Updated pathophysiological overview of functional MR (ventricular and atrial).

Basic mechanism of ventricular functional mitral regurgitation (FMR) is subvalvular tethering. Left ventricular (LV) dilatation, in association with mitral valve (MV) annular dilatation, causes outward displacement of papillary muscles (PMs), which abnormally pulls or tethers MV leaflets, resulting in MV tenting, reduction in leaflets coaptation and MR. Because surgical annuloplasty does shorten distance between anterior and posterior MV annuli to improve coaptation but does not address this subvalvular tethering, ventricular FMR frequently persists or recurs in the chronic stage after surgical annuloplasty. This high incidence of persistent/recurrent MR requires additional procedures to reduce subvalvular tethering. Although patients occasionally show marked improvements after annuloplasty with surgical tethering reduction procedures such as PM approximation, evidence to support benefits of such surgery is limited, requiring further trials. Recently, MV adaptation or MV leaflets tissue growth associated with LV dilatation attracts attention. Patients with larger MV leaflets with significant LV dilatation/dysfunction show less MV tethering and MR compared to those with smaller MV leaflets but with similar LV remodeling, suggesting the protective or beneficial role of MV leaflets tissue growth against LV remodeling. The MV leaflets tissue growth has the potential to lead to novel strategies of treatment for ventricular FMR. It is well known that atrial FMR is frequent in patients with left atrial dilatation, typically in those with isolated atrial fibrillation. The degree of atrial FMR is usually mild, even when it is present, and occasionally moderate, and severe atrial FMR is really rare. It is known that only severe regurgitation causes heart failure in primary MR, resulting in description on indications of surgery or intervention for only severe MR in current guidelines. Therefore, this atrial FMR up to moderate degree did not attract attention for a long time. However, recent studies have shown that patients with only moderate atrial FMR develop severe heart failure, suggesting more aggressive indication of MV surgery or intervention for "moderate" regurgitation in patients with atrial FMR. Therefore, atrial FMR is now recognized highly important. The unveiled malignant nature of atrial FMR arises many questions, including (1) why patients with only moderate atrial FMR develop heart failure? (2) do patients with mild atrial FMR develop heart failure or not?, and many others. Atrial FMR seems even more mysterious after the unveiling of its significance.

Cyclophilin D induces necrotic core formation by mediating mitochondria-associated macrophage death in advanced atherosclerotic lesions.

BACKGROUND AND AIMS: In advanced atherosclerotic lesions, macrophage deaths result in necrotic core formation and plaque vulnerability. Cyclophilin D (CypD) is a mitochondria-specific cyclophilin involved in the process of cell death after organ ischemia-reperfusion. However, the role of CypD in atherosclerosis, especially in necrotic core formation, is unknown. Therefore, this experiment aims to clarify the role of CypD in necrotic core formation. METHODS: To clarify the specific role of CypD, encoded by Ppif in mice, apolipoprotein-E/CypD-double knockout (Apoe-/-Ppif-/-) mice were generated. These mice were fed a high-fat diet containing 0.15 % cholesterol for 24 weeks to accelerate atherosclerotic lesion development. RESULTS: Deletion of CypD decreased the necrotic core size, accompanied by a reduction of macrophage apoptosis compared to control Apoe-/- mice. In RAW264.7 cells, siRNA-mediated knockdown of CypD attenuated the release of cytochrome c from the mitochondria to the cytosol induced by endoplasmic reticulum stress inducer thapsigargin. In addition, necroptosis, induced by TNF-α and caspase inhibitor, was attenuated by knockdown of CypD. Ly-6Chigh inflammatory monocytes in peripheral blood leukocytes and mRNA expression of Il1b in the aorta were decreased by deletion of CypD. In contrast, siRNA-mediated knockdown of CypD did not significantly decrease Il1b nor Ccl2 mRNA expression in RAW264.7 cells treated with LPS and IFN-γ, suggesting that inhibition of inflammation in vivo is likely due to decreased cell death in the atherosclerotic lesions rather than a direct action of CypD deletion on the macrophage. CONCLUSIONS: These results indicate that CypD induces macrophage death and mediates necrotic core formation in advanced atherosclerotic lesions. CypD could be a novel therapeutic target for treating atherosclerotic vascular diseases.

Proximal superficial femoral artery puncture using an ascending approach for stent re-occlusion in the common femoral artery.

We aimed to describe a technique for approaching the common femoral artery (CFA) in cases where doing so is difficult owing to an occluded lesion caused by a previously implanted stent. A 72-year-old woman had severe stenotic lesions in both iliac arteries that required an approach via the bilateral femoral arteries. The right CFA had a previously implanted stent and a completely occluded lesion that extended from the superficial femoral artery (SFA). A 20G needle was inserted through the proximal SFA, and the needle tip was advanced into the CFA stent and passed through the occluded lesion using a microcatheter and guide wire (GW). This allowed us to insert a guide catheter via the GW into the occluded lesion. No complications, such as bleeding, were observed after the procedure. When the CFA is occluded by a stent, an ascending approach through the proximal SFA is a viable treatment option. Learning objective: An occluded lesion due to a previously implanted stent makes approaching the common femoral artery difficult. Hence, alternative approaches are needed. In this regard, an approach via the proximal superficial femoral artery may prove useful.

Potential Effects of Mild Atrial Secondary Mitral Regurgitation in Patients With Isolated Atrial Fibrillation.

BACKGROUND: Patients with only moderate atrial secondary mitral regurgitation (asMR) frequently develop heart failure (HF). Mechanisms of HF with moderate asMR and the impact of mild asMR remain unclarified. Although mild/moderate primary mitral regurgitation is compensated by left ventricular (LV) dilatation, the LV is not dilated in asMR. We hypothesized that patients with mild asMR without LV dilatation may have impaired hemodynamics and higher risks of subsequent symptomatic HF deterioration. METHODS: Stroke volume, cardiac output, and systolic pulmonary artery pressure were measured by echocardiography in 142 patients with isolated atrial fibrillation and 30 healthy controls. The prognosis of patients with isolated atrial fibrillation was followed up. RESULTS: In the 142 patients with isolated atrial fibrillation, asMR was no/trivial in 55, mild in 83, moderate in 4, while none had severe asMR. Compared with controls and patients with no/trivial asMR, LV end-diastolic volume index was not increased and hemodynamic parameters were abnormal in patients with mild asMR (LV end-diastolic volume index, 65±6 versus 58±8 versus 60±8 mL/m²; stroke volume index, 42±4 versus 35±4 versus 29±6 mL/m²; P<0.001 versus other 2 groups; cardiac output index, 2.8±0.4 versus 2.8±0.5 versus 2.3±0.6 L/min per m²; P<0.001; systolic pulmonary artery pressure, 21±3 versus 26±5 versus 37±9 mm Hg; P<0.001). Although the event-free rate of HF symptomatic deterioration or hospitalization in patients with no/trivial asMR during a median 13.9 months follow-up was 86.9% and 100%, the rate in mild asMR was 59.4% and 85.0% (P<0.001 or P=0.032), respectively. CONCLUSIONS: In the presence of isolated AF and no compensatory LV dilatation, impaired hemodynamics and higher risks of symptomatic HF deterioration were associated with mild asMR, requiring further studies of causalities.

A microsurgical technique for catheter insertion in the rat femoral artery

Abstract Purpose: To modify a surgical catheterization method using the bent needle introducer in small animals. Methods: Eight-week-old male Lewis rats were used in the study. A needle introducer was created by bending a 21G injection needle at 45°. The bent needle introducer was used for catheter insertion into the left femoral artery of the rats under anesthesia. As a control, a catheter was directly inserted into the blood vessel without the introducer. The insertion time of each method was measured. Blood pressure and heart rate were measured 24 h after catheter insertion using the telemetry system. Results: Using the introducer, the catheter was successfully inserted within a short time in all rats. Without the introducer, a longer duration was required for catheter insertion. The frequency of the insertion with no catheter-based errors with the introducer tended to be higher than that without the introducer. The mean arterial pressure and heart rate 24 h after catheter insertion in each group were almost the same. Conclusions: We developed a surgical catheterization method using the introducer in small animals. This could potentially reduce the frequency of the insertion with catheter-based errors and insertion time.