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BackgroundFamilial hypercholesterolemia (FH) is a common genetic disorder with markedly increased risk of coronary artery diseases (CAD), especially acute myocardial infarction (AMI). However, genetic tests for FH are not always necessary in the current diagnostic criteria of FH, which might lead to underestimation of the prevalence of FH and a lack of awareness of FH-associated CAD and AMI. We aimed to explore the prevalence of genetically defined FH in the hospital-based population and to determine the impact of FH risk variants on CAD and AMI.MethodsThe study participants were recruited between June 24, 2019 and May 12, 2021, at a medical center in Taiwan, in cooperation with the Taiwan Precision Medicine Initiative (TPMI) project. The prevalence of FH was calculated and the effects of FH pathogenic variants on CAD and AMI were analyzed by logistic regression models and shown as ORs and 95% CI.ResultsThe prevalence of genetically defined FH was 1.13% in the hospital-based population in Taiwan. Highest LDL and total cholesterol levels were observed in patients with LDLR rs28942084 (LDL 219.4±55.2; total cholesterol 295.8±55.4). There was an approximately 4-fold increased risk of hyperlipidemia in subjects with the LDLR rs769446356 polymorphism (OR, 4.42; 95% CI, 1.92-10.19) and AMI in individuals with the LDLR rs730882109 polymorphism (OR, 3.79; 95% CI, 2.26-6.35), and a 2-fold increased risk of CAD in those with the LDLR rs749038326 polymorphism (OR, 2.14; 95% CI, 1.31-3.50), compared with the groups without pathogenic variants of FH.ConclusionsThe prevalence of genetically defined FH was 1.13% in the hospital-based population in Taiwan, which was higher than the rate observed in individuals with clinically defined FH. The risk of CAD and AMI was increased to varying degrees in subjects with different FH risk alleles. Close monitoring and risk stratification strategy are essential in high-risk patients with FH risk alleles to facilitate early detection and treatments.

BackgroundGenetic variants could be identified in subjects with idiopathic and heritable pulmonary arterial hypertension (PAH). The 6th World Symposium on Pulmonary Hypertension (WSPH) provided a list of genes with evidence of association with PAH. However, reports using whole exome sequencing (WES) from southeastern Asian PAH cohorts were scarce.MethodsSubjects with idiopathic and heritable PAH (N = 45) from two medical centers in central Taiwan were screened for PAH related gene variants. The genomic DNA was prepared from peripheral blood lymphocytes. We performed WES for all patients enrolled in this study. All identified gene variants were validated by polymerase-chain reaction and Sanger sequencing. The clinical and hemodynamic data were compared between bone morphogenetic protein receptor type-2 (BMPR2) gene variants carriers vs. non-carriers.ResultsEight patients (8/45 = 17.8%) was identified carrying BMPR2 gene variants and 8 patients (8/45 = 17.8%) had other WSPH-listed PAH-related gene variants (1 with ACVRL1, 1 with ENG, 1 with SMAD9, 1 with SMAD1, 1 with ATP13A3 and 3 with AQP1). In addition, a total of 14 non-WSPH-listed PAH-related genetic variant sites (ABCC8, NOTCH1, NOTCH2, NOTCH3, JAG1, BMP10, GGCX, FBLN2, ABCA3 and PTGIS) were found in this PAH cohort. Subjects carrying BMPR2 gene variant (N = 8) were younger at diagnosis of PAH (30 ± 11 vs 49 ± 13 years, p = 0.001) than the non-carrier group (N = 37). BMPR2 variant carriers had a trend toward having higher mean pulmonary arterial pressure (PAP) (61 ± 19 vs. 51 ± 13 mmHg, p = 0.076) than the non-carriers upon initial diagnosis. Pulmonary vascular resistance, right atrial pressure, cardiac output, as well as functional class were similar between BMPR2 variant carriers and non-carriers at initial diagnosis.ConclusionsWe identified 17.8% of patients with BMPR2 gene variants and 17.8% subjects with other 6th WSPH-listed PAH-related gene variants in a Taiwanese idiopathic and heritable PAH cohort. PAH patients carrying BMPR2 variants presented at a younger age with a trend toward having higher mean PAP at initial diagnosis.

Background: Transcatheter aortic valve replacement (TAVR) is indicated for treating symptomatic severe aortic valve stenosis (AS) with intermediate-to-high surgical risks. Few reports are available on managing leaflet thrombosis after TAVR with worsening heart failure.Case Summary: A 77-year-old man with severe AS and coronary artery disease (CAD) received a successful TAVR with Edwards Sapien 3 valve. A year later, the patient developed a worsening heart failure with pulmonary edema, new-onset atrial fibrillation (Af), an increase in mean trans-aortic valve pressure gradient to 48 mmHg, worsening mitral regurgitation (MR), and pulmonary hypertension (PH). The response of the patient to intravenous diuretics and inotropic treatments was poor. Multi-slice CT (MDCT) revealed hypo-attenuated thrombus and thickened transcatheter heart valve leaflets. A non-vitamin K antagonist oral anti-coagulant (NOAC) was added to treat the new-onset Af and leaflet thrombosis on top of the con-current single antiplatelet for CAD. A series of follow-up echocardiograms showed a progressive decrease in trans-aortic valve pressure gradient to 17 mmHg and reductions in MR and PH. Three months after the NOAC treatment, MDCT revealed the resolution of hypo-attenuated thrombus and thickened leaflets. Symptoms of heart failure were also improved gradually.Discussion: Worsening heart failure or an increase in trans-aortic valve pressure gradient after TAVR warranted further MDCT studies. Leaflet thrombosis can be resolved after using NOAC as in our present case.

Life education, also known as life and death education, is an important subject in Taiwan with institutions (e.g., high school) offering degree programs and courses that focus on quality learning and implementation of life education. What is interesting from the perspective of Taiwanese education is that the teaching of life education also incorporates a number of Eastern-derived and conceptualized tenets, for example, Buddhist teaching and the importance of spiritual wisdom. This premise contends then that life education in Taiwan, in general, is concerned with the promotion, fulfillment, and cherishing of quality life experiences (e.g., personal contentment, happiness). One example of life education, which resonates with other spiritual beliefs and religious faiths (e.g., Hinduism), is related to spiritual cultivation and the enlightenment of life wisdom. Our own teaching of the subject, likewise, places emphasis on the goal of teaching students to seek meaningful understanding of and appreciation for three major, interrelated components of life education: life wisdom, life practice, and life care. It has been acknowledged, to a certain degree, that life education has made meaningful contributions, such as the creation and facilitation of a civil, vibrant society, and that many Taiwanese individuals show dignity, respect for elders, and reverence for spiritual and religious faiths. For example, aside from high-quality hospice care, many Taiwanese engage in different types of benevolent acts (e.g., providing spiritual advice to someone who is dying), where possible. Life education is a beneficial subject for teaching and learning as its theoretical understanding may help individuals cope with pathologies and negative conditions and life experiences. One negative life experience, in this case, is the ultimate fate of humankind: death. Approaching death and/or the onset of grief is something that we all have to experience. How does one approach death? It is not easy feat, and of course, grief for a loved one is personal, and some of us struggle with this. We contend that spiritual cultivation and enlightenment, arising from life education, may assist us with the topic of death (e.g., the possibility of transcendence beyond the realm of life). More importantly however, from our own teaching experiences and research development, we strongly believe and rationalize that the subject of life education could, indeed, coincide with and support the paradigm of positive psychology (Seligman, 1999, 2010; Seligman and Csíkszentmihályi, 2000). Forming the premise of the present conceptual analysis article, we propose that a person’s “spiritual and enlightened self,” reflecting the convergence of three major aspects of life education (i.e., philosophical reflection, enrichment of personal well-being, and spiritual cultivation), would result in the initiation and creation of a number of virtues and positive characteristics, for example, having a positive outlook in life, having a perceived sense of spirituality, showing compassion, forgiveness, etc. These virtues and quality characteristics, from our philosophical reasoning, are equivalent to those qualities that the paradigm of positive psychology advocates for. In summary, we conceptualize that the subject of life education, from the perspective of Taiwanese education, may intertwine with the paradigm of positive psychology. A person’s spiritual and enlightened self, or his/her “holistic self,” from our rationalization, is the ultimate optimal life experience that he/she may have, enabling him/her to address the gamut of life conditions and experiences. The distinctive nature of life education in this case, as a point of summary, is that it incorporates spiritual beliefs and religious faiths (e.g., Buddhist faith), encouraging a person to seek nature and divine–human relationships, as well as to contemplate and to explore the complex nature of his/her inner self. The notion of Buddhist samsâra, for example, as “evidence” of spirituality, entailing the endless cycle of birth, rebirth, and redeath, may provide a person with hope into the afterlife. Such esoteric discourse, we contend, is positive and optimistic, allowing individuals to discard the dividing line between life and death.