Shifts in Clinical Characteristics, Treatment, and Outcome for Rheumatic Mitral Stenosis: Insights From a 20-Year Multicentre Registry Study in Korea.

BACKGROUND: The rapid economic development of South Korea provides a unique model to study changes in the clinical characteristics, treatment approaches, and clinical outcomes of patients with rheumatic mitral stenosis (MS) relative to socioeconomic growth. METHODS: From the Multicenter mitrAl STEnosis with Rheumatic etiology (MASTER) registry, 2,337 patients diagnosed with moderate or severe rheumatic MS between January 2001 and December 2020 were analyzed. Patients were grouped into consecutive 5-year intervals based on their year of diagnosis. Clinical characteristics, echocardiographic data, and clinical outcomes were assessed. RESULTS: Over 20 years, the severity of mitral stenosis increased from 79.1% to 90.2%; similarly, the average age at diagnosis increased from 54.3 to 63.0 years (all P < 0.001). Comorbidities such as hypertension and atrial fibrillation increased (6.3% to 29.5% and 41.4% to 46.9%, respectively; all P for trend < 0.05). The rate of mitral intervention within five years after diagnosis increased from 31.2% to 47.4% (P for trend < 0.001). However, clinical outcomes of rheumatic mitral stenosis deteriorated over time in the composite outcomes (log-rank test, P < 0.001). Conversely, the incidence of stroke remained stable (60.6-73.7%; P < 0.001), which might be attributed to the increased use of anticoagulation therapy. CONCLUSION: This study observed an increase in patient age, comorbidities, and valve disease severity as the country transitioned from a developing to developed status. Despite a rise in mitral valve interventions, clinical outcomes deteriorated over 20 years, highlighting the need for modified treatment approaches to improve patient outcomes.

The Third Nationwide Korean Heart Failure III Registry (KorHF III): The Study Design Paper.

With advancements in both pharmacologic and non-pharmacologic treatments, significant changes have occurred in heart failure (HF) management. The previous Korean HF registries, namely the Korea Heart Failure Registry (KorHF-registry) and Korean Acute Heart Failure Registry (KorAHF-registry), no longer accurately reflect contemporary acute heart failure (AHF) patients. Our objective is to assess contemporary AHF patients through a nationwide registry encompassing various aspects, such as clinical characteristics, management approaches, hospital course, and long-term outcomes of individuals hospitalized for AHF in Korea. This prospective observational multicenter cohort study (KorHF III) is organized by the Korean Society of Heart Failure. We aim to prospectively enroll 7,000 or more patients hospitalized for AHF at 47 tertiary hospitals in Korea starting from March 2018. Eligible patients exhibit signs and symptoms of HF and demonstrate either lung congestion or objective evidence of structural or functional cardiac abnormalities in echocardiography, or isolated right-sided HF. Patients will be followed up for up to 5 years after enrollment in the registry to evaluate long-term clinical outcomes. KorHF III represents the nationwide AHF registry that will elucidate the clinical characteristics, management strategies, and outcomes of contemporary AHF patients in Korea. Trial Registration: ClinicalTrials.gov Identifier: NCT04329234.

Heart Failure Statistics 2024 Update: A Report From the Korean Society of Heart Failure.

Background and Objectives: The number of people with heart failure (HF) is increasing worldwide, and the social burden is increasing as HF has high mortality and morbidity. We aimed to provide updated trends on the epidemiology of HF in Korea to shape future social measures against HF. Methods: We used the National Health Information Database of the National Health Insurance Service to determine the prevalence, incidence, hospitalization rate, mortality rate, comorbidities, in-hospital mortality, and healthcare cost of patients with HF from 2002 to 2020 in Korea. Results: The prevalence of HF in the total Korean population rose from 0.77% in 2002 to 2.58% (1,326,886 people) in 2020. Although the age-standardized incidence of HF decreased over the past 18 years, the age-standardized prevalence increased. In 2020, the hospitalization rate for any cause in patients with HF was 1,166 per 100,000 persons, with a steady increase from 2002. In 2002, the HF mortality was 3.0 per 100,000 persons, which rose to 15.6 per 100,000 persons in 2020. While hospitalization rates and in-hospital mortality for patients with HF increased, the mortality rate for patients with HF did not (5.8% in 2020), and the one-year survival rate from the first diagnosis of HF improved. The total healthcare costs for patients with HF were approximately $2.4 billion in 2020, a 16-fold increase over the $0.15 billion in 2002. Conclusions: The study's results underscore the growing socioeconomic burden of HF in Korea, driven by an aging population and increasing HF prevalence.

Optimizing Percutaneous Mitral Valvuloplasty for Rheumatic Mitral Stenosis　- Clinical Significance of Changes in Mitral Valve Area.

BACKGROUND: Percutaneous mitral valvuloplasty (PMV) is a standard treatment for severe rheumatic mitral stenosis (RMS). However, the prognostic significance of the change in mitral valve area (∆MVA) during PMV is not fully understood.Methods and Results: This study analyzed data from the Multicenter mitrAl STEnosis with Rheumatic etiology (MASTER) registry, which included 3,140 patients with severe RMS. We focused on patients with severe RMS undergoing their first PMV. Changes in echocardiographic parameters, including MVA quantified before and after PMV, and composite outcomes, including mitral valve reintervention, heart failure admission, stroke, and all-cause death, were evaluated. An optimal result was defined as a postprocedural MVA ≥1.5 cm2without mitral regurgitation greater than Grade II. Of the 308 patients included in the study, those with optimal results and ∆MVA >0.5 cm² had a better prognosis (log-rank P<0.001). Patients who achieved optimal results but with ∆MVA ≤0.5 cm² had a greater risk of composite outcomes than those with optimal outcomes and ∆MVA >0.5 cm² (nested Cox regression analysis, hazard ratio 2.27; 95% confidence interval 1.09-4.73; P=0.028). CONCLUSIONS: Achieving an increase in ∆MVA of >0.5 cm2was found to be correlated with improved outcomes. This suggests that, in addition to achieving traditional optimal results, targeting an increase in ∆MVA of >0.5 cm2could be a beneficial objective in PMV treatment for RMS.

Temporal Trends, Risk Factors, and Clinical Outcomes of De Novo Lymphoproliferative Disorders After Heart Transplantation.

BACKGROUND: Post-transplant lymphoproliferative disorder (PTLD) is an important cause of morbidity and mortality in heart transplant (HTx) recipients. However, previous studies of PTLD after HTx are limited to single-center analyses or extrapolated from all solid organ transplantations. OBJECTIVES: The authors analyzed the temporal trends, risk factors, and clinical outcome of de novo PTLD specifically after HTx. METHODS: Using multi-institutional, multinational data from the International Society for Heart and Lung Transplantation Thoracic Organ Transplant Registry, the authors evaluated the real-world data of PTLD after HTx, transplanted between January 2000 and June 2015. Multivariable analysis was done to identify risk factors for PTLD development after HTx. RESULTS: Among 28,136 HTx recipients, 1,069 (3.8%) developed PTLD within 10 years of transplantation. PTLD showed a bimodal age pattern with peak incidence in patients of pediatric age and late adulthood at transplantation. The early transplant era (2000-2007 vs 2008-2015), male recipient, and EBV donor-positive-recipient-negative match were independent risk factors of PTLD development within 3 years of transplantation, whereas maintenance therapy with cyclosporine vs tacrolimus at initial discharge was associated with a lower incidence. PTLD development within 3 years of transplantation was significantly associated with mortality (HR: 2.42 [95% CI: 2.01-2.91]; P < 0.001). Survival after PTLD diagnosis was higher in the recent transplant era. CONCLUSIONS: PTLD is relatively rare, but potentially fatal, post-transplant malignancy. PTLD incidence and mortality after HTx have decreased in the recent era. Strategies to minimize the risk of PTLD, and ensure early diagnosis and effective treatment are likely to improve outcomes in HTx.

Outcomes of Severe Mitral Stenosis With the Revised Severity Criteria: Mitral Valve Replacement vs Percutaneous Mitral Valvuloplasty.

BACKGROUND: This study aimed to compare the outcomes, according to percutaneous mitral valvuloplasty (PMV) vs mitral valve replacement (MVR), of severe mitral stenosis (MS) with the updated criteria (MVA ≤ 1.5 cm2). METHODS: From the Multicenter Mitral Stenosis With Rheumatic Etiology (MASTER) registry of 3140 patients, we included patients with severe MS who underwent PMV or MVR between January 2000 and December 2021 except for previous valvular surgery/intervention, at least moderate other valvular dysfunction, and thrombus at the left atrium/appendage. Moderately severe MS (MS-MS) and very severe MS (VS-MS) were defined as 1.0 cm2 < MVA ≤ 1.5 cm2 and MVA ≤ 1.0 cm2, respectively. Primary outcomes were a composite of cardiovascular (CV) death and heart failure (HF) hospitalization. Secondary outcomes were a composite of primary outcomes and redo intervention. RESULTS: Among 442 patients (mean 56.5 ±11.9 years, women 77.1%), the MVR group (n = 260) was older, had more comorbidities, higher echoscore, larger left chambers, and higher right ventricular systolic pressure than the PMV group (n = 182). During a mean follow-up of 6.9 ± 5.2 years with inverse probability-weighted matching, primary outcomes did not differ, but the MVR group experienced fewer secondary outcomes (P = 0.010). In subgroup analysis of patients with MS-MS and VS-MS, primary outcomes did not differ. However, the MVR group in patients with VS-MS showed better secondary outcomes (P = 0.012). CONCLUSIONS: PMV or MVR did not influence CV mortality or HF hospitalization in both MS-MS and VS-MS. However, because of increased early redo intervention in the PMV group in VS-MS, MVR would be the preferable option without clear evidence of suitable morphology for PMV.

The Impact of Different Cooking Methods on the Flavor Profile of Fermented Chinese Spicy Cabbage.

Chinese spicy cabbage (CSC) is a common traditional fermented vegetable mainly made of Chinese cabbage. In addition to eating raw, boiling and stir-frying are the most common cooking methods for CSC. To identify the impacts of boiling or stir-frying on the quality of CSC, the physicochemical properties, flavor compounds, and sensory properties of CSC were analyzed. A total of 47 volatile flavor compounds (VFCs) were detected by gas chromatography-mass spectrometry. Sulfide was determined as the main flavor compound of CSC, mainly contributed by cabbage, garlic, and onion odors. The content of sulfide decreased significantly after cooking. Nonanal, geranyl acetate, and linalool were newly generated after boiling with odor activity value (OAV) > 1, and contributed fatty, sweet, fruity, and floral odors to BL-CSC. 1-Octen-3-one, 1-octen-3-ol, octanal, nonanal, and (E)-2-nonenal were newly generated after stir-frying with OAV > 1, and contributed mushroom, fatty, and green odors to SF-CSC. Diallyl trisulfide, nonanal, (E)-ß-ionone, ß-sesquiphellandrene, and (E)-2-decenal were considered as the potential key aroma compounds (KACs) to distinguish the CSCs after different heat treatment. After cooking, the total titratable acidity of CSC increased and the sensory properties changed significantly. This study provides valuable information and guidance on the sensory and flavor changes of thermal processing fermented vegetables.

Three year post heart transplant outcomes of desensitized durable mechanical circulatory support patients.

BACKGROUND: The risks and benefits of desensitization therapy (DST) in highly sensitized mechanical circulatory support (MCS) patients are not well known. We investigated 3 year post-transplant outcomes of desensitized durable MCS patients. METHODS: Among 689 consecutively enrolled heart transplantation recipients between 2010 and 2016, we categorized them into Group A (desensitized MCS patients, n = 21), Group B (desensitized non-MCS patients, n = 28) and Group C (all nondesensitized patients, n = 640). Post-transplant outcomes included the incidence of primary graft dysfunction, 3-year survival, freedom from cardiac allograft vasculopathy, nonfatal major adverse cardiac events, any treated rejection, acute cellular rejection, antibody mediated rejection (AMR) and infectious complications. RESULTS: The types of DST in Groups A and B were similar and included combinations of rituximab/intravenous immunoglobulin and plasmapheresis/bortezomib. Group A, compared with Group B, showed significantly higher pre-DST panel reactive antibody (PRA) (92.2 ± 9.8 vs. 83.3 ± 15.6, P = 0.007) and higher PRA reduction after DST (-22.2 ± 26.9 vs. -6.3 ± 7.5, P = 0.015). Groups A and C showed comparable primary graft dysfunction, 3-year survival, freedom from cardiac allograft vasculopathy, nonfatal major adverse cardiac events, any treated rejection, acute cellular rejection, and AMR. Although statistically not significant, Group A showed numerically higher 3-year freedom from AMR than Group B. Infectious complications were similar in both Groups A and B. CONCLUSIONS: DST for MCS patients showed significant PRA reduction, resulting in an expansion of the donor pool. The post-transplant outcome of desensitized MCS patients showed comparable clinical outcomes to non-desensitized control patients in the same study period, revealing the safety and efficacy of DST.

Implications of the Mitral Leaflet Coaptation Pattern on Clinical Outcomes in Patients With Functional Mitral Regurgitation.

The classification of secondary mitral regurgitation (MR) is based on atrial functional MR (AFMR) or ventricular functional MR (VFMR) and volume changes, but the mitral leaflet coaptation angle also contributes to the MR mechanism. The clinical implications of the coaptation angle on cardiovascular (CV) outcomes have not been well evaluated. A total of 469 consecutive patients (265 AFMR vs 204 VFMR) with more than moderate MR were evaluated for the occurrence of heart failure, mitral valve operations, and CV death. The coaptation angle was assessed by measuring the internal angle between both leaflets at mid-systole using the apical 3-chamber view. A coaptation angle ≥130° was classified as leaflet flattening, and an angle <130° was classified as leaflet tethering. AFMR and VFMR were associated with higher frequencies of leaflet flattening and tethering, respectively. AFMR was more likely to be associated with older age, atrial fibrillation, and preserved ejection fraction, all of which were related to leaflet flattening. During a follow-up of 2.3 years, 83 patients had heart failure (17.7%), 21 patients underwent mitral valve operations (4.5%), and 34 patients died (7%). Compared with leaflet tethering, leaflet flattening was more significantly related to CV events, whereas CV event rates were less markedly different in A/VFMR. Irrespective of A/VFMR, leaflet flattening and atrial fibrillation were associated with a higher frequency of CV events. Adjusted analysis showed that leaflet flattening remained an independent predictor of CV events (hazard ratio 3.5, 95% confidence interval 1.11 to 4.88, p = 0.003), whereas A/VFMR did not. In conclusion, the leaflet coaptation angle in patients with functional MR could provide risk stratification superior to that of A/VFMR. Leaflet flattening appears to be associated with unfavorable clinical outcomes.

Human induced pluripotent stem cell line YCMi007-A generated from a dilated cardiomyopathy patient with a heterozygous dominant c.613C > T (p. Arg205Trp) variant of the TNNT2 gene.

Cardiac muscle troponin T protein binds to tropomyosin and regulates the calcium-dependent actin-myosin interaction on thin filaments in cardiomyocytes. Recent genetic studies have revealed that TNNT2 mutations are strongly linked to dilated cardiomyopathy (DCM). In this study, we generated YCMi007-A, a human induced pluripotent stem cell (hiPSC) line from a DCM patient with a p. Arg205Trp mutation in the TNNT2 gene. The YCMi007-A cells show high expression of pluripotent markers, normal karyotype, and differentiation into three germ layers. Thus, YCMi007-A-an established iPSC-could be useful for the investigation of DCM.

Epidemiologic Profile of Patients With Valvular Heart Disease in Korea: A Nationwide Hospital-Based Registry Study.

BACKGROUND: Valvular heart disease (VHD) is a common cause of cardiovascular morbidity and mortality worldwide; however, its epidemiological profile in Korea requires elucidation. METHODS: In this nationwide retrospective cohort study from the Korean valve survey, which collected clinical and echocardiographic data on VHD from 45 medical centers, we identified 4,089 patients with VHD between September and October 2019. RESULTS: The aortic valve was the most commonly affected valve (n = 1,956 [47.8%]), followed by the mitral valve (n = 1,598 [39.1%]) and tricuspid valve (n = 1,172 [28.6%]). There were 1,188 cases of aortic stenosis (AS) and 926 cases of aortic regurgitation. The most common etiology of AS was degenerative disease (78.9%). The proportion of AS increased with age and accounted for the largest proportion of VHD in patients aged 80-89 years. There were 1,384 cases of mitral regurgitation (MR) and 244 cases of mitral stenosis (MS). The most common etiologies for primary and secondary MR were degenerative disease (44.3%) and non-ischemic heart disease (63.0%), respectively, whereas rheumatic disease (74.6%) was the predominant cause of MS. There were 1,172 tricuspid regurgitation (TR) cases, of which 46.9% were isolated and 53.1% were associated with other valvular diseases, most commonly with MR. The most common type of TR was secondary (90.2%), while primary accounted for 6.1%. CONCLUSIONS: This report demonstrates the current epidemiological status of VHD in Korea. The results of this study can be used as fundamental data for developing Korean guidelines for VHD.

Effect of Atorvastatin on Serial Changes in Coronary Physiology and Plaque Parameters.

Background: The effects of statin on coronary physiology have not been well evaluated. Objectives: The authors performed this prospective study to investigate changes in coronary flow indexes and plaque parameters, and their associations with atorvastatin therapy in patients with coronary artery disease (CAD). Methods: Ninety-five patients with intermediate CAD who received atorvastatin therapy underwent comprehensive physiological assessments with fractional flow reserve (FFR), coronary flow reserve, index of microcirculatory resistance, and intravascular ultrasound at the index procedure, and underwent the same evaluations at 12-month follow-up. Optimal low-density lipoprotein cholesterol (LDL-C) was defined as LDL-C <70 mg/dL or ≥50% reduction from the baseline. The primary endpoint was a change in the FFR. Results: Baseline FFR, minimal lumen area, and percent atheroma volume (PAV) were 0.88 ± 0.05, 3.87 ± 1.28, 55.92 ± 7.30, respectively. During 12 months, the percent change in LDL-C was -33.2%, whereas FFR was unchanged (0.87 ± 0.06 at 12 months; P = 0.694). Vessel area, lumen area, and PAV were significantly decreased (all P values <0.05). The achieved LDL-C level and the change of PAV showed significant inverse correlations with the change in FFR. In patients with optimally modified LDL-C, the FFR had increased (0.87 ± 0.06 vs 0.89 ± 0.07; P = 0.014) and the PAV decreased (56.81 ± 6.44% vs 55.18 ± 8.19%; P = 0.031), whereas in all other patients, the FFR had decreased (0.88 ± 0.05 vs 0.86 ± 0.06; P = 0.025) and the PAV remained unchanged. Conclusions: In patients with CAD, atorvastatin did not change FFR despite a decrease in the PAV. However, in patients who achieved the optimal LDL-C target level with atorvastatin, the FFR had significantly increased with decrease of the PAV. (Effect of Atorvastatin on Fractional Flow Reserve in Coronary Artery Disease [FORTE]; NCT01946815).

Nationwide Trends of Gatekeeper to Invasive Coronary Angiography in Suspected Coronary Artery Disease.

BACKGROUND AND OBJECTIVES: Real-world trends in the utility and type of gatekeeping studies in invasive coronary angiography (ICA) requires further investigation. METHODS: We identified outpatients who underwent noninvasive cardiac tests or directly ICA for suspected coronary artery disease (CAD) from the nationwide Korea Health Insurance Review and Assessment Service-National Patient Sample database between 2012 and 2018. RESULTS: Among 71,401 patients, the percentage of patients who were evaluated for suspected CAD was 34.7% for treadmill test (TMT), 4.2% for single-photon emission computed tomography (SPECT), 24.2% for coronary computed tomography angiography (CCTA), 1.6% for multiple gatekeepers, and 32.3% for directly ICA without noninvasive studies. The proportion of CCTA as a gatekeeper showed linear increase, (18.6% in 2012 and 28.8% in 2018; p<0.001), while those of TMT, SPECT, and direct ICA have decreased (p<0.001, p=0.03, and p<0.001, respectively). The overall incidence of downstream ICA after gatekeeper was 13.8% (6,662/48,346), and SPECT showed higher ICA rate in pairwise comparison with TMT and CCTA (p<0.001). Patients who performed gatekeepers before ICA showed higher rate of subsequent PCI (34.7% vs. 32.3%; p<0.001) and CABG (3.5% vs. 1.0%; p<0.001), compared to those who directly underwent ICA, and CCTA was associated with higher revascularization rate after ICA in pairwise comparison with TMT and SPECT (p<0.001). CONCLUSIONS: Nationwide database demonstrated that CCTA is utilized increasingly as a gatekeeper for ICA and is associated with high revascularization rate after ICA in outpatients with suspected CAD.

Characteristics and outcomes of heart transplant recipients with a pretransplant history of malignancy.

We aimed to investigate the characteristics and outcomes of HTx recipients with a history of pretransplant malignancy (PTM). Among 1062 HTx recipients between 1997 and 2013, 73 (7.1%) patients had PTMs (77 cancer cases). We analyzed post-HTx outcome, recurrence of PTM, and development of de novo malignancies. Post-HTx outcome included overall survival, 10-year survival, 10-year freedom from cardiac allograft vasculopathy (CAV), non-fatal major adverse cardiac events (NF-MACE), any treated rejection (ATR), acute cellular rejection (ACR), and antibody-mediated rejection (AMR). Four most common PTMs were lymphoproliferative disorders (18.2%), prostate cancers (18.2%), non-melanoma skin cancers (18.2%), and breast cancers (13.0%). Median time from PTM and HTx was 9.0 years. During a median follow-up of 8.6 years after HTx, patients with PTM, compared to those without, showed significantly higher incidence of posttransplant malignancies (43.8% vs. 20.8%, p < .001) including 9.6% (n = 7) of PTM recurrences. However, patients with PTM, compared to those without, showed comparable overall survival, 10-year survival, 10-year freedom from CAV, NF-MACE, ATR, ACR, and AMR. Therefore, a history of PTM should not disqualify patients from HTx listing, while further research is necessary for early detection of posttransplant malignancies in these patients.

A multicenter study of altered level of consciousness in the emergency room.

New-onset altered level of consciousness (ALC) is a challenge in real-world clinical practice. Although its presentation is nonspecific and its etiology is intricate, the term ALC is frequently used in the emergency room (ER). This study aimed to clarify and classify the etiologies and outcomes of the ALC in the ER. We retrospectively investigated ALC patients in the ER of four tertiary referral centers from February 2018 to January 2020. The etiology of ALC was comprehensively analyzed by a consortium of university professors, board-certified clinicians in neurology, emergency medicine, or internal medicine. The time point to determine the etiology of ALC was at the time of discharge from the ER. A total of 315,526 patients who visited ER due to ALC were reviewed and found 7988 eligible patients, of which 4298 (53.8%) were male and 5282 (66.1%) were older than 60. The overall mortality was 13.5%. Except undetermined, the 9 etiologies (n = 7552) were categorized into extra- (n = 4768, 63.1%) or intracranial etiology (n = 2784, 36.9%). The most common etiology of ALC in the ER was metabolic cause (n = 1972, 24.7%), followed by systemic infection (n = 1378, 17.3%). The majority of ALC in the ER was derived from extracranial etiology. ALC in the ER is a neurological manifestation of diverse etiologies; not all can be confirmed in the ER. Not only neurological but also critical systemic illnesses should be considered to assess the protean manifestations of ALC in the ER.