Effect of empagliflozin on ketone bodies in patients with stable chronic heart failure.

BACKGROUND: Recent studies indicated that sodium glucose cotransporter (SGLT)2 inhibition increases levels of ketone bodies in the blood in patients with type 1 and 2 diabetes. Other studies suggested that in patients with chronic heart failure (CHF), increased myocardial oxygen demand can be provided by ketone bodies as a fuel substrate. Experimental studies reported that ketone bodies, specifically beta-hydroxybutyrate (ß-OHB) may increase blood pressure (BP) by impairing endothelium-dependant relaxation, thereby leading to increased vascular stiffness. In our study we assessed whether the SGLT 2 inhibition with empagliflozin increases ketone bodies in patients with stable CHF and whether such an increase impairs BP and vascular function. METHODS: In a prospective, double blind, placebo controlled, parallel-group single centre study 75 patients with CHF (left ventricular ejection fraction 39.0 ± 8.2%) were randomised (2:1) to the SGLT-2 inhibitor empagliflozin 10 mg orally once daily or to placebo, 72 patients completed the study. After a run-in phase we evaluated at baseline BP by 24 h ambulatory blood pressure (ABP) monitoring, vascular stiffness parameters by the SphygmoCor system (AtCor Medical, Sydney, NSW, Australia) and fasting metabolic parameters, including ß-OHB by an enzymatic assay (Beckman Coulter DxC 700 AU). The same measurements were repeated 12 weeks after treatment. In 19 of the 72 patients serum levels of ß-OHB were beneath the lower border of our assay (< 0.05 mmol/l) therefore being excluded from the subsequent analysis. RESULTS: In patients with stable CHF, treatment with empagliflozin (n = 36) was followed by an increase of ß-OHB by 33.39% (p = 0.017), reduction in 24 h systolic (p = 0.038) and diastolic (p = 0.085) ABP, weight loss (p = 0.003) and decrease of central systolic BP (p = 0.008) and central pulse pressure (p = 0.008). The increase in ß-OHB was related to an attenuated decrease of empagliflozin-induced 24 h systolic (r = 0.321, p = 0.069) and diastolic (r = 0.516, p = 0.002) ABP and less reduction of central systolic BP (r = 0.470, p = 0.009) and central pulse pressure (r = 0.391, p = 0.033). No significant changes were seen in any of these parameters after 12 weeks of treatment in the placebo group (n = 17). CONCLUSION: In patients with stable CHF ketone bodies as assessed by ß-OHB increased after treatment with empagliflozin. This increase led to an attenuation of the beneficial effects of empagliflozin on BP and vascular parameters. Trial registration The study was registered at http://www.clinicaltrials.gov (NCT03128528).

[Diamond-Forrester and cardiac CT : Is there a need to redefine the pretest probability of coronary artery disease?]. / Diamond-Forrester und Kardio-CT : Muss die KHK-Vortestwahrscheinlichkeit neu definiert werden?

Apart from the Diamond-Forrester classification, which is widely used particularly in the USA for the pretest probability of coronary artery disease, other scores also exist, such as an updated version of the classification table by Genders et al., the Morise score and the Duke clinical risk score. These scores estimate the probability of coronary artery disease, defined as the presence of at least one high-grade stenosis, based on symptom characteristics, age, gender and other parameters. All of the scores were derived from patient cohorts in which invasive coronary angiography had been performed for clinical reasons. It has subsequently been shown that these scores, especially those developed several decades ago, substantially overestimate the pretest probability of coronary artery disease. When these risk scores are applied to patients for whom a non-invasive work-up of suspected coronary artery disease is planned, for example by coronary computed tomography (CT) angiography, the expected prevalence of significant coronary stenosis will be overestimated. This, in turn, influences the test characteristics and the significance of the non-invasive examination (positive and negative predictive values) and needs to be taken into account when interpreting test results.

Leaflet thrombosis following transcatheter aortic valve implantation.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is increasingly being offered to high-risk patients with symptomatic aortic valve stenosis. Recent reports have suggested a high incidence of subclinical leaflet thrombosis following bioprosthestic aortic valve replacement. We report the frequency and clinical presentation of leaflet thrombosis identified by cardiac CT in patients referred for follow-up contrast enhanced CT angiography following TAVI. METHODS: 91 consecutive patients referred for follow-up contrast-enhanced CT angiography following TAVI were screened for inclusion in this analysis. Out of these, 13 patients were excluded. All CT examinations were performed using a 2nd or a 3rd generation dual-source system (Somatom Definition Flash/Force, Forchheim, Germany). In all patients, retrospectively ECG-gated spiral acquisition with tube modulation was performed to allow for assessment of leaflet motion. All prostheses were analyzed for presence of leaflet thrombosis defined as hypo-attenuated leaflet thickening with or without leaflet restriction. Post-procedural antithrombotic regimen as well as symptom status was documented in all patients. RESULTS: 78 consecutive patients (35 males, 81 ± 4 years) were analyzed. TAVI had been performed in all patients (76 transfemoral access, 2 transapical access) with either balloon-expandable prostheses (4 Sapien XT, 64 Sapien 3) or self-expandable prostheses (5 SJM Portico, 5 Symetis Acurate). Follow-up CT angiography was performed at a median of 4 months following index procedure (Interquartile range 1 month). Leaflet thrombosis was detected in 18 patients (23%, 14 Sapien 3, 1 Sapien XT, 2 SJM Portico, 1 Symetis Acurate). In patients with leaflet thickening on CT, only 11% were on either oral anticoagulation or new oral anticoagulants versus 50% for patients with no leaflet thickening (p 0.002). In patients with leaflet thrombosis, 3 leaflets were affected in 5 patients, 2 leaflets in 5 patients and in 8 patient only 1 leaflet was affected. Clinical symptoms (angina, dyspnea or both) were reported in 2/18 patients with leaflet thrombosis (11%) and in both patients a significant increase of the mean echocardiographic gradient over the prosthesis was documented. The peak and mean echocardiographic gradients obtained at the day of CT examination was significantly higher in symptomatic patients versus asymptomatic patients (peak 46 ± 7 vs. 23 ± 11 mmHg, mean 29 ± 7 vs. 12 ± 6 mmHg, p = 0.01 and 0.002, respectively). Follow-up CT was available for 4 patients with complete resolution of the hypo-attenuated leaflet thickening following treatment. CONCLUSION: Leaflet thrombosis following TAVI is a relatively frequent finding in patients referred for contrast enhanced CT angiography following TAVI. In the majority of patients it follows a subclinical course and is substantially more frequent in individuals who are not on oral anticoagulation. However, in patients with relevant increase in prosthetic gradients, symptomatic presentations are possible.