Percutaneous edge-to-edge mitral valve repair for mitral regurgitation improves heart failure symptoms in heart failure with preserved ejection fraction patients.

AIMS: Therapeutic options for patients with heart failure with preserved ejection fraction (HFpEF) are sparse. Mitral regurgitation (MR) is a common feature of HFpEF and worsens heart failure symptoms and prognosis. Our study examines the outcome of patients with preserved left ventricular ejection fraction (LVEF) and elevated left atrial (LAP) or left ventricular filling pressures (LVEDP), indicative of HFpEF, after undergoing percutaneous edge-to-edge mitral valve repair (pMVR) for moderate-severe MR. METHODS AND RESULTS: Two hundred eleven patients with preserved LVEF (>50%), who underwent pMVR, were dichotomized by LAP (< / ≥15 mmHg) and LVEDP (< / ≥16 mmHg). Forty-nine per cent of patients showed elevated LAP, and LVEDP was elevated in 55%, both indicating HFpEF. Patients with elevated filling pressures featured typical clinical characteristics of HFpEF, higher N-terminal pro-brain natriuretic peptide levels (5544.9 pg/mL in high LAP group vs. 3071.7 pg/mL in normal LAP group, P = 0.06; 5061.0 pg/mL in high LVEDP group vs. 3230.3 pg/mL in normal LVEDP group, P = 0.08), and higher prevalence of pulmonary hypertension (mean pulmonary artery pressure 36.4 mmHg in high LAP group vs. 26.3 mmHg in normal LAP group, P < 0.001; 35.2 mmHg in high LVEDP group vs. 29.7 mmHg in normal LVEDP group, P = 0.004) and atrial fibrillation (78.8% in normal LAP group vs. 61.0% in high LAP group, P = 0.04; 75.3% in high LVEDP group vs. 67.5% in normal LVEDP group, P = 0.25). Pre-treatment MR grade and New York Heart Association (NYHA) class were similar in both normal filling pressure and HFpEF groups. pMVR in HFpEF patients achieved effective heart failure symptom relief comparable with patients with normal filling pressures: significant decrease of MR grade and NYHA class, as well as significant reduction of heart failure hospitalizations 12 months after compared with 12 months before MitraClip. CONCLUSION: Percutaneous edge-to-edge mitral valve repair for moderate-severe MR is an effective treatment option for symptom relief in HFpEF patients.

Anti-tumor necrosis factor-α therapy increases plaque burden in a mouse model of experimental atherosclerosis.

BACKGROUND AND AIMS: Atherosclerosis is critically fueled by vascular inflammation through oxidized lipids and inflammatory cytokines such as tumor necrosis factor (TNF)-α. Genetic disruption of Tnf-α reduces atherosclerosis in experimental mouse models. However, less is known about the therapeutic potential of Tnf-α blockage by pharmacological inhibitors such as monoclonal antibodies, which are already approved for several inflammatory disorders in patients. Therefore, we investigated the effect of pharmacological TNF-α inhibition on plaque development in experimental atherosclerosis. RESULTS: 10 week old male Ldlr-/- mice were divided into 4 groups (n = 7-10) and fed a high fat, high cholesterol diet for 6 and 12 weeks. Simultaneously, the mouse-specific anti-Tnf-α monoclonal antibody CNTO5048 (CNT) or a control IgG was administered. RESULTS: CNT reduced circulating inflammatory markers without affecting body weight and glucose metabolism. Unexpectedly, CNT treatment increased plasma triglyceride levels and pro-atherogenic very-low-density lipoprotein (VLDL) cholesterol as well as plaque burden in the thoracoabdominal aorta and in the aortic root. In addition, we observed decreased smooth muscle cell content in the lesions and a trend towards reduced collagen deposition upon Tnf-α inhibition. Furthermore, inflammatory gene expression in the aortic arch was increased following Tnf-α inhibitor treatment. CONCLUSIONS: Although up to 12-week pharmacological inhibition of TNF-α in Ldlr-/- mice diminishes systemic inflammation, experimental plaque burden and vascular inflammatory gene expression are increased, while markers of plaque stability decrease. These observations may be explained by the development of a pro-atherogenic plasma lipid profile.