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A 32-year-old man, who had developed fulminant myocarditis leading to asystole, underwent implantation of an EVAHEART 2 left ventricular assist system with a double-cuff tipless inflow cannula and a concurrent Fontan operation. Approximately 2 years after the simultaneous EVAHEART 2 implantation and the Fontan operation, the patient underwent heart transplantation. There was no device-related thromboembolism or pump malfunction under adequate antithrombotic management during the postoperative support period. Computed tomography showed no malposition of the inflow cannula irrespective of the left ventricular chamber size. Macroscopically, the left ventricular cavity of the excised heart revealed a smooth inflow ostium with appropriate intimal proliferation and without pannus or wedge thrombus formation. These findings suggest the utility of the double-cuff tipless inflow cannula for long-term clinical applications, which may lead to favorable outcomes during long-term patient management. The double-cuff tipless inflow cannula, which does not protrude into the left ventricular cavity, potentially contributes to the prevention of suction events and the collision of the inflow cannula with the interventricular septum and left ventricular free wall. Further investigation is required to confirm the role of the unique EVAHEART 2 inflow cannula in reducing thromboembolic events.

We report a case with a retrosternal gastric tube after oesophagectomy, who required left atrial myxoma resection, pulmonary vein isolation and left atrial appendage closure. A right mini-thoracotomy approach was adopted to avoid neo-oesophagus injury, and nitric oxide inhalation was useful to facilitate one-lung ventilation while dissecting the pleural adhesion.

Cardiac development and function require actin–myosin interactions in the sarcomere, a highly organized contractile structure. Sarcomere assembly mediated by formin homology 2 domain-containing 3 (Fhod3), a member of formins that directs formation of straight actin filaments, is essential for embryonic cardiogenesis. However, the role of Fhod3 in the neonatal and adult stages has remained unknown. Here, we generated floxed Fhod3 mice to bypass the embryonic lethality of an Fhod3 knockout (KO). Perinatal KO of Fhod3 in the heart caused juvenile lethality at around day 10 after birth with enlarged hearts composed of severely impaired myofibrils, indicating that Fhod3 is crucial for postnatal heart development. Tamoxifen-induced conditional KO of Fhod3 in the adult heart neither led to lethal effects nor did it affect sarcomere structure and localization of sarcomere components. However, adult Fhod3-deleted mice exhibited a slight cardiomegaly and mild impairment of cardiac function, conditions that were sustained over 1 year without compensation during aging. In addition to these age-related changes, systemic stimulation with the α1-adrenergic receptor agonist phenylephrine, which induces sustained hypertension and hypertrophy development, induced expression of fetal cardiac genes that was more pronounced in adult Fhod3-deleted mice than in the control mice, suggesting that Fhod3 modulates hypertrophic changes in the adult heart. We conclude that Fhod3 plays a crucial role in both postnatal cardiac development and functional maintenance of the adult heart.

Summary Heart development requires organized integration of actin filaments into the sarcomere, the contractile unit of myofibrils, although it remains largely unknown how actin filaments are assembled during myofibrillogenesis. Here we show that Fhod3, a member of the formin family of proteins that play pivotal roles in actin filament assembly, is essential for myofibrillogenesis at an early stage of heart development. Fhod3−/− mice appear normal up to embryonic day (E) 8.5, when the developing heart, composed of premyofibrils, initiates spontaneous contraction. However, these premyofibrils fail to mature and myocardial development does not continue, leading to embryonic lethality by E11.5. Transgenic expression of wild-type Fhod3 in the heart restores myofibril maturation and cardiomyogenesis, which allow Fhod3−/− embryos to develop further. Moreover, cardiomyopathic changes with immature myofibrils are caused in mice overexpressing a mutant Fhod3, defective in binding to actin. These findings indicate that actin dynamics, regulated by Fhod3, participate in sarcomere organization during myofibrillogenesis and thus play a crucial role in heart development.

Actin filament assembly in nonmuscle cells is regulated by the actin polymerization machinery, including the Arp2/3 complex and formins. However, little is known about the regulation of actin assembly in muscle cells, where straight actin filaments are organized into the contractile unit sarcomere. Here, we show that Fhod3, a myocardial formin that localizes to thin actin filaments in a striated pattern, regulates sarcomere organization in cardiomyocytes. RNA interference-mediated depletion of Fhod3 results in a marked reduction in filamentous actin and disruption of the sarcomeric structure. These defects are rescued by expression of wild-type Fhod3 but not by that of mutant proteins carrying amino acid substitution for conserved residues for actin assembly. These findings suggest that actin dynamics regulated by Fhod3 are critical for sarcomere organization in striated muscle cells.

Fhod3 is a cardiac member of the formin family proteins that play pivotal roles in actin filament assembly in various cellular contexts. The targeted deletion of mouse Fhod3 gene leads to defects in cardiogenesis, particularly during myofibrillogenesis, followed by lethality at embryonic day (E) 11.5. However, it remains largely unknown how Fhod3 functions during myofibrillogenesis. In this study, to assess the mechanism whereby Fhod3 regulates myofibrillogenesis during embryonic cardiogenesis, we generated transgenic mice expressing Fhod3 selectively in embryonic cardiomyocytes under the control of the β-myosin heavy chain (MHC) promoter. Mice expressing wild-type Fhod3 in embryonic cardiomyocytes survive to adulthood and are fertile, whereas those expressing Fhod3 (I1127A) defective in binding to actin die by E11.5 with cardiac defects. This cardiac phenotype of the Fhod3 mutant embryos is almost identical to that observed in Fhod3 null embryos, suggesting that the actin-binding activity of Fhod3 is crucial for embryonic cardiogenesis. On the other hand, the β-MHC promoter-driven expression of wild-type Fhod3 sufficiently rescues cardiac defects of Fhod3-null embryos, indicating that the Fhod3 protein expressed in a transgenic manner can function properly to achieve myofibril maturation in embryonic cardiomyocytes. Using the transgenic mice, we further examined detailed localization of Fhod3 during myofibrillogenesis in situ and found that Fhod3 localizes to the specific central region of nascent sarcomeres prior to massive rearrangement of actin filaments and remains there throughout myofibrillogenesis. Taken together, the present findings suggest that, during embryonic cardiogenesis, Fhod3 functions as the essential reorganizer of actin filaments at the central region of maturating sarcomeres via the actin-binding activity of the FH2 domain.

左室心筋緻密化障害は左室心筋の緻密化が障害された先天性の心筋症であり，心不全が進行する予後不良の疾患である．今回我々は，左室心筋緻密化障害を有する成人例に生じた右房粘液腫に対して腫瘍切除術を施行したので報告する．症例は69歳女性，労作時の息切れを主訴に入院となり，心エコーで左室緻密化障害を伴う左心機能障害（EF＝16%）および右房腫瘍を認めた．保存的に心不全をコントロールした後，心停止下に右房腫瘍切除術を施行した．右房腫瘍の病理組織診断は粘液腫であった．緻密化障害を有する心筋における虚血障害が危惧されたが，工夫した心筋保護を行った結果，術後早期の経過は良好で，術後19日目に退院した．左室心筋緻密化障害の予後を考慮すると，今後も厳重な経過観察が必要である．

A 54-year old man underwent redo mitral valve (MV) plasty because of recurrent mitral regurgitation (MR). Intraoperative transoesophageal echocardiography revealed severe MR and turbulent flow at the left ventricular (LV) outflow tract associated with systolic anterior motion of the MV. Various medical treatments, additional surgical correction, and atrial and right ventricular pacing had failed to resolve the MR associated with systolic anterior motion. LV pacing, however, markedly attenuated MR. Temporary LV pacing was discontinued on postoperative day 2, and subsequently MR associated with systolic anterior motion has not recurred. LV dyssynchrony resulting from conduction disturbances might cause systolic anterior motion immediately after MV plasty. We speculate that LV pacing eliminated LV dyssynchrony and improved the MR associated with systolic anterior motion. Temporary LV pacing can be performed easily and safely at the time of MV plasty. LV pacing can be a complementary treatment for systolic anterior motion and resultant MR.

Immunoglobulin G4-related disease, a newly emerging systemic autoimmune disorder, can potentially involve the cardiovascular system. The standard treatment for immunoglobulin G4-related cardiovascular disease has not been established. We encountered a very rare case of an immunoglobulin G4-related inflammatory abdominal aortic aneurysm coexisting with a coronary artery aneurysm and periarteritis. The patient underwent surgical resection for the abdominal aortic aneurysm, followed by successful corticosteroid therapy for the coronary artery lesions. This is the first report of steroid-sensitive immunoglobulin G4-related coronary artery disease. A carefully planned treatment strategy for the multiple cardiovascular lesions was invaluable in the present case.

The formin family proteins play pivotal roles in actin filament assembly via the FH2 domain. The mammalian formin Fhod3 is highly expressed in the heart, and its mRNA in the adult heart contains exons 11, 12, and 25, which are absent from non-muscle Fhod3 isoforms. In cultured neonatal cardiomyocytes, Fhod3 localizes to the middle of the sarcomere and appears to function in its organization, although it is suggested that Fhod3 localizes differently in the adult heart. Here we show, using immunohistochemical analysis with three different antibodies, each recognizing distinct regions of Fhod3, that Fhod3 localizes as two closely spaced bands in middle of the sarcomere in both embryonic and adult hearts. The bands are adjacent to the M-line that crosslinks thick myosin filaments at the center of a sarcomere but distant from the Z-line that forms the boundary of the sarcomere, which localization is the same as that observed in cultured cardiomyocytes. Detailed immunohistochemical and immuno-electron microscopic analyses reveal that Fhod3 localizes not at the pointed ends of thin actin filaments but to a more peripheral zone, where thin filaments overlap with thick myosin filaments. We also demonstrate that the embryonic heart of mice specifically expresses the Fhod3 mRNA isoform harboring the three alternative exons, and that the characteristic localization of Fhod3 in the sarcomere does not require a region encoded by exon 25, in contrast to an essential role of exons 11 and 12. Furthermore, the exon 25-encoded region appears to be dispensable for actin-organizing activities both in vivo and in vitro, albeit it is inserted in the catalytic FH2 domain.

Background We evaluated the results of surgery for an anomalous origin of the right pulmonary artery from the ascending aorta. Methods From August 1986 to December 2005, 8 children (6 neonates) aged 7 to 180 days (mean, 35 ± 59 days) with anomalous origin of the right pulmonary artery from the ascending aorta underwent surgical repair at our institute. All except one child, who had the distal form, had the proximal form. Cardiac catheterization showed that the left pulmonary artery to systemic pressure ratio was 1.0 or more. Surgery was performed by direct anastomosis in 7 patients and by graft interposition in 1. Results There were no operative or late deaths. All patients postoperatively underwent cardiac catheterization that showed decreased left pulmonary artery to systemic pressure ratio ranging from 0.2 to 0.6. Follow-up periods ranged from 2 months to 13 years. We undertook reoperations for two infrequent postoperative causes. One patient exhibited significant supravalvar aortic stenosis and required patch enlargement of the ascending aorta 3 years after operation. The other patient (with the distal form) needed a reoperation after 1 month because of progressive stenosis at the anatomic site. Graft interposition was performed, and histopathologic examination showed that the tissue from the stenotic region looked like that of a ductus. Conclusions We undertook surgical repair for anomalous origin of the right pulmonary artery from the ascending aorta. Pulmonary hypertension was improved in all patients. Careful follow-up was necessary to detect supravalvar aortic and anastomotic stenosis early and late after operation.

We evaluated the clinical results of commissure plication annuloplasty for mitral regurgitation (MR) in children.Twenty-eight patients underwent a valve repair with commissure plication annuloplasty for MR from 1988 to 2005. The mean age was 2.7 +/- 3.3 years. Several appropriate techniques were combined (cleft closure in 5 patients, chordal shortening in 2 patients, artificial chordal replacement in 4 patients, leaflet fixation in 2 patients, and so on). The mean follow-up period was 6.2 years.There was one operative death (3.6%) and no late deaths. Two patients underwent a second repair 19 and 23 months after their initial repairs. The actuarial freedom from the reoperation rate was 90.4% +/- 0.6% at 10 years. The freedom from moderate MR or more was shown to decrease over time, 87.8% +/- 0.7% at 5 years and 78.0% +/- 11.0% at 10 years. Furthermore, the 10-year freedom from mild MR or more was 56.5% +/- 11.9%. A progression of MR was seen. Most of the residual or recurrent MR cases weighed less than 10 kg at operation.The combination of commissure plication annuloplasty and several appropriate techniques provided adequate results for MR in children. Since a progression of MR was observed, a careful follow-up is therefore needed in such cases.