Three-vessel coronary infusion of cardiosphere-derived cells for the treatment of heart failure with preserved ejection fraction in a pre-clinical pig model.

Heart failure with preserved ejection fraction (HFpEF) is a major public health concern. Its outcome is poor and, as of today, barely any treatments have been able to decrease its morbidity or mortality. Cardiosphere-derived cells (CDCs) are heart cell products with anti-fibrotic, anti-inflammatory and angiogenic properties. Here, we tested the efficacy of CDCs in improving left ventricular (LV) structure and function in pigs with HFpEF. Fourteen chronically instrumented pigs received continuous angiotensin II infusion for 5 weeks. LV function was investigated through hemodynamic measurements and echocardiography at baseline, after 3 weeks of angiotensin II infusion before three-vessel intra-coronary CDC (n = 6) or placebo (n = 8) administration and 2 weeks after treatment (i.e., at completion of the protocol). As expected, arterial pressure was significantly and similarly increased in both groups. This was accompanied by LV hypertrophy that was not affected by CDCs. LV systolic function remained similarly preserved during the whole protocol in both groups. In contrast, LV diastolic function was impaired (increases in Tau, LV end-diastolic pressure as well as E/A, E/E'septal and E/E'lateral ratios) but CDC treatment significantly improved all of these parameters. The beneficial effect of CDCs on LV diastolic function was not explained by reduced LV hypertrophy or increased arteriolar density; however, interstitial fibrosis was markedly reduced. Three-vessel intra-coronary administration of CDCs improves LV diastolic function and reduces LV fibrosis in this hypertensive model of HFpEF.

Computed tomography for transcatheter tricuspid valve development.

BACKGROUND: Patients with severe symptomatic tricuspid regurgitation (TR) are often deemed ineligible for surgical valve repair due to comorbidities. In this setting, transcatheter tricuspid valve replacement (TTVR) is undergoing development, but delivery technique and prosthesis design have yet to be optimized. We sought to assess the challenges of TTVR and the determinants of venous route using computed tomography (CT) analysis. METHODS AND RESULTS: A total of 195 end-diastolic cardiac CT performed prior to surgical correction of a severe TR (n = 38), transcatheter aortic valve replacement (n = 89), or left atrial appendage closure (n = 68) were analyzed. Patients with TR (n = 68; 19 primary and 49 secondary) were compared with patients without (n = 127). Continuous variables with normal and non-normal distributions were compared using Student t test or Mann-Whitney test respectively. The angle from the tricuspid annulus (TA) to the inferior vena cava was tighter (mean = 101 ± 18°) with a broader range of value (44° to 164°) than to the superior vena cava (mean = 143 ± 9°). Patients with TR had rounder TA (eccentricity index of 0.88 ± 0.08, p < 0.001), with a larger area (p < 0.0001), and septolateral (45.3 ± 8.0 mm, p < 0.0001) and anteroposterior (44.4 ± 7.4 mm, p < 0.0001) diameters than patients without. The distances from the TA to the coronary sinus, the right ventricular outflow tract, and the moderator band were respectively 11.4 ± 3.8 mm, 17.2 ± 3.4 mm, and 31.0 ± 6.7 mm, without differences between groups. CONCLUSION: The transjugular access for TTVR is straighter and more reproducible than the transfemoral access. Prosthesis development may be challenged by the close position of the coronary sinus, the presence of a moderator band, and the large TA size of patients with severe TR. KEY POINTS: • The tricuspid annulus is larger in patients with severe tricuspid regurgitation, confirming existing data. • The coronary sinus ostium is close to the tricuspid annulus, requiring a prosthesis with a short atrial length. • The transjugular venous route may be the preferred access to the tricuspid annulus, straighter with less inter-individual variations than the transfemoral route.

Refractory cor pulmonale under extracorporeal membrane oxygenation for acute respiratory distress syndrome: the role of conversion to veno-pulmonary arterial assist-a case series.

Introduction: Pulmonary vascular dysfunction during severe acute respiratory distress syndrome (ARDS) may lead to right ventricle (RV) dysfunction and acute cor pulmonale (ACP). The occurrence/persistence of ACP despite conventional extracorporeal membrane oxygenation (ECMO) is a challenging situation. We explored the usefulness of a specific dual-lumen cannula that bypasses the RV, and on which a veno-pulmonary arterial assist (V-P ECMO) was mounted, in ARDS patients. Methods: We report a case-series of ARDS patients put on conventional veno-arterial or veno-venous ECMO and presented refractory ACP as an indication for a reconfiguration to V-P ECMO using the ProtekDuo cannula. The primary endpoint was the mitigation of RV and pulmonary vascular dysfunction as assessed by the change in end-diastolic RV/left ventricle (LV) surface ratio. Results: Six patients had their conventional ECMO reconfigured to V-P ECMO to treat refractory ACP. There was a decrease in end-diastolic RV/LV surface ratio, as well as end-systolic LV eccentricity index, and lactatemia immediately after V-P ECMO initiation. The resolution of refractory ACP was immediately achieved in four of our six (66%) patients. The V-P ECMO was weaned after a median of 26 [8-93] days after implantation. All but one patient were discharged home. We detected one case of severe hemolysis with V-P ECMO and two suspected cases of right-sided infective endocarditis. Conclusion: V-P ECMO is useful to mitigate RV overload and to improve hemodynamics in case of refractory ACP despite conventional ECMO.

A Randomized Controlled Trial of Nonfasting vs Fasting Before Interventional Coronary Procedures: The TONIC Trial.

BACKGROUND: Fasting before coronary procedures is currently recommended to reduce complications despite the lack of scientific evidence. OBJECTIVES: The TONIC (Comparison Between Fasting and No Fasting Before Interventional Coronary Intervention on the Occurrence of Adverse Events) noninferiority trial investigated the safety and comfort of a nonfasting strategy (ad libitum food and drinks) vs traditional fasting (>6 hours for solid food and liquids) before coronary procedures. METHODS: In this monocentric, prospective, single-blind randomized controlled trial, 739 patients undergoing coronary procedures were included and randomized to a fasting or a nonfasting strategy. Emergency procedures were excluded. The primary endpoint was a composite of vasovagal reaction, hypoglycemia (defined by blood sugar ≤0.7 g/L), and isolated nausea and/or vomiting. Noninferiority margin was 4%. Secondary endpoints were contrast-induced nephropathy and patients' satisfaction. RESULTS: Among the 739 procedures (697 elective and 42 semiurgent), 517 angiographies, and 222 angioplasties (including complex and high-risk procedures) were performed. The primary endpoint occurred in 30 of 365 nonfasting patients (8.2%) vs 37 of 374 fasting patients (9.9%), demonstrating noninferiority (absolute between-group difference, -1.7%; 1-sided 95% CI upper limit: 1.8%). No food-related adverse event occurred, and contrast-related acute kidney injuries were similar between groups. Overall, procedure satisfaction and perceived pain were similar in both groups, but nonfasting patients reported less hunger and thirst (P < 0.01). In case of redo coronary procedures, most patients (79%) would choose a nonfasting strategy. CONCLUSIONS: The TONIC randomized trial demonstrates the noninferiority of a nonfasting strategy to the usual fasting strategy for coronary procedures regarding safety, while improving patients' comfort.