follow-up compared with initial presentation, symptom improvements (93%), physiologic improvements (heart rate 72 beats/min vs 106 beats/min, P < .01), oxygen requirement improvements (fraction of inspired oxygen 20% vs 28%, P < .01), and right ventricular systolic pressure improvements by echocardiography (30 mm Hg vs 47 mm Hg, P < .01) were observed. CONCLUSIONS: CDT for acute submassive PE was associated with low complications and mortality, decreased right ventricular systolic pressure, high rates of clinical improvement, and improved intermediate-term clinical outcomes.

Progressive mitochondrial protein lysine acetylation and heart failure in a model of Friedreich's ataxia cardiomyopathy.

INTRODUCTION: The childhood heart disease of Friedreich's Ataxia (FRDA) is characterized by hypertrophy and failure. It is caused by loss of frataxin (FXN), a mitochondrial protein involved in energy homeostasis. FRDA model hearts have increased mitochondrial protein acetylation and impaired sirtuin 3 (SIRT3) deacetylase activity. Protein acetylation is an important regulator of cardiac metabolism and loss of SIRT3 increases susceptibility of the heart to stress-induced cardiac hypertrophy and ischemic injury. The underlying pathophysiology of heart failure in FRDA is unclear. The purpose of this study was to examine in detail the physiologic and acetylation changes of the heart that occur over time in a model of FRDA heart failure. We predicted that increased mitochondrial protein acetylation would be associated with a decrease in heart function in a model of FRDA. METHODS: A conditional mouse model of FRDA cardiomyopathy with ablation of FXN (FXN KO) in the heart was compared to healthy controls at postnatal days 30, 45 and 65. We evaluated hearts using echocardiography, cardiac catheterization, histology, protein acetylation and expression. RESULTS: Acetylation was temporally progressive and paralleled evolution of heart failure in the FXN KO model. Increased acetylation preceded detectable abnormalities in cardiac function and progressed rapidly with age in the FXN KO mouse. Acetylation was also associated with cardiac fibrosis, mitochondrial damage, impaired fat metabolism, and diastolic and systolic dysfunction leading to heart failure. There was a strong inverse correlation between level of protein acetylation and heart function. CONCLUSION: These results demonstrate a close relationship between mitochondrial protein acetylation, physiologic dysfunction and metabolic disruption in FRDA hypertrophic cardiomyopathy and suggest that abnormal acetylation contributes to the pathophysiology of heart disease in FRDA. Mitochondrial protein acetylation may represent a therapeutic target for early intervention.