Preemptive angioplasty for contralateral leg stenosis following EXCLUDER Iliac Branch Endoprosthesis implantation.

The GORE EXCLUDER Iliac Branch Endoprosthesis (IBE) device is designed to seal off a common iliac artery (CIA) aneurysm, preserving the internal iliac artery during endovascular aortic repair. We report the case of an 84-year-old man with isolated saccular right CIA aneurysm (35 mm) and a relatively small terminal aorta (24 mm). The IBE device was successfully placed, and intraoperative angiography revealed no leakage or delay. However, postoperative computed tomography revealed marked compression of the contralateral leg by a bridging component. Although his ankle-brachial index was preserved, its acute occlusion was judged highly possible; we decided to perform preemptive angioplasty. The angiography revealed the stenosis only in the left anterior oblique view, and angioplasty was uneventfully performed. The leg was successfully patent at 1-year follow-up. When compression by IBE and bridging component in the terminal aorta is expected, caution should be preserved at intraoperative angiography following the device deployment.

Extended Posterior Leaflet Augmentation for Ischemic Mitral Regurgitation　- Augmented Posterior Leaflet Snuggling up to Anterior Leaflet.

BACKGROUND: The ideal surgical technique for ischemic mitral regurgitation (MR) is controversial. We introduced an extended posterior mitral leaflet (PML) augmentation technique for functional MR with severe tethering, which detached the PML from the annulus almost completely and augmented it with a large 3×6-cm oval pericardial patch. Methods and Results: A total of 17 mitral repairs using the new technique were performed for ischemic MR with no 30-day mortality and 2 hospital deaths. The NYHA class was III in 47% and IV in 13%. The EuroSCORE II was 9.7±4.9. The ring size was 32±1.4 mm. Concomitant coronary bypass was performed in 67% and left ventricular repair in 28%. The mechanism of leaflet closure was evaluated using transthoracic echocardiography in 15 survivors. MR decreased to none or trivial with a significant increase in coaptation length (Pre: 4.6±0.8 mm vs. Post: 9.8±2.5 mm; P<0.001). The PML flexibly moved forward and tightly contacted as if "snuggling up" to the anterior leaflet. There were no late deaths, heart failure readmissions or MR recurrences during follow-up (850±181 days). All patients remained in NYHA I or II. CONCLUSIONS: Extended PML augmentation for ischemic MR showed excellent early results with deep leaflet coaptation through a "snuggling up" phenomenon, which would help prevent late MR recurrence.

Post-cardiotomy venovenous extracorporeal membrane oxygenation without heparinization.

We present the cases of eight patients (mean age 75 years; EuroSCORE II 17.0 ± 22.0) who underwent post-cardiotomy venovenous extracorporeal membrane oxygenation (ECMO) without heparinization due to serious bleeding. Three liver cirrhosis, two chronic hemodialysis, three redo sternotomy, and two urgent surgery cases were included. Respiratory ECMO Survival Prediction score was - 5.1 ± 4.2 (estimated survival rate: approximately 30%). Mean ECMO duration was 14 days with 9 circuit exchanges. Five patients were weaned from ECMO and three were discharged alive at 90 days (survival 37.5%). There was a case of pump-head thrombosis requiring urgent circuit exchange. All experienced bleeding complications without clinically apparent pulmonary thromboembolism. Disseminated Intravascular Coagulation scores (Pre 1.3 ± 0.8 vs. Post 3.8 ± 1.7; p < 0.05) significantly increased (N = 6). Post-cardiotomy ECMO without heparinization facilitated patient rescue at a reasonable survival rate. However, bleeding complications were still observed. More sophisticated management protocols are warranted.

Long-standing persistent effects of atrial volume reduction combined with pulmonary vein isolation.

Although surgical left atrial (LA) volume reduction combined with mitral valve surgery and/or surgical ablation for atrial fibrillation has been reported to be effective, its long-term outcomes in the absence of mitral procedure are not well established. A 74-year-old man with two previous sternotomies-the first for pericardiectomy due to constrictive pericarditis and the second for mitral valve replacement with mechanical valve and tricuspid annuloplasty-presented with heart failure and thrombus in his giant left atrium (1291 mL), complicated by cerebral infarction. His electrocardiogram showed rate-controlled persistent atrial fibrillation. His mechanical valve was functioning well. A third atrial volume reduction combined with pulmonary vein isolation, without valve surgery, was performed. The postoperative course was uneventful, and the patient has remained asymptomatic with regular junctional rhythm and without any episodes of thromboembolism or re-dilation of LA (approximately 550 mL). His left ventricular filling improved with end-diastolic volume (96 mL vs 140 mL) and forced vital capacity (2.60 L vs 2.89 L) increased. Both remained relatively constant for 6 years. The combination of atrial volume reduction with pulmonary vein isolation prevented thromboembolism, improved left ventricular filling, and continued to improve symptoms associated with heart failure and respiratory condition for 6 years. .

Successful management of prolonged venovenous extracorporeal membrane oxygenation in an octogenarian.

Venovenous extracorporeal membrane oxygenation is now an established treatment for acute respiratory distress syndrome. However, this treatment remains rare in octogenarians and is associated with poor outcomes. An 81-year-old man with a history of chronic obstructive pulmonary disease and heavy smoking underwent mitral and tricuspid valve repair and the Maze procedure for mitral and tricuspid regurgitation and paroxysmal atrial fibrillation. Although he was extubated the following day, his postoperative course was complicated with pneumonia followed by acute respiratory distress syndrome. He was reintubated on day 7. Ratio of partial pressure of arterial oxygen to fraction of inspired oxygen continuously dropped to less than 100 mmHg, and venovenous extracorporeal membrane oxygenation support was induced on day 18. His lung condition showed slow and steady recovery, and he was successfully weaned from mechanical support on day 44 (total support, 27 days). Bleeding complication from tracheotomy (day 31) due to disseminated intravascular coagulation was successfully managed using recombinant human soluble thrombomodulin. He was ambulatory and discharged to a nursing facility without tracheotomy on day 172. Proper extracorporeal membrane oxygenation management, while challenging to keep the elderly patient away from further complications, saved an 81-year-old patient.

Matricellular Protein CCN5 Reverses Established Cardiac Fibrosis.

BACKGROUND: Cardiac fibrosis (CF) is associated with increased ventricular stiffness and diastolic dysfunction and is an independent predictor of long-term clinical outcomes of patients with heart failure (HF). We previously showed that the matricellular CCN5 protein is cardioprotective via its ability to inhibit CF and preserve cardiac contractility. OBJECTIVES: This study examined the role of CCN5 in human heart failure and tested whether CCN5 can reverse established CF in an experimental model of HF induced by pressure overload. METHODS: Human hearts were obtained from patients with end-stage heart failure. Extensive CF was induced by applying transverse aortic constriction for 8 weeks, which was followed by adeno-associated virus-mediated transfer of CCN5 to the heart. Eight weeks following gene transfer, cellular and molecular effects were examined. RESULTS: Expression of CCN5 was significantly decreased in failing hearts from patients with end-stage heart failure compared to nonfailing hearts. Trichrome staining and myofibroblast content measurements revealed that the established CF had been reversed by CCN5 gene transfer. Anti-CF effects of CCN5 were associated with inhibition of the transforming growth factor beta signaling pathway. CCN5 significantly inhibited endothelial-mesenchymal transition and fibroblast-to-myofibroblast transdifferentiation, which are 2 critical processes for CF progression, both in vivo and in vitro. In addition, CCN5 induced apoptosis in myofibroblasts, but not in cardiomyocytes or fibroblasts, both in vivo and in vitro. CCN5 provoked the intrinsic apoptotic pathway specifically in myofibroblasts, which may have been due the ability of CCN5 to inhibit the activity of NFκB, an antiapoptotic molecule. CONCLUSIONS: CCN5 can reverse established CF by inhibiting the generation of and enhancing apoptosis of myofibroblasts in the myocardium. CCN5 may provide a novel platform for the development of targeted anti-CF therapies.

Successful Repair of Regurgitant Pentacuspid Pulmonary Valve Combined With Pulmonary Artery Aneurysm.

Pentacuspid pulmonary valve is an extremely rare congenital anomaly. A 71-year-old woman presented with dyspnea on exertion. The preoperative examination showed a large pulmonary artery aneurysm with severe pulmonary regurgitation. The pentacuspid pulmonary valve was an intraoperative finding with four equivalent leaflets and one hypoplastic leaflet. The valve was successfully repaired by use of a bicuspidization technique combined with annuloplasty, and pulmonary artery reduction was performed. Postoperatively, the patient remained asymptomatic with trivial pulmonary regurgitation 1 year later. To our knowledge, this is the first report of a pentacuspid pulmonary valve repair.

The role of SUMO-1 in cardiac oxidative stress and hypertrophy.

AIMS: Small ubiquitin-like modifier type 1 (SUMO-1) has been shown to play a critical role in the dysfunction of the cardiac isoform of sarcoplasmic reticulum calcium ATPase (SERCA2a) pump in the setting of heart failure. In cardiac hypertrophy, the role of SUMO-1 has not been defined and our study's goals were to examine the effects of modulating SUMO-1 on the hypertrophic response both in vitro and in vivo and to examine whether oxidative stress (during cardiac hypertrophy) is abrogated by SUMO-1 gene transfer. RESULTS: In mice undergoing transverse aortic constriction (TAC), SUMO-1 levels increased slightly during the compensated stage of hypertrophy and then dropped sharply during the transition to heart failure. In isolated cardiomyocytes, SUMO-1 gene transfer inhibited the hypertrophic response in the presence of phenylephrine. Adeno-associated vector type 9 (AAV9) gene transfer of SUMO-1 prevented the heart from undergoing hypertrophy after TAC and prevented the development of left ventricular dysfunction. Furthermore, SUMO-1 gene transfer blocked the negative effects of H2O2 on SERCA2a activity in cardiac myocytes, while in vivo indices of oxidative stress were decreased by SUMO-1 in cardiac hypertrophy and heart failure. INNOVATION AND CONCLUSION: The results of this study indicate that post-translational modifications of SERCA2a caused by the toxic environment of the hypertrophied and failing myocardium can be prevented by SUMO-1. Antioxid. Redox Signal. 21, 1986-2001.

Inhibition of miR-25 improves cardiac contractility in the failing heart.

Heart failure is characterized by a debilitating decline in cardiac function, and recent clinical trial results indicate that improving the contractility of heart muscle cells by boosting intracellular calcium handling might be an effective therapy. MicroRNAs (miRNAs) are dysregulated in heart failure but whether they control contractility or constitute therapeutic targets remains speculative. Using high-throughput functional screening of the human microRNAome, here we identify miRNAs that suppress intracellular calcium handling in heart muscle by interacting with messenger RNA encoding the sarcoplasmic reticulum calcium uptake pump SERCA2a (also known as ATP2A2). Of 875 miRNAs tested, miR-25 potently delayed calcium uptake kinetics in cardiomyocytes in vitro and was upregulated in heart failure, both in mice and humans. Whereas adeno-associated virus 9 (AAV9)-mediated overexpression of miR-25 in vivo resulted in a significant loss of contractile function, injection of an antisense oligonucleotide (antagomiR) against miR-25 markedly halted established heart failure in a mouse model, improving cardiac function and survival relative to a control antagomiR oligonucleotide. These data reveal that increased expression of endogenous miR-25 contributes to declining cardiac function during heart failure and suggest that it might be targeted therapeutically to restore function.

Left ventricular mechanical and energetic changes in long-term isoproterenol-induced hypertrophied hearts of SERCA2a transgenic rats.

Overexpression of cardiac sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a) has been suggested as a strategic intervention for cardiac failure. However, its benefit in wild-type (WT) rats with normal SERCA2a levels seems to be small. To investigate whether it would be beneficial in a cardiac failure model with down-regulated SERCA2a levels, we made a cardiac hypertrophy model using isoproterenol infusion (1.2mgkg(-1)day(-1) for 1 or 4weeks; TG-ISO1w and TG-ISO4w, respectively) in SERCA2a transgenic (TG) rats and compared these rats with littermate WT rats that underwent the same treatments (WT-ISO1w and WT-ISO4w). We analyzed the left ventricular (LV) mechanoenergetics in the excised heart using our original cross-circulation system. The downward shift of curvilinear LV end-systolic pressure-volume relations (ESPVRs) observed in WT-ISO4w rats was abolished in TG-ISO4w rats. The slope and VO2 intercept of the VO2 (myocardial oxygen consumption per beat)-PVA (systolic pressure-volume area: total mechanical energy per beat) linear relation did not differ in any of the groups. The most important finding was a significantly smaller O2 cost of LV contractility in the TG-ISO4w group, which means that less O2 is needed to exert the same LV contractility, compared with the other groups. The increased ratio of SERCA2a/phospholamban returned to the level of the WT-control group only in the TG-ISO4w group. Longer-term up-regulation of mitochondrial transcription factor A for genes of mitochondrial enzymes producing ATP was observed in TG rats. In conclusion, longer-term overexpression of SERCA2a will be beneficial in the present cardiac failure model with down-regulated SERCA2a levels.

Reconstruction of the intraparenchymal pulmonary artery aneurysm.

Pulmonary artery aneurysms are rare and often arise in the left main trunk. Because they are uncommon, standardized treatment and clinical management are not clearly established. We present the case of a pulmonary artery aneurysm arising intraparenchymally and its surgical reconstruction using autologous pericardium. In terms of preserving pulmonary function, this procedure is effective compared with surgical procedures such as removal of part of the lungs.

Evaluation of left ventricular mechanical work and energetics of normal hearts in SERCA2a transgenic rats.

Cardiac sarcoplasmic reticulum (SR) Ca(2+)-ATPase (SERCA2a) is responsible for most of the Ca(2+) removal during diastole and a larger Ca(2+) handling energy consumer in excitation-contraction (E-C) coupling. To understand the cardiac performance under long-term SERCA2a overexpression conditions, we established SERCA2a transgenic (TG) Wistar rats to analyze cardiac mechanical work and energetics in normal hearts during pacing at 300 beats/min. SERCA2a protein expression was increased in TGI and TGII rats (F2 and F3 of the same father and different mothers). Mean left ventricular (LV) end-systolic pressure (ESP) and systolic pressure-volume area (PVA; a total mechanical energy per beat) at midrange LV volume (mLVV) were significantly larger in TGI rats and were unchanged in TGII rats, compared to those in non-TG [wildtype (WT)] littermates. Mean myocardial oxygen consumption per minute for E-C coupling was significantly increased, and the mean slope of myocardial oxygen consumption per beat (VO(2))-PVA (systolic PVA) linear relation was smaller, but the overall O(2) cost of LV contractility for Ca(2+) is unchanged in all TG rats. Mean Ca(2+) concentration exerting maximal ESP(mLVV) in TGII rats was significantly higher than that in WT rats. The Ca(2+) overloading protocol did not elicit mitochondrial swelling in TGII rats. Tolerance to higher Ca(2+) concentrations may support the possibility for enhanced SERCA2a activity in TGII rats. In conclusion, long-term SERCA2a overexpression enhanced or maintained LV mechanics, improved contractile efficiency under higher energy expenditure for Ca(2+) handling, and improved Ca(2+) tolerance, but it did not change the overall O(2) cost of LV contractility for Ca(2+) in normal hearts of TG rats.

NHE-1 blockade reversed changes in calcium transient in myocardial slices from isoproterenol-induced hypertrophied rat left ventricle.

We previously reported that left ventricular (LV) slices from isoproterenol (ISO)-induced hypertrophied rat hearts showed an increase of energy expenditure due to remodeling of Ca(2+) handling in excitation-contraction coupling, i.e., suppressed SERCA2a activity and enhanced Na(+)/Ca(2+)exchanger-1 (NCX-1) activity. Na(+)/H(+) exchanger-1 (NHE-1) inhibitor (NHEI) has been demonstrated to exert beneficial effects in the development of cardiac remodeling. We hypothesized that a novel NHE-1 selective inhibitor, BIIB723 prevents remodeling of Ca(2+) handling in LV slices of ISO-induced hypertrophied rat hearts mediated by inhibiting NCX-1 activity. The significant shortening in duration of multi-cellular Ca(2+) transient in ISO group was normalized in ISO+BIIB723 group. The significant increase in amplitude of multi-cellular Ca(2+) waves (CaW) generated at high [Ca(2+)](o) of LV slices in ISO group was also normalized in ISO+BIIB723 group. However, the enhanced NCX-1 activity was not antagonized by BIIB723. We recently reported that ISO-induced down-regulation of a Ca(2+) handling protein, SERCA2a, was normalized by BIIB723. Therefore, it seems likely that BIIB723 normalized shortened multi-cellular Ca(2+) transient duration and increased CaW amplitude in LV slices mediated via normalization of SERCA2a activity. Furthermore, the results presented here suggest the multi-cellular Ca(2+) transient duration and CaW amplitude in LV slices might be better indices reflecting SERCA2a activity than SERCA2a protein expression level.

NHE-1 participates in isoproterenol-induced downregulation of SERCA2a and development of cardiac remodeling in rat hearts.

Impaired Ca(2+) handling is one of the main characteristics in heart failure patients. Recently, we reported abnormal expressions of Ca(2+)-handling proteins in isoproterenol (ISO)-induced hypertrophied rat hearts. On the other hand, Na(+)/H(+) exchanger (NHE)-1 inhibitor has been demonstrated to exert beneficial effects in ischemic-reperfusion injury and in the development of cardiac remodeling. The aims of the present study are to investigate the role of NHE-1 on Ca(2+) handling and development of cardiac hypertrophy in ISO-infused rats. Male Wistar rats were randomly divided into vehicle [control (CTL)] and ISO groups without or with pretreatment with a selective NHE-1 inhibitor, BIIB-723. ISO infusion for 1 wk significantly increased the ratios of heart to body weight and left ventricle (LV) to body weight and collagen accumulation. All of these increases were antagonized by coadministration with BIIB-723. The ISO-induced significant increase in LV wall thickness was suppressed significantly (P < 0.05) by BIIB-723. ISO-induced decreases in cardiac stroke volume and a total mechanical energy per beat index, systolic pressure-volume area at midrange LV volume, were normalized by BIIB-723. The markedly higher expression of NHE-1 protein in the ISO group than that in CTL group was suppressed (P < 0.05) by BIIB-723. Surprisingly, ISO induced downregulation of the important Ca(2+)-handling protein sarcoplasmic reticulum Ca(2+)-ATPase 2a, the expression of which was also normalized by BIIB-723 without changes in phosphorylated phospholamban (PLB)/PLB expression. We conclude that NHE-1 contributes to ISO-induced abnormal Ca(2+) handling associated with cardiac hypertrophy. Inhibition of NHE-1 ameliorates cardiac Ca(2+)-handling impairment and prevents the development of cardiac dysfunction in ISO-infused rats.

Reoperation for mid-term failure of a freestyle bioprosthesis using a full root technique --a surgical case--.

The aortic root of a 30-year-old man was replaced with a Freestyle stentless aortic bioprosthesis for aortic regurgitation associated with annuloaortic ectasia. His clinical course was uneventful, and he was discharged without complications. Three years and six months after surgery, he presented with a high fever. Four years after surgery, transthoracic echocardiography revealed severe aortic regurgitation. We performed exploratory surgery and discovered a torn left coronary cusp of the Freestyle bioprosthesis. Organized vegetation was adherent to the left coronary cusp leaflet. The non-coronary cusp and the right coronary cusp were normal. The diagnosis was aortic regurgitation due to valve failure related to infective endocarditis. Consequently, we reconstructed the aortic root with a composite graft (26-mm Valsalva graft and a 21-mm ON-X mechanical valve).