Concomitant Mitral Regurgitation in Severe Aortic Stenosis　- Insights From the CURRENT AS Registry-2.

BACKGROUND: Data on concomitant mitral regurgitation (MR) in patients with severe aortic stenosis (AS) are scarce.Methods and Results: We investigated the risk of concomitant MR in patients with severe AS in the CURRENT AS Registry-2 according to initial treatment strategy (transcatheter aortic valve implantation [TAVI], surgical aortic valve replacement [SAVR], or conservative). Among 3,365 patients with severe AS, 384 (11.4%) had moderate/severe MR (TAVI: n=126/1,148; SAVR: n=68/591; conservative: n=190/1,626). The cumulative 3-year incidence for death or heart failure (HF) hospitalization was significantly higher in the moderate/severe than no/mild MR group in the entire population (54.6% vs. 34.3%, respectively; P<0.001) and for each treatment strategy (TAVI: 45.0% vs. 31.8% [P=0.006]; SAVR: 31.9% vs. 18.7% [P<0.001]; conservative: 67.8% vs. 41.6% [P<0.001]). The higher adjusted risk of moderate/severe MR relative to no/mild MR for death or HF hospitalization was not significant in the entire population (hazard ratio [HR] 1.15; 95% confidence interval [CI] 0.95-1.39; P=0.15); however, the risk was significant in the SAVR (HR 1.92; 95% CI 1.04-3.56; P=0.04) and conservative (HR 1.30; 95% CI 1.02-1.67; P=0.04) groups, but not in the TAVI group (HR 1.03; 95% CI 0.70-1.52; P=0.86), despite no significant interaction (Pinteraction=0.37). CONCLUSIONS: Moderate/severe MR was associated with a higher risk for death or HF hospitalization in the initial SAVR and conservative strategies, while the association was less pronounced in the initial TAVI strategy.

Serum proteomic identification and validation of two novel atherosclerotic aortic aneurysm biomarkers, profilin 1 and complement factor D.

BACKGROUND: Effective diagnostic biomarkers for aortic aneurysm (AA) that are detectable in blood tests are required because early detection and rupture risk assessment of AA can provide insights into medical therapy and preventive treatments. However, known biomarkers for AA lack specificity and reliability for clinical diagnosis. METHODS: We performed proteome analysis of serum samples from patients with atherosclerotic thoracic AA (TAA) and healthy control (HC) subjects to identify diagnostic biomarkers for AA. Serum samples were separated into low-density lipoprotein, high-density lipoprotein, and protein fractions, and the major proteins were depleted. From the proteins identified in the three fractions, we narrowed down biomarker candidates to proteins uniformly altered in all fractions between patients with TAA and HC subjects and evaluated their capability to discriminate patients with TAA and those with abdominal AA (AAA) from HC subjects using receiver operating characteristic (ROC) analysis. For the clinical validation, serum concentrations of biomarker candidates were measured in patients with TAA and AAA registered in the biobank of the same institute, and their capability for the diagnosis was evaluated. RESULTS: Profilin 1 (PFN1) and complement factor D (CFD) showed the most contrasting profiles in all three fractions between patients with TAA and HC subjects and were selected as biomarker candidates. The PFN1 concentration decreased, whereas the CFD concentration increased in the sera of patients with TAA and AAA when compared with those of HC subjects. The ROC analysis showed that these proteins could discriminate patients with TAA and AAA from HC subjects. In the validation study, these candidates showed significant concentration differences between patients with TAA or AAA and controls. PFN1 and CFD showed sufficient area under the curve (AUC) in the ROC analysis, and their combination further increased the AUC. The serum concentrations of PFN1 and CFD also showed significant differences between patients with aortic dissection and controls in the validation study. CONCLUSION: PFN1 and CFD are potential diagnostic biomarkers for TAA and AAA and measurable in blood samples; their diagnostic performance can be augmented by their combination. These biomarkers may facilitate the development of diagnostic systems to identify patients with AA.

[Operation for the Shaggy Aorta Syndrome].

Although mortality and complication rates of cardiovascular surgery have been reduced, shaggy aorta, which is defined as an extensive severe atherosclerosis of the thoracic and abdominal aorta, is considered a risk factor for perioperative mortality and complications. The shaggy aorta often leads a poor prognosis, and a very high hospital mortality rate when embolization occurs in multiple organs. Therefore, it is important to prevent embolism through detailed evaluation of the disease with preoperative contrast-enhanced computed tomography (CT) scan and intraoperative transesophageal echocardiogram, appropriate individualized treatment decisions, and careful surgical manipulation.

Antithrombotic Therapy for Patients With Atrial Fibrillation and Bioprosthetic Valves　- Real-World Data From the Multicenter, Prospective, Observational BPV-AF Registry.

BACKGROUND: Although bioprosthetic valve (BPV) replacements are becoming more common within our aging society, there are limited prospective data on the appropriate antithrombotic therapy for East Asian patients with atrial fibrillation (AF) and BPV replacement. Antithrombotic therapy and thrombotic and hemorrhagic event rates in Japanese patients with AF and BPV replacement are investigated.Methods and Results:This multicenter, prospective, observational study enrolled patients with BPV replacement and AF. The primary efficacy outcome was stroke or systemic embolism, and the primary safety outcome was major bleeding. Of the 894 patients analyzed, 54.7%, 29.4%, and 9.6%, were treated with warfarin-based therapy, direct oral anticoagulant (DOAC)-based therapy, or antiplatelet therapy without anticoagulants, respectively; 6.3% did not receive any antithrombotic drugs. The mean observation period was 15.3±4.0 months. The event rates for stroke or systemic embolism and major bleeding were 1.95%/year and 1.86%/year, respectively. The multivariate adjusted hazard ratios for DOAC vs. warfarin were 1.02 (95% confidence intervals [CI], 0.30-3.41 [P=0.979]) for systemic embolic events and 0.96 (95% CI, 0.29-3.16 [P=0.945]) for major bleeding. CONCLUSIONS: Approximately 30% of patients with AF and BPV replacement were treated with DOAC. The risks of major bleeding and stroke or systemic embolism were similar between warfarin- and DOAC-treated patients with AF who had BPV replacement. Treatment with DOACs could be an alternative to warfarin in this population.

Comparison of Direct Oral Anticoagulants and Warfarin in Patients With Atrial Fibrillation and an Aortic Bioprosthetic Valve.

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.

Rationale, Design, and Baseline Characteristics of the CURRENT AS Registry-2.

BACKGROUND: There is scarce data evaluating the current practice pattern and clinical outcomes for patients with severe aortic stenosis (AS), including both those who underwent surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI) and those who were managed conservatively in the TAVI era.Methods and Results: The Contemporary outcomes after sURgery and medical tREatmeNT in patients with severe Aortic Stenosis (CURRENT AS) Registry-2 is a prospective, physician-initiated, multicenter registry enrolling consecutive patients who were diagnosed with severe AS between April 2018 and December 2020 among 21 centers in Japan. The rationale for the prospective enrollment was to standardize the assessment of symptomatic status, echocardiographic evaluation, and other recommended diagnostic examinations such as computed tomography and measurement of B-type natriuretic peptide. Moreover, the schedule of clinical and echocardiographic follow up was prospectively defined and strongly recommended for patients who were managed conservatively. The entire study population consisted of 3,394 patients (mean age: 81.6 years and women: 60%). Etiology of AS was degenerative in 90% of patients. AS-related symptoms were present in 60% of patients; these were most often heart failure symptoms. The prevalence of high- and low-gradient AS was 58% and 42%, respectively, with classical and paradoxical low-flow low-gradient AS in 4.6% and 6.7%, respectively. CONCLUSIONS: The CURRENT AS Registry-2 might be large and meticulous enough to determine the appropriate timing of intervention for patients with severe AS in contemporary clinical practice.

Evaluations for surrounding tissue incorporation after implantation of synthetic vascular prostheses in animal models.

Incorporation of surrounding tissues after implantation of synthetic vascular prostheses potentially varies in accordance with implanted prostheses. To evaluate post-implant tissue incorporation, we examined surgical, histological and ultrastructural findings after implantation in animal models. Three types of commercially available prostheses were tested (Gelweave™; Group G, J Graft SHIELD NEO®; Group J and Triplex®; Group T). Prostheses were implanted into Sprague-Dawley rats subcutaneously or sutured on abdominal aorta of Japanese white rabbits. The tissues were surgically examined for adhesion and were subjected to histological evaluations for cellular and tissue infiltration and ultrastructural observations by scanning electron microscopy (SEM). Group G exhibited less tendency in adhesion formation in early phase (rat: G vs J, P < 0.0001; G vs T, P < 0.0001/rabbit: G vs J, P < 0.0001; G vs T, P = 0.059). In late phase, Group J showed highest adhesion (rat: G vs J, P = 0.0004; J vs T, P = 0.015/rabbit: G vs J, P = 0.0015; J vs T, P = 0.0044). In group G, a gap was observed between implants and surrounding tissues forming capsulation, whereas other groups exhibited tissue infiltration inside of the implants wall which were also confirmed by SEM. The tissue permeation toward the implants and adhesion was positively correlated (P < 0.0001). Surrounding tissue conformation varied in accordance with the type of prostheses. It is desirable to elucidate characteristics of each prosthesis to select suitable grafts for each patient to achieve a better surgical outcome.

Is this the final answer for the aortopathy with bicuspid aortic valve.

There have been changes in the guidelines for surgical indications for aortopathy associated with bicuspid aortic valves over the last 10 years. Although the results of the last 3 years adhering to the latest guidelines have been shown to be good, careful follow-up and accumulation of new research findings are still required.

Updates in aortic wall pathology.

Several studies have investigated the pathogenesis of aortic wall abnormalities such as aortic dissection or aneurysm; however, the comprehensive pathological in situ event involved in the development of the disease is not understood well. The vasa vasorum form a network of capillaries or venules around the adventitia and outer media, which play an important role in the aortic wall structure and function. Impairment of their function may induce tissue hypoxia, impede the transfer of cellular nutrients, and cause aortic medial degeneration, which is considered the major predisposing factor to this aortic wall pathology. This review updates our understanding of the pathological changes in the aortic media and vasa vasorum of patients with aortic dissection and aortic aneurysm.

[Emergency Surgical Management for Stanford Type B Acute Aortic Dissection].

Since a certain number of patients with Stanford type B acute aortic dissection have complications such as rupture and malperfusion (complicated type B), it is important to understand the pathogenesis of this condition and to avoid misjudging the timing and methods of invasive treatment such as thoracic endovascular aortic repair( TEVAR) and graft replacement. TEVAR is widely accepted as a less invasive treatment than conventional surgery, and is usually recognized as the first-line treatment, especially for complicated type B. On the other hand, there is still little clear evidence for TEVAR for uncomplicated type B without rupture or malperfusion, and careful selection of cases is considered necessary. In this review article, we describe the acute treatment of Stanford type B acute aortic dissection with reference to recent guidelines and literature.

Long-Term Impact of Diabetes Mellitus on Initially Conservatively Managed Patients With Severe Aortic Stenosis.

BACKGROUND: Although diabetes mellitus (DM) is a common comorbidity of aortic stenosis (AS), clinical evidence about the long-term effect of DM on patients with AS is insufficient.Methods and Results:Data were acquired from CURRENT AS, a large Japanese multicenter registry that enrolled 3,815 patients with severe AS. Patients without initial valve replacement were defined as the conservative group; among them, 621 (23.4%) had DM, whereas 1997 did not. The DM group was further divided into 2 groups according to insulin treatment (insulin-treated DM, n=130; non-insulin treated DM, n=491). The primary outcome was a composite of aortic valve (AV)-related death and heart failure (HF) hospitalization. Secondary outcomes were AV-related death, HF hospitalization, all-cause death, cardiovascular death, sudden death, and surgical or transcatheter AV replacement during follow up. As a result, DM was associated with higher risk for the primary outcome (52.8% vs. 42.9%, P<0.001), with a statistically significant adjusted hazard ratio (HR 1.33, 95% confidence interval: 1.14-1.56, P<0.001). All secondary outcomes were not significantly different between DM and non-DM patients after adjusting for confounding factors, except for HF hospitalization. Insulin use was not associated with higher incidence of primary or secondary outcome. CONCLUSIONS: In initially conservatively managed patients with AS, DM was independently associated with higher risk for a composite of AV-related death or HF hospitalization; however, insulin use was not associated with poor outcomes.

Aggressive strategy to save the brain in a case of acute aortic dissection.

The case report by Sicim et al. is the placement of extra-anatomical bypasses in bilateral common carotid arteries. The similar previous reports of the extra-anatomical bypass usually indicate unilateral bypass. Whether or not the Willis' circle is incomplete is difficult to judge during emergency surgery, and the authors' judgment seems to have been correct in the sense that it could maintain cerebral perfusion reliably and quickly. The direct perfusion and extra-anatomical bypass of the carotid artery is a reasonable strategy in patients with cerebral malperfusion.

Thyroid storm after mitral valve repair in a patient with Becker muscular dystrophy.

A 40-year-old male with Becker muscular dystrophy presented with severe mitral regurgitation and underwent mitral valve repair. Following the surgery, the patient became tachycardic and developed a continuous high-grade fever and hyperbilirubinemia. The patient's condition worsened and we eventually tested his thyroid levels and discovered abnormally high thyroid levels. After diagnosing a severe thyroid storm, the patient was treated with oral administration of Lugol's iodine and thiamazole, as well as an intravenous steroid, which led to an immediate improvement of symptoms. The incidence of thyroid storm after open-heart surgery is extremely rare but highly life-threatening if unrecognized.

[Operation for Aortic Regurgitation after Replacement of Ascending Aorta].

It is not uncommon for aortic regurgitation to occur after ascending aortic replacement. There are various causes of the aortic valve insufficiency after ascending aorta replacement. Among them, most common is a reoperation after open repair of Stanford type A acute aortic dissection. Although it is becoming safer to perform reoperative cardiac surgery, the risks of operative mortality and morbidity is still higher than those of non-reoperative cardiac surgeries. In order to improve the mortality and morbidity rate, we should select the best strategies with a thorough preoperative evaluation. Moreover, a careful observation after the operation is required to find the complications, especially the patients who have the risk of aortic valve insufficiency.

[Initial Experiences of Valve-sparing Aortic Root Replacement Using New Designed Valsalva Graft:Report of Three Cases].

Valve sparing aortic root replacement( VSRR) is currently an established option for patients with annuloaortic ectasia( AAE). A newly designed Valsalva graft, the J Graft Shield Neo Valsalva, was used for VSRR in three cases. All operations were successful and postoperative courses were uneventful. Graft designs closer in shape to the native Valsalva may contribute to the improvement of late outcomes in VSRR.

[One-stage Radical Surgery for Aortoesophageal Fistula after Graft Replacement of Descending Aorta].

A 31-year-old woman was referred to our institution because of aortoesophageal fistula (AEF) six months after the descending aortic replacement for acute aortic dissection. We operated one-stage repair of the AEF. Thoracoscopic esophagectomy was firstly performed in prone position from right thoracic cavity, and then the esophagus was reconstructed with gastric conduit via posterior mediastinal route with omental flap. Secondly, graft replacement of the descending aorta using lateral oblique straight incision was performed and the graft was covered with omental flap simultaneously. The postoperative course was uneventful, and she started oral intake on the 13th day after surgery. Although the one-stage surgery for the AEF is highly invasive, it could be a good option for selected cases.

Percutaneous coronary intervention versus coronary arterial bypass grafting in patients with multi-vessel coronary revascularization (from the CREDO-Kyoto PCI/CABG registry/cohort-2).

OBJECTIVE: To assess long-term outcomes after percutaneous coronary intervention (PCI) with drug-eluting stent only compared with coronary artery bypass grafting (CABG) in patients with triple-vessel disease. BACKGROUND: Selection between PCI and CABG is still a clinically relevant issue in the management of patients with multi-vessel coronary artery disease. METHODS: Among 15,939 patients enrolled in the CREDO-Kyoto PCI/CABG registry/cohort-2, the current study population consisted of 2,193 patients who underwent elective multi-vessel coronary revascularization including left anterior descending coronary artery (LAD) either by PCI with sirolimus-eluting stent (SES) only (N = 945) or CABG (N = 1,248). RESULTS: The cumulative 5-year incidence of and the adjusted risk for the primary outcome measure (a composite of all-cause death, myocardial infarction [MI], or stroke) were not significantly different between PCI and CABG groups (22.6% vs. 23.0%, p = .40, and HR: 1.13, 95%CI: 0.91-1.40, p = .26). The risk of PCI relative to CABG for all-cause death and stroke was also insignificant (HR: 1.19, 95%CI: 0.92-1.53, p = .19; HR: 0.89, 95%CI: 0.62-1.27, p = .51). The adjusted 5-year risk for MI, hospitalization for heart failure (HF), any coronary revascularization and major bleeding was significantly different between the groups (HR: 1.59, 95%CI: 1.10-2.30, p = .01; HR: 1.49, 95%CI: 1.05-2.11, p = .02; HR: 3.70, 95%CI: 2.91-4.70, p < .0001; HR: 0.18, 95%CI: 0.14-0.22, p < .0001). CONCLUSIONS: In patients who underwent coronary revascularization for multiple vessels including LAD, PCI using SES as compared with CABG was associated with a comparable 5-year risk for death/MI/stroke as well as for mortality, but with a markedly higher risk for any coronary revascularization.

Elective Non-Cardiac Surgery in Patients With Severe Aortic Stenosis　- Observations From the CURRENT AS Registry.

BACKGROUND: Patients with severe aortic stenosis (AS) might be at high risk for adverse cardiovascular events at the time of non-cardiac surgery.Methods and Results:The current study population included 348 patients who underwent elective non-cardiac surgery under general or spinal anesthesia during the follow up of 3,815 patients in the CURRENT AS (Contemporary outcomes after sURgery and medical tREatmeNT in patients with severe Aortic Stenosis) registry. There were 187 patients with untreated severe AS at time of surgery (untreated severe AS group) and 161 patients who had undergone aortic valve replacement (AVR) before surgery (prior AVR group), including 23 patients with prophylactic AVR. The primary outcome measure was 30-day mortality after non-cardiac surgery. At 30 days after non-cardiac surgery, 8 patients (4.3%) died in the untreated severe AS group, while no patients died in the prior AVR group (P=0.008). The causes of death were cardiovascular in 6 out of 8 patients. Mortality at 30 days was higher in untreated severe AS patients with AS-related symptoms before surgery than in those without AS-related symptoms (7.2% vs. 3.1%). Higher surgical risk estimates of the non-cardiac surgery incrementally increased the risk of 30-day mortality in patients with untreated severe AS, though the difference was not statistically significant (low-risk: 0%, intermediate-risk: 4.3%, and high-risk: 6.6 %, P=0.46). CONCLUSIONS: Symptomatic and asymptomatic severe AS might be associated with higher risk of 30-day mortality if untreated before elective intermediate- and high-risk non-cardiac surgery, while no patient with prior AVR died after elective non-cardiac surgery.

Age-Related Differences in the Effects of Initial Aortic Valve Replacement vs. Conservative Strategy on Long-Term Outcomes in Asymptomatic Patients With Severe Aortic Stenosis.

BACKGROUND: This study aimed to evaluate the effect of the initial aortic valve replacement (AVR) strategy relative to a conservative strategy on long-term outcomes stratified by age among asymptomatic patients with severe aortic stenosis (AS).Methods and Results:Among 1,808 asymptomatic severe AS patients in the CURRENT AS registry, there were 1,166 patients aged ≥75 years (initial AVR: n=124, and conservative: n=1,042), and 642 patients with age <75 years (initial AVR: n=167, and conservative: n=475). Median follow-up interval was 1,280 (interquartile range [IQR]: 1,012-1,611) days, and 1461 (IQR: 1,132-1,886) days in patients aged ≥ and <75 years, respectively. The favorable effect of the initial AVR strategy relative to conservative strategy for heart failure (HF) hospitalization was seen regardless of the age stratum (≥75 years: adjusted hazard ratio [HR] 0.13, 95% confidence interval [CI] 0.05-0.34, and <75 years: HR 0.37, 95% CI 0.14-0.99, interaction P=0.35). However, the lower mortality risk of the initial AVR strategy relative to conservative strategy was significant in patients aged ≥75 years, but not in patients <75 years, with significant interaction (HR 0.35, 95% CI 0.20-0.61, and HR 0.69, 95% CI 0.41-1.16, interaction P=0.016). CONCLUSIONS: The benefit of initial AVR in reducing HF hospitalization in asymptomatic patients with severe AS was consistently seen regardless of age. The magnitude of mortality benefit of initial AVR was greater in super-elder patients than in non-super-elder patients.

Hypothermic circulatory arrest for aortic dissection with cryoglobulinemia.

Cryoglobulinemia is a cold-reactive autoimmune disease. A 64-year-old man with active cryoglobulinemia presented Stanford type A acute aortic dissection. He had been treated with immunosuppressive drugs and plasma exchange (PE) at our hospital; subsequently, qualitative analysis of cryoglobulin (CG) was negative. He underwent emergency ascending aorta replacement using cardiopulmonary bypass (CPB) under deep hypothermia circulatory arrest with selective cerebral perfusion. The total CPB time, aortic cross-clamp time, and selective cerebral perfusion time were 255, 153, 56 minutes, respectively, and the minimal nasopharyngeal temperature was 17.3°C. Our patient had no significant perioperative complications. Hence, if PE is performed appropriately and CG is negative, patients with cryoglobulinemia who exhibit severe preoperative symptoms can safely undergo surgery with deep hypothermia.