Kentaro Hayashida

Transfemoral aortic valve implantation new criteria to predict vascular complications.

OBJECTIVES This study sought to evaluate the incidence, impact, and predictors of vascular complications in transcatheter aortic valve implantation (TAVI). BACKGROUND Vascular complications increase morbidity and mortality in transfemoral TAVI; however, there remains a paucity of data describing these serious events. METHODS We performed a prospective cohort study of 130 consecutive transfemoral TAVI recipients. Vascular complications were defined by the Valve Academic Research Consortium (VARC) criteria. The ratio of the sheath outer diameter (in millimeters) to the minimal femoral artery diameter (in millimeters) defined the sheath to femoral artery ratio (SFAR). RESULTS In our cohort of elderly patients (83.3 ± 5.9 years), the logistic EuroScore was 25.8% ± 11.9%. The Edwards valve was used in 102 cases (18- to 24-F) and the CoreValve in 27 (18-F). The minimal femoral artery diameter was 8.17 ± 1.14 mm, and the calcification (0 to 3) and tortuosity scores (0 to 3) were 0.58 ± 0.72 and 0.28 ± 0.53, respectively. The mean sheath diameter was 8.10 ± 0.82 mm, and the mean SFAR was 0.99 ± 0.16. Vascular complications occurred in 27.6% (VARC major: 17.3%, minor: 10.2%), and major vascular complications predicted 30-day mortality (22.7% vs. 7.6%, p = 0.049). The SFAR (hazard ratio [HR]: 186.20, 95% confidence interval [CI]: 4.41 to 7,855.11), center experience (HR: 3.66, 95% CI: 1.17 to 11.49), and femoral calcification (HR: 3.44, 95% CI: 1.16 to 10.17) predicted major complications by multivariate analysis. An SFAR threshold of 1.05 (area under the curve = 0.727) predicted a higher rate of VARC major complications (30.9% vs. 6.9%, p = 0.001) and 30-day mortality (18.2% vs. 4.2%, p = 0.016). CONCLUSIONS Vascular complications in transfemoral TAVI are relatively frequent. VARC major vascular complications increase 30-day mortality and are predicted by experience, femoral calcification, and SFAR. Routine application of SFAR will improve patient selection for transfemoral TAVI and may improve outcome.

Percutaneous Transluminal Pulmonary Angioplasty for the Treatment of Chronic Thromboembolic Pulmonary Hypertension

Background—Chronic thromboembolic pulmonary hypertension leads to pulmonary hypertension and right-sided heart failure. The purpose of this study was to investigate the efficacy of percutaneous transluminal pulmonary angioplasty (PTPA) for the treatment of chronic thromboembolic pulmonary hypertension. Methods and Results—Twenty-nine patients with chronic thromboembolic pulmonary hypertension underwent PTPA. One patient had a wiring perforation as a complication of PTPA and died 2 days after the procedure. In the remaining 28 patients, PTPA did not produce immediate hemodynamic improvement at the time of the procedure. However, after follow-up (6.0 ± 6.9 months), New York Heart Association functional classifications and levels of plasma B-type natriuretic peptide significantly improved (both P<0.01). Hemodynamic parameters also significantly improved (mean pulmonary arterial pressure, 45.3 ± 9.8 versus 31.8 ± 10.0 mm Hg; cardiac output, 3.6 ± 1.2 versus 4.6 ± 1.7 L/min, baseline versus follow-up, respectively; both P<0.01). Twenty-seven of 51 procedures in total (53%), and 19 of 28 first procedures (68%), had reperfusion pulmonary edema as the chief complication. Patients with severe clinical signs and/or severe hemodynamics at baseline had a high risk of reperfusion pulmonary edema. Conclusions—PTPA improved subjective symptoms and objective variables, including pulmonary hemodynamics. PTPA may be a promising therapeutic strategy for the treatment of chronic thromboembolic pulmonary hypertension. Clinical Trial Registration—URL: http://www.umin.ac.jp. Unique identifier: UMIN000001572.

Sex-related differences in clinical presentation and outcome of transcatheter aortic valve implantation for severe aortic stenosis.

OBJECTIVES The purpose of this study was to clarify the impact of sex-related differences in transcatheter aortic valve implantation (TAVI) for high-risk patients with severe aortic stenosis. BACKGROUND Although TAVI is becoming a mature technique, the impact of sex differences remains unclear. METHODS The TAVI patients were included prospectively in a dedicated database from October 2006. The proportion of women (n = 131) was similar to that of men (n = 129). The Edwards valve (85.4%) and CoreValve (14.6%) were used through the transfemoral (65.0%), subclavian (3.1%), or transapical (31.9%) approach. All events were defined according to Valve Academic Research Consortium criteria. RESULTS Age was similar (83.1 ± 6.3 years), but women had less coronary and peripheral disease, less previous cardiac surgery, higher ejection fraction, and lower EuroSCORE (European System for Cardiac Operative Risk Evaluation [22.3 ± 9.0% vs. 26.2 ± 13.0%, p = 0.005]). Minimal femoral size (7.74 ± 1.03 mm vs. 8.55 ± 1.34 mm, p < 0.001), annulus size (20.9 ± 1.4 vs. 22.9 ± 1.7 mm, p < 0.001), and valve size (23.9 ± 1.6 mm vs. 26.3 ± 1.5 mm, p < 0.001) were smaller in women. Device success was similar (90.8% vs. 88.4%, p = 0.516) despite more frequent iliac complications (9.0% vs. 2.5%, p = 0.030). Residual mean aortic pressure gradient (11.6 ± 4.9 vs. 10.9 ± 4.9, p = 0.279) was also similar. The 1-year survival rate was higher for women, 76% (95% confidence interval: 72% to 80%), than for men, 65% (95% confidence interval: 60% to 69%); and male sex (hazard ratio: 1.62, 95% confidence interval: 1.03 to 2.53, p = 0.037) was identified as a predictor of midterm mortality by Cox regression analysis. CONCLUSIONS Female sex is associated with better baseline clinical characteristics and improved survival, and is identified as a predictor of midterm survival after TAVI.

Impact of post-procedural aortic regurgitation on mortality after transcatheter aortic valve implantation

OBJECTIVES The goal of the study was to clarify the impact of post-procedural aortic regurgitation (post-AR) grade 2/4 on clinical outcomes. BACKGROUND Post-AR >2/4 is known to be associated with poor short- to midterm outcome after transcatheter aortic valve implantation (TAVI). METHODS We compared clinical outcomes in 400 consecutive TAVI recipients according to post-AR grade: grade 0 or 1 (group 1 = 74.8%), grade 2 (group 2 = 22.2%), or grade 3 or 4 (group 3 = 3.0%). RESULTS The mean age was similar in the 3 groups (83.4 ± 6.1 years) as was the logistic EuroSCORE (22.5 ± 11.4%, 24.5 ± 11.6%, and 21.5 ± 9.4%, p = 0.28) and annulus size (22.0 ± 1.8, 22.2 ± 2.1, and 22.5 ± 2.1 mm, p = 0.53). The Edwards valve was most frequently used in group 1 compared with groups 2 and 3 (89.3%, 78.7%, and 83.3%, p = 0.03), and the implanted valve size was similar in all groups (25.6 ± 2.0, 25.4 ± 2.2, and 25.5 ± 2.2 mm, respectively, p = 0.69). Post-dilation was required more frequently in group 3 (4.7%, 24.1%, and 50.0%, respectively, p < 0.01). Post-procedural increase in mitral regurgitation was in line with the post-AR grade (0.78 ± 0.73, 1.22 ± 0.80, and 1.89 ± 0.78, respectively, p < 0.01). Despite the absence of difference in 30-day mortality, longer-term outcome was significantly poorer in patients with AR grade 2 than in those with AR grade 0 or 1 (log-rank p < 0.01), albeit better than in patients with AR grade 3 or 4 (p = 0.04), regardless of TAVI type and left ventricular function. Post-AR ≥2/4 was also identified as an independent predictor of mid- to long-term mortality (hazard ratio: 1.68, 95% confidence interval: 1.21 to 1.44, p < 0.01). CONCLUSIONS Post-AR grade 2/4 after TAVI is associated with worse outcome compared with grade 0 or 1. Careful valve selection and post-dilation when required to avoid post-AR grade 2 may contribute to improved clinical outcome after TAVI.

Transcatheter Aortic Valve Implantation for Patients With Severe Bicuspid Aortic Valve Stenosis

Background—Bicuspid aortic valve (BAV) is regarded as a relative contraindication to transcatheter aortic valve implantation attributable to the risk of uneven expansion of the bioprosthesis. The purpose of this study was to evaluate the efficacy and safety of transcatheter aortic valve implantation in patients with BAV. Methods and Results—Of 470 patients included in our prospective transcatheter aortic valve implantation database (October 2006–January 2012), 229 consecutive patients undergoing both echocardiography and multidetector computed tomography were analyzed. We compared clinical outcomes in patients with vs patients without BAV. In this series of 229 patients, BAV was detected by multidetector computed tomography in 21 patients (9.2%). BAV was identified by transthoracic and transoesophagal echocardiography in only 9 of these 21 patients. Patients were 83.1±6.6 years old, and European system for cardiac operative risk evaluation score was 20.0%±11.4%. The BAV group was similar to the non-BAV group except for diabetes mellitus (4.8% vs 24.0%; P=0.05). The aortic annulus diameter in BAV patients was not significantly larger by multidetector computed tomography (24.7±3.0 vs 23.7±1.9 mm; P=0.07). The CoreValve was used more frequently in the BAV group (47.6% vs 16.3%; P=0.002). There was no significant difference in device success (100% vs 92.8%; P=0.37), risk of annulus rupture (0% vs 1.4%; P=1.00), or valve migration (0% vs 1.4%; P=1.00) in BAV patients compared with non-BAV patients. Postprocedural mean gradient (10.0±3.4 vs 9.7±4.1 mm Hg; P=0.58), aortic regurgitation ≥2 of 4 (19.0% vs 14.9%; P=0.54), 30-day mortality (4.8% vs 8.2%; P=1.00), and 30-day combined safety end point (14.3% vs 13.5%; P=1.00) were also similar in both groups. Conclusions—In selected BAV patients, transcatheter aortic valve implantation may be associated with low complication rate, efficacy, and acceptable outcomes similar to those in non-BAV patients.

Glucocorticoid protects rodent hearts from ischemia/reperfusion injury by activating lipocalin-type prostaglandin D synthase–derived PGD2 biosynthesis

Lipocalin-type prostaglandin D synthase (L-PGDS), which was originally identified as an enzyme responsible for PGD2 biosynthesis in the brain, is highly expressed in the myocardium, including in cardiomyocytes. However, the factors that control expression of the gene encoding L-PGDS and the pathophysiologic role of L-PGDS in cardiomyocytes are poorly understood. In the present study, we demonstrate that glucocorticoids, which act as repressors of prostaglandin biosynthesis in most cell types, upregulated the expression of L-PGDS together with cytosolic calcium-dependent phospholipase A2 and COX2 via the glucocorticoid receptor (GR) in rat cardiomyocytes. Accordingly, PGD2 was the most prominently induced prostaglandin in vivo in mouse hearts and in vitro in cultured rat cardiomyocytes after exposure to GR-selective agonists. In isolated Langendorff-perfused mouse hearts, dexamethasone alleviated ischemia/reperfusion injury. This cardioprotective effect was completely abrogated by either pharmacologic inhibition of COX2 or disruption of the gene encoding L-PGDS. In in vivo ischemia/reperfusion experiments, dexamethasone reduced infarct size in wild-type mice. This cardioprotective effect of dexamethasone was markedly reduced in L-PGDS-deficient mice. In cultured rat cardiomyocytes, PGD2 protected against cell death induced by anoxia/reoxygenation via the D-type prostanoid receptor and the ERK1/2-mediated pathway. Taken together, these results suggest what we believe to be a novel interaction between glucocorticoid-GR signaling and the cardiomyocyte survival pathway mediated by the arachidonic acid cascade.

Renal function-based contrast dosing predicts acute kidney injury following transcatheter aortic valve implantation.

OBJECTIVES This study sought to assess whether the volume of contrast media (CM) influences the occurrence of acute kidney injury (AKI) following transcatheter aortic valve implantation (TAVI). BACKGROUND The volume of CM has been shown to be associated with increasing risk of AKI; however, in a high-risk elderly TAVI population, the predictive value and optimal threshold of CM dose on AKI remain uncertain. METHODS Data of 415 consecutive transfemoral TAVI patients (age 83.6 ± 6.8 years, logistic EuroSCORE 23.0 ± 12.2%) were analyzed. AKI was defined by Valve Academic Research Consortium criteria. Based on a previous formula, the ratio of CM to serum creatinine (SCr) and body weight (BW) (CM × SCr/BW) was calculated as defining the degree of CM use. The association between CM dose and incidence of AKI, as well as predictive factors and prognosis of AKI, were investigated. RESULTS AKI occurred in 63 patients (15.2%). Cumulative 1-year mortality showed significant differences between the AKI and non-AKI groups (47.9% vs. 15.7%, p < 0.001). Mean CM × SCr/BW ratio was higher in the AKI group than in the non-AKI group (4.1 ± 2.9 vs. 2.9 ± 1.6, p < 0.001). By multivariate analysis, CM × SCr/BW per 1.0 increase, ejection fraction <40%, and transfusion were associated with the occurrence of AKI (odds ratio [OR]: 1.16; 95% confidence interval [CI]: 1.03 to 1.20; p = 0.017, OR: 3.01; 95% CI: 1.49 to 5.00; p = 0.001, OR: 2.73; 95% CI: 1.54 to 6.15; p = 0.001, respectively). A threshold value of CM × SCr/BW for predicting AKI was statistically identified as 2.7. CONCLUSIONS Although mechanisms of AKI following TAVI are multifactorial, the present study identified a relationship between CM dose increment and high prevalence of AKI. Therapeutic efforts not to exceed the threshold value may reduce the risk of AKI.

Are the effects of α-glucosidase inhibitors on cardiovascular events related to elevated levels of hydrogen gas in the gastrointestinal tract?

The major side‐effect of treatment with α‐glucosidase inhibitors, flatulence, occurs when undigested carbohydrates are fermented by colonic bacteria, resulting in gas formation. We propose that the cardiovascular benefits of α‐glucosidase inhibitors are partly attributable to their ability to neutralise oxidative stress via increased production of H2 in the gastrointestinal tract. Acarbose, which is an α‐glucosidase inhibitor, markedly increased H2 production, with a weaker effect on methane production. Our hypothesis is based on our recent discovery that H2 acts as a unique antioxidant, and that when inhaled or taken orally as H2‐dissolved water it ameliorates ischaemia–reperfusion injury and atherosclerosis development.

Bone Marrow–Derived Cells Are Involved in the Pathogenesis of Cardiac Hypertrophy in Response to Pressure Overload

Background— Bone marrow (BM) cells possess broad differentiation potential and can form various cell lineages in response to pathophysiological cues. The present study investigated whether BM-derived cells contribute to the pathogenesis of cardiac hypertrophy, as well as the possible cellular mechanisms involved in such a role. Methods and Results— Lethally irradiated wild-type mice were transplanted with BM cells from enhanced green fluorescent protein–transgenic mice. The chimeric mice were subjected to either prolonged hypoxia or transverse aortic constriction. BM-derived enhanced green fluorescent protein–expressing cardiomyocytes increased in number over time, emerging predominantly in the pressure-overloaded ventricular myocardium, although they constituted <0.01% of recipient cardiomyocytes. To determine whether BM-derived cardiomyocytes were derived from cell fusion or transdifferentiation at the single-cell level, lethally irradiated Cre mice were transplanted with BM cells from the double-conditional Cre reporter mouse line Z/EG. BM-derived cardiomyocytes were shown to arise from both cell fusion and transdifferentiation. Interestingly, BM-derived myofibroblasts expressing both vimentin and &agr;-smooth muscle actin were concentrated in the perivascular fibrotic area. These cells initially expressed MAC-1/CD14 but lost expression of these markers during the chronic phase, which suggests that they were derived from monocytes. A similar phenomenon occurred in cultured human monocytes, most of which ultimately expressed vimentin and &agr;-smooth muscle actin. Conclusions— We found that BM-derived cells were involved in the pathogenesis of cardiac hypertrophy via the dual mechanisms of cell fusion and transdifferentiation. Moreover, the present results suggest that BM-derived monocytes accumulating in the perivascular space might play an important role in the formation of perivascular fibrosis via direct differentiation into myofibroblasts.

Potential mechanism of annulus rupture during transcatheter aortic valve implantation

Although annulus rupture is one of the most severe complications of transcatheter aortic valve implantation (TAVI), the incidence and mechanism of this complication remain unclear. Out of 387 consecutive TAVI cases in our institution, the incidence of annulus rupture was 1.0% (4/387). The first two patients died because of hemodynamic collapse due to tamponade on day 0. Both surviving patients had undergone preprocedural multidetector computed tomography which revealed large calcifications in the epicardial fat part of the aortic annulus. In both cases, annulus rupture occurred after deployment of a balloon expandable valve suggesting that mechanical compression of this “vulnerable area” by calcification may cause annulus rupture.