Two decades ago, it was recognized that lipoprotein(a) (Lp(a)) concentrations were elevated in patients with cardiovascular disease (CVD). However, the importance of Lp(a) was not strongly established due to a lack of both Lp(a)-lowering therapy and evidence that reducing Lp(a) levels improves CVD risk. Recent advances in clinical and genetic research have revealed the crucial role of Lp(a) in the pathogenesis of CVD. Mendelian randomization studies have shown that Lp(a) concentrations are causal for different CVDs, including coronary artery disease, calcified aortic valve disease, stroke, and heart failure, despite optimal low-density lipoprotein cholesterol (LDL-C) management. Lp(a) consists of apolipoprotein (apo) B100 covalently bound to apoA. Thus, Lp(a) has atherothrombotic traits of both apoB (from LDL) and apoA (thrombo-inflammatory aspects). Although conventional pharmacological therapies, such as statin, niacin, and cholesteryl ester transfer protein, have failed to significantly reduce Lp(a) levels, emerging new therapeutic strategies using proprotein convertase subtilisin-kexin type 9 inhibitors or antisesnse oligonucleotide technology have shown promising results in effectively lowering Lp(a). In this review we discuss the revisited important role of L(a) and strategies to overcome residual risk in the statin era.

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Author's summary Pulmonary hypertension (PH) is a disease that eventually causes right heart failure by remodeling pulmonary blood vessels. Based on the histopathological characteristics, PH is categorized into five subgroups. Rarely, a severe clinical entity is pulmonary arterial hypertension (PAH), subgroup 1. This disease process results in pulmonary vascular alterations through dysfunction of the pulmonary endothelium and disturbance of immune responses. Although medical treatments based on these pathophysiologic concepts have been applied for more than 30 years, PAH still cannot be cured. This review addresses the feasibility of and perspectives on stem cell therapy, including the role of exosomes in PAH.

Pulmonary arterial hypertension (PAH) is known as one of diseases with the worst prognosis. Recently, targeted PAH drugs have been developed and approved for use; therefore, the treatment strategy and goals have changed, and the prognosis has improved over two decades. We reviewed the case of a female who showed the natural disease course of heritable PAH in treatment with the targeted PAH drugs under the Korean Health Insurance policy. At the age of 15, she visited the outpatient clinic for dyspnea on exertion that occurred 3 years ago. At that time, severe pulmonary hypertension was revealed by an echocardiography and there was no evidence of significant shunt lesion or embolism. After 4 years of loss to follow-up, her performance was WHO functional class III and she still suffered from dyspnea. The initial monotherapy using an endothelin receptor antagonist was started in 2008. After 2 years, BMPR 2 mutation was detected. Her clinical symptoms gradually worsened because of poor compliance. To escalate therapy, combination therapy was given, and finally, triple maximal therapy was maintained. The next step is to consider intravenous prostanoids. Various combinations of targeted therapy have been tried, and several trials have been confirmed that improve the prognosis. Initial upfront combination therapy and a more enthusiastic approach make good a better prognosis. In this area, active support of the government insurance policy is indispensable in Korea.

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Background Pulmonary arterial hypertension (PAH) is a progressive, chronic disease without curative treatment. Large registry data of these patient populations have been published, although, phenotypic variants within each subtype of PAH have not been elucidated. As interest towards personalized medicine grows, the need for a PAH cohort with a comprehensive understanding of patient phenotypes through multiomics approaches, called deep phenotyping, is on the rise. The PAH Platform for Deep Phenotyping in Korean Subjects (PHOENIKS) cohort is designed to collect clinical data as well as biological specimens for deep phenotyping in patients with idiopathic PAH (IPAH) and heritable PAH (HPAH) in Korea. Methods A total of 17 regional hospitals are currently working on enrolling up to 100 consecutive IPAH/HPAH patients for obtaining clinical data and biological specimens across Korea. The diagnosis of PAH is based on right heart catheterization. All clinical data is stored in a government-based online database. Each participating hospitals collect a whole blood sample from each patient, through which DNA, RNA, serum, plasma, and peripheral blood mononuclear cells will be extracted from the buffy coat layer for further multiomics analysis. Results Not applicable. Conclusions The PHOENIKS cohort is enrolling IPAH and HPAH patients across Korea to determine the prognosis and drug response in different phenotypic variant. The data generated by this cohort are expected to open new doors for personalized medicine in PAH patients of South Korea. Trial registration ClinicalTrials.gov NCT03933579. Registered on May 1st, 2019.

Background and Objectives: Transesophageal echocardiography (TEE) guidance is the current gold standard for catheter-based procedures in the treatment of structural heart diseases. Intracardiac echocardiography (ICE), which can be performed under local anesthesia, has been recently introduced and is becoming more widely used. We aimed to compare the efficacy and safety of ICE and TEE in patent foramen ovale (PFO) device closure. Materials and Methods: All 74 patients with a history of cryptogenic stroke undergoing PFO closure for secondary prophylaxis were selected from our registry. Intraprocedural TEE was performed by echocardiographer-cardiologists with the patient under general anesthesia. Conversely, ICE was performed with the patient under local anesthesia. Baseline characteristics, procedural details, and immediate outcomes were compared between the TEE and ICE groups (n = 49 and n = 25, respectively). Results: Although patients in the ICE group were older (47 ± 10 vs. 57 ± 7 years, p < 0.001), sex and comorbidity variables were similar between the two groups. The degree of inducible right-to-left shunt via the PFO, assessed using preprocedural TEE, was also comparable. Notably, fluoroscopy time (22 ± 18 vs. 16 ± 7 min, p = 0.030), radiation dose (498 ± 880 vs. 196 ± 111 mGy, p = 0.022), and total procedural time in the catheter laboratory (99 ± 30 vs. 67 ± 12 min, p < 0.001) were significantly lower in the ICE group than those in the TEE group. The entire hospital stay was similar between groups (3.8 ± 2.2 vs. 3.4 ± 1.3 days, p = 0.433). No procedural complications, such as device embolization, pericardial hemorrhage, major bleeding, mortality, or access-related vascular injury were reported in either group. Conclusions: ICE-guided PFO device closure is quicker and less hazardous in terms of radiation exposure than the TEE-guided procedure, with similar procedural outcomes and duration of hospital stay.

Adiponectin is an adipocyte-derived cytokine known for its cardioprotective effects in preclinical studies. Early epidemiologic studies replicated these findings and drew great interest. Subsequent large-scale prospective cohorts, however, showed that adiponectin levels seemed not to relate to incident coronary artery disease (CAD). Even more surprisingly, a paradoxical increase of all-cause and cardiovascular (CV) mortality with increased adiponectin levels was reported. The adiponectin-mortality paradox has been explained by some groups asserting that adiponectin secretion is promoted by elevated natriuretic peptides (NP). Other groups have proposed that adiponectin is elevated due to adiponectin resistance in subjects with metabolic syndrome or heart failure (HF). However, there is no unifying theory that can clearly explain this paradox. In patients with HF with reduced ejection fraction (HFrEF), stretched cardiomyocytes secrete NPs, which further promote release of adiponectin from adipose tissue, leading to adiponectin resistance. On the other hand, adiponectin biology may differ in patients with heart failure with preserved ejection fraction (HFpEF), which constitutes 50% of all of HF. Most HFpEF patients are obese, which exerts inflammation and myocardial stiffness, that is likely to prevent myocardial stretch and subsequent NP release. This segment of the patient population may display a different adiponectin biology from its HFrEF counterpart. Dissecting the adiponectin-mortality relation in terms of different HF subtypes may help to comprehensively understand this paradox. Mendelian Randomization (MR) analyses claimed that adiponectin levels are not causally related to CAD or metabolic syndrome. Results from MR studies, however, should be interpreted with great caution because the underlying history of CAD or CHF were not taken into account in these analyses, an issue that may substantially confound the results. Here, we discuss many aspects of adiponectin; cardiometabolic traits, therapeutic interventions, and the ongoing debate about the adiponectin paradox, which were recently described in basic, epidemiologic, and clinical studies.