The Efficacy and Tolerability of Irbesartan/Amlodipine Combination Therapy in Patients With Essential Hypertension Whose Blood Pressure Were not Controlled by Irbesartan Monotherapy.

PURPOSE: This study aimed to evaluate the efficacy and tolerability of irbesartan (IRB) and amlodipine (AML) combination therapy in patients with essential hypertension whose blood pressure (BP) was not controlled by IRB monotherapy. METHODS: Two multicenter, randomized, double-blind, placebo-controlled, phase III studies were conducted in Korea (the I-DUO 301 study and the I-DUO 302 study). After a 4-week run-in period with either 150 mg IRB (I-DUO 301 study) or 300 mg IRB (I-DUO 302 study), patients with uncontrolled BP (ie, mean sitting systolic BP [MSSBP] ≥140 mmHg to <180 mmHg and mean sitting diastolic BP <110 mmHg) were randomized to the placebo, AML 5 mg, or AML 10 mg group. A total of 428 participants were enrolled in the 2 I-DUO studies. In the I-DUO 301 study, 271 participants were randomized in a 1:1:1 ratio to receive either IRB/AML 150/5 mg, IRB/AML 150/10 mg, or IRB 150 mg/placebo. In the I-DUO 302 study, 157 participants were randomized in a 1:1 ratio to receive IRB/AML 300/5 mg or IRB 300 mg/placebo. The primary endpoint was the change in MSSBP from baseline to week 8. Tolerability was assessed according to the development of treatment-emergent adverse events (TEAEs) and clinically significant changes in physical examination, laboratory tests, pulse, and 12-lead electrocardiography. FINDINGS: In I-DUO 301, the mean (SD) changes of MSSBP at week 8 from baseline were -14.78 (12.35) mmHg, -21.47 (12.78) mmHg, and -8.61 (12.19) mmHg in the IRB/AML 150/5 mg, IRB/AML 150/10 mg, and IRB 150 mg/placebo groups, respectively. In I-DUO 302, the mean (SD) changes of MSSBP at week 8 from baseline were -13.30 (12.47) mmHg and -7.19 (15.37) mmHg in the IRB/AML 300/5 mg and IRB 300 mg/placebo groups, respectively. In both studies, all combination groups showed a significantly higher reduction in MSSBP than the IRB monotherapy groups (P < 0.001 for both). TEAEs occurred in 10.00%, 10.99%, and 12.22% of participants in the IRB/AML 150/5 mg, IRB/AML 150/10 mg, and IRB 150 mg/placebo groups, respectively, in I-DUO 301 and in 6.33% and 10.67% of participants in the IRB/AML 300/5 mg and IRB 300 mg/placebo groups, respectively, in I-DUO 302, with no significant between-group differences. Overall, there was one serious adverse event throughout I-DUO study. IMPLICATIONS: The combination of IRB and AML has superior antihypertensive effects compared with IRB alone over an 8-week treatment period, with placebo-like tolerability. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05476354 (I-DUO 301), NCT05475665 (I-DUO 302).

Machine Learning-Based Discrimination of Cardiovascular Outcomes in Patients With Hypertrophic Cardiomyopathy.

Background: Current risk stratification strategies for patients with hypertrophic cardiomyopathy (HCM) are limited to traditional methodologies. Objectives: The authors aimed to establish machine learning (ML)-based models to discriminate major cardiovascular events in patients with HCM. Methods: We enrolled consecutive HCM patients from 2 tertiary referral centers and used 25 clinical and echocardiographic features to discriminate major adverse cardiovascular events (MACE), including all-cause death, admission for heart failure (HF-adm), and stroke. The best model was selected for each outcome using the area under the receiver operating characteristic curve (AUROC) with 20-fold cross-validation. After testing in the external validation cohort, the relative importance of features in discriminating each outcome was determined using the SHapley Additive exPlanations (SHAP) method. Results: In total, 2,111 patients with HCM (age 61.4 ± 13.6 years; 67.6% men) were analyzed. During the median 4.0 years of follow-up, MACE occurred in 341 patients (16.2%). Among the 4 ML models, the logistic regression model achieved the best AUROC of 0.800 (95% CI: 0.760-0.841) for MACE, 0.789 (95% CI: 0.736-0.841) for all-cause death, 0.798 (95% CI: 0.736-0.860) for HF-adm, and 0.807 (95% CI: 0.754-0.859) for stroke. The discriminant ability of the logistic regression model remained excellent when applied to the external validation cohort for MACE (AUROC = 0.768), all-cause death (AUROC = 0.750), and HF-adm (AUROC = 0.806). The SHAP analysis identified left atrial diameter and hypertension as important variables for all outcomes of interest. Conclusions: The proposed ML models incorporating various phenotypes from patients with HCM accurately discriminated adverse cardiovascular events and provided variables with high importance for each outcome.

Integrative Assessment of Cardiopulmonary Fitness Using Cardiopulmonary Exercise Test With Supine Bicycle Echocardiography in Patients Presenting Dyspnea.

BACKGROUND: Cardiopulmonary exercise test (CPET) with supine bicycle echocardiography (SBE) enables comprehensive physiologic assessment during exercise. We characterized cardiopulmonary fitness by integrating CPET-SBE parameters and evaluated its prognostic value in patients presenting with dyspnea. METHODS AND RESULTS: We retrospectively reviewed 473 consecutive patients who underwent CPET-SBE for dyspnea evaluation. A dimensionality reduction process was applied, transforming 24 clinical and CPET-SBE parameters into a 2-dimensional feature map, followed by patient clustering based on the data distribution. Clinical and exercise features were compared among the clusters in addition to the 5-year risk of clinical outcome (a composite of cardiovascular death and heart failure hospitalization). Maximum exercise effort (R >1) was achieved in 95% of cases. Through dimensionality reduction, 3 patient clusters were derived: Group 1 (n=157), 2 (n=104), and 3 (n=212). Median age and female proportion increased from Group 1 to 2, and 3, although resting echocardiography parameters showed no significant abnormalities among the groups. There was a worsening trend in the exercise response from Group 1 to 2 and 3, including left ventricular diastolic function, oxygen consumption, and ventilatory efficiency. During follow-up (median 6.0 [1.6-10.4] years), clinical outcome increased from Group 1 to 2 and 3 (5-year rate 3.7% versus 7.0% versus 13.0%, respectively; log-rank P=0.02), with higher risk in Group 2 (hazard ratio, 1.94 [95% CI, 0.52-7.22]) and Group 3 (3.92 [1.34-11.42]) compared with Group 1. CONCLUSIONS: Comprehensive evaluation using CPET-SBE can reveal distinct characteristics of cardiopulmonary fitness in patients presenting with dyspnea, potentially enhancing outcome prediction.

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.

Age-dependent implications of left ventricular hypertrophy regression in patients with hypertension.

Left ventricular hypertrophy (LVH) is a significant risk factor for cardiovascular mortality and morbidity in patients with hypertension. However, the effect of age on LVH regression or persistence and its differential prognostic value remain unclear. Therefore, we investigated the clinical implications of LVH regression in 1847 patients with hypertension and echocardiography data (at baseline and during antihypertensive treatment at an interval of 6-18 months) according to age. LVH was defined as a left ventricular mass index (LVMI) > 115 g/m2 and >95 g/m2 in men and women, respectively. LVH prevalence at baseline was not different according to age (age < 65 years: 42.6%; age ≥65 years: 45.7%; p = 0.187), but LVH regression was more frequently observed in the younger group (36.4% vs. 27.5%; p = 0.008). Spline curves and multiple linear regression analysis showed a significant relationship between reductions in systolic blood pressure and LVMI in the younger group (ß = 0.425; p < 0.001), but not the elderly group (ß = 0.044; p = 0.308). LVH regression was associated with a lower risk of the study outcome (composite of cardiovascular death and hospitalization for heart failure) regardless of age. In conclusion, the association between the reduction in blood pressure and LVH regression was prominent in patients with age < 65 years, but not in those with age ≥65 years. However, an association between LVH regression and lower risk of cardiovascular death and hospitalization for heart failure was observed regardless of patient age, suggesting the prognostic value of the LVH regression not only in the younger patients but also in elderly patients.

Increased Blood Pressure Variability Over a 16-Year Period Is Associated With Left Ventricular Diastolic Dysfunction in a Population-Based Cohort.

BACKGROUND: Left ventricular diastolic dysfunction (LVDD) is often associated with elevated blood pressure (BP). It is prevalent among hypertensive patients. Additionally, increased BP variability has been linked to LVDD. However, the precise connection between LVDD and BP variability within the general population remains unclear. Thus, this study aimed to evaluate this association in a general population. METHODS: A total of 2,578 participants(1,311 females) with a mean age of 47.8 ±â€…6.7 years who had echocardiographic data from the Korean Genome and Epidemiology study with 16 years of follow-up were analyzed. LVDD was identified through the last echocardiography during the follow-up period. BP variability was assessed using mean, standard deviation (SD), and coefficient of variance (CV). RESULTS: LVDD was detected in 249 individuals. The cohort was divided into an LVDD group and a normal LV diastolic function group. The LVDD group had a higher percentage of females, more advanced age, higher body mass index (BMI), higher BP and BUN levels, lower heart rate, lower hemoglobin, and lower serum creatinine than the normal LV diastolic function group. Remarkably, LVDD was associated with higher BP variability. In the multivariate analysis, LVDD was associated with increased age, female sex, increased BMI, hypertension, and increased BUN. Elevated mean systolic and diastolic BPs, SD of systolic BP, mean pulse pressure (PP), SD of PP, and CV of PP were significantly linked to LVDD even after adjusting for other significant variables in the multivariate analysis. CONCLUSIONS: LVDD was identified in 249 (9.7%) participants. Increased long-term BP variability was significantly associated with LVDD in this population-based cohort.

Irreversible myocardial injury attenuates the benefits of sacubitril/valsartan in heart failure patients.

BACKGROUND: Despite the established benefits of angiotensin receptor-neprilysin inhibitor (ARNI) in heart failure with reduced ejection fraction (HFrEF) across various etiologies, there are controversies regarding the effects of ARNI in patients with irreversible myocardial injury. The aim of this study is to investigate the impact of irreversible myocardial injury on the benefits of ARNI treatment in patients with HFrEF, consisted of both ischemic and non-ischemic etiologies. METHODS AND RESULTS: We conducted a retrospective single-center study including 409 consecutive patients with HFrEF treated with ARNI between March 2017 and May 2020. Irreversible myocardial injury was defined as nonviable myocardium without contractile reserve, which suggests a limited potential for recovery of left ventricular function and geometry. At baseline, irreversible myocardial injury was observed in 129 (31.5%) patients. Composite outcome was cardiovascular death or hospitalization for heart failure, which occurred in 56 (43.4%) and 61 (21.8%) patients with and without irreversible myocardial injury, respectively. On multivariable analysis, irreversible injury presence, but not ischemic etiology, was an independent predictor of composite outcome (hazard ratio 2.16, 95% confidence interval 1.33-3.49). Mediation analysis revealed that the increased risk of the composite outcome due to irreversible myocardial injury was mediated by attenuated LV reverse remodeling (Z value = 2.02, P = 0.043). CONCLUSIONS: The presence of irreversible myocardial injury was significantly associated with the response to ARNI treatment in patients with HFrEF, regardless of etiology.

Prognostic and Safety Implications of Renin-Angiotensin-Aldosterone System Inhibitors in Hypertrophic Cardiomyopathy: A Real-World Observation Over 2,000 Patients.

BACKGROUND AND OBJECTIVES: The prognostic or safety implication of renin-angiotensin-aldosterone system inhibitors (RASi) in hypertrophic cardiomyopathy (HCM) are not well established, mainly due to concerns regarding left ventricular outflow tract (LVOT) obstruction aggravation. We investigated the implications of RASi in a sizable number of HCM patients. METHODS: We enrolled 2,104 consecutive patients diagnosed with HCM in 2 tertiary university hospitals and followed up for five years. RASi use was defined as the administration of RASi after diagnostic confirmation of HCM. The primary and secondary outcomes were all-cause mortality and hospitalization for heart failure (HHF). RESULTS: RASi were prescribed to 762 patients (36.2%). During a median follow-up of 48.1 months, 112 patients (5.3%) died, and 94 patients (4.5%) experienced HHF. Patients using RASi had less favorable baseline characteristics than those not using RASi, such as older age, more frequent history of comorbidities, and lower ejection fraction. Nonetheless, there was no difference in clinical outcomes between patients with and without RASi use (log-rank p=0.368 for all-cause mortality and log-rank p=0.443 for HHF). In multivariable analysis, patients taking RASi showed a comparable risk of all-cause mortality (hazard ratio [HR], 0.70, 95% confidence interval [CI], 0.43-1.14, p=0.150) and HHF (HR, 1.03, 95% CI, 0.63-1.70, p=0.900). In the subgroup analysis, there was no significant interaction of RASi use between subgroups stratified by LVOT obstruction, left ventricular (LV) ejection fraction, or maximal LV wall thickness. CONCLUSIONS: RASi use was not associated with worse clinical outcomes. It might be safely administered in patients with HCM if clinically indicated.

Impact of glycemic control on the progression of aortic stenosis: a single-center cohort study using a common data model.

BACKGROUND: Diabetes mellitus (DM) is a well-established risk factor for the progression of degenerative aortic stenosis (AS). However, no study has investigated the impact of glycemic control on the rate of AS progression. We aimed to assess the association between the degree of glycemic control and the AS progression, using an electronic health record-based common data model (CDM). METHODS: We identified patients with mild AS (aortic valve [AV] maximal velocity [Vpeak] 2.0-3.0 m/sec) or moderate AS (Vpeak 3.0-4.0 m/sec) at baseline, and follow-up echocardiography performed at an interval of ≥ 6 months, using the CDM of a tertiary hospital database. Patients were divided into 3 groups: no DM (n = 1,027), well-controlled DM (mean glycated hemoglobin [HbA1c] < 7.0% during the study period; n = 193), and poorly controlled DM (mean HbA1c ≥ 7.0% during the study period; n = 144). The primary outcome was the AS progression rate, calculated as the annualized change in the Vpeak (△Vpeak/year). RESULTS: Among the total study population (n = 1,364), the median age was 74 (IQR 65-80) years, 47% were male, the median HbA1c was 6.1% (IQR 5.6-6.9), and the median Vpeak was 2.5 m/sec (IQR 2.2-2.9). During follow-up (median 18.4 months), 16.1% of the 1,031 patients with mild AS at baseline progressed to moderate AS, and 1.8% progressed to severe AS. Among the 333 patients with moderate AS, 36.3% progressed to severe AS. The mean HbA1c level during follow-up showed a positive relationship with the AS progression rate (ß = 2.620; 95% confidence interval [CI] 0.732-4.507; p = 0.007); a 1%-unit increase in HbA1c was associated with a 27% higher risk of accelerated AS progression defined as △Vpeak/year values > 0.2 m/sec/year (adjusted OR = 1.267 per 1%-unit increase in HbA1c; 95% CI 1.106-1.453; p < 0.001), and HbA1c ≥ 7.0% was significantly associated with an accelerated AS progression (adjusted odds ratio = 1.524; 95% CI 1.010-2.285; p = 0.043). This association between the degree of glycemic control and AS progression rate was observed regardless of the baseline AS severity. CONCLUSION: In patients with mild to moderate AS, the presence of DM, as well as the degree of glycemic control, is significantly associated with accelerated AS progression.

Endocardial versus whole-myocardial tracking global longitudinal strain analysis in patients with hypertrophic cardiomyopathy: A preliminary comparative study.

BACKGROUND AND OBJECTIVES: We investigated whether the feasibility of left ventricular (LV) global longitudinal strain (GLS) in hypertrophic cardiomyopathy (HCM) varies according to the methodology (e.g. endocardial vs. whole myocardial tracking techniques). METHODS: We retrospectively analyzed 111 consecutive patients with HCM (median age, 58 years; male, 68.5%) who underwent both transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging (apical 29.7%, septal 33.3%, and diffuse or mixed 37.0%). TTE-whole myocardial and TTE-endocardial GLS were measured and compared in terms of association with late gadolinium enhancement (LGE) extent and discrimination performance for extensive LGE (>15% of the LV myocardium). RESULTS: Although TTE-whole myocardial and TTE-endocardial GLS were significantly correlated, absolute TTE-endocardial GLS values (19.3 [16.2-21.9] %) were higher than TTE-whole myocardial GLS values (13.3[10.9-15.6] %, p<0.001). Both TTE-derived GLS parameters were significantly correlated with the LGE extent and independently associated with extensive LGE (odds ratio [OR] 1.30, p = 0.022; and OR 1.24, p = 0.013, respectively). Discrimination performance for extensive LGE was comparable between TTE-whole myocardial and TTE-endocardial GLS (area under the curve [AUC], 0.747 and 0.754, respectively, pdifference = 0.610). However, among patients with higher LV mass index (>70 g/m2), only TTE-whole myocardial GLS correlated with LGE extent and was independently associated with extensive LGE (OR 1.35, p = 0.042), while TTE-endocardial GLS did not. Additionally, TTE-whole myocardial GLS had better discrimination performance for extensive LGE than TTE-endocardial GLS (AUC, 0.705 and 0.668, respectively, pdifference = 0.006). CONCLUSION: TTE-derived GLS using either the endocardial or whole myocardial tracking technique is feasible in patients with HCM. However, in those with severe hypertrophy, TTE-whole myocardial GLS is better than TTE-endocardial GLS.

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.

Rate of Change in 10-Year Atherosclerotic Cardiovascular Disease Risk and Its Implications for Primary Prevention.

BACKGROUND: Contemporary cardiovascular primary prevention is based on the assessment of the 10-year risk of atherosclerotic cardiovascular disease (ASCVD). However, the clinical implications of temporal change in the 10-year ASCVD risk estimate (∆10-year ASCVD risk/year) are unknown. METHODS: A total of 211 077 participants without established ASCVD and with repetitive 10-year ASCVD risk assessment at an interval of 4 to 5 years were selected from the Korean National Health Insurance Service data. The primary end point was a composite of myocardial infarction, stroke, coronary revascularization, and all-cause death. RESULTS: ASCVD event rates were proportional to the ∆10-year ASCVD risk/year regardless of the baseline 10-year ASCVD risk. Adjusted hazard ratio for ASCVD events per 1% increase in ∆10-year ASCVD risk/year was 1.53 (95% CI, 1.44-1.63), 1.24 (95% CI, 1.15-1.32), 1.18 (95% CI, 1.13-1.23), and 1.05 (95% CI, 1.00-1.10) in those with a baseline 10-year ASCVD risk of <5%, 5% to 7.5%, 7.5% to 20%, and ≥20%, respectively. Appropriate control of risk factors, including low-density lipoprotein cholesterol, blood pressure, body mass index, exercise habits, and smoking status, was associated with lower ASCVD event rates, whereas failure to control these risk factors resulted in higher ASCVD event rates. CONCLUSIONS: The temporal change in 10-year ASCVD risk over a period of 4 to 5 years reflects success or failure in controlling major cardiovascular risk factors and indicates the risk of future ASCVD events. The ∆10-year ASCVD risk/year can be used as an indicator of primary prevention and guide the application of preventive measures.

The Risk of Heart Failure Progression in Patients With Patent Foramen Ovale: Differential Risk Associated With Device Closure.

BACKGROUND: A patent foramen ovale (PFO) can unload left atrial pressure via an interatrial shunt. We investigated whether device closure of PFO is associated with a subsequent risk of heart failure (HF), particularly in patients with structural heart disease or atrial fibrillation (AF). METHODS: We enrolled 4,804 consecutive patients who underwent transesophageal echocardiography at tertiary medical centers in Korea between 2007 and 2019. The primary outcome was the 4-year risk of HF hospitalization. Underlying structural heart disease was determined by echocardiography. RESULTS: A PFO was observed in 981 (20.4%) patients, where 161 underwent device closure. During follow-up (median, 3.5 [1.4-6.4] years), the primary outcome was lower in patients with PFO than in those without (2.6% vs 4.0%; adjusted hazard ratio [aHR], 0.65; 95% CI, 0.45-0.94; P = .021). Among the patients with PFO, the primary outcome was higher in the device closure group than in the no-closure group (5.5% vs 1.2%; aHR, 5.59; 95% CI, 4.26-7.34; P < .001). A consistent result was found in patients with structural heart disease or AF (9.6% vs 3.9%; aHR, 2.55; 95% CI, 1.95-3.33; P < .001), demonstrating an increased risk of the primary outcome proportionate to the number of combined structural abnormalities. However, no significant association was observed between the primary outcome and PFO closure in those without structural heart disease or AF (1.7% vs 1.5%; aHR, 1.22; 95% CI, 0.99-1.50; P = .054). CONCLUSION: Patients with underlying structural heart disease or AF may be predisposed to symptomatic HF progression after PFO closure. Therefore, careful medical surveillance with optimal risk management is needed in these patients.

Impact of coronary artery revascularization on long-term outcome in hypertrophic cardiomyopathy patients: a nationwide population-based cohort study.

Limited data are available on the long-term outcomes in patients with hypertrophic cardiomyopathy (HCM) patients with significant coronary artery disease (CAD) requiring revascularization. We investigated the risk of cardiovascular outcomes in HCM patients who underwent coronary revascularization compared to the control group without HCM. HCM patients aged ≥ 20 years were enrolled from the Korean National Health Insurance Database. Information on the diagnosis and previous medical history was obtained from the claims data. Cardiovascular outcomes were identified during 8-year after coronary revascularization in HCM patients (HCM group) and matched controls without HCM (non-HCM control group). A total of 431 patients in the HCM group and 1968 in the non-HCM control group were analyzed. The risk of all-cause death, cardiovascular death, sudden cardiac death (SCD), ischemic stroke, and hospitalization due to heart failure was significantly higher in the HCM group than in the non-HCM group, with prominent risk increase of cardiovascular death (adjusted hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.63-3.15, P < 0.001) and ischemic stroke (adjusted HR 2.38, 95% CI 1.55-3.64, P < 0.001). Beyond 1-year after revascularization, the HCM group still had a significantly higher risk of cardiovascular death, SCD, and ventricular fibrillation/tachycardia compared to the non-HCM group. Mortality and major cardiovascular outcomes occurred more frequently in HCM patients with significant CAD requiring revascularization, compared to the matched non-HCM control group. Active and regular surveillance for concomitant risk factors and relevant intervention are warranted in HCM patients at increased risk for CAD.

Comparison of efficacy and safety between third-dose triple and third-dose dual antihypertensive combination therapies in patients with hypertension.

We compared the efficacy and safety of third-standard-dose triple and third-standard-dose dual antihypertensive combination therapies in patients with mild to moderate hypertension. This was a phase II multicenter, randomized, double-blind, parallel-group trial. After a 4-week placebo run-in period, 245 participants were randomized to the third-dose triple combination (ALC group; amlodipine 1.67 mg + losartan potassium 16.67 mg + chlorthalidone 4.17 mg) or third-dose dual combination (AL group; amlodipine 1.67 mg + losartan potassium 16.67 mg, LC group; losartan potassium 16.67 mg + chlorthalidone 4.17 mg, AC group; amlodipine 1.67 mg + chlorthalidone 4.17 mg) therapy groups and followed up for 8 weeks. The mean systolic blood pressure (BP) reduction was -18.3 ± 13.2, -13.0 ± 13.3, -16.3 ± 12.4, and -13.8 ± 13.2 mmHg in the ALC, AL, LC, and AC groups, respectively. The ALC group showed significant systolic BP reduction compared to the AL and AC groups at weeks 4 (P = .010 and P = .018, respectively) and 8 (P = .017 and P = .036, respectively). At week 4, the proportion of systolic BP responders was significantly higher in the ALC group (42.6%) than in the AL (22.0%), LC (23.3%), and AC (27.1%) groups (P = .013, P = .021, and P = .045, respectively). At week 8, the proportion of systolic and diastolic BP responders was significantly higher in the ALC group (59.7%) than in the AL (39.3%) and AC (42.4%) groups (P = .022 and P = .049, respectively) at week 8. Third-standard-dose triple antihypertensive combination therapy demonstrated early effective BP control compared to third-standard-dose dual combination therapies, without increasing adverse drug reactions in patients with mild-to-moderate hypertension.

Data-driven mortality risk prediction of severe degenerative mitral regurgitation patients undergoing mitral valve surgery.

AIMS: The outcomes of mitral valve replacement/repair (MVR) in severe degenerative mitral regurgitation (MR) patients depend on various risk factors. We aimed to develop a risk prediction model for post-MVR mortality in severe degenerative MR patients using machine learning. METHODS AND RESULTS: Consecutive severe degenerative MR patients undergoing MVR were analysed (n = 1521; 70% training/30% test sets). A random survival forest (RSF) model was constructed, with 3-year post-MVR all-cause mortality as the outcome. Partial dependency plots were used to define the thresholds of each risk factor. A simple scoring system (MVR-score) was developed to stratify post-MVR mortality risk. At 3 years following MVR, 90 patients (5.9%) died in the entire cohort (59 and 31 deaths in the training and test sets). The most important predictors of mortality in order of importance were age, haemoglobin, valve replacement, glomerular filtration rate, left atrial dimension, and left ventricular (LV) end-systolic diameter. The final RSF model with these six variables demonstrated high predictive performance in the test set (3-year C-index 0.880, 95% confidence interval 0.834-0.925), with mortality risk increased strongly with left atrial dimension >55 mm, and LV end-systolic diameter >45 mm. MVR-score demonstrated effective risk stratification and had significantly higher predictability compared to the modified Mitral Regurgitation International Database score (3-year C-index 0.803 vs. 0.750, P = 0.034). CONCLUSION: A data-driven machine learning model provided accurate post-MVR mortality prediction in severe degenerative MR patients. The outcome following MVR in severe degenerative MR patients is governed by both clinical and echocardiographic factors.

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.

Cardioprotection Using Strain-Guided Management of Potentially Cardiotoxic Cancer Therapy: 3-Year Results of the SUCCOUR Trial.

BACKGROUND: Global longitudinal strain (GLS) can predict cancer therapeutics-related cardiac dysfunction and guide initiation of cardioprotection (CPT). OBJECTIVES: In this study, the authors sought to determine whether echocardiography GLS-guided CPT provides less cardiac dysfunction in survivors of potentially cardiotoxic chemotherapy, compared with usual care at 3 years. METHODS: In this international multicenter prospective randomized controlled trial, patients were enrolled from 28 international sites. All patients treated with anthracyclines with another risk factor for heart failure were randomly allocated to GLS-guided (>12% relative reduction in GLS) or ejection fraction (EF)-guided (>10% absolute reduction of EF to <55%) CPT. The primary end point was the change in 3-dimensional (3D) EF (ΔEF) from baseline to 3 years. RESULTS: Among 331 patients enrolled, 255 (77%, age 54 ± 12 years, 95% women) completed 3-year follow-up (123 in the EF-guided group and 132 in the GLS-guided group). Most had breast cancer (n = 236; 93%), and anthracycline followed by trastuzumab was the most common chemotherapy regimen (84%). Although 67 (26%) had hypertension and 32 (13%) had diabetes mellitus, left ventricular function was normal at baseline (EF: 59% ± 6%, GLS: 20.7% ± 2.3%). CPT was administered in 18 patients (14.6%) in the EF-guided group and 41 (31%) in the GLS-guided group (P = 0.03). Most patients showed recovery in EF and GLS after chemotherapy; 3-year ΔEF was -0.03% ± 7.9% in the EF-guided group and -0.02% ± 6.5% in the GLS-guided (P = 0.99) group; respective 3-year EFs were 58% ± 6% and 59% ± 5% (P = 0.06). At 3 years, 17 patients (5%) had cancer therapeutics-related cardiac dysfunction (11 in the EF-guided group and 6 in the GLS guided group; P = 0.16); 1 patient in each group was admitted for heart failure. CONCLUSIONS: Among patients taking potentially cardiotoxic chemotherapy for cancer, the 3-year data showed improvement of LV dysfunction compared with 1 year, with no difference in ΔEF between GLS- and EF-guided CPT. (Strain Surveillance of Chemotherapy for Improving Cardiovascular Outcomes [SUCCOUR]; ACTRN12614000341628).