Assessing lung fluid status using noninvasive bioelectrical impedance analysis in patients with acute heart failure: A pilot study.

BACKGROUND: Outpatient monitoring of pulmonary congestion in heart failure (HF) patients may reduce hospitalization rates. This study tested the feasibility of non-invasive high-frequency bioelectrical impedance analysis (HF-BIA) for estimating lung fluid status. METHODS: This prospective study included 70 participants: 50 with acute HF (HF group) and 20 without HF (control group). All participants underwent a supine chest CT scan to measure lung fluid content with lung density analysis software. Concurrently, direct segmental multi-frequency BIA was performed to assess the edema index (EI) of the trunk, entire body, and extremities. RESULTS: The correlation coefficients between lung fluid content and EI measured using HF-BIA were r = 0.566 (p < 0.001) and r = 0.550 (p < 0.001) for the trunk and whole body, respectively. In the HF group, the trunk EI (0.402 ± 0.015) and whole body EI (0.402 ± 0.016) were significantly higher than those of the control group (trunk EI, 0.383 ± 0.007; whole body EI, 0.383 ± 0.007; all p < 0.001). The lung fluid content was significantly higher in the HF than that in the control group (23.7 ± 5.3 vs. 15.5 ± 2.8%, p < 0.001). The log value of NT pro-BNP was significantly correlated with trunk EI (r = 0.688, p < 0.001) and whole-body EI (r = 0.675, p < 0.001) measured by HF-BIA, and the lung fluid content analyzed by CT (r = 0.686, p < 0.001). CONCLUSIONS: BIA-based EI measurements of the trunk and whole body significantly correlated with lung fluid content and NT pro-BNP levels. Non-invasive BIA could be a promising screening tool for lung fluid status monitoring in acute HF patients.

Mildly Reduced Renal Function Is Associated With Increased Heart Failure Admissions in Patients With Hypertrophic Cardiomyopathy.

BACKGROUND: The association between renal dysfunction and cardiovascular outcomes has yet to be determined in patients with hypertrophic cardiomyopathy (HCM). We aimed to investigate whether mildly reduced renal function is associated with the prognosis in patients with HCM. METHODS: Patients with HCM were enrolled at two tertiary HCM centers. Patients who were on dialysis, or had a previous history of heart failure (HF) or stroke were excluded. Patients were categorized into 3 groups by estimated glomerular filtration rate (eGFR): stage I (eGFR ≥ 90 mL/min/1.73 m², n = 538), stage II (eGFR 60-89 mL/min/1.73 m², n = 953), and stage III-V (eGFR < 60 mL/min/1.73 m², n = 265). Major adverse cardiovascular events (MACEs) were defined as a composite of cardiovascular death, hospitalization for HF (HHF), or stroke during median 4.0-year follow-up. Multivariable Cox regression model was used to adjust for covariates. RESULTS: Among 1,756 HCM patients (mean 61.0 ± 13.4 years; 68.1% men), patients with stage III-V renal function had a significantly higher risk of MACEs (adjusted hazard ratio [aHR], 2.71; 95% confidence interval [CI], 1.39-5.27; P = 0.003), which was largely driven by increased incidence of cardiovascular death and HHF compared to those with stage I renal function. Even in patients with stage II renal function, the risk of MACE (vs. stage I: aHR, 2.21' 95% CI, 1.23-3.96; P = 0.008) and HHF (vs. stage I: aHR, 2.62; 95% CI, 1.23-5.58; P = 0.012) was significantly increased. CONCLUSION: This real-world observation showed that even mildly reduced renal function (i.e., eGFR 60-89 mL/min/1.73 m²) in patients with HCM was associated with an increased risk of MACEs, especially for HHF.

Differing Efficacy of Dapagliflozin Versus Empagliflozin on the Risk of Incident Atrial Fibrillation in Patients With Type 2 Diabetes: A Real-World Observation Using a Nationwide, Population-Based Cohort.

BACKGROUND: Meta-analyses of large clinical trials investigating SGLT2 (sodium-glucose cotransporter-2) inhibitors have suggested their protective effects against atrial fibrillation in patients with type 2 diabetes. However, the results were predominantly driven from trials involving dapagliflozin. METHODS AND RESULTS: We used a nationwide, population-based cohort of patients with type 2 diabetes who initiated either dapagliflozin or empagliflozin between May 2016 and December 2018. An active-comparator, new-user design was used, and the 2 groups of patients were matched using propensity scores. The primary outcome was incident nonvalvular atrial fibrillation, which was analyzed using both the main intention-to-treat and sensitivity analysis that censored patients who skipped their medications for ≥30 days. Men ≥55 years of age and women ≥60 years of age with ≥1 traditional risk factor or those with established cardiovascular disease were categorized as high cardiovascular risk group. Patients not included in the high-risk group were categorized as low risk. After 1:1 propensity-score matching, a total of 137 928 patients (mean age, 55 years; 58% men) were included and followed up for 2.2±0.6 years. The risk of incident atrial fibrillation was significantly lower in the dapagliflozin group in both the main (hazard ratio [HR], 0.885 [95% CI, 0.789-0.992]) and sensitivity analyses (HR, 0.835 [95% CI, 0.719-0.970]). Notably, this was consistent in both the low and high cardiovascular risk groups. There was no effect modification by age, sex, body mass index, duration of diabetes, or renal function. CONCLUSIONS: This real-world, population-based study demonstrates that patients with type 2 diabetes using dapagliflozin may have a lower risk of developing nonvalvular atrial fibrillation than those using empagliflozin.

Association between cardiac arrhythmia before pregnancy and gestational diabetes: a nationwide population-based study in Korea.

Given the higher prevalence of cardiac arrhythmias in individuals with diabetes, we investigated the relationship between cardiac arrhythmias and the incidence of gestational diabetes (GDM). This retrospective cohort study utilized data from the Korean Health Insurance Service database, encompassing 1,113,729 women who gave birth between January 2007 and December 2015. After excluding those who did not undergo National Health Screening tests within 1 year prior to pregnancy, those with multifetal pregnancies, and those diagnosed with diabetes, we analyzed 365,880 singleton pregnancies without a history of diabetes. Of these, 3,253 (0.9%) had cardiac arrhythmias, including premature extra beats, supraventricular tachyarrhythmias, and/or atrial flutter/fibrillation. GDM occurred in 31,938 (8.7%) subjects during pregnancy, and was more prevalent in women with cardiac arrhythmia than in those without (14.9% vs. 8.7%, p<0.001). In the multivariate analysis, the association between cardiac arrhythmia and GDM remained statistically significant (adjusted odds ratio, 1.78; 95% CI, 1.615-1.970; p<0.001). Subgroup analysis revealed that the risk of GDM was consistently statistically significant in subjects with cardiac arrhythmia, regardless of age, body mass index, and the presence or absence of chronic hypertension. Therefore, cardiac arrhythmias before and during pregnancy appear to be associated with an increased risk of developing GDM.

Left ventricular global longitudinal strain as a prognosticator in hypertrophic cardiomyopathy with a low-normal left ventricular ejection fraction.

AIMS: The aim of this study was to investigate the prognostic utility of left ventricular (LV) global longitudinal strain (LV-GLS) in patients with hypertrophic cardiomyopathy (HCM) and an LV ejection fraction (LVEF) of 50-60%. METHODS AND RESULTS: This retrospective cohort study included 349 patients with HCM and an LVEF of 50-60%. The primary outcome was a composite of cardiovascular death, including sudden cardiac death (SCD) and SCD-equivalent events. The secondary outcomes were SCD/SCD-equivalent events, cardiovascular death (including SCD), and all-cause death. The final analysis included 349 patients (mean age 59.2 ± 14.2 years, men 75.6%). During a median follow-up of 4.1 years, the primary outcome occurred in 26 (7.4%), while the secondary outcomes of SCD/SCD-equivalent events, cardiovascular death, and all-cause death occurred in 15 (4.2%), 20 (5.7%), and 34 (9.7%), respectively. After adjusting for age, atrial fibrillation, ischaemic stroke, LVEF, and left atrial volume index, absolute LV-GLS (%) was independently associated with the primary outcome [adjusted hazard ratio (HR) 0.88, 95% confidence interval (CI) 0.788-0.988, P = 0.029]. According to receiver operating characteristic analysis, 10.5% is an optimal cut-off value for absolute LV-GLS in predicting the primary outcome. Patients with an absolute LV-GLS ≤ 10.5% had a higher risk of the primary outcome than those with an absolute LV-GLS > 10.5% (adjusted HR 2.54, 95% CI 1.117-5.787, P = 0.026). Absolute LV-GLS ≤ 10.5% was an independent predictor for each secondary outcome (P < 0.05). CONCLUSIONS: LV-GLS was an independent predictor of a composite of cardiovascular death, including SCD/SCD-equivalent events, in patients with HCM and an LVEF of 50-60%. Therefore, LV-GLS can help in risk stratification in these patients.

Comparative cardiovascular outcomes in type 2 diabetes patients taking dapagliflozin versus empagliflozin: a nationwide population-based cohort study.

BACKGROUND: Sodium-glucose co-transporter-2 inhibitors displayed cardiovascular benefits in type 2 diabetes mellitus in previous studies; however, there were some heterogeneities regarding respective cardiovascular outcomes within the class. Furthermore, their efficacies in Asians, females, and those with low cardiovascular risks were under-represented. Thus, we compared the cardiovascular outcomes between new users of dapagliflozin and empagliflozin in a broad range of patients with type 2 diabetes mellitus using a nationwide population-based real-world cohort from Korea. METHODS: Korean National Health Insurance registry data between May 2016 and December 2018 were extracted, and an active-comparator new-user design was applied. The primary outcome was a composite of heart failure (HF)-related events (i.e., hospitalization for HF and HF-related death), myocardial infarction, ischemic stroke, and cardiovascular death. The secondary outcomes were individual components of the primary outcome. RESULTS: A total of 366,031 new users of dapagliflozin or empagliflozin were identified. After 1:1 nearest-neighbor propensity score matching, 72,752 individuals (mean age approximately 56 years, 42% women) from each group were included in the final analysis, with a follow-up of 150,000 ~ person-years. Approximately 40% of the patients included in the study had type 2 diabetes mellitus as their sole cardiovascular risk factor, with no other risk factors. The risk of the primary outcome was not different significantly between dapagliflozin and empagliflozin users (hazard ratio [HR] 0.93, 95% confidence interval [CI] 0.855-1.006). The risks of secondary outcomes were also similar, with the exception of the risks of HF-related events (HR 0.84, 95% CI 0.714-0.989) and cardiovascular death (HR 0.76, 95% CI 0.618-0.921), which were significantly lower in the dapagliflozin users. CONCLUSIONS: This large-scale nationwide population-based real-world cohort study revealed no significant difference in composite cardiovascular outcomes between new users of dapagliflozin and empagliflozin. However, dapagliflozin might be associated with lower risks of hospitalization or death due to HF and cardiovascular death than empagliflozin in Asian patients with type 2 diabetes mellitus.

Development and validation of equation for cardiorespiratory fitness in patients with heart failure with preserved ejection fraction.

BACKGROUND/AIMS: Cardiorespiratory fitness (CRF), as measured by maximal oxygen consumption (VO2max), is an important independent predictive factor of cardiovascular outcomes in patients with heart failure (HF). However, it is unclear whether conventional equations for estimating CRF are applicable to patients with HF with preserved ejection fraction (HFpEF). METHODS: This study included 521 patients with HFpEF (EF ≥ 50%) whose CRF was directly measured by cardiopulmonary exercise test using a treadmill. We developed a new equation (Kor-HFpEF) for half of the patients in the HFpEF cohort (group A, n = 253) and validated it for the remaining half (group B, n = 268). The accuracy of the Kor-HFpEF equation was compared to that of the other equations in the validation group. RESULTS: In the total HFpEF cohort, the directly measured VO2max was significantly overestimated by the FRIEND and ACSM equations (p < 0.001) and underestimated by the FRIEND-HF equation (p <0.001) (direct 21.2 ± 5.9 mL/kg/min; FRIEND 29.1 ± 11.8 mL/kg/min; ACSM 32.5 ± 13.4 mL/kg/min; FRIEND-HF 14.1 ± 4.9 mL/kg/min). However, the VO2max estimated by the Kor-HFpEF equation (21.3 ± 4.6 mL/kg/min) was similar to the directly measured VO2max (21.7 ± 5.9 mL/kg/min, p = 0.124), whereas the VO2max estimated by the other three equations was still significantly different from the directly measured VO2max in group B (all p < 0.001). CONCLUSION: Traditional equations used to estimate VO2max were not applicable to patients with HFpEF. We developed and validated a new Kor-HFpEF equation for these patients, which had a high accuracy.

Central Facial Nervous System Biomolecules Involved in Peripheral Facial Nerve Injury Responses and Potential Therapeutic Strategies.

Peripheral facial nerve injury leads to changes in the expression of various neuroactive substances that affect nerve cell damage, survival, growth, and regeneration. In the case of peripheral facial nerve damage, the injury directly affects the peripheral nerves and induces changes in the central nervous system (CNS) through various factors, but the substances involved in these changes in the CNS are not well understood. The objective of this review is to investigate the biomolecules involved in peripheral facial nerve damage so as to gain insight into the mechanisms and limitations of targeting the CNS after such damage and identify potential facial nerve treatment strategies. To this end, we searched PubMed using keywords and exclusion criteria and selected 29 eligible experimental studies. Our analysis summarizes basic experimental studies on changes in the CNS following peripheral facial nerve damage, focusing on biomolecules that increase or decrease in the CNS and/or those involved in the damage, and reviews various approaches for treating facial nerve injury. By establishing the biomolecules in the CNS that change after peripheral nerve damage, we can expect to identify factors that play an important role in functional recovery from facial nerve damage. Accordingly, this review could represent a significant step toward developing treatment strategies for peripheral facial palsy.

Left atrial reservoir strain as a novel predictor of new-onset atrial fibrillation in light-chain-type cardiac amyloidosis.

AIMS: To investigate whether left arterial reservoir strain (LASr) could predict new-onset atrial fibrillation (NOAF) in patients with light-chain-type cardiac amyloidosis (ALCA). METHODS AND RESULTS: This study enrolled 427 patients with CA from two tertiary centres between 2005 and 2019. LASr was measured using a vendor-independent analysis programme. The primary outcome was NOAF. A total of 287 patients with ALCA were included [median age 63.0 (56.0-70.0) years, 53.3% male]. The median LASr was 13.9% (10.5-20.8%). During the median follow-up of 0.85 years, AF occurred in 34 patients (11.8%). In the receiver operating characteristics curve analysis, the optimal cut-off of LASr for predicting NOAF was 14.4%. Patients with LASr ≤14.4% had a higher risk of NOAF than those with LASr >14.4% (18.1% vs. 5.1%, P < 0.010). In the multivariate analysis adjusting for confounding factors, including left arterial volume index and left ventricular global longitudinal strain (LV-GLS), higher LASr (%) was independently associated with lower risk for NOAF [adjusted hazard ratio (aHR): 0.936, 95% confidence interval (95% CI): 0.879-0.997, P = 0.039]. Furthermore, LASr ≤14.4% was an independent predictor for NOAF (aHR: 3.370, 95% CI: 1.337-8.492, P = 0.010). This remained true after accounting for all-cause death as a competing risk. Compared with Model 1 (LV-GLS) and Model 2 (LV-GLS plus LAVI), Model 3, including LASr showed a better reclassification ability for predicting NOAF (net reclassification index = 0.735, P < 0.001 compared with Model 1; net reclassification index = 0.514, P = 0.003 compared with Model 2). CONCLUSION: LASr was an independent predictor of NOAF in patients with ALCA.

Atrial Functional Tricuspid Regurgitation: Importance of Atrial Fibrillation and Right Atrial Remodeling and Prognostic Significance.

BACKGROUND: Little is known about the determinants and outcomes of significant atrial functional tricuspid regurgitation (AFTR). OBJECTIVES: The authors aimed to identify risk factors for significant TR in relation to atrial fibrillation-flutter (AF-AFL) and assess its prognostic implications. METHODS: The authors retrospectively studied patients with mild TR with follow-up echocardiography examinations. Significant TR was defined as greater than or equal to moderate TR. AFTR was defined as TR, attributed to right atrial (RA) remodeling or isolated tricuspid annular dilatation, without other primary or secondary etiology, except for AF-AFL. The Mantel-Byar test was used to compare clinical outcomes by progression of AFTR. RESULTS: Of 833 patients with mild TR, 291 (34.9%) had AF-AFL. During the median 4.6 years, significant TR developed in 35 patients, including 33 AFTRs. Significant AFTR occurred in patients with AF-AFL more predominantly than in those patients without AF-AFL (10.3% vs 0.6%; P < 0.001). In Cox analysis, AF-AFL was a strong risk factor for AFTR (adjusted HR: 8.33 [95% CI: 2.34-29.69]; P = 0.001). Among patients with AF-AFL, those who developed significant AFTR had larger baseline RA areas (23.8 vs 19.4 cm2; P < 0.001) and RA area-to-right ventricle end-systolic area ratio (3.0 vs 2.3; P < 0.001) than those who did not. These parameters were independent predictors of AFTR progression. The 10-year major adverse cardiovascular event was significantly higher after progression of AFTR than before or without progression (79.8% vs 8.6%; Mantel-Byar P < 0.001). CONCLUSIONS: In patients with mild TR, significant AFTR developed predominantly in patients with AF-AFL, conferring poor prognosis. RA enlargement, especially with increased RA area-to-right ventricle end-systolic area ratio, was a strong risk factor for progression of AFTR.

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.

Prognosis of patients with hypertrophic cardiomyopathy and low-normal left ventricular ejection fraction.

OBJECTIVE: To investigate whether low-normal left ventricular ejection fraction (LVEF) is associated with adverse outcomes in hypertrophic cardiomyopathy (HCM) and evaluate the incremental value of predictive power of LVEF in the conventional HCM sudden cardiac death (SCD)-risk model. METHODS: This retrospective study included 1858 patients with HCM from two tertiary hospitals between 2008 and 2019. We classified LVEF into three categories: preserved (≥60%), low normal (50%-60%) and reduced (<50%); there were 1399, 415, and 44 patients with preserved, low-normal, and reduced LVEF, respectively. The primary outcome was a composite of SCD, ventricular tachycardia/fibrillation and appropriate implantable cardioverter-defibrillator shocks. Secondary outcomes were hospitalisation for heart failure (HHF), cardiovascular death and all-cause death. RESULTS: During the median follow-up of 4.09 years, the primary outcomes occurred in 1.9%. HHF, cardiovascular death, and all-cause death occurred in 3.3%, 1.9%, and 5.3%, respectively. Reduced LVEF was an independent predictor of SCD/equivalent events (adjusted HR (aHR) 5.214, 95% CI 1.574 to 17.274, p=0.007), adding predictive value to the HCM risk-SCD model (net reclassification improvement 0.625). Compared with patients with HCM with preserved LVEF, those with low-normal and reduced LVEF had a higher risk of HHF (LVEF 50%-60%, aHR 2.457, 95% CI 1.423 to 4.241, p=0.001; LVEF <50%, aHR 7.937, 95% CI 3.315 to 19.002, p<0.001) and cardiovascular death (LVEF 50%-60%, aHR 2.641, 95% CI 1.314 to 5.309, p=0.006; LVEF <50%, aHR 5.405, 95% CI 1.530 to 19.092, p=0.009), whereas there was no significant association with all-cause death. CONCLUSIONS: Low-normal LVEF was an independent predictor of HHF and cardiovascular death in patients with HCM.

Differential diagnosis of common etiologies of left ventricular hypertrophy using a hybrid CNN-LSTM model.

Differential diagnosis of left ventricular hypertrophy (LVH) is often obscure on echocardiography and requires numerous additional tests. We aimed to develop a deep learning algorithm to aid in the differentiation of common etiologies of LVH (i.e. hypertensive heart disease [HHD], hypertrophic cardiomyopathy [HCM], and light-chain cardiac amyloidosis [ALCA]) on echocardiographic images. Echocardiograms in 5 standard views (parasternal long-axis, parasternal short-axis, apical 4-chamber, apical 2-chamber, and apical 3-chamber) were obtained from 930 subjects: 112 with HHD, 191 with HCM, 81 with ALCA and 546 normal subjects. The study population was divided into training (n = 620), validation (n = 155), and test sets (n = 155). A convolutional neural network-long short-term memory (CNN-LSTM) algorithm was constructed to independently classify the 3 diagnoses on each view, and the final diagnosis was made by an aggregate network based on the simultaneously predicted probabilities of HCM, HCM, and ALCA. Diagnostic performance of the algorithm was evaluated by the area under the receiver operating characteristic curve (AUC), and accuracy was evaluated by the confusion matrix. The deep learning algorithm was trained and verified using the training and validation sets, respectively. In the test set, the average AUC across the five standard views was 0.962, 0.982 and 0.996 for HHD, HCM and CA, respectively. The overall diagnostic accuracy was significantly higher for the deep learning algorithm (92.3%) than for echocardiography specialists (80.0% and 80.6%). In the present study, we developed a deep learning algorithm for the differential diagnosis of 3 common LVH etiologies (HHD, HCM and ALCA) by applying a hybrid CNN-LSTM model and aggregate network to standard echocardiographic images. The high diagnostic performance of our deep learning algorithm suggests that the use of deep learning can improve the diagnostic process in patients with LVH.

Augmented risk of ischemic stroke in hypertrophic cardiomyopathy patients without documented atrial fibrillation.

Although atrial fibrillation (AF) is a well-established risk factor for ischemic stroke (IS) in hypertrophic cardiomyopathy (HCM), the risk of IS in HCM patients without documented AF is less recognized. This nationwide population-based cohort study using Korean National Health Insurance database included 8,328 HCM patients without documented AF and 1:2 propensity score-matched 16,656 non-HCM controls between 2010 and 2016. The primary outcome was an incident IS. During a mean follow-up of 6.1 years, IS occurred in 328/8,328 (3.9%) patients with HCM and 443/16,656 (2.7%) controls. The overall incidence of IS was 0.72/100 person-years in the HCM group, which was significantly higher than that in the control group (0.44/100 person-years) (HR 1.64; 95% CI 1.424-1.895; P < 0.001). The overall incidence of IS was 1.36/100 person-years in HCM patients aged ≥ 65 and 2.32/100 person-years years in those with heart failure, respectively. In the HCM group, age ≥ 65 years (adjusted HR 2.74; 95% CI 2.156-3.486; P < 0.001) and chronic heart failure (adjusted HR 1.75; 95% CI 1.101-2.745; P = 0.018) were independent risk factors for IS. HCM patients without documented AF are at a greater risk of IS, especially in those 65 years of age or older or those with chronic heart failure.

Network Analysis of Cardiac Remodeling by Primary Mitral Regurgitation Emphasizes the Role of Diastolic Function.

BACKGROUND: Topological data analysis (TDA) can generate patient-patient similarity networks by analyzing large, complex data and derive new insights that may not be possible with standard statistics. OBJECTIVES: The purpose of this paper was to discover novel phenotypes of chronic primary mitral regurgitation (MR) patients and to analyze their clinical implications using network analysis of echocardiographic data. METHODS: Patients with chronic moderate to severe primary MR were prospectively enrolled from 11 Asian tertiary hospitals (n = 850; mean age 56.9 ± 14.2 years, 57.9% men). We performed TDA to generate network models using 14 demographic and echocardiographic variables. The patients were grouped by phenotypes in the network, and the prognosis was compared by groups. RESULTS: The network model by TDA revealed 3 distinct phenogroups. Group A was the youngest with fewer comorbidities but increased left ventricular (LV) end-systolic volume, representing compensatory LV dilation commonly seen in chronic primary MR. Group B was the oldest with high blood pressure and a predominant diastolic dysfunction but relatively preserved LV size, an unnoticed phenotype in chronic primary MR. Group C showed advanced LV remodeling with impaired systolic, diastolic function, and LV dilation, indicating advanced chronic primary MR. During follow-up (median 3.5 years), 60 patients received surgery for symptomatic MR or died of cardiovascular causes. Kaplan-Meier curves demonstrated that although group C had the worst clinical outcome (P < 0.001), group B, characterized by diastolic dysfunction, had an event-free survival comparable to group A despite preserved LV chamber size. The grouping information by the network model was an independent predictor for the composite of MR surgery or cardiovascular death (adjusted HR: 1.918; 95% CI: 1.257-2.927; P = 0.003). CONCLUSIONS: The patient-patient similarity network by TDA visualized diverse remodeling patterns in chronic primary MR and revealed distinct phenotypes not emphasized currently. Importantly, diastolic dysfunction deserves equal attention when understanding the clinical presentation of chronic primary MR.

Left Atrial Reservoir Strain-Based Left Ventricular Diastolic Function Grading and Incident Heart Failure in Hypertrophic Cardiomyopathy.

BACKGROUND: The echocardiographic assessment of left ventricular (LV) diastolic dysfunction (LVDD) in patients with hypertrophic cardiomyopathy is complex and not well-established. We investigated whether the left atrial reservoir strain (LARS) could be used to categorize LVDD and whether this grading is predictive of heart failure (HF) events in hypertrophic cardiomyopathy. METHODS: A total of 414 patients with hypertrophic cardiomyopathy (aged 58.3±12.8 years; 65.7% male) were categorized using LARS-defined LVDD (LARS-DD) grades: ≥35% (grade 0), ≥24% to <35%, ≥19% to <24%, and <19% (grade 3). Patients were followed for a median of 6.9 years to assess hospitalization for HF or HF-related death. RESULTS: An increase in LARS-DD grade was associated with worse conventional echocardiographic parameters of LVDD, such as lower e', higher E/e' ratio, greater maximum tricuspid regurgitation velocity, and restrictive mitral inflow pattern. Higher LARS-DD grade was also associated with parameters reflecting increased LV filling pressure, such as greater LV wall thickness, greater extent of fibrosis, obstructive physiology, and decreased LV longitudinal strain. Furthermore, higher LARS-DD grade was associated with worse HF-free survival (log-rank P<0.001). Patients with LARS-DD grades 0, 1, 2, and 3 showed 10-year HF-free survival of 100%, 91.6%, 84.1%, and 67.5%, respectively. LARS-DD grade was an independent predictor of HF events after adjusting for clinical and echocardiographic variables (hazard ratio, 1.53 [95% CI, 1.03-2.28], per 1-grade increase). The LARS-DD grade also had incremental prognostic value for incident HF events over the traditional echocardiographic LVDD parameters and grading system. The prognostic value of advanced LARS-DD grade was consistent in sensitivity analyses and various patient subgroups. CONCLUSIONS: LARS can be used as a simple single or supplemental index to categorize LV diastolic function and predict HF events in hypertrophic cardiomyopathy.

U-Shaped Associations Between Body Weight Changes and Major Cardiovascular Events in Type 2 Diabetes Mellitus: A Longitudinal Follow-up Study of a Nationwide Cohort of Over 1.5 Million.

OBJECTIVE: Despite the benefits of weight loss on metabolic profiles in patients with type 2 diabetes mellitus (T2DM), its association with myocardial infarction (MI), ischemic stroke (IS), atrial fibrillation (AF), heart failure (HF), and all-cause death remains elusive. RESEARCH DESIGN AND METHODS: Using the National Health Insurance Service Database, we screened subjects who underwent general health checkups twice in a 2-year interval between 2009 and 2012. After identifying 1,522,241 patients with T2DM without a previous history of MI, IS, AF, and HF, we followed them until December 2018. Patients were stratified according to the magnitude of weight changes between two general health checkups: ≤ -10%, -10 to ≤ -5%, -5 to ≤5%, 5 to ≤10%, and >10%. RESULTS: During the follow-up (median 7.0 years), 32,106 cases of MI, 44,406 cases of IS, 34,953 cases of AF, 68,745 cases of HF, and 84,635 all-cause deaths occurred. Patients with weight changes of -5 to ≤5% showed the lowest risk of each cardiovascular event. Both directions of weight change were associated with an increased cardiovascular risk. Stepwise increases in the risks of MI, IS, AF, HF, and all-cause death were noted with progressive weight gain (all P < 0.0001). Similarly, the more weight loss occurred, the higher the cardiovascular risks observed (all P < 0.0001). The U-shaped associations were consistently observed in both univariate and multivariate analyses. Explorative subgroup analyses also consistently showed a U-shaped association. CONCLUSIONS: Both weight loss and gain >5% within a 2-year interval were associated with an increased risk of major cardiovascular events in patients with T2DM.

Emergency department utilization in patients with hypertrophic cardiomyopathy: a nationwide population-based study.

Despite the increasing burden of hypertrophic cardiomyopathy (HCM) on healthcare resources, data on emergency department (ED) utilization in HCM are lacking. This nationwide population-based study extracted 14,542 HCM patients from the National Health Insurance Service database between 2015-2016, and investigated their ED utilization during a one-year period. The reason for ED utilization was defined as the primary diagnosis upon discharge from EDs. The clinical outcome was defined as hospitalization or all-cause mortality within 90 days after the ED visits. A total of 3209 (22.1%) HCM patients visited EDs within a one-year period (mean age, 66.8 ± 13.8 years; male, 57.4%). The majority (71.1%) of HCM patients who visited the EDs were aged ≥ 60 years. The ED utilization rate was higher in women than in men (26.3% versus 19.7%, P < 0.001). Cardiovascular diseases were the most common reason for ED visits (n = 1333, 41.5%). Among HCM patients who visited EDs, 1195 (37.2%) were hospitalized, and 231 (7.2%) died within 90 days. ED visits for cardiovascular disease was associated with a higher 90-day all-cause mortality (adjusted odds ratio, 2.72; 95% confidence interval 1.79-4.12). These findings would serve as a basis for future research to establish medical policies on ED utilization in HCM.

Age-related sex differences in the outcomes of patients with hypertrophic cardiomyopathy.

BACKGROUND: We aimed to clarify the sex differences in various cardiovascular and non-cardiovascular outcomes, and to investigate whether sex differences in outcomes are affected by age in hypertrophic cardiomyopathy (HCM). METHODS: A cohort of 835 patients with HCM initially evaluated during 2007-2019 were followed for a median of 6.4 years. Study outcomes were all-cause death, cardiovascular and non-cardiovascular death, sudden cardiac death (SCD)/SCD equivalent events, heart failure (HF) events, and the composite cardiovascular outcome including cardiovascular death, SCD/SCD equivalent events, admission for HF, and heart transplantation. RESULTS: Women were 5 years older (women 59.9±13.5 vs. men 54.9±11.4 years), had worse dyspnea, and greater left ventricular (LV) diastolic dysfunction and obstructive physiology at presentation. Women compared to men had higher all-cause mortality and cardiovascular event rates, driven by more cardiovascular deaths and heart failure (HF) events. Conversely, non-cardiovascular mortality was not different between the sexes. Female sex was independently associated with all-cause death (HR 1.88, 95% CI 1.11-3.20) and composite cardiovascular events (HR 3.60, 95% CI 2.00-6.49), independent of age, body mass index, New York Heart Association class, SCD risk score, and LV ejection fraction. When stratified by the age of 60, sex differences were not significant at <60 years; however, at ≥60 years, women had worse LV diastolic function, greater obstructive physiology, as well as worse survival and composite cardiovascular outcomes. Sex differences in outcomes remained consistent after propensity score matching for age and other clinical characteristics. CONCLUSIONS: Women with HCM have worse cardiovascular prognosis than men, driven by higher cardiovascular mortality and HF events. The negative impact of female sex on cardiac function and cardiovascular outcome became prominent at age ≥60 years, suggesting age-related sex differences in the prognosis of HCM.