Objectives
We investigated the effect of the maze procedure with intensive pulmonary vein isolation (PVI) guided by ganglionated plexus (GP) mapping (the Maze with GP ablation group) on a long-term ...postoperative maintenance of sinus rhythm in patients with permanent atrial fibrillation (AF) and compared with that in patients undergoing the maze procedure with the conventional PVI (the Maze group).
Methods and results
We investigated 48 patients who underwent the maze procedure with GP ablation for persistent AF and 43 patients who underwent the maze procedure. The Maze procedure was conducted by the endocardial application of bipolar radiofrequency ablation and cryoablation. Conventional PVI was applied three times for the entrance of right and left PVs, respectively. Intensive PVI for GP ablation was repeated six-to-eight times for both sides of PVs to cover the bilateral GP regions identified by GP mapping. The duration of permanent AF, the prevalence of concomitant primary heart diseases, and the postoperative follow-up period were comparable between the two groups. At discharge, 1 year, 5 years after the surgery, sinus rhythm was maintained in 74.4%, 61%, and 40.5% of the Maze group. In contrast, it was maintained in 93.7%, 88.9%, and 75.7% of the Maze with GP ablation group. The cumulative freedom rate from AF at 10 years after surgery was significantly higher in the Maze with GP ablation group.
Conclusions
More intense PV isolation including adjacent GP may improve long-term results of maze procedure in patients with permanent AF.
We hypothesized that a small molecule CXCR4 antagonist, AMD3100 (AMD), could augment the mobilization of bone marrow (BM)-derived endothelial progenitor cells (EPCs), thereby enhancing ...neovascularization and functional recovery after myocardial infarction. Single-dose AMD injection administered after the onset of myocardial infarction increased circulating EPC counts and myocardial vascularity, reduced fibrosis, and improved cardiac function and survival. In mice transplanted with traceable BM cells, AMD increased BM-derived cell incorporation in the ischemic border zone. In contrast, continuous infusion of AMD, although increasing EPCs in the circulation, worsened outcome by blocking EPC incorporation. In addition to its effects as a CXCR4 antagonist, AMD also up-regulated VEGF and matrix metalloproteinase 9 (MMP-9) expression, and the benefits of AMD were not observed in the absence of MMP-9 expression in the BM. These findings suggest that AMD3100 preserves cardiac function after myocardial infarction by enhancing BM-EPC—mediated neovascularization, and that these benefits require MMP-9 expression in the BM, but not in the ischemic region. Our results indicate that AMD3100 could be a potentially useful therapy for the treatment of myocardial infarction.
Aortic stenosis (AS), a late complication of thoracic radiation therapy for chest lesions, is often coincident with porcelain aorta or hostile thorax. We herein report a 59-year-old man with a ...history of mediastinal Hodgkin lymphoma treated with radiation therapy but later presenting with heart failure caused by severe AS. Severe calcification in the mediastinum and around the ascending aorta made it difficult to perform surgical aortic valve replacement. The patient therefore underwent transcatheter aortic valve implantation (TAVI). It is important to recognize radiation-induced AS early, now that TAVI is a well-established treatment required by increasing numbers of successfully treated cancer patients.
Background: Current guidelines equally recommend direct oral anticoagulants (DOACs) and warfarin for atrial fibrillation (AF) patients with a bioprosthetic valve (BPV); however, there are limited ...data comparing DOACs and warfarin in AF patients with an aortic BPV.Methods and Results: This post-hoc subgroup analysis of a multicenter, prospective, observational registry (BPV-AF Registry) aimed to compare DOACs and warfarin in AF patients with an aortic BPV. The primary outcome was a composite of stroke, systemic embolism, major bleeding, heart failure requiring hospitalization, all-cause death, or BPV reoperation. The analysis included 479 patients (warfarin group, n=258; DOAC group, n=221). Surgical aortic valve replacement was performed in 74.4% and 36.7% of patients in the warfarin and DOAC groups, respectively. During a mean follow up of 15.5 months, the primary outcome occurred in 45 (17.4%) and 32 (14.5%) patients in the warfarin and DOAC groups, respectively. No significant difference was found in the primary outcome between the 2 groups (adjusted hazard ratio: 0.88, 95% confidence interval: 0.51–1.50). No significant multiplicative interaction was observed between the anticoagulant effects and type of aortic valve procedure (P=0.577).Conclusions: Among AF patients with an aortic BPV, no significant difference was observed in the composite outcome of adverse clinical events between patients treated with warfarin and those treated with DOACs, suggesting that DOACs can be used as alternatives to warfarin in these patients.
We hypothesized that estrogen-induced acceleration of reendothelialization might be mediated in part by effects involving mobilization and incorporation of bone marrow-derived endothelial progenitor ...cells (EPCs).
Carotid injury was induced in ovariectomized wild-type mice receiving either 17beta-estradiol or placebo. Estradiol treatment significantly accelerated reendothelialization of injured arterial segments within 7 days and resulted in a significant reduction of medial thickness 14 and 21 days after the injury. Significant increases in circulating EPCs 3 days after the injury were observed in the estradiol group compared with placebo-treated mice. These data were further supported by fluorescence-activated cell sorting analysis, which disclosed a significant increase in Sca-1/Flk-1-positive cells in estradiol versus control mice. To evaluate the effects of estradiol on bone marrow-derived EPC incorporation at sites of reendothelialization, carotid injury was established in ovariectomized wild-type mice transplanted with bone marrow from transgenic donors expressing beta-galactosidase transcriptionally regulated by the Tie-2 promoter. Significantly greater numbers of X-gal-positive cells were observed at reendothelialized areas in the estradiol group 3 days after injury as compared with placebo. Fluorescent immunohistochemistry 14 days after the injury documented a marked increase in cells expressing both beta-gal, indicating bone marrow origin and Tie-2 expression, and isolectin B4, also indicating endothelial lineage, in the estradiol group compared with control. In contrast, estradiol did not accelerate reendothelialization or augment EPC mobilization into the peripheral circulation after injury in endothelial nitric oxide synthase-deficient mice (eNOS-/-). Furthermore, estradiol exhibited direct stimulatory effects on EPC mitogenic and migration activity and inhibited EPC apoptosis.
Estradiol accelerates reendothelialization and attenuates medial thickening after carotid injury in part by augmenting mobilization and proliferation of bone marrow-derived EPCs and their incorporation into the recovering endothelium at the site of injury.
The function of bone marrow-derived endothelial progenitor cells (EPCs) in repair of ischemic tissue has been the subject of intense scrutiny, and the capacity of these cells to contribute ...significantly to new blood vessels remains controversial. The possibility that EPCs could act as reservoirs of cytokines has been implied by several observations; however, a specific role for cytokine delivery has not been identified.
We performed a series of experiments that revealed the rapid recruitment of EPCs to the myocardium by very short periods of ischemia, so-called ischemic preconditioning. The recruited EPCs express an array of potentially cardioprotective cytokines including nitric oxide synthase isoforms. Bone marrow transplantation studies, using donor marrow null for nitric oxide synthase isoforms, revealed that both endothelial and inducible nitric oxide synthase derived from bone marrow cells play essential roles in the cardioprotective effect that normally occurs after ischemic preconditioning.
These findings provide novel insights about the role of bone marrow-derived cells in ischemic preconditioning and also reveal that distinct mechanisms regulate recovery after ischemia-reperfusion and chronic ischemic injury.
Sonic hedgehog (Shh) is a prototypical morphogen known to regulate epithelial-mesenchymal interaction during embryonic development. Recent observations indicate that exogenous administration of Shh ...can induce angiogenesis and may accelerate repair of ischemic myocardium and skeletal muscle. Because angiogenesis plays a pivotal role in wound repair, we hypothesized that activation of the hedgehog pathway may promote a favorable effect on microvascular remodeling during cutaneous wound healing and thereby accelerate wound closure. Because diabetes is associated with impaired wound healing, we tested this hypothesis in a diabetic model of cutaneous wound repair.
In Ptc1-LacZ mice, cutaneous injury resulted in LacZ expression, indicating that expression of the Shh receptor Patched was induced and therefore that the Shh signaling pathway was intact postnatally and upregulated in the process of wound repair. In diabetic mice, topical gene therapy with the use of naked DNA encoding for Shh resulted in significant local gene expression and acceleration of wound recovery. The acceleration in wound healing was notable for increased wound vascularity. In bone marrow transplantation models, the enhanced vascularity of the wound was shown to be mediated, at least in part, by enhanced recruitment of bone marrow-derived endothelial progenitor cells. In vitro, Shh promoted production of angiogenic cytokines from fibroblasts as well as proliferation of dermal fibroblasts. Furthermore, Shh directly promoted endothelial progenitor cell proliferation, migration, adhesion, and tube formation.
These findings suggest that a simple strategy of topically applied Shh gene therapy may have significant therapeutic potential for enhanced wound healing in patients with impaired microcirculation such as occurs in diabetes.
Several studies have reported a correlation between right ventricular (RV) and left ventricular (LV) systolic dysfunction in adults with repaired tetralogy of Fallot (TOF). However, data are lacking ...regarding the relationship between RV and LV diastolic dysfunction assessed by 2-dimensional speckle-tracking echocardiography. We studied 69 adults with repaired TOF (mean age 34 years, 61% male) who had been regularly followed up and had routinely undergone echocardiography. In addition to conventional echocardiography, global longitudinal strain (GLS) and early diastolic strain rate (SRe) of both ventricles were assessed using 2-dimensional speckle-tracking echocardiography. Results were compared with 30 age- and sex-matched controls. RV and LV GLS were decreased in TOF patients compared with controls (− 18.4 ± 3.3% vs. −23.5 ± 4.2%, p < 0.001 and − 16.0 ± 3.8% vs. −20.0 ± 3.0%, p < 0.001, respectively). RV and LV SRe were also decreased in TOF patients compared with controls (1.22 ± 0.34 sec
− 1
vs. 1.47 ± 0.41 sec
− 1
, p = 0.003 and 1.29 ± 0.42 sec
− 1
vs. 1.63 ± 0.42 sec
− 1
, p < 0.001, respectively). A correlation between RV and LV SRe was found in TOF patients (r = 0.43, p < 0.001) as well as between RV and LV GLS (r = 0.45, p < 0.001). Two-dimensional speckle-tracking echocardiography reveals subclinical RV and LV diastolic dysfunction in adults with repaired TOF. A correlation is observed between RV and LV diastolic dysfunction as well as between RV and LV systolic dysfunction.
The prevalence of migraine is higher in patients with atrial septal defect (ASD) (24.2%) than in the general Japanese population (9.4%). A few studies have reported that transcatheter closure of an ...interatrial shunt is known to attenuate migraine. We experienced hat surgical closure of the ASD improved migraine that was refractory to medication therapy. A 46-year-old man presented to a neurologist for evaluation of severe headache and was diagnosed with migraine. Brain magnetic resonance imaging (MRI) revealed evidence of previous multiple cerebral infarctions. Transesophageal echocardiography detected inferior sinus venosus-type ASD, and a bubble study showed the presence of a right-to-left shunt. Owing to the high index of clinical suspicion for paradoxical embolism via the ASD and the fact that percutaneous catheter closure was contraindicated for inferior sinus venosus-type ASD, we performed surgical closure of the ASD in this patient. The patient's migraine symptoms disappeared immediately after surgery, and no recurrence has been observed eight months after surgery. This is the first case report that surgical closure of ASD led to attenuate migraine. Our study highlights the association between right-to-left shunts and migraine, as well as the usefulness of the surgical closure of ASD as a therapeutic strategy for patients with migraine.
Ischemia resulting from myocardial infarction (MI) promotes VEGF expression, leading to vascular permeability (VP) and edema, a process that we show here contributes to tissue injury throughout the ...ventricle. This permeability/edema can be assessed noninvasively by MRI and can be observed at the ultrastructural level as gaps between adjacent endothelial cells. Many of these gaps contain activated platelets adhering to exposed basement membrane, reducing vessel patency. Following MI, genetic or pharmacological blockade of Src preserves endothelial cell barrier function, suppressing VP and infarct volume, providing long-term improvement in cardiac function, fibrosis, and survival. To our surprise, an intravascular injection of VEGF into healthy animals, but not those deficient in Src, induced similar endothelial gaps, VP, platelet plugs, and some myocyte damage. Mechanistically, we show that quiescent blood vessels contain a complex involving Flk, VE-cadherin, and beta-catenin that is transiently disrupted by VEGF injection. Blockade of Src prevents disassociation of this complex with the same kinetics with which it prevents VEGF-mediated VP/edema. These findings define a molecular mechanism to account for the Src requirement in VEGF-mediated permeability and provide a basis for Src inhibition as a therapeutic option for patients with acute MI.
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