[The Mid-term Results of Transapical Transcatheter Aortic Valve Implantation for Aortic Stenosis].

We aimed to evaluate the results of transapical transcatheter aortic valve implantation (TAVI) for aortic stenosis. Thirty patients who had aortic stenosis and underwent transapical TAVI between 2016 and 2020 were enrolled. Medical records were reviewed, and the following data were retrieved and analyzed:basic demographic data, and intraoperative data and postoperative outcomes. Mean age was 85.8 years. There were 3 intraoperative complications (1 apex bleeding, 1 coronary stenosis and 1 mitral regurgitation). Extracorporeal membrane oxygenation was initiated due to unstable hemodynamics in two patients. One patient was converted to mitral valve replacement due to severe mitral regurgitation. There were 2 in-hospital complications (1 with sick sinus syndrome and 1 with cerebral infarction). One patient died of cerebral infarction and eventually, the 30-day mortality was 3%. Median observational period was 1.3 years. Three-year survival was 87.3%. Left ventricular ejection fraction increased by six months after the procedure and then, reached plateau. Left ventricular mass index decreased constantly throughout the observational period. Both parameters at one year after the procedure were significantly higher than preoperative ones. In conclusion, survival after transapical TAVI was favorable because of the low critical complication rate. Both left ventricular functional improvement and reverse remodeling were obtained.

The interference with transapical transcatheter aortic valve implantation by the anterior chordae tendineae preserved at previous mitral valve replacement.

Preserved anterior chordae tendineae is a possible risk factor for disturbing delivery of a transcatheter heart valve. Inserting a sheath just below the aortic valve for delivery of the transcatheter heart valve might be proposed as an alternative to avoid the chordae tendineae.

Clinical Outcomes After Implantation of Overlapping Bioresorbable Scaffolds vs New Generation Everolimus Eluting Stents.

INTRODUCTION AND OBJECTIVES: There is limited evidence on procedural and clinical outcomes in patients treated with overlapping bioresorbable scaffolds vs overlapping everolimus-eluting stents. We evaluated the outcomes of propensity-matched patients treated with overlapping scaffolds vs everolimus-eluting stents. METHODS: After propensity matching, 70 consecutive stable angina patients treated with overlapping bioresorbable scaffolds and 70 patients treated with overlapping new generation everolimus stents were included in this study. The primary outcome was the 1-year rate of major adverse cardiovascular events, defined as the composite of all-cause mortality, nonprocedural myocardial infarction, and target-vessel revascularization. RESULTS: Patients in the 2 groups had similar age (scaffold vs stent: 64.5 ± 10.3 vs 66 ± 9.7 years; P=.381), sex, diabetes, previous cardiovascular history, and SYNTAX score (scaffold vs stent: 18.6 ± 9.2 vs 19.4 ± 10.4; P=.635). Postprocedural acute gain was significantly lower in patients treated with scaffolds (1.82±0.66 vs 2.03±0.68mm; P=.033). At 1-year follow up, the estimated major adverse cardiovascular event rate was not significantly different between the 2 groups (scaffold vs stent: 14.5% vs 14.6%; Plog-rank=.661). Similarly, no significant differences were seen in 1-year rates of target vessel (scaffold vs stent: 14.5% vs 10%; Plog-rank=.816) or target lesion revascularization (scaffold vs stent: 9.7% vs 8.3%; Plog-rank=.815). CONCLUSIONS: Treating long lesions with overlapping scaffolds is feasible with acceptable 1-year outcomes.

Bioresorbable Vascular Scaffolds for Heavily Calcified Lesions: How to Tackle the Rugged Passage?

We present a case of a heavily calcified left anterior descending artery lesion successfully treated with bioresorbable vascular scaffold (BVS). Despite a 360° heavy calcification at the site of the culprit lesion and prior implantation of a proximal metal stent, meticulous lesion preparation with scoring balloon and use of a deep-seated child catheter facilitated the successful deployment of two BVSs. This case report demonstrates how optimal lesion preparation, adequate dedicated device support, and careful assessment with the use of intracoronary imaging device can facilitate implantation of BVS in complex lesions.

[Mitral valve replacement and papillary muscle approximation after ineffective cardiac resynchronization therapy in a patient with adriamycin-induced cardiomyopathy].

We report a case of adriamycin-induced cardiomyopathy with severe functional mitral regurgitation and congestive heart failure (CHF). Mitral valve replacement (MVR) and papillary muscle approximation (PMA) were effective for this case. A 68-year-old man had adriamycin-induced cardiomyopathy and had required repetitive hospitalizations for CHF for the past 10 years. He also required additional CHF hospitalizations after implantation of a device to perform cardiac resynchronization therapy. His echocardiogram showed severe mitral regurgitation and reduced left ventricular function. We performed MVR and PMA for his functional mitral regurgitation. We preserved the tendinous cords of the anterior and posterior leaflets of the mitral valve. His echocardiogram showed improved left ventricular systolic function and reduced left ventricular volume. He has made satisfactory progress after the operation and he has not required further hospitalizations for CHF. MVR with preservation of bilateral tendinous cords and PMA are very effective procedures for functional mitral regurgitation and intractable cardiomyopathy.

Antimicrobial activities of cinnamyl rifamycin derivatives, T-9 and T-11, against Mycobacterium tuberculosis and Mycobacterium avium complex (MAC) with special reference to the activities against intracellular MAC.

The mycobacterial activities of cinamyl rifamycin derivatives, T-9 and T-11, especially against extracellular and intracellular Mycobacterium avium complex residing within macrophages and type II pneumocytes were compared with those of other rifamycins. The activities of test rifamycins were found to be in the order rifalazil, rifabutin, T-9, T-11, and rifampicin.

Antimicrobial activity of picolinic acid against extracellular and intracellular Mycobacterium avium complex and its combined activity with clarithromycin, rifampicin and fluoroquinolones.

OBJECTIVES: A natural metal ion chelator, picolinic acid (PA), is known to potentiate macrophage antimycobacterial activity. Here, we studied the antimicrobial activity of PA against extracellular and intramacrophage Mycobacterium avium complex (MAC) organisms. METHODS: MAC organisms, MAC-infected macrophages or MAC-infected type II pneumocytes were cultured in the presence or absence of PA with or without antimycobacterial drugs, and residual bacterial cfu of extracellular or intracellular MAC were counted on 7H11 agar plates. RESULTS: First, PA exhibited antimicrobial activity against extracellular and intramacrophage MAC. The effect of PA was mimicked by other metal ion-chelating agents, such as ethylenediamine tetraacetic acid and O,O'-bis (2-aminophenyl) ethyleneglycol-N,N,N',N'-tetraacetic acid. Second, PA potentiated antimicrobial effects of a two-drug combination of clarithromycin/rifampicin and some fluoroquinolones (levofloxacin, sitafloxacin and gatifloxacin) against extracellular and intramacrophage MAC. Similar combined effects of PA with clarithromycin/rifampicin were also seen in the case of MAC residing within type II alveolar epithelial cells. CONCLUSIONS: PA exerted an appreciable anti-MAC activity, when used singly or in combination with some antimycobacterial drugs (clarithromycin/rifampicin and fluoroquinolones), suggesting the usefulness of PA as an adjunct for clinical antimicrobial chemotherapy of MAC infections.

Combined effects of ATP on the therapeutic efficacy of antimicrobial drug regimens against Mycobacterium avium complex infection in mice and roles of cytosolic phospholipase A2-dependent mechanisms in the ATP-mediated potentiation of antimycobacterial host resistance.

ATP, which serves as a mediator of intramacrophage signaling pathways through purinoceptors, is known to potentiate macrophage antimycobacterial activity. In this study we examined the effects of ATP in potentiating host resistance to Mycobacterium avium complex (MAC) infection in mice undergoing treatment with a drug regimen using clarithromycin and rifamycin and obtained the following findings. First, the administration of ATP in combination with the clarithromycin and rifamycin regimen accelerated bacterial elimination in MAC-infected mice without causing changes in the histopathological features or the mRNA expression of pro- or anti-inflammatory cytokines from those in the mice not given ATP. Second, ATP potentiated the anti-MAC bactericidal activity of macrophages cultivated in the presence of clarithromycin and rifamycin. This effect of ATP was closely related to intracellular Ca2+ mobilization and was specifically blocked by a cytosolic phospholipase A2 (cPLA2) inhibitor, arachidonyl trifluoromethylketone. Third, intramacrophage translocation of membranous arachidonic acid molecules to MAC-containing phagosomes was also specifically blocked by arachidonyl trifluoromethylketone. In the confocal microscopic observation of MAC-infected macrophages, ATP enhanced the intracellular translocation of cPLA2 into MAC-containing phagosomes. These findings suggest that ATP increases the host anti-MAC resistance by potentiating the antimycobacterial activity of host macrophages and that the cPLA2-dependent generation of arachidonic acid from the phagosomal membrane is essential for such a phenomenon.

Effects of type II alveolar epithelial cells on T cell mitogenic responses to concanavalin A and purified protein derivatives.

To investigate the role of type II alveolar epithelial cells during the T cell-dependent host immune response to Mycobacterium tuberculosis (MTB), effects of MTB-infected A-549 human type II alveolar epithelial cells (A-549 cells) on T cell mitogenesis in response to concanavalin A (Con A) and purified protein derivatives (PPD) were studied. Human peripheral blood mononuclear cells (PBMCs) were cocultivated with uninfected or MTB-infected A-549 cells and Con A-and PPD-induced T cell mitogeneses were examined, and the following findings were obtained. T cell mitogenesis was inhibited by uninfected as well as MTB-infected A-549 cells, even when a dual-chamber culture system was used to prevent direct cell contact between PBMCs and A-549 cells. Therefore, it appears that A-549 cells suppress T cell mitogenesis by producing some unknown humoral suppressor factors.

[Profiles of the expression of phospholipase A2 family mRNAs by macrophages infected with Mycobacterium tuberculosis].

Previously, we found that collaboration of reactive nitrogen intermediates (RNI) and free fatty acids (FFA) plays crucial roles in the expression of macrophage (Mphi) antimicrobial activity against Mycobacterium tuberculosis (MTB). Phospholipase A2 (PLA2) families hydrolyze phospholipids and release FFA from their sn-2 position. In the present study, we examined profiles of the mRNA expression of PLA2 families by Mphis stimulated with MTB by using RT-PCR method, and the following results were obtained. First, the expression of type IV cytosolic PLA2 (cPLA2), which is highly specific to arachidnic acid moiety, was significantly up-regulated by MTB stimulation of Mphis. Second, the expression of type IIa secretory PLA2 (sPLA2) was not observed for Mphis with or without MTB stimulation. Third, the profile of mRNA expression of type V sPLA2 was nearly the same as that of type IV cPLA2 for Mphis before and after MTB stimulation. These findings suggest that type IV cPLA2 and type V sPLA2 both play important roles in the FFA-mediated Mphi Cap antimicrobial activity against MTB organisms.

Interaction of antimycobacterial drugs with the anti-Mycobacterium avium complex effects of antimicrobial effectors, reactive oxygen intermediates, reactive nitrogen intermediates, and free fatty acids produced by macrophages.

The profiles of the interaction of antimycobacterial drugs with macrophage (MPhi) antimicrobial mechanisms have yet to be elucidated in detail. We examined the effects of various antimycobacterial drugs on the anti-Mycobacterium avium complex (MAC) antimicrobial activity of reactive oxygen intermediates (ROIs), especially of an H(2)O(2)-halogen (H(2)O(2)-Fe(2+)-NaI)-mediated bactericidal system, reactive nitrogen intermediates (RNIs), and free fatty acids (FFAs), which are known as central antimicrobial effectors of host MPhis against mycobacterial pathogens. We have found that certain drugs, such as rifampin (RIF), rifabutin (RFB), isoniazid (INH), clofazimine (CLO), and some fluoroquinolones, strongly or moderately reduced the anti-MAC activity of the H(2)O(2)-Fe(2+)-NaI system, primarily by inhibiting the generation of hypohalite ions and in part by interfering with the halogenation reaction of bacterial cell components due to the H(2)O(2)-Fe(2+)-NaI system. This phenomenon is specific to the H(2)O(2)-Fe(2+)-NaI system, since these drugs did not reduce the anti-MAC activity of RNIs and FFAs. From the perspective of the chemotherapy of MAC infections, the present findings indicate an important possibility that certain antimycobacterial drugs, such as rifamycins (RIF and RFB), INH, CLO, and also some types of fluoroquinolones, may interfere with the ROI-mediated antimicrobial mechanisms of host MPhis against intracellular MAC organisms.

Comparative profiles of intramacrophage behavior of Mycobacterium tuberculosis and Mycobacterium avium complex with different levels of virulence.

Mycobacterium tuberculosis (MTB) and M. avium complex (MAC) strains with different levels of virulence in mice were examined for profiles of interaction with murine peritoneal macrophages (Mphis). Their growth rates in Mphis were in these orders: H37Ra strain (attenuated) > H37Rv strain (virulent) for MTB, and N-260 strain (moderate virulence) > MAC N-444 strain (low virulence) for MAC. MTB but not MAC caused the necrotic death of host Mphis in terms of increased release of lactate dehydrogenase from infected Mphis. The MTB H37Ra strain induced a greater production of reactive nitrogen intermediates (RNI) by Mphis than the MTB H37Rv strain did. However, this phenomenon was not observed with MAC, implying less important roles of RNI in the expression of Mphi antimicrobial activity against MAC organisms.

Type II alveolar cells play roles in macrophage-mediated host innate resistance to pulmonary mycobacterial infections by producing proinflammatory cytokines.

Roles of type II pneumocytes in macrophage (Mphi)-mediated host resistance to pulmonary Mycobacterium tuberculosis (MTB) and M. avium complex (MAC) infections were studied. Electron microscopy of the lung sections of mice given intratracheal infection indicated that the organisms invaded both Mphis and type II pneumocytes. When Mono-Mac-6 Mphis(MM6-Mphis) and A-549 type II pneumocytes (A-549 cells) were cocultivated, bacterial growth in MM6-Mphis was reduced by A-549 cell-derived soluble factors, indicating the roles of type II pneumocytes in Mphi-mediated host resistance to mycobacteria. MTB- or MAC-infected A-549 cells showed increased mitochondrial RNA expression of cytokines and surfactant proteins (SPs), in the order tumor necrosis factor-alpha (TNF-alpha) > or = granulocyte-Mphi colony-stimulating factor (GM-CSF) > Mphi chemoattractant protein > or = interleukin-8 > SP-D. Anti-TNF-alpha and anti-GM-CSF antibodies attenuated A-549 cell-dependent inhibition of intramacrophage mycobacteria, indicating their crucial roles in A-549 cell-mediated potentiation of Mphi antimycobacterial activity.

Antimicrobial activities of clarithromycin, gatifloxacin and sitafloxacin, in combination with various antimycobacterial drugs against extracellular and intramacrophage Mycobacterium avium complex.

We studied the activities of clarithromycin and fluoroquinolones (gatifloxacin, sitafloxacin, levofloxacin) in combination with other antimycobacterial drugs against extracellular and intramacrophage Mycobacterium avium complex (MAC). Clarithromycin potentiated the activities of rifampicin and rifalazil against both extracellular and intramacrophage MAC. In contrast, all the test quinolones exhibited antagonistic effects against extracellular MAC when combined with either clarithromycin or rifamycins. Such an antagonism was not observed for the activity of these combinations against intramacrophage MAC. Combined effects were observed with combinations of these fluoroquinolones with either ethambutol or streptomycin. Similar profiles were seen for the activities of two-drug combinations of clarithromycin or fluoroquinolones with other drugs against intramacrophage MAC isolated from pulmonary and disseminated MAC infections.

Intramacrophage passage of Mycobacterium tuberculosis and M. avium complex alters the drug susceptibilities of the organisms as determined by intracellular susceptibility testing using macrophages and type II alveolar epithelial cells.

Mycobacterium tuberculosis and M. avium complex strains given intramacrophage passage (I-type) were compared with those cultured in a liquid medium (E-type) for their drug susceptibilities when they were replicating in Mono-Mac-6 macrophages or A-549 cells. Their intracellular susceptibilities to rifalazil, clarithromycin, and levofloxacin were decreased more in I-type organisms than in E-type organisms, except that their rifalazil susceptibility inside A-549 cells was markedly increased in I-type organisms.