Joule-class sub-nanosecond pulses produced by end-pumped direct bonded YAG/sapphire modular amplifier.

A Joule-class room-temperature diode-pumped solid-state laser was developed. The energy scaling of the 100 mJ 1064 nm seed pulse was realized by a series of two diode-pumped amplifiers. The gain medium consists in free combinations of Nd:YAG ceramics bonded to sapphire transparent heat sinks, to relax the thermal load induced by the 34 kW pump power. At low repetition rate, parasitic lasing was the main limitation to energy scaling. By choosing a gain module combination producing a step-like gradual doping concentration profile, mitigation of parasitic oscillations was observed, and the system delivered 2.8 J, 800 ps pulses at 2 Hz.

Efficacy and Safety of Warfarin for the Treatment of Venous Thromboembolism　- A Multicenter Prospective Observational Cohort Study in Japan (AKAFUJI Study).

BACKGROUND: A large-scale prospective study of the efficacy and safety of warfarin for the treatment of venous thromboembolism (VTE) has not been conducted in Japan. Therefore, we conducted a real-world prospective multicenter observational cohort study (AKAFUJI Study; UMIN000014132) to investigate the efficacy and safety of warfarin for VTE.Methods and Results: Between May 2014 and March 2017, 352 patients (mean [±SD] age 67.7±14.8 years; 57% female) with acute symptomatic/asymptomatic VTE were enrolled; 284 were treated with warfarin. The cumulative incidence of recurrent symptomatic VTE was higher in patients without warfarin than in those treated with warfarin (8.7 vs. 2.2 per 100 person-years, respectively; P=0.018). The cumulative incidence of bleeding complications was not significantly different between the 2 groups. The mean prothrombin time-international normalized ratio (PT-INR) during warfarin on-treatment was <1.5 in 180 patients, 1.5-2.5 in 97 patients, and >2.5 in 6 patients. The incidence of bleeding complications was significantly higher in patients with PT-INR >2.5, whereas the incidence of recurrent VTE was not significantly different between the 3 PT-INR groups. The cumulative incidence of recurrent VTE and bleeding complications did not differ significantly among those in whom VTE was provoked by a transient risk factor, was unprovoked, or was associated with cancer. CONCLUSIONS: Warfarin therapy with an appropriate PT-INR according to Japanese guidelines is effective without increasing bleeding complications, regardless of patient characteristics.

Calcification of a Hydrophilic Acrylic Intraocular Lens after Glaucoma Surgery.

A Japanese woman in her 70s was referred to our hospital for the evaluation and treatment of high intraocular pressure (IOP) in her right eye. She had undergone bilateral cataract surgeries and the insertion of hydrophilic acrylic intraocular lenses (IOLs). We performed trabeculotomy and trabeculectomy to lower her right IOP; thereafter, a circular opacity was observed on the right eye's IOL surface. We removed the right IOL because that eye's vision had decreased due to IOL opacification. The analysis of the removed IOL revealed that the main opacity component was calcium phosphate. This is the first post-glaucoma-surgery IOL calcification case report.

Balloon Pulmonary Angioplasty in the Management of Chronic Thromboembolic Pulmonary Hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH), which is classified as group 4 pulmonary hypertension (PH) in the 2015 European Society of Cardiology/European Respiratory Society guidelines for the diagnosis and treatment of PH, is regarded as a complication of pulmonary embolism and is caused by the transformation of incompletely resolved thrombi into fibrous tissue that occludes the pulmonary arteries. The current established reference standard curative therapy for CTEPH is pulmonary endarterectomy (PEA), which provides good long-term outcomes with a low mortality rate. For patients with inoperable disease with inaccessible lesions and risk factors for surgery or patients who are diagnosed with residual or recurrent PH after PEA, medical therapy with riociguat is recommended. Balloon pulmonary angioplasty (BPA) is an emerging alternative treatment option for patients with inoperable disease or those with residual or recurrent PH after PEA. BPA has been reported to improve hemodynamics, cardiac function, exercise capacity, and symptoms, as well as PEA. A detailed assessment of thromboembolic lesions in pulmonary arteries by using multiple imaging techniques and treatment strategies with multiple staged procedures based on the patient's condition is important for safe and effective BPA. However, this new technique may still induce life-threatening complications, such as reperfusion pulmonary edema, wire perforation, vessel dissection, and vessel rupture. Meticulous attention to technique is mandatory to minimize serious complications owing to the nature of the anatomic territory involved. The authors summarize the current roles, goals, and complications of BPA in patients with CTEPH and demonstrate ways to formulate an effective and safe treatment strategy. The future perspective of BPA is also discussed. Online supplemental material is available for this article. ©RSNA, 2022.

Two cases of pregnancy after achieving complete remission of chronic active Epstein-Barr virus infection.

Chronic active Epstein-Barr virus (CAEBV) infection characterized by persistent infectious mononucleosis-like symptoms can lead to cardiovascular diseases. We encountered two pregnant women with CAEBV histories complicated with cardiovascular diseases. A 36-year-old woman with a history of myocardial infarction due to CAEBV and coronary artery bypass grafting became pregnant. Her left ventricular ejection fraction (LVEF) decreased, and cesarean section was performed at 36 weeks of gestation. Her LVEF recovered after delivery. A 32-year-old woman with a history of CAEBV and chronic hypertension was diagnosed with mild pulmonary arterial hypertension (PAH) after conception. She strongly desired to continue the pregnancy. She became complicated with severe superimposed preeclampsia at 31 weeks of gestation, and cesarean section was performed. Her PAH did not deteriorate during pregnancy or the postpartum period. Women treated for CAEBV, even with complete remission, require a preconception evaluation focused on the cardiovascular system and careful management of their pregnancy.

Beneficial Effect of Endovascular Treatment on Villalta Score in Japanese Patients With Chronic Iliofemoral Venous Thrombosis and Post-Thrombotic Syndrome.

BACKGROUND: Post-thrombotic syndrome (PTS), the most common complication of deep venous thrombosis (DVT), develops in ≥50% of patients with iliofemoral DVT. However, the benefit of endovascular treatment in Japanese patients with chronic DVT and PTS remains unclear. Methods and Results: Between June 2014 and May 2016, endovascular treatment was performed in 11 consecutive Japanese patients with chronic iliofemoral DVT and PTS refractory to anticoagulant therapy and elastic compression stockings. We evaluated the technical success rate, complications, patency, Villalta score, calf circumference, and popliteal vein reflux in both the acute stage (the day following endovascular treatment) and chronic stage (after 6 months). Imaging follow-up included venous duplex scanning and/or magnetic resonance venography. The technical success rate was 81.8%, without complications. In patients with successful intervention, the Villalta score improved significantly, from 9.0±3.7 preoperatively to 3.6±2.5 in the acute phase (P<0.01) and 2.9±2.1 in the chronic phase (P<0.001). The bilateral difference in lower thigh circumference also improved significantly, from 2.6±1.0 cm preoperatively to 1.4±1.0 cm in the chronic phase (P<0.001). However, popliteal vein reflux did not improve. In patients with successful intervention, venous patency rate was 100% at 6 months post-intervention. CONCLUSIONS: Endovascular treatment is safe and effective in Japanese patients with chronic iliofemoral DVT and PTS.

Congenitally Corrected Transposition of the Great Arteries and Situs Inversus in an Octogenarian With Systemic Right Ventricular Failure.

Systemic right ventricular (RV) failure in patients with congenitally corrected transposition of the great arteries (ccTGA), a major cause of mortality in the long-term follow-up, is usually induced by concomitant severe morphologically tricuspid regurgitation (TR) with/without Ebstein's anomaly or progressive conduction tissue disturbances. However, whether or not myocardial fibrosis is a common cause of systemic RV failure in patients with ccTGA remains unclear. Here, we describe an 82-year-old man who had been diagnosed previously as having uncomplicated ccTGA and situs inversus and recently developed systemic RV failure, which was neither associated with severe TR nor advanced conduction tissue abnormalities. Cardiovascular magnetic resonance (CMR) with delayed-enhancement imaging clearly detected extensive myocardial scars (presumably fibrosis) in the RV wall as well as prominent dilatation, hypertrophy, and systolic dysfunction of the systemic RV. These findings suggest that myocardial fibrosis can cause systemic RV failure in elderly patients with uncomplicated ccTGA despite the absence of severe TR or advanced conduction tissue abnormalities and that CMR may be a useful examination to accurately detect systemic RV failure associated with myocardial fibrosis and to subsequently clarify the prognosis in these patients.

Right ventricular reverse remodelling after balloon pulmonary angioplasty.

Balloon pulmonary angioplasty (BPA) has been reported to improve haemodynamics and functional capacity, with an acceptable risk, in patients with chronic thromboembolic pulmonary hypertension (CTEPH) who are not candidates for pulmonary endarterectomy. However, right ventricular (RV) function, an important predictor in CTEPH, remains to be elucidated. We aimed to examine the impact of BPA on RV remodelling and dysfunction relative to haemodynamic improvements in patients with inoperable CTEPH. 20 consecutive patients with inoperable CTEPH who underwent BPA with cardiovascular magnetic resonance before and after BPA were retrospectively studied. BPA led to significant amelioration of the mean pulmonary arterial pressure, cardiac index and pulmonary vascular resistance (PVR), without death or major complications. Furthermore, BPA significantly ameliorated right-sided heart failure symptoms and signs, and exercise capacity. Cardiovascular magnetic resonance revealed a marked improvement in RV end-diastolic and end-systolic volume index, with concomitant improvements in RV ejection fraction, mass and interventricular septal bowing after BPA. Changes in RV volumes strongly correlated with changes in cardiac index and PVR. BPA induced RV reverse remodelling and improved systolic dysfunction safely by ameliorating haemodynamics in patients with inoperable CTEPH. Evaluating RV function with cardiovascular magnetic resonance may be effective for noninvasively monitoring BPA efficacy.

Early and long-term outcomes of venous stent implantation for iliac venous stenosis after catheter-directed thrombolysis for acute deep vein thrombosis.

BACKGROUND: Although stent implantation is used worldwide for peripheral arterial disease, there is little data on the safety and long-term patency of stents implanted for venous disease. METHODS AND RESULTS: We studied 13 patients with 14 lesions (6 males, 7 females, mean age: 63.2±10.2 years) diagnosed with venous stenosis and who underwent venous stenting. We examined the location of the stenosis, safety of venous stenting, implantation success rate, and long-term stent patency rate. All patients were suffering from venous stenosis in the left common iliac vein because of iliac vein compression syndrome. No major complications occurred during stent implantation. Acute stent occlusion occurred in 1 patient, who was given additional thrombolytic therapy. Of the 13 patients, 10 underwent venography or contrast-enhanced computed tomography (CT) during mid-term follow-up (mean: 12.9±16.1 months), and only 1 stent was occluded, resulting in a patency rate of 90.0%. The latter patient decided to stop taking warfarin soon after stent implantation. Furthermore, 5 patients underwent contrast-enhanced CT to assess the long-term patency of their stents (mean: 79.6±31.2 months), and none was occluded. CONCLUSIONS: Venous stents display a high long-term patency rate, and hence are a useful tool for treating iliac venous stenosis.

Calcium channel blockers in patients with pulmonary arterial hypertension receiving PAH-specific treatment.

BACKGROUND: Calcium channel blockers (CCB) are the first effective therapy for vasoreactive patients with idiopathic pulmonary arterial hypertension (IPAH). However, the advent of modern PAH-specific drugs may undermine the role of vasoreactivity tests and CCB treatment. We aimed to clarify the effect of acute vasoreactivity testing and CCB on patients with IPAH receiving PAH-specific treatment. METHODS: We retrospectively investigated consecutive patients with IPAH (n = 136) diagnosed between 2000 and 2020 and collected data from patients who underwent acute vasoreactivity testing using inhaled nitric oxide (NO). The effects of vasoreactivity testing and CCB therapy were reviewed. Long-term survival was analysed using the Kaplan-Meier method. RESULTS: Acute vasoreactivity testing was performed in 49% of patients with IPAH (n = 67), including 23 patients (34%) receiving PAH-specific therapy without vasoreactivity testing. Eight patients (12%), including three patients (4.4%) receiving PAH-specific therapy, presented acute responses at vasoreactivity testing. They received high-dose CCB therapy (CCB monotherapy for five patients [7.5%] and CCB therapy and PAH-specific therapy for three patients [4.4%]). They presented a significant improvement in clinical parameters and near-normalisation of haemodynamics (mean pulmonary arterial pressure decreased from 46 [interquartile range: 40-49] to 19.5 [interquartile range: 18-23] mmHg [P < .001] at 1-year follow-up). All eight vasoreactive responders receiving CCB therapy showed better long-term survival than non-responders treated with PAH-specific therapy (P < .001). CONCLUSIONS: CCB therapy benefited patients with IPAH who showed acute response to vasoreactivity testing using inhaled NO, even when receiving modern PAH-specific therapy. Acute vasoreactive responders may benefit more from CCB than from PAH-specific therapy.

Recurrent pulmonary hypertension after balloon pulmonary angioplasty for inoperable chronic thromboembolic pulmonary hypertension.

BACKGROUND: Balloon pulmonary angioplasty improves the hemodynamics of patients with inoperable chronic thromboembolic pulmonary hypertension; however, the clinical impact of recurrent pulmonary hypertension after balloon pulmonary angioplasty remains unclear. METHODS: We retrospectively reviewed 262 consecutive patients with chronic thromboembolic pulmonary hypertension who underwent balloon pulmonary angioplasty between July 2009 and December 2020; 158 (65 ± 12 years; males, 20%; median follow-up period, 45 [26, 66] months) with follow-up right heart catheterization and no residual pulmonary hypertension were included. Recurrent pulmonary hypertension was defined as mean pulmonary arterial pressure <25 mm Hg at the first evaluation after balloon pulmonary angioplasty and ≥25 mm Hg at follow-up evaluation requiring additional treatment with balloon pulmonary angioplasty or pulmonary vasodilators. RESULTS: Recurrent pulmonary hypertension was observed in 11 patients; the state occupation probability of recurrence at 5 years was 9.0% (95% confidence interval: 5.0%-18.9%). Only 1 case (0.6%) of recurrent pulmonary hypertension showed vascular restenosis and reocclusion of previously treated lesions, with more significant hemodynamic and exercise capacity deterioration than the other cases. Additional treatments for recurrent pulmonary hypertension (balloon pulmonary angioplasty in 9 patients, pulmonary vasodilators in 4 patients) improved the mean pulmonary arterial pressure from 27 [26, 29] to 22 [19, 23] mm Hg (p < 0.01). Recurrence had a low probability of transitioning to death in an illness-death model. No specific risk factors for recurrent pulmonary hypertension were identified. CONCLUSIONS: Symptomatic recurrent pulmonary hypertension due to vascular restenosis or reocclusion after balloon pulmonary angioplasty was extremely rare. Most cases of recurrent pulmonary hypertension were mild, did not worsen clinically, and had favorable prognoses.

Balloon pulmonary angioplasty for chronic thromboembolic pulmonary disease without pulmonary hypertension.

Balloon pulmonary angioplasty (BPA) is beneficial for patients with chronic thromboembolic pulmonary disease (CTEPD) with pulmonary hypertension (PH). However, the clinical benefit of BPA for the patients with CTEPD without PH remains unknown. In this study, we aimed to evaluate the efficacy, safety, and long-term outcomes of BPA in patients with CTEPD without PH. We retrospectively analyzed the data from 84 CTEPD patients with mean pulmonary artery pressure (mPAP) < 25 mmHg and 39 CTEPD patients with mPAP ≤ 20 mmHg (without PH). Among the 39 patients with CTEPD without PH, 14 underwent BPA (BPA-treated group), and the remaining 25 received no treatment (untreated group). In the patients with CTEPD without PH, BPA led to improvements in symptoms, pulmonary vascular resistance (3.6 ± 1.6 to 2.6 ± 1.1 Wood units, p < 0.001), peak oxygen consumption (16.1 ± 4.0 to 18.8 ± 4.3 mL/kg/min, p = 0.033), minute ventilation versus carbon dioxide production slope (41.4 ± 12.2 to 35.1 ± 6.7, p = 0.026), and mPAP/cardiac output slope (7.0 ± 2.6 to 4.4 ± 2.0 mmHg/L/min, p = 0.004) and facilitated the discontinuation of home oxygenation therapy, with no serious complications. Kaplan-Meier analysis showed no significant difference in all-cause mortality between the untreated and BPA-treated groups. BPA may be a safe treatment option for the patients with CTEPD without PH that can alleviate symptoms, improve exercise capacity, and facilitate weaning from home oxygen therapy. Further prospective randomized trials are needed to confirm these findings.

Clinical outcomes of upfront combination therapy for portopulmonary hypertension.

Background: Limited data exists on upfront combination therapy for portopulmonary hypertension. We evaluated the clinical efficacy, long-term outcomes, and safety of upfront combination therapy in patients with portopulmonary hypertension. Methods: We performed a retrospective, single-center cohort study involving a final analysis of 33 consecutive patients diagnosed with portopulmonary hypertension who were taking pulmonary arterial hypertension-specific medication. We compared hemodynamic parameters, risk profiles, composite clinical worsening events, and safety between monotherapy (n = 23) and upfront combination therapy (n = 10). Results: Twenty-seven patients (82 %) were classified into the Child-Pugh A stage. The change ratios of pulmonary vascular resistance (-32 % vs. -57 %, P = 0.006) were significantly better with upfront combination therapy. Upfront combination therapy also showed significant improvement in risk profiles. Kaplan-Meier analysis showed that the composite event-free rate was significantly lower in patients who received upfront combination therapy than in those who received monotherapy (P = 0.016), although no statistical differences were observed in all-cause death. In the univariate Cox proportional hazards analysis, upfront combination therapy was a factor for decreasing composite clinical worsening outcomes (hazard ratio 0.190, 95 % confidence interval 0.042-0.854; P = 0.030). No significant hepatic impairments were observed over 2 years of follow-up in the upfront combination group. Conclusions: In patients with portopulmonary hypertension, upfront combination therapy significantly improved symptoms and short-term hemodynamics, and reduced long-term clinical worsening events without serious adverse effects. This study's findings suggest that patients with portopulmonary hypertension presenting with mild hepatic impairment benefit from upfront combination therapy.

Three Cases of Unprovoked Venous Thromboembolism with Prothrombin p.Arg596Gln Variant and a Literature Review of Antithrombin Resistance.

Antithrombin resistance (ATR) is a newly identified strong genetic predisposition to venous thromboembolism (VTE) caused by genetic variations in prothrombin with substitutions of Arg at position 596 with either Leu, Gln, or Trp. In the present report, we identified a missense variant p.Arg596Gln in 3 patients from 2 families with unprovoked VTE who each experienced their first VTE event at 19, 67, and 19 years old. The three patients did not show any positive markers for thrombophilia on routine testing, suggesting that patients with unprovoked VTE who have negative findings on thrombophilia tests may carry a prothrombin variant with ATR.

Long-term outcomes of combined pulmonary endarterectomy and additional balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension.

BACKGROUND: The early and long-term outcomes after pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension (CTEPH) have been established by several high-volume centers, but the impact of postoperative residual pulmonary hypertension affecting postoperative clinical parameters remains unclear. This study aims to investigate the institutional surgical results of PEA and to evaluate the efficacy of additional balloon pulmonary angioplasty (BPA) for residual pulmonary hypertension. PATIENTS AND METHODS: We retrospectively reviewed 222 patients (57.7 ± 12.9 years old, 141 female) who underwent PEA for CTEPH at the National Cerebral and Cardiovascular Center between 2000 and 2020. RESULTS: The preoperative mean pulmonary artery pressure (mPAP) was 45.6 ± 9.7 mmHg and pulmonary vascular resistance (PVR) was 1062 ± 451 dyne*sec/cm-5. Postoperative mPAP (23.4 ± 11 mmHg, 204 patients, P < 0.001) and PVR (419 ± 291 dyne*sec/cm-5, 199 patients, P < 0.001) significantly improved after PEA. Since 2011, 62 patients (28%) underwent BPA after PEA for "catecholamine dependent" residual PH 1 month after PEA in 14, "scheduled" BPA with residual PH 1 year after PEA in 32, and 16 "symptomatic" patients without residual PH. Their mPAP had significantly improved by PEA (48.1 ± 7.7 to 32.0 ± 10.2 mmHg, P < 0.001), and further improved (33.8 ± 11.1 to 26.5 ± 9.1 mmHg, P < 0.001) after BPA. CONCLUSIONS: PEA provided immediate and substantial improvements in pulmonary hemodynamics and favorable long-term survival. In addition, postoperative BPA improved postoperative clinical parameters for eligible patients regardless of the presence of residual PH.

Dimerization processes for light-regulated transcription factor Photozipper visualized by high-speed atomic force microscopy.

Dimerization is critical for transcription factors (TFs) to bind DNA and regulate a wide variety of cellular functions; however, the molecular mechanisms remain to be completely elucidated. Here, we used high-speed atomic force microscopy (HS-AFM) to observe the dimerization process for a photoresponsive TF Photozipper (PZ), which consists of light-oxygen-voltage-sensing (LOV) and basic-region-leucine-zipper (bZIP) domains. HS-AFM visualized not only the oligomeric states of PZ molecules forming monomers and dimers under controlled dark-light conditions but also the domain structures within each molecule. Successive AFM movies captured the dimerization process for an individual PZ molecule and the monomer-dimer reversible transition during dark-light cycling. Detailed AFM images of domain structures in PZ molecules demonstrated that the bZIP domain entangled under dark conditions was loosened owing to light illumination and fluctuated around the LOV domain. These observations revealed the role of the bZIP domain in the dimerization processes of a TF.

Pulmonary arterial hypertension sensitive to calcium channel blocker, but not advanced pulmonary hypertension treatment: a case report.

Background: Calcium channel blockers (CCB), the first accepted treatment, is effective only in a small number of idiopathic pulmonary arterial hypertension (I-PAH) patients with vasoreactivity [these patients are identified by a positive acute pulmonary vasoreactive test (AVT) response]. While the majority of I-PAH patients is non-vasoreactive and CCB non-responders, modern advanced pulmonary hypertension (PH)-specific therapies, which act on one of the three different mechanistic pathways-endothelin, nitric oxide (NO), and prostacyclin pathways, are effective. Treatment response to advanced PH-specific vasodilators in PAH patients with vasoreactivity is unknown. Case summary: A 30-year-old woman with I-PAH was referred to our centre with worsening symptoms and deteriorating PH. She was being administered oral triple combination of advanced PH-specific treatment including a phosphodiesterase-5 inhibitor, an endothelin receptor antagonist, and a long-acting prostacyclin analogue. The patient showed positive AVT with NO inhalation while on these advanced PH-specific drugs. We added high-dose CCB, which dramatically normalized her pulmonary blood pressure without further symptoms, and she has remained stable for 5 years. Discussion: Our case describes a PAH patient with vasoreactivity, who was resistant to three different types of advanced PH-specific vasodilators but was exclusively sensitive to CCB treatment. Some CCB responders may have a specific CCB-sensitive PAH phenotype refractory to other pulmonary vasodilators. This case highlights the role of identifying CCB responders in this era of use of modern, advanced PH-specific vasodilators. The investigation of the mechanisms underlying CCB sensitivity in PAH is necessary.