No abstract

BACKGROUND: The human heart primarily metabolizes fatty acids, and this decreases as alternative fuel use rises in heart failure with reduced ejection fraction (HFrEF). Patients with severe obesity and diabetes are thought to have increased myocardial fatty acid metabolism, but whether this is found in those who also have heart failure with preserved ejection fraction (HFpEF) is unknown. METHODS: Plasma and endomyocardial biopsies were randomly selected from a 2-center derived biobank of HFpEF (n=38), HFrEF (n=30), and nonfailing donor control (n=20) tissue. Quantitative targeted metabolomics measured organic acids, amino acids, and acylcarnitines in myocardium (72 metabolites) and plasma (69 metabolites). The results were integrated with reported RNA sequencing data. Metabolomics were analyzed using agnostic clustering tools, Kruskal-Wallis test with Dunn test, and machine learning. RESULTS: Agnostic clustering of myocardial but not plasma metabolites separated disease groups. Despite more obesity and diabetes in HFpEF versus HFrEF (body mass index, 39.8 kg/m 2 versus 26.1 kg/m 2 ; diabetes, 70% versus 30%; both P <0.0001), medium- and long-chain acylcarnitines (mostly metabolites of fatty acid oxidation) were markedly lower in myocardium from both heart failure groups versus control. In contrast, plasma levels were no different or higher than control. Gene expression linked to fatty acid metabolism was generally lower in HFpEF versus control. Myocardial pyruvate was higher in HFpEF whereas the tricarboxylic acid cycle intermediates succinate and fumarate were lower, as were several genes controlling glucose metabolism. Non–branched-chain and branched-chain amino acids (BCAA) were highest in HFpEF myocardium, yet downstream BCAA metabolites and genes controlling BCAA metabolism were lower. Ketone levels were higher in myocardium and plasma of patients with HFrEF but not HFpEF. HFpEF metabolomic-derived subgroups showed few differences in BCAA metabolites but little else. CONCLUSIONS: Despite marked obesity and diabetes, HFpEF myocardium exhibited lower fatty acid metabolites compared with HFrEF. Ketones and metabolites of the tricarboxylic acid cycle and BCAA were also lower in HFpEF, suggesting insufficient use of alternative fuels. These differences were not detectable in plasma and challenge conventional views of myocardial fuel use in HFpEF with marked diabetes and obesity and suggest substantial fuel inflexibility in this syndrome.

Objective Thoracoabdominal aortic aneurysm (TAAA) repair remains a significant challenge with considerable perioperative morbidity and mortality. A hybrid approach visceral debranching with endovascular aneurysm exclusion has been used to treat high-risk patients and therefore to allow repair in more patients. Limited data exist regarding long-term outcomes with this procedure as well as comparison to conventional open repair. This study describes our institutional algorithmic approach to TAAA repair using both open and hybrid techniques. Methods Hybrid and open TAAA repairs performed between July 2005 and August 2015 were identified from a prospectively maintained institutional aortic surgery database. Perioperative morbidity and mortality, freedom from reintervention, and long-term and aorta-specific survival were calculated and compared between the two groups. Results During the study period, 165 consecutive TAAA repairs were performed, including 84 open repairs and 81 hybrid repairs. Patients in the hybrid repair group were significantly older, were more frequently female, and had a generally greater comorbid disease burden, including significantly more chronic kidney disease. Despite the older and sicker cohort, there was no difference in in-hospital mortality between the two groups (9.9% hybrid vs 7.1% open; P = .59). Major morbidity rates differed by procedure, with patients undergoing open repair having a significantly higher rate of postoperative stroke (9.5% open vs 0% hybrid; P = .017), whereas patients undergoing hybrid repair had a higher rate of new permanent dialysis (14.8% hybrid vs 3.6% open; P = .043). There was no difference between groups in the rate of postoperative permanent paraplegia/paresis (8.3% open vs 7.4% hybrid; P = .294). There was a significantly increased rate of reintervention in the hybrid repair group (12.3% hybrid vs 1.2% open, P = .004), with all hybrid reinterventions performed because of endoleak. One-year survival was similar between groups at 69% in hybrid repairs vs 77% in open repairs. Long-term survival was worse in the hybrid group (5-year survival, 32% hybrid vs 56% open), although late survival appeared to be influenced mainly by comorbid disease burden, given the similar long-term aorta-specific survival between groups. Conclusions Use of an algorithmic approach whereby higher risk patients with TAAA are treated by a hybrid approach and lower risk patients with conventional open repair yields satisfactory short- and long-term outcomes. The availability of multiple options for TAAA repair within a single center likely allows repair in more patients with consequent decrease in the risk of aorta-related death, at the expense of increased reinterventions for endoleak.

Objective The role of hybrid repair in the management of aortic arch pathology, and long-term outcomes with these techniques, remains uncertain. We report a decade of experience with hybrid arch repair (HAR) and assess institutional practice patterns with regard to the use of hybrid and open techniques. Methods Hybrid and open total and distal arch procedures performed between July 2005 and January 2015 were identified from a prospectively maintained, institutional aortic surgery database. Perioperative morbidity and mortality, freedom from reintervention, and long-term survival were calculated. Hybrid and open procedural volumes over the study period were assessed to evaluate for potential practice pattern changes. Results During the study period 148 consecutive procedures were performed for repair of transverse and distal aortic arch pathology, including 101 hybrid repairs and 47 open total or distal arch repairs. Patients in the hybrid repair group were significantly older with a greater incidence of chronic kidney disease, peripheral vascular disease, and chronic lung disease. Perioperative mortality and outcomes were not significantly different between the hybrid and open groups, aside from decreased median length of stay after hybrid repair. Need for subsequent reintervention was significantly greater after hybrid repair. Unadjusted long-term survival was superior after open repair (70% 5-year survival open vs 47% hybrid; P = .03), although aorta-specific survival was similar (98% 5-year aorta-specific survival open vs 93% hybrid; P = .59). Institutional use of HAR decreased over the final 3 years of the study, with an associated increased use of open total or distal arch repairs. This was primarily the result of decreased use of native zone 0 hybrid procedures. Concurrent with this apparent increased stringency around patient selection for HAR, perioperative morbidity and mortality was reduced, including avoidance of retrograde type A dissection. Conclusions HAR remains a viable option for higher-risk patients with transverse arch pathology with perioperative outcomes and long-term aorta-specific survival similar to open repair, albeit at a cost of increased reintervention. This observational single-institution study would suggest decreased use in more recent years in favor of open repair due to avoidance of native zone 0 hybrid procedures. This decline in the institutional use of native zone 0 hybrid repairs was associated with improved perioperative outcomes.