C hronic thromboembolic pulmonary hypertension (CTEPH) is classified into group 4 as a cause of pulmonary hypertension according to the latest guideline for pulmonary hypertension.1 It results from organized thrombi causing pulmonary artery stenosis/occlusion and leads to abnormal pulmonary blood flow distribution in lung perfusion scanning. Furthermore, it results in pulmonary hypertension, hypoxia, and right ventricular failure.2 If left untreated, the 3-year survival rate for patients with a mean pulmonary arterial pressure of ≥30 mm Hg at the time of definitive diagnosis is poor. 3,4 Pulmonary endarterectomy (PEA) is the only curative treatment for selected CTEPH patients.2 Although the mortality rate among the most experienced institutes is as low as 2.2%, 5 these excellent outcomes are not applicable worldwide, where it can be as high as 14.3%. [6][7][8][9] Moreover, the rate of inoperable CTEPH varies from 12.0% to 60.9%. Balloon pulmonary angioplasty (BPA) is an alternative therapy for CTEPH patients who are ineligible for PEA. 10,11 Recently, the efficacy of BPA in improving hemodynamics and exercise capacity has been established by case series reported by several groups, including our group. 12,13 There is a learning curve to safely and successfully perform BPA, as previously mentioned.12 As our group has accumulated experience with BPA, we noted that some types of lesions were associated with better BPA success and a lower rate of complications when compared with other types of lesions. This is similar to the variance in outcomes and complications associated with specific types of lesions when performing percutaneous coronary intervention (PCI) for patients with coronary artery diseases. PCI is performed based on a classification of coronary angiogram. In PCI, a classification of lesion type based on the success rate of the procedure is widely used.14 There are several classifications Background-Balloon pulmonary angioplasty (BPA) is an alternative therapy for patients with chronic thromboembolic pulmonary hypertension who are ineligible for standard therapy, pulmonary endarterectomy. Although there are several classifications of vascular lesions, these classifications are based on the features of the specimen removed during pulmonary endarterectomy. Because organized thrombi are not removed during balloon pulmonary angioplasty, we attempted to establish a new classification of vascular lesions based on pulmonary angiographic images. We evaluated the success and complication rate of BPA in accordance with the location and morphology of thromboembolic lesions. Methods and Results-We reviewed 500 consecutive procedures (1936 lesions) of BPA in 97 patients with chronic thromboembolic pulmonary hypertension and investigated the outcomes of BPA based on the lesion distribution and the angiographic characteristics of the thromboembolic lesions, as follows: type A, ring-like stenosis lesion; type B, web lesion; type C, subtotal lesion; type D, total occlusion lesion, and type E, tortuous lesion. The success ...

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Although several cytokines and neurotrophic factors induce sympathetic neurons to transdifferentiate into cholinergic neurons in vitro, the physiological and pathophysiological roles of this remain unknown. During congestive heart failure (CHF), sympathetic neural tone is upregulated, but there is a paradoxical reduction in norepinephrine synthesis and reuptake in the cardiac sympathetic nervous system (SNS). Here we examined whether cholinergic transdifferentiation can occur in the cardiac SNS in rodent models of CHF and investigated the underlying molecular mechanism(s) using genetically modified mice. We used Dahl salt-sensitive rats to model CHF and found that, upon CHF induction, the cardiac SNS clearly acquired cholinergic characteristics. Of the various cholinergic differentiation factors, leukemia inhibitory factor (LIF) and cardiotrophin-1 were strongly upregulated in the ventricles of rats with CHF. Further, LIF and cardiotrophin-1 secreted from cultured failing rat cardiomyocytes induced cholinergic transdifferentiation in cultured sympathetic neurons, and this process was reversed by siRNAs targeting Lif and cardiotrophin-1. Consistent with the data in rats, heart-specific overexpression of LIF in mice caused cholinergic transdifferentiation in the cardiac SNS. Further, SNS-specific targeting of the gene encoding the gp130 subunit of the receptor for LIF and cardiotrophin-1 in mice prevented CHF-induced cholinergic transdifferentiation. Cholinergic transdifferentiation was also observed in the cardiac SNS of autopsied patients with CHF. Thus, CHF causes target-dependent cholinergic transdifferentiation of the cardiac SNS via gp130-signaling cytokines secreted from the failing myocardium. IntroductionCardiac function is tightly controlled by the balance between the sympathetic nervous system (SNS) and the parasympathetic nervous system (PNS). The SNS produces norepinephrine (NE) and increases the heart rate, conduction velocity, and myocardial contraction and relaxation, while the PNS produces acetylcholine (Ach) that reduces cardiac performance. In congestive heart failure (CHF), sympathetic neural tone is upregulated, and excess SNS activation leads to pathophysiological effects, such as myocardial damage, decline of cardiac function, and lethal arrhythmia (1, 2), and also causes depletion of cardiac NE content (3). This depletion of NE in CHF has been considered to be the result of excess NE secretion, disturbance of NE reuptake, and loss of noradrenergic nerve terminals (4, 5). However, we recently reported that the attenuation of NE in CHF was caused by downregulation of NE synthesis, concomitant with the reduced NE reuptake (6). However, the molecular mechanisms underlying the reduction in catecholaminergic characteristics of cardiac SNS in CHF remain poorly understood.

HALT with reduced leaflet motion was not rare but usually subclinical. Valve hemodynamics and mid-term outcomes were uneventful even without additional anticoagulant therapy in our limited number of cases. Male sex, larger sinus and bioprosthesis size, and elevated D-dimer levels during follow-up were associated with this phenomenon.