A prospective randomized controlled trial to determine the safety and efficacy of extracorporeal shock waves therapy for primary prevention of subclinical cardiotoxicity in breast cancer patients without a cardiovascular risk treated with doxorubicin.

Background: Doxorubicin is a highly effective anti-cancer drug that causes left ventricular (LV) dysfunction and induces late-onset cardiomyopathy. However, an effective and clinically applicable preventive treatment is yet to be discovered. Objective: Cardiac-Extracorporeal shockwave therapy (C-ESWT) has been suggested to treat inflammatory and ischemic diseases and protect cardiomyocytes from doxorubicin-induced cardiomyopathy. This study aims to assess the safety and efficacy of C-ESWT in the prevention of subclinical cardiotoxicity. Methods: We enrolled 64 breast cancer patients. C-ESWT group 33 patients were treated with our C-ESWT (200 shots/spot at 0.09 mJ/mm2 for 20 spots, 3 times every six weeks). The efficacy endpoints were the difference in left ventricular global longitudinal strain (LVGLS) change by 2D speckle tracking echocardiography and chemotherapy-related cardiac dysfunction (CTRCD). Echocardiography was performed on the baseline line and every 4 cycles of chemotherapy, followed by a follow-up 3,6 months after chemotherapy to compare the incidence of cardiomyopathy of subclinical LV dysfunction due to chemotherapy between the two groups. Results: Participants averaged 50 ± 9 years in age, 100% female. In the results of follow-up 6 months after the end of chemotherapy, there was a significant difference in delta LVGLS between the C-ESWT group and the control group (LVGLS; -1.1 ± 10.9% vs. -11.5 ± 11.6% p-value; <0.001). A total of 23% (15 patients) of patients developed CTRCD (Control group; 13 vs. C-ESWT group; (2). C-ESWT was performed safely without any serious adverse events. Conclusion: In this prospective study, C-ESWT established efficacy in preventing subclinical cardiotoxicity, especially in breast cancer patients using doxorubicin chemotherapy, and the safety of C-ESWT. Clinical Trial Registration: ClinicalTrials.gov, identifier (NCT05584163).

Dynamic changing smoking habits and cardiovascular events in patients newly diagnosed with hypertension, diabetes, or dyslipidemia: a national cohort study.

Background and aims: This study aimed to examine the association between dynamic smoking habit change and cardiovascular risk in a population newly diagnosed with hypertension, diabetes, and dyslipidemia. Methods: This study included 49,320 individuals who had received health examinations provided by the Korea National Health Insurance Service. To determine the hazard ratios (HRs) and 95% confidence intervals (CIs) for incident major adverse cardiac events (MACE) and all-cause mortality based on dynamic smoking habit changes for 2 years, multivariable Cox proportional hazard models were utilized. Results: During the follow-up, there were 1,004 (2.2%), 3,483 (7.6%), and 334 (0.7%) cases of myocardial infarction, stroke events, and cardiovascular death, respectively. The group with worsening smoking habits had an increased risk of cardiovascular events and death (HR: 1.33, 95% CI: 1.26-1.40) compared to improved smoking habits. The robustness of the results determined by a series of sensitivity analyses further strengthened the main findings. Conclusions: Our findings suggest that worsening of smoking habits, even for a short period of time, may increase the risk of myocardial infarction, stroke, and cardiovascular death in patients diagnosed with hypertension, diabetes, and dyslipidemia. For the primary prevention of cardiovascular events in patients with underlying diseases, dynamic modification of smoking habits should be actively considered.

Incremental prognostic value of triglyceride glucose index additional to coronary artery calcium score in asymptomatic low-risk population.

BACKGROUND: The triglyceride glucose (TyG) index has been suggested as a reliable surrogate marker of insulin resistance which is a substantial risk factor for atherosclerotic cardiovascular disease (ASCVD). Several recent studies have shown the relationship between the TyG index and cardiovascular disease; however, the role of the TyG index in coronary artery calcification (CAC) progression has not been extensively assessed especially in low-risk population. METHODS: We enrolled 5775 Korean adults who had at least two CAC evaluations. We determined the TyG index using ln (fasting triglycerides [mg/dL] x fasting glucose [mg/dL]/2). The CAC progression was defined as either incident CAC in a CAC-free population at baseline or an increase of ≥ 2.5 units between the square roots of the baseline and follow-up coronary artery calcium scores (CACSs) of subjects with detectable CAC at baseline. RESULTS: CAC progression was seen in 1,382 subjects (23.9%) during mean 3.5 years follow-up. Based on the TyG index, subjects were stratified into four groups. Follow-up CACS and incidence of CAC progression were markedly elevated with rising TyG index quartiles (group I [lowest]:17.6% vs. group II:22.2% vs. group III:24.6% vs. group IV [highest]: 31.3%, p < 0.001). In multivariate logistic regression analysis, the TyG index was independent predictor of CAC progression (odds ratio: 1.57; 95% confidence interval: 1.33 to 1.81; p < 0.001) especially in baseline CACS ≤ 100 group. CONCLUSION: The TyG index is an independent predictor of CAC progression in low-risk population. It adds incremental risk stratification over established factors including baseline CACS.

Clinical Implications of Heart Rate Control in Heart Failure With Atrial Fibrillation: Multi-Center Prospective Observation Registry (CODE-AF Registry).

Background: Atrial fibrillation (AF) is treated by heart rate (HR) control. However, the optimal HR target in AF patients with heart failure (HF) remains unclear. To evaluate the clinical implication of the resting HR in AF patients with HF accompanied by preserved, mid-range, or reduced ejection fraction (HFpEF, HFmrEF, or HFrEF, respectively). Methods: Echocardiographic data from June 2016 to April 2020 in a prospective, multicenter, observational registry from 11,104 patients were analyzed. The follow-up duration was 2.2 years. The main outcome was composite of death and hospitalization. We categorized patients according to the HF type and resting HR: ≤ 60 bpm, 61-80 bpm, 81-110 bpm, and >110 bpm. Results: A total of 1,421 patients were enrolled in the study: 582 in the HFpEF group, 506 in the HFmrEF group, and 333 in the HFrEF group. The patients had a mean age of 69 ± 11 years and consisted of 872 (61.4%) men. Primary endpoint rates among HFpEF patients with 60 < HR ≤ 110 bpm were lower than those with HR ≤ 60 bpm (61-80 bpm group: hazard ratio, 0.66; 95% CI, 0.46-0.94; p = 0.021; 81-110 bpm group: hazard ratio, 0.60; 95% CI, 0.40-0.90; p = 0.013). Especially, HFpEF patients with HR 81-110 bpm had a lower incidence of hospitalization caused by HF aggravation than those with other HR strata (HR ≤ 80bpm strata or HR >110 bpm strata). In HFmrEF and HFrEF patients, the survival rates did not differ significantly among patients in the three groups with HR ≤ 110 bpm. Moreover, the event rates increased significantly in HFmrEF patients with HR >110 bpm (hazard ratio, 1.91; 95% CI, 1.16-3.14, p = 0.011). Conclusion: In patients with AF and HFpEF, the resting HR has U-shaped associations with the overall primary endpoint. A lower or higher resting HR is associated with increased cardiovascular outcomes, especially in patients with HFpEF and AF.

Characteristics and prognostic implications of tricuspid regurgitation in patients with arrhythmogenic cardiomyopathy.

AIMS: Arrhythmogenic cardiomyopathy (AC) is characterized by right ventricular (RV) dilatation and dysfunction and is often seen in combination with tricuspid regurgitation (TR). The aim of this study was to investigate the characteristics and prognostic implications of TR in patients with AC. METHODS AND RESULTS: Clinical, echocardiographic, and cardiac magnetic resonance data of 52 patients with AC fulfilling 2010 Task Force criteria in a single centre were retrospectively evaluated. TR in AC was classified as no/mild, moderate, or severe on the basis of the current guidelines. Significant TR was defined as at least moderate TR. The primary endpoint was a composite of death, heart transplantation, and tricuspid valve surgery. There were seven patients (13.4%) with moderate TR and 13 patients (25.0%) with severe TR at initial diagnosis. Patients with severe TR showed a higher prevalence of atrial fibrillation and a higher mean NT-pro-BNP than other groups (68%, P = 0.013; 2423 ± 1578 pg/mL, P < 0.001, respectively). Patients with significant TR revealed a higher incidence of heart failure at initial presentation than did those without significant TR (30.0 vs. 3.1%, P = 0.022). Patients with severe TR showed significantly larger RV and lower RV and left ventricular functional parameters. During a mean follow-up of 4.2 years, three groups classified by TR severity considerably discriminated clinical outcomes (log rank P = 0.019). Patients with significant TR had a poorer prognosis than those with no or mild TR (42.9 vs. 3.1%, log rank P = 0.005). Cox regression analysis showed significant TR as an independent prognostic factor (hazard ratio 11.41, 95% confidential interval 1.30-99.92, P = 0.028). CONCLUSIONS: Significant TR at initial diagnosis in patients with AC is a poor prognostic factor.

Progression and Outcomes of Non-dysfunctional Bicuspid Aortic Valve: Longitudinal Data From a Large Korean Bicuspid Aortic Valve Registry.

Background: Using echocardiographic surveillance, many patients are diagnosed with bicuspid aortic valve (BAV) without significant valve dysfunction. Limited data are available regarding the progression and outcomes of non-dysfunctional BAV. Methods and Results: We investigated 1,307 BAV patients (984 male, mean age 56 years) diagnosed from Jan 2003 through Dec 2018 in a single tertiary center. Seven hundred sixty-one patients underwent follow-up echocardiography at ≥1 year post-diagnosis. Non-dysfunctional BAV was defined as BAV without moderate aortic stenosis (AS) or aortic regurgitation (AR). The presence of aortopathy was defined as an ascending aorta diameter >37mm. Progression to significant BAV dysfunction, progression to severe aortopathy (ascending aorta diameter ≥45mm), and incidence of valve or aorta operation were analyzed. One hundred eighty-seven (25%) patients showed non-dysfunctional BAV. Among them, 104 (56%) had mild AS or AR, and 81 (43%) had aortopathy at indexed echocardiography. At 6.0 ± 3.8 years post-diagnosis, 56 (29%) progressed to dysfunctional BAV, 28 (15%) progressed to severe aortopathy, 22 (12%) underwent valve operation, and 19 (10%) experienced aorta operation. Eighty-nine percent of patients with normal BAV function and 61% of patients with mild AS or AR maintained non-dysfunctional BAV. More patients with aortopathy progressed to severe aortopathy (35 vs. 0% without aortopathy, p < 0.001), with a higher incidence of aorta operation (21 vs. 2%, p < 0.001). Conclusions: In patients with non-dysfunctional BAV, initial BAV function and degree of aorta dilatation might be important for progression and outcomes. Patients without any dysfunction or aortopathy tend to maintain good structure and function for 6 years.

Comparing the feasibility and accuracy of three-dimensional ultrasound to two-dimensional ultrasound and computed tomography angiography in the assessment of carotid atherosclerosis.

AIMS: Two-dimensional ultrasound (2D-US) is the mainstay imaging technique used to evaluate carotid atherosclerosis. An automated single sweep three-dimensional ultrasound (3D-US) technique became available. We evaluated the feasibility and accuracy of 3D-US in the assessment of carotid plaques compared to those of 2D-US. Carotid computed tomography angiography (CTA) was used as a reference. METHODS AND RESULTS: Among 126 stroke patients who underwent carotid 2D-US, 73 underwent 3D-US and carotid CTA. 3D-US was pursued when there were carotid plaques or when area stenosis was ≥ 20% by 2D-US. Both 2D- and 3D-US images of the carotid arteries were acquired using a dedicated ultrasound system that was equipped with the single sweep volumetric transducer. In total, 266 arteries from 73 patients were selected for comparison of the detection rate of carotid plaques between 2D- and 3D-US. Among the 73 patients, carotid CTA detected 139 plaques. 3D-US demonstrated a higher detection rate of carotid plaques than did 2D-US (108 plaques (77.9%) vs. 70 plaques (50.4%)) when using carotid CTA as a reference standard. Carotid plaque volume (PV) of 133 vessels from 73 patients were quantitatively evaluated using both 3D-US and carotid CTA. Plaque volume of carotid artery was comparable between 3D-US and CTA (148.5 ± 133.0 mm3 vs. 154.1 ± 134.6 mm3 , P = .998, R: 0.9825, P-value for r < .001). CONCLUSION: 3D-US using a single sweep technique was a feasible and accurate method of detecting arterial plaques and assessing plaque volume.

Efficacy and Safety of Udenafil for the Treatment of Pulmonary Arterial Hypertension: a Placebo-controlled, Double-blind, Phase IIb Clinical Trial.

PURPOSE: Udenafil is an oral phosphodiesterase-5 inhibitor approved for the treatment of erectile dysfunction. In a multicenter, placebo-controlled, randomized Phase IIa study, the reduction of pulmonary vascular resistance index was greater with a 50-mg baseline dose of udenafil than with the 100-mg dose, the cardiac index did not decrease at most points, and the safety was excellent, suggesting that 50-mg udenafil could be used in a Phase IIb trial. METHODS: In this 16-week, double-blind, placebo-controlled study, 63 patients with pulmonary arterial hypertension were randomized to receive 50-mg udenafil or a placebo BID. The primary efficacy end point was the 6-min walking distance. The secondary efficacy end points were the Borg dyspnea score and time to clinical worsening. Patients who completed the 16-week study could participate in a long-term extension study. FINDINGS: In terms of the difference between the baseline and 16-week 6-min walking distance in both groups, the mean placebo-corrected treatment effect was 25 (58) m (P = 0.0873). Among the patients with a history of endothelin receptor antagonist therapy, the treatment effect at week 16 between the udenafil and placebo groups was 34 (60) m (P = 0.0460). However, there were no significant differences in the Borg dyspnea score and time to clinical worsening between groups. The safety profile and adverse effects of udenafil were similar to those of typical phosphodiesterase-5 inhibitors seen in previous studies. IMPLICATIONS: Udenafil has a favorable safety profile and improves exercise capacity in patients with pulmonary arterial hypertension. ClinicalTrials.gov identifier: NCT01553721.

Effect of Niacin on Carotid Atherosclerosis in Patients at Low-Density Lipoprotein-Cholesterol Goal but High Lipoprotein (a) Level: a 2-Year Follow-Up Study.

OBJECTIVE: To examine the effect of niacin on the progression of carotid intima-media thickness (IMT) in patients with high level of lipoprotein (Lp) (a). METHODS: Patients at low-density lipoprotein-cholesterol goal but with Lp (a) >25 mg/dL and mean carotid IMT >0.75 mm were included. Eligible patients were randomized at a 1:2 ratio into one of two groups for 24 months: control or 1,500 mg extended release niacin. The primary study outcomes were the percentage changes in mean and maximal carotid IMT. The percentage change in lipid profiles including Lp (a) was analyzed as a secondary study outcome. RESULTS: Among 96 randomized patients, 31 completed the study (mean age: 65 years; male: 44%). At follow-up, the percentage change in mean carotid IMT was not significantly different between the two groups (-1.4%±15.5% and -1.1%±7.3% in the control and niacin groups, respectively, p=0.95). The percentage change in maximal carotid IMT was also similar in the two groups (0.7%±16.5% and -4.4%±11.6%, respectively, p=0.35). Elevation of high-density lipoprotein-cholesterol tended to be higher in the niacin group (p=0.07), and there was a significant difference in the percentage change in hemoglobin A1c between the two groups (-1.9%±2.2% and 3.3%±6.7%, respectively, p=0.02). Reduction of Lp (a) was greater in the niacin-treated group compared to placebo, but the difference was not statistically significant. CONCLUSION: Treatment with niacin for two years did not inhibit the progression of carotid intima-media thickening in patients with high Lp (a) level. However, this study may have been underpowered to evaluate the primary study outcome.

Demographics, treatment trends, and survival rate in incident pulmonary artery hypertension in Korea: A nationwide study based on the health insurance review and assessment service database.

Epidemiologic data regarding pulmonary arterial hypertension (PAH) have relied on registries from Western countries. We assessed the current status of PAH in the Korean population. The Health Insurance Review and Assessment Service (HIRA) claim database, which comprises nationwide medical insurance data of Koreans from 2008-2016, was assessed to determine the current status of PAH. Overall, 1,307 patients were newly diagnosed with PAH from 2008-2016 (0.0005%, annual incidence: 4.84 patients/1 million people/year). The mean age at diagnosis was 44±13 years (range 18-65) and patients were mostly women (n = 906, 69.3%). Cases of idiopathic PAH (51.6%) accounted for the largest proportion, followed by acquired PAH (APAH) associated with congenital heart disease (25.8%) and APAH with connective tissue disease (17.2%). Overall, 807 (61.7%) patients received a single PAH-specific treatment based on their last prescription, of which bosentan (50.6%) was the most frequently used. Only 240 (18.4%) patients received combination therapy, with the bosentan-beraprost combination (32.9%) being the most common. During the mean follow-up of 1.9 years, the 1-, 2-, 3-, and 5-year estimated survival rates were 85%, 62%, 54%, and 46%, respectively. The prevalence and incidence of PAH in the Korean population is currently comparable with that in previous registries. The 5-year survival rate was slightly higher in the Korean population than previously reported.

Simultaneous Closure of a Left Atrial Appendage through an Atrial Septal Defect and the Atrial Septal Defect.

Left atrial appendage (LAA) occlusion can be employed as an alternative treatment to oral anticoagulation in patients with atrial fibrillation to prevent embolic events. Atrial septal defect (ASD) may be related with right heart dysfunction and allow paradoxical embolism to occur. However, occlusion of both LAA through atrial access with ostium secundum ASD and ASD in the same setting is unusual. Therefore, we report a case in which a LAA and an ASD was sequentially occluded.

Relation of Chronic Obstructive Pulmonary Disease to Cardiovascular Disease in the General Population.

Chronic obstructive pulmonary disease (COPD) is a major health problem that contributes to substantial morbidity and mortality globally. This study investigated the relation between COPD and the risk of cardiovascular disease in the general population. We evaluated the cardiovascular effect of COPD using Korean National Health Insurance Service data from 2002 to 2013. We compared selected cardiovascular disease risk factors depending on pulmonary function using the Korean Health and Nutritional Examination Survey (KNHANES, n = 24,429) data. COPD was diagnosed in 11,771 patients (2.4%) in the National Health Insurance Service cohort. During the follow-up period (45.5 ± 14.9 months), subjects with COPD had lower cumulative survival rate for all-cause mortality, cardiovascular mortality, and sudden cardiac death (SCD, all p values <0.001). COPD was associated with an increased risk of all-cause mortality even after adjustment for potential confounding variables (hazard ratio [HR] 1.43, 95% confidence interval [CI] 1.33 to 1.55, p <0.001). However, COPD did not significantly increase the risk of cardiovascular mortality (HR 1.02, 95% CI 0.84 to 1.22, p = 0.876) and SCD (HR 1.07, 95% CI 0.79 to 1.44, p = 0.664) when adjusted for potential confounding variables. Analysis of the KNHANES cohort showed that systolic blood pressure, current smoking status, and Framingham risk score increased progressively with a decrease in pulmonary function (all p <0.001). In conclusion, COPD was associated with all-cause mortality, but not with cardiovascular mortality and SCD, whereas poor pulmonary function was associated with a heightened cardiovascular risk.