RECENTLY, CHINA VALVE (HANGZHOU) 2024, HOSTED BY THE SECOND AFFILIATED HOSPITAL OF ZHEJIANG UNIVERSITY SCHOOL OF MEDICINE AND THE STRUCTURAL HEART CONFERENCE CSI, WAS HELD IN HANGZHOU IN A COMBINATION OF ONLINE + OFFLINE. At the keynote research forum, Professor Wang Jian'an from the Second Affiliated Hospital of Zhejiang University School of Medicine gave a lecture entitled "Opportunities and Challenges in the Field of Diagnosis and Treatment of Aortic Valve Disease", and comprehensively shared the experience of diagnosis and treatment of aortic valve disease from three parts: the upstream management of interventional treatment of aortic valve disease, the interventional treatment itself and the downstream management of interventional treatment.
Center Diagram
Upstream management of interventional therapy for aortic valve disease
01 Epidemiology
(1) Morbidity and mortality of aortic valve disease
Coffey, S et al., published in Nat Rev Cardiol, showed that globally, rheumatic heart disease occurs mainly in young people, and calcific aortic valve disease (CAVD) occurs mainly in older people. With the improvement of diagnosis and treatment, the mortality rate of rheumatic heart disease is on the rise, but the mortality rate of non-rheumatic CAVD and non-rheumatic degenerative mitral valve disease is still increasing. Overall, the prevalence of rheumatic heart disease, non-rheumatic CAVD, and non-rheumatic degenerative mitral valve disease is on the rise.
Fig.1 Epidemiology of aortic valve disease
At present, aortic valve disease is still a geriatric disease, especially in developed countries or developed regions, the incidence of aortic stenosis (AS) increases with the aging of the population.
Fig.2 Incidence of valvular disease
and (2) regional differences in the incidence and mortality of aortic valve disease
The incidence of aortic valve disease varies greatly between regions. Rheumatic heart disease occurs mainly in Oceania (with the highest age-standardized mortality rate), followed by Africa and Asia. The incidence of CAVD is highest in Australia, Europe, and North America.
Fig. 3 Regional differences in incidence and mortality of aortic valve disease
and (3) hospital-based reports of aortic valve disease in China
A study from Zhongshan Hospital of Fudan University screened 3,673 (1.1%) bicuspid aortic valve (BAV) patients among 325,910 patients who visited the hospital from 2011 to 2015, with a high prevalence in younger patients. The Second Affiliated Hospital of Zhejiang University screened 392 patients with severe AS among the 139496 patients who visited the hospital from 2010 to 2015, of which 40 were BAV, and the proportion of young patients was still high.
Fig.4 Screening results of the Second Affiliated Hospital of Zhejiang University (left) and Zhongshan Hospital of Fudan University (right).
02 Pathogenesis
(1) Pathogenesis of CAVD
The pathogenesis of CAVD involves many aspects, including pathogenic factors (age, gender, hypertension, etc.) and calcification progression factors (including oxidative stress and nitric oxide synthase [NOS] uncoupling).
Fig.5 Pathogenesis of CAVD
(2) Pathogenesis and drug innovation
A study by Han D et al., published in Circulation, showed that a novel piRNA can help block aortic valve calcification, providing new insights into piRNA-guided diagnosis and treatment of CAVD.
(3) ADAMTS16 defects lead to BAV formation
Ten years ago, we reported for the first time a patient with BAV caused by the ADAMTS16 p.H357Q mutation. A new BAV-causing ADAMTS16 p.H357Q variant has been discovered. Suggestive ADAMTS16 defect can lead to BAV formation.
and (4) a new mechanism of CAVD
Therapeutic targets targeting other pathogenesis, including MS-444 targeting HuR and MSI-1436 targeting PTP1B, are also being explored to block valve degeneration and calcification.
03Early diagnosis
Artificial intelligence can be used to assist in the screening and diagnosis of aortic valve disease, including population screening through deep learning of ordinary ECG, detection of AS murmur with earbuds, and detection of significant AS by single-lead ECG.
Fig.6 AI-assisted screening and diagnosis of aortic valve disease
Interventional treatment of aortic valve disease
01Preventive interventions
(1) Prophylactic aortic valve replacement (AVR) treatment for AS
Symptomatic, asymptomatic with rapid stenosis or ejection fraction less than 50% are markers for interventional therapy, but the need for interventional therapy is unclear for asymptomatic patients with severe AS and patients with "at-risk" moderate AS.
and (2) when valvular intervention should be performed
A national multicenter cohort study showed that moderate AS was associated with a poor prognosis compared with the general population. Decreased left ventricular ejection fraction (LVEF) is strongly associated with poor prognosis in patients with moderate AS.
Figure 7 Cohort study results
02 Expansion of indications for transcatheter aortic valve replacement (TAVR).
(1)TAVR适应证扩大——BAV
➤ Compared with the Western population, the prevalence of BAV is higher in TAVR patients in China, and the proportion of type 0 is higher in BAV patients.
➤ Most RCTs excluded people with BAV.
➤ Cohort studies have shown that patients with BAV treated with TAVR have a good medium- and long-term prognosis and a reduced risk of all-cause mortality.
Fig.8 Prognosis of BAV patients treated with TAVR
➤The TAILOR-TAVR study is a prospective, multicenter, randomized controlled trial to explore the use of a downsizing strategy versus a standard-sizing strategy for the treatment of BAV (type 0). The trial is still in the enrollment stage, and it is expected that the results of the study will provide more clinical evidence for the interventional treatment of BAV.
(2) Expansion of TAVR indications - severe simple aortic regurgitation (AR)
Professor Wang Jian'an said that the biggest problem with the use of ordinary valves is the slippage of the valve, if the patient has a narrow outflow tract, it may prevent the valve from slipping, otherwise it is difficult for the valve leaflets without calcification to get stuck in the annulus.
(3) Expansion of TAVR indications - young patients
For low-risk and younger patients, AVR decisions should be based on different long-term priorities, and whether or not to perform TAVR needs to be based on a multidisciplinary team discussion. Overall, the proportion of young people receiving TAVR is increasing year by year, and in 2021< 47.5% of 65-year-olds received TAVR.
Fig.9 Proportion of patients of different age groups receiving TAVR treatment
Professor Wang Jian'an said that when young patients undergo TAVR treatment, they also need to ensure that the coronary arteries are not blocked. If the coronary artery is blocked, it will be significantly more difficult to perform intervention at a later stage.
03Reduce complications
(1) Stroke and brain protection
➤ Stroke is associated with higher morbidity and mortality.
➤ The prognosis of brain protection devices remains controversial, and the brain protection system SENTINEL CEPD has been shown to reduce the risk of stroke in clinical trials.
➤ The results of the cohort study published in JACC by Fan JQ et al. showed that BAV patients had more severe brain damage in the early postoperative period after TAVR, with a higher number of lesions and a larger lesion volume. Suggests that patients with BAV may need more brain protection.
➤ The TAVR cohort study showed that the cognitive function of the patients with postoperative brain injury decreased (P=0.023), and the cognitive function of the people without postoperative brain injury showed an upward trend (P=0.330).
Fig.10 Medium- and long-term cognitive function after TAVR
(2) Conduction disorders
Ochiai T等人发表在J Am Coll Cardiol Intv上的研究结果显示,经导管心脏瓣膜(THV)高位植入联合瓣尖点重叠技术可降低TAVR术后传导障碍。
(3) Vascular complications
In the past, TAVR access closure was mostly done with double closure devices, but many patients still have femoral artery stenosis. THE SINGLE-CLOSURE STUDY, WHICH COMPARES THE USE OF SINGLE CLOSURE DEVICES VERSUS DOUBLE CLOSURE DEVICES IN TAVR PATHWAY CLOSURE, HAS BEEN ENROLLED IN 19 CENTERS IN CHINA.
04New therapy
(1) New therapies for CAVD
Professor Wang Jian'an said that his team is currently exploring the treatment of CAVD through the shock wave valve therapy system TaurusWave, but the current efficacy is not satisfactory. In addition, there are also studies exploring the use of Cardiawave, a non-invasive ultrasound therapy device, to alleviate AS.
and (2) new therapies for AR
AR can be treated with the help of experience in surgical aortic valve repair to design devices.
Figure 11 New therapies for AR
Downstream management of interventional therapy for aortic valve disease
01Anticoagulation therapy
The risk of bleeding and thrombosis needs to be balanced after TAVR. Antiplatelet therapy is sufficient for patients without an indication for anticoagulation, anticoagulation is the main treatment for patients with an indication for anticoagulation, and there are still many future studies worth exploring for patients with both anticoagulation and antiplatelet indications.
Fig.12 Anticoagulation strategy
02 Durability of bioprosthetic valves
As more young patients undergo TAVR and the valve remains in place for longer periods of time, it is critical to increase the durability of the valve. Our team is exploring the dual network hydrogel armor decellularized porcine pericardium as a long-lasting bioartificial heart valve in the hope of increasing antithrombotic and anticalcification capabilities. Academician Ge Junbo of Zhongshan Hospital Affiliated to Fudan University is also exploring new synthetic material valves, looking forward to better efficacy.
Summary
➤ Aortic valve disease poses a major global health challenge and places a heavy burden on the healthcare system.
➤ The management of aortic valve disease includes the upstream management of interventional treatment of aortic valve disease, the interventional treatment itself and the downstream management of interventional treatment.
➤ Understanding the pathogenesis of aortic valve disease is essential to improve aortic valve disease prevention and treatment strategies.
➤ In the future, the results of TAVR need to be further optimized and the indications for TAVR expanded.
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