The effect of sustained-release CARvedilol in patients with hypErtension and heart failure with preserved ejection fraction: a study protocol for a pilot randomized controlled trial (CARE-preserved HF).

Background: Although beta-blockers improve clinical outcomes in heart failure with reduced ejection fraction, the benefit of beta-blockers in heart failure with preserved ejection fraction (HFpEF) is uncertain. Global longitudinal strain (GLS) is a robust predictor of heart failure outcomes, and recent studies have shown that beta-blockers are associated with improved survival in those with low GLS (GLS <14%) but not in those with GLS ≥14% among patients with LVEF ≥40%. Therefore, the objective of this trial is to evaluate the effect of sustained-release carvedilol (carvedilol-SR) on the outcome [N-terminal pro-B-natriuretic peptide (NT-proBNP) concentration] in patients with hypertension and HFpEF and will assess the differential effects of these drugs on the outcome, according to the GLS categories. Methods: This prospective randomized double-blind multicenter trial (CARE-preserved HF) will include 100 patients with HFpEF from three tertiary hospitals in South Korea. Patients with HFpEF and hypertension aged ≥20 years who have evidence of functional and structural heart disease on echocardiography and elevated natriuretic peptide will be enrolled. Eligible participants will be randomized 1:1 to either the carvedilol-SR group (n = 50) or the placebo group (n = 50). Patients in the carvedilol-SR group will receive 8, 16, 32, or 64 mg carvedilol-SR once daily for 6 months, and the dose of carvedilol will be up-titrated at the discretion of the treating physicians. The primary efficacy outcome was the time-averaged proportional change in N-terminal pro-B-natriuretic peptide concentration from baseline to months 3 and 6. We will also evaluate the differential effects of carvedilol-SR on primary outcomes according to GLS, using a cut-off of 14% or the median value. Discussion: This randomized controlled trial will investigate the efficacy and safety of carvedilol-SR in patients with HFpEF and hypertension. Clinical Trial Registration: ClinicalTrial.gov, identifier NCT05553314.

Ertugliflozin for Functional Mitral Regurgitation Associated With Heart Failure: EFFORT Trial.

BACKGROUND: The morbidity and mortality rates of patients with heart failure (HF) and functional mitral regurgitation (MR) remain substantial despite guideline-directed medical therapy for HF. We evaluated the efficacy of ertugliflozin for reduction of functional MR associated with HF with mild to moderately reduced ejection fraction. METHODS: The EFFORT trial (Ertugliflozin for Functional Mitral Regurgitation) was a multicenter, double-blind, randomized trial to examine the hypothesis that the sodium-glucose cotransporter 2 inhibitor ertugliflozin is effective for improving MR in patients with HF with New York Heart Association functional class II or III, 35%≤ejection fraction<50%, and effective regurgitant orifice area of chronic functional MR >0.1 cm2 on baseline echocardiography. We randomly assigned 128 patients to receive either ertugliflozin or placebo in addition to guideline-directed medical therapy for HF. The primary end point was change in effective regurgitant orifice area of functional MR from baseline to the 12-month follow-up. Secondary end points included changes in regurgitant volume, left ventricular (LV) volume indices, left atrial volume index, LV global longitudinal strain, and NT-proBNP (N-terminal pro-B-type natriuretic peptide). RESULTS: The treatment groups were generally well-balanced with regard to baseline characteristics: mean age, 66±11 years; 61% men; 13% diabetes; 51% atrial fibrillation; 43% use of angiotensin receptor-neprilysin inhibitor; ejection fraction, 42±8%; and effective regurgitant orifice area, 0.20±0.12 cm2. The decrease in effective regurgitant orifice area was significantly greater in the ertugliflozin group than in the placebo group (-0.05±0.06 versus 0.03±0.12 cm2; P<0.001). Compared with placebo, ertugliflozin significantly reduced regurgitant volume by 11.2 mL (95% CI, -16.1 to -6.3; P=0.009), left atrial volume index by 6.0 mL/m2 (95% CI, -12.16 to 0.15; P=0.005), and LV global longitudinal strain by 1.44% (95% CI, -2.42% to -0.46%; P=0.004). There were no significant between-group differences regarding changes in LV volume indices, ejection fraction, or NT-proBNP levels. Serious adverse events occurred in one patient (1.6%) in the ertugliflozin group and 6 (9.2%) in the placebo group (P=0.12). CONCLUSIONS: Among patients with functional MR associated with HF, ertugliflozin significantly improved LV global longitudinal strain and left atrial remodeling, and reduced functional MR. Sodium-glucose cotransporter 2 inhibitors may be considered for patients with functional MR. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04231331.

Validation of TRI-SCORE for Outcome Prediction After Isolated Tricuspid Valve Surgery in Asian Patients.

BACKGROUND: TRI-SCORE was recently developed in Europe as a risk model for predicting in-hospital death after isolated tricuspid valve surgery. We aimed to validate TRI-SCORE in an Asian population and investigate its value for predicting long-term outcomes. METHODS AND RESULTS: The TRI-SCORE was calculated for 202 patients (65±11 years, 61% women, 81% functional tricuspid regurgitation) who underwent isolated tricuspid valve surgery for severe tricuspid regurgitation at 2 Korean centers and was based on 8 parameters: age, New York Heart Association class, right-sided heart failure signs, furosemide daily dose, glomerular filtration rate, bilirubin, left ventricular ejection fraction, and moderate/severe right ventricular dysfunction. The primary outcome was all-cause death during follow-up; the secondary outcome was in-hospital death. During a median follow-up duration of 50 (interquartile range, 21-82) months after isolated tricuspid valve surgery, 23 (11.4%) patients experienced the primary outcome, and 7 (3.5%) patients experienced the secondary outcome. Observed all-cause death and in-hospital death increased by up to 50% in those with higher scores. Patients with the primary outcome had a higher TRI-SCORE (4.5±2.4 versus 2.9±2.1; P=0.001) than those without. The TRI-SCORE showed a significant association with the primary outcome (concordance index, 0.77, cutoff value, 4) and in-hospital death (area under the curve, 0.84; cutoff value, 3). Using the Kaplan-Meier analysis, patients with a high TRI-SCORE exhibited a poor outcome for all-cause death at follow-up (log-rank P<0.001) and in-hospital death (log-rank P=0.004). CONCLUSIONS: TRI-SCORE was validated in an Asian population and helped predict long-term outcomes after isolated tricuspid valve surgery.

Perioperative Risk of Noncardiac Surgery in Patients With Asymptomatic Significant Aortic Stenosis: A 10-Year Retrospective Study.

BACKGROUND: Aortic stenosis (AS) is a representative geriatric disease, and there is an anticipated rise in the number of patients requiring noncardiac surgeries in patients with AS. However, there is still a lack of research on the primary predictors of noncardiac perioperative complications in patients with asymptomatic significant AS. METHODS AND RESULTS: Among the cohort of noncardiac surgeries under general anesthesia, with an intermediate to high risk of surgery from 2011 to 2019, at Samsung Medical Center, 221 patients were identified to have asymptomatic significant AS. First, to examine the impact of significant AS on perioperative adverse events, the occurrences of major adverse cardiovascular events and perioperative adverse cardiovascular events were compared between patients with asymptomatic significant AS and the control group. Second, to identify the factors influencing the perioperative adverse events in patients with asymptomatic significant AS, a least absolute shrinkage and selection operator regression model was used. There was no significant difference between the control group and the asymptomatic significant AS group in the event rate of major adverse cardiovascular events (4.6% at control group versus 5.5% at asymptomatic significant AS group; P=0.608) and perioperative adverse cardiovascular events (13.8% at control group versus 18.3% at asymptomatic significant AS group; P=0.130). Cardiac damage stage was a significant risk factor of major adverse cardiovascular events and perioperative adverse cardiovascular events. CONCLUSIONS: There was no significant difference in major postoperative cardiovascular events between patients with asymptomatic significant AS and the control group. Advanced cardiac damage stage in significant AS is an important factor in perioperative risk of noncardiac surgery.

Usefulness of cardiopulmonary exercise test combined with exercise stress echocardiography in mild chronic thromboembolic pulmonary disease.

PURPOSE: Chronic thromboembolic pulmonary disease (CTEPD) can lead to exercise limitations even without right ventricular (RV) dysfunction or pulmonary hypertension at rest. Combining exercise stress echocardiography with cardiopulmonary exercise testing (ESE-CPET) for RV function and pressure changes combined measuring overall function may be useful for CTEPD evaluation. This study aims to investigate CPET and ESE results to elucidate the mechanisms of exercise limitation in mild CTEPD cases. METHODS: Among our CTEPD registry, 50 patients who performed both right heart catheterization data of mild disease (less than 30 mm Hg of mean pulmonary arterial pressure (mPAP)) and ESE-CPET were enrolled. Echocardiography and CPET-derived parameters were compared with hemodynamic parameters measured through right heart catheterization. RESULTS: Peak VO2 (maximal oxygen consumption) was decreased in overall population (71.3 ± 16.3% of predictive value). Peak VO2 during exercise was negatively correlate with mPAP and pulmonary vascular resistance at rest. A substantial increase in RV systolic pressure (RVSP) was observed during exercise (RVSP: pre-exercise 37.2 ± 11.8 mm Hg, postexercise 64.3 ± 24.9 mm Hg, p-value < .001). Furthermore, RV function deteriorated during exercise when compared to the baseline (RV fractional area change: 31.5 ± 10.0% to 37.8 ± 7.0%, p-value < .001; RV global longitudinal strain: -17.1 ± 4.2% to -17.7 ± 3.3%, p-value < .001) even though basal RV function was normal. While an excessive increase in RVSP during exercise was noticed in both groups, dilated RV and RV dysfunction during exercise were demonstrated only in the impaired exercise capacity group. CONCLUSION: CTEPD patients with mild PH or without PH exhibited limited exercise capacity alongside an excessive increase in RVSP during exercise. Importantly, RV dysfunction during exercise was significantly associated with exercise capacity. ESE-CPET could aid in comprehending the primary cause of exercise limitation in these patients.

Prognostic implication of left atrial strain in patients experiencing early recurrence of atrial fibrillation after totally thoracoscopic ablation.

Background: Although early atrial fibrillation (AF) events during the blanking period after AF ablation are risk factors for late recurrence, data on predictors of late recurrence in patients who experience early AF events are limited. In this study, we investigated the implications of left atrial (LA) strain with respect to long-term outcomes in patients experiencing early AF during the blanking period after totally thoracoscopic ablation (TTA). Methods: A total of 128 patients who underwent TTA between 2012 and 2015 were enrolled from a tertiary center. Peak longitudinal LA strain was measured preoperatively. Early recurrence (ER) was defined as any AF within the 3-month blanking period after TTA. The primary outcome was late recurrence of AF for 5 years, detected on 12-lead electrocardiogram or 24-hour Holter monitoring, excluding the blanking period. Results: Out of 128 patients, 42 (32.8%) experienced ER during the blanking period. Patients who experienced ER had a significantly higher risk of 5-year AF recurrence compared with those who did not [72.7% vs. 29.6%, hazard ratio (HR) =3.69, 95% confidence interval (CI): 2.14-6.36, P<0.001]. Within the group of 42 patients experiencing ER, LA strain with a best cutoff value of 18.6% was the only independent predictor of 5-year AF recurrence (adjusted HR =4.20, 95% CI: 1.08-16.29, P=0.038). Patients with ER and LA strain ≥18.6% had a risk of 5-year AF recurrence, similar to those without ER (35.2% vs. 29.6%, HR =1.21, 95% CI: 0.36-4.04, P=0.755). Patients with ER and LA strain <18.6% had a significantly higher risk of 5-year AF recurrence compared to those without ER (83.0% vs. 29.6%, HR =4.83, 95% CI: 2.75-8.48, P<0.01). Conclusions: Early AF during the blanking period is common in patients undergoing TTA. In patients with ER, LA strain was an independent predictor of long-term AF recurrence.

Randomized, multicenter, parallel, open, phase 4 study to compare the efficacy and safety of rosuvastatin/amlodipine polypill versus atorvastatin/amlodipine polypill in hypertension patient with dyslipidemia.

The authors performed this study to investigate the efficacy and safety of a rosuvastatin (RSV)/amlodipine (AML) polypill compared with those of atorvastatin (ATV)/AML polypill. We included 259 patients from 21 institutions in Korea. Patients were randomly assigned to 1 of 3 treatment groups: RSV 10 mg/AML 5 mg, RSV 20 mg/AML 5 mg, or ATV 20 mg /AML 5 mg. The primary endpoint was the efficacy of the RSV 10.20 mg/AML 5 mg via percentage changes in LDL-C after 8 weeks of treatment, compared with the ATV 20 mg /AML 5 mg. There was a significant difference in the mean percentage change of LDL-C at 8 weeks between the RSV 10 mg/AML 5 mg and the ATV 20 mg/AML 5 mg (full analysis set [FAS]: -7.08%, 95% CI: -11.79 to -2.38, p = .0034, per-protocol analysis set [PPS]: -6.97%, 95% CI: -11.76 to -2.19, p = .0046). Also, there was a significant difference in the mean percentage change of LDL-C at 8 weeks between the RSV 20 mg/AML 5 mg and the ATV 20 mg/AML 5 mg (FAS: -10.13%, 95% CI: -15.41 to -4.84, p = .0002, PPS: -10.96%, 95% CI: -15.98 to -5.93, p < .0001). There was no significant difference in the adverse events rates between RSV 10 mg/AML 5 mg, RSV 20 mg/AML 5 mg, and ATV 20 mg/AML 5 mg. In conclusion, while maintaining safety, RSV 10 mg/AML 5 mg and the RSV 20 mg/AML 5 mg more effectively reduced LDL-C compared with the ATV 20 mg /AML 5 mg (Clinical trial: NCT03951207).

Topographical Association Between Left Ventricular Strain and Brain Lesions in Patients With Acute Ischemic Stroke and Normal Cardiac Function.

Background Although it is well known that the disordered brain provokes cardiac autonomic dysfunction, the detailed location of brain lesions related to cardiac function warrants further investigation. We aimed to elucidate the brain lesions topographically associated with left ventricular (LV) systolic function measured by myocardial strain in patients with acute ischemic stroke without preexisting primary cardiac dysfunction by using support vector regression lesion-symptom mapping. Methods and Results Subjects were those with LV ejection fraction of 50% or more among patients with acute ischemic stroke registered in the Samsung Medical Center stroke registry between 2016 and 2017. To evaluate LV systolic performance and contractility, we measured LV ejection fraction and LV global and regional longitudinal strain using 2-dimensional speckle-tracking echocardiography. The association between stroke lesion location and cardiac strain was assessed using support vector regression lesion-symptom mapping. Of a total of 776 patients, 286 subjects (mean age of 67.0 years, 65.4% men) were finally enrolled in this study. The mean global longitudinal strain was -17.0±3.4%, and the mean LV ejection fraction was 64.7±5.7%. The support vector regression lesion-symptom mapping analysis revealed that the right insula and peri-insular regions and left parietal cortex were associated with impaired LV global longitudinal strain in patients with acute ischemic stroke. In addition, impaired regional longitudinal strain showed topographical associations with these regions. Conclusions This study suggests that brain lesions in the right insula and peri-insular regions and left parietal cortex are topographically associated with impaired LV strain in patients with acute ischemic stroke without preexisting cardiac dysfunction.

Left atrial strain predicts fibrosis of left atrial appendage in patients with atrial fibrillation undergoing totally thoracoscopic ablation.

Background: Left atrial (LA) fibrosis is related with development and severity of atrial fibrillation (AF). The aim of this study was to investigate the association between LA strain and LA fibrosis in patients undergoing totally thoracoscopic ablation (TTA) for AF. Methods: Between February 2012 and March 2015, a total of 128 patients who underwent TTA were enrolled from a tertiary hospital. Left atrial appendage (LAA) was harvested during surgery to determine the degree of fibrosis. LAA fibrosis was classified as mild (1st quartile), moderate (2nd and 3rd quartile), or severe (4th quartile). Clinical outcome was 5-year recurrence rate of AF detected on electrocardiogram or 24 h Holter monitoring. Results: The mean age was 54.3 ± 8.8 years and 18.8% had paroxysmal AF. Patients with mild LAA fibrosis had a significantly lower rate of recurrent AF (23.3%) at 5 years after TTA compared with those with moderate (51.4%; hazard ratio [HR] 2.69; 95% confidence interval [CI] 1.19-6.12) or severe (53.2%; HR 2.84; 95% CI 1.16-6.97) fibrosis. Among clinical and echocardiographic parameters, peak LA strain was the only predictor of mild LAA fibrosis (coefficient 0.10, p = 0.005) with the best cutoff value of 14.7% (area under the curve 0.732). The prevalence of mild LAA fibrosis was 40.6% in patients with peak LA strain ≥14.7%, but only 6.8% in those with peak LA strain <14.7%. Conclusions: In patients undergoing TTA for AF, mild LAA fibrosis was associated with a lower risk of 5-year AF recurrence. LA strain was the only predictor of mild LAA fibrosis that reflects a lower risk of 5-year AF recurrence.

Pattern of pericardial calcification determines mid-term postoperative outcomes after pericardiectomy in chronic constrictive pericarditis.

OBJECTIVES: Although pericardiectomy is an effective treatment for constrictive pericarditis (CP), clinical outcomes are not always successful. Pericardial calcification is a unique finding in CP, although the amount and localization of calcification can vary. We investigated how the pattern and amount of pericardial calcification affect mid-term postoperative outcomes after pericardiectomy to treat CP. METHODS: All patients of total pericardiectomy in our hospital from 2010 to 2020 were enrolled. Preoperative Computed tomography (CT) scans of 98 consecutive patients were available and analyzed. Medical records were reviewed retrospectively. Cardiovascular events were defined as cardiovascular death or hospitalization associated with a heart failure symptom, and all-cause events were defined as any event that required admission. CT scans were analyzed, and the volume and localization pattern of peri-calcification were determined. Pericardium calcium scores are presented using Agatston scores. RESULTS: Of the 98 patients, 25 (25.5%) were hospitalized with heart failure symptoms after pericardiectomy. The median follow-up duration for all patients was 172 weeks. The group with a cardiovascular event had a lower calcium score than patients without an event. Multivariate Cox proportional analysis showed that high ln(calcium score+1) before pericardiectomy was a dependent predictor of cardiovascular event (hazard ratio, 0.90; p = 0.04) after pericardiectomy. When we set the cut-off value (ln(calcium score+1) = 7.22), there was a significant difference in cardiovascular events in the multivariate Cox proportional analysis (p = 0.04). CONCLUSION: A low burden of pericardial calcification was associated with a high rate of mid-term clinical events after pericardiectomy to treat CP.

Clinical Implication of Left Atrial Appendage Emptying Velocity in Thoracoscopic Ablation of Atrial Fibrillation.

BACKGROUND: There are limited data about predictors of atrial fibrillation (AF) recurrence after totally thoracoscopic ablation (TTA). This study investigated the clinical implication of left atrial appendage emptying velocity (LAAV) in patients undergoing TTA.Methods and Results: Patients who underwent TTA between 2012 and 2015 at a tertiary hospital were prospectively enrolled in this study. LAAV was measured and averaged over five heart beats from preoperative transesophageal echocardiography. The primary outcome was a freedom from recurrent AF or atrial flutter (AFL) detected on 24-h Holter monitoring or an electrocardiogram over a 3-year period after TTA. In all, 129 patients were eligible for analysis in this study. The mean (±SD) patient age was 54.4±8.8 years, and 95.3% were male. During the 3 years after TTA, the overall event-free survival rate was 65.3%. LAAV was an independent predictor of recurrent AF/AFL during the 3-year period after TTA (per 1-cm/s increase, adjusted hazard ratio [aHR] 0.95; 95% confidence interval [CI] 0.91-0.99; P=0.016). Event-free survival was significantly lower among patients with a low LAAV (<20 cm/s; n=21) compared with those with a normal (≥40 cm/s; n=38; aHR 6.11; 95% CI 1.42-26.15; P=0.015) or intermediate (LAAV ≥20 and <40 cm/s; n=70; aHR 2.74, 95% CI 1.29-5.83; P=0.009) LAAV. CONCLUSIONS: In patients with AF, LAAV was significantly associated with the risk of long-term recurrence of AF after TTA.

Impact of Atrial Fibrillation on Patients Undergoing Transcatheter Aortic Valve Implantation (TAVI): The K-TAVI Registry.

PURPOSE: The incidence and prognostic implications of atrial fibrillation (AF) in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI) are controversial, especially for Korean patients. Furthermore, the pattern of antithrombotic therapy for these patients is unknown. The present study sought to identify the impact of AF on Korean patients undergoing TAVI and demonstrate the status of antithrombotic therapy for these patients. MATERIALS AND METHODS: A total of 660 patients who underwent TAVI for severe AS were recruited from the nationwide K-TAVI registry in Korea. The enrolled patients were stratified into sinus rhythm (SR) and AF groups. The primary endpoint was all-cause death at 1-year. RESULTS: AF was recorded in 135 patients [pre-existing AF 108 (16.4%) and new-onset AF 27 (4.1%)]. The rate of all-cause death at 1 year was significantly higher in patients with AF than in those with SR [16.2% vs. 6.4%, adjusted hazard ratio (HR): 2.207, 95% confidence interval (CI): 1.182-4.120, p=0.013], regardless of the onset timing of AF. The rate of new pacemaker insertion at 1 year was also significantly higher in patients with AF than in those with SR (14.0% vs. 5.5%, adjusted HR: 3.137, 95%CI: 1.621-6.071, p=0.001). Among AF patients, substantial number of patients received the combination of multiple antithrombotic agents (77.8%), and the most common combination was that of aspirin and clopidogrel (38.1%). CONCLUSION: AF was an independent predictor of 1-year mortality and new pacemaker insertion in Korean patients undergoing TAVI.

Role of cardiovascular magnetic resonance imaging and cardiopulmonary exercise test in predicting composite clinical outcomes in patients with hypertrophic cardiomyopathy.

We aimed to evaluate the additive value of cardiovascular magnetic resonance imaging (CMR) and cardiopulmonary exercise test (CPET) to predict clinical outcomes in patients with HCM. We enrolled 373 patients with HCM and normal left ventricular systolic function who underwent CPET and CMR. The primary outcome was a clinical composite of all-cause death, cardiac transplantation, stroke, heart failure requiring hospitalization and defibrillator implantation. During a follow-up of 70.70 ± 30.74 months, there were 84 composite clinical events. Peak oxygen consumption during CPET was significantly lower (18.51±13.25 vs. 24.59±13.28 mL/kg/min, p < 0.001) and abnormal hemodynamic response to exercise was more frequently detected (41.7 vs. 20.8%, p<0.001) in the group with composite clinical events. The extent of late gadolinium enhancement was larger in the event group (15.39±10.53 vs. 11.97±9.53%LV, p<0.001). Selective parameters were added stepwise to conventional clinical parameters; the final model, where CPET and CMR parameters were added, was verified to have the highest increment value for clinical outcome prediction (p<0.001). This study demonstrated that CPET and CMR findings may be important clinical tools for risk stratification in HCM. Exercise capacity was an independent predictor of composite outcomes in patients with HCM, with incremental value as a risk factor when added to the alleged parameters. These findings could help physicians monitor and manage patients with HCM in the real clinical field.

Efficacy and Safety of Coadministered Ezetimibe-Rosuvastatin plus Telmisartan in South Korean Patients with Dyslipidemia and Hypertension: A Multicenter, Randomized, Double-Blind, Active-Controlled, Phase III Trial.

BACKGROUND: The introduction of a fixed-dose combination (FDC) is expected to improve treatment compliance. METHODS: There were 181 subjects who were randomized to three groups: ezetimibe-rosuvastatin 10/20 mg + telmisartan 80 mg, ezetimibe-rosuvastatin 10/20 mg, and telmisartan 80 mg. The primary outcomes were change in mean sitting systolic blood pressure (MSSBP) and percentage change in low-density-lipoprotein cholesterol (LDL-C) compared to baseline at week 8. RESULTS: The least-square mean (SE) in MSSBP changes between the ezetimibe-rosuvastatin 10/20 mg + telmisartan 80 mg group and the ezetimibe-rosuvastatin 10/20 mg group were -25.81 (2.34) mmHg and -7.66 (2.45) mmHg. There was a significant difference between the two groups (-18.15 (2.83) mmHg, 95% CI -23.75 to -12.56, p < 0.0001). Changes in least-square mean (SE) in LDL-C between the ezetimibe-rosuvastatin 10/20 mg + telmisartan 80 mg group and the telmisartan 80 mg group were -63.82 (2.87)% and -2.48 (3.12)%. A significant difference was observed between the two groups (-61.34 (3.33)%, 95% CI -67.91 to -54.78, p < 0.0001). No serious adverse events were observed. CONCLUSIONS: Ezetimibe-rosuvastatin plus telmisartan treatment is effective and safe when compared to either ezetimibe-rosuvastatin or telmisartan.

Systemic proinflammatory-profibrotic response in aortic stenosis patients with diabetes and its relationship with myocardial remodeling and clinical outcome.

BACKGROUND: Previous studies have mainly focused more on how diabetes affects the valve than the myocardium in aortic stenosis (AS). In the pressure-overloaded heart, myocardial fibrosis is an important driver of the progression from compensated hypertrophy to heart failure. Using comprehensive noninvasive imaging and plasma proteomics, we investigated whether and how diabetes aggravates the remodeling of the myocardium and its relation with prognosis in AS patients. METHODS: Severe AS patients were enrolled in two prospective cohorts for imaging and biomarker analysis. The imaging cohort (n = 253) underwent echocardiography and cardiac magnetic resonance, and the biomarker cohort (n = 100) blood sampling with multiplex proximity extension assay for 92 proteomic biomarkers. The composite outcome of hospitalization for heart failure admissions and death was assessed in the imaging cohort. RESULTS: Diabetic patients were older (70.4 ± 6.8 versus 66.7 ± 10.1 years) with more advanced ventricular diastolic dysfunction and increased replacement and diffuse interstitial fibrosis (late gadolinium enhancement % 0.3 [0.0-1.6] versus 0.0 [0.0-0.5], p = 0.009; extracellular volume fraction % 27.9 [25.7-30.1] versus 26.7 [24.9-28.5], p = 0.025) in the imaging cohort. Plasma proteomics analysis of the biomarker cohort revealed that 9 proteins (E-selectin, interleukin-1 receptor type 1, interleukin-1 receptor type 2, galectin-4, intercellular adhesion molecule 2, integrin beta-2, galectin-3, growth differentiation factor 15, and cathepsin D) were significantly elevated and that pathways related to inflammatory response and extracellular matrix components were enriched in diabetic AS patients. During follow-up (median 6.3 years), there were 53 unexpected heart failure admissions or death in the imaging cohort. Diabetes was a significant predictor of heart failure and death, independent of clinical covariates and aortic valve replacement (HR 1.88, 95% CI 1.06-3.31, p = 0.030). CONCLUSIONS: Plasma proteomic analyses indicate that diabetes potentiates the systemic proinflammatory-profibrotic milieu in AS patients. These systemic biological changes underlie the increase of myocardial fibrosis, diastolic dysfunction, and worse clinical outcomes in severe AS patients with concomitant diabetes.

Impact of maze procedure in patients with severe tricuspid regurgitation and persistent atrial fibrillation.

OBJECTIVE: Patients with severe tricuspid regurgitation and persistent atrial fibrillation may not be good candidates for maze procedure due to preoperative atrial remodeling and various comorbidities. We attempted to evaluate the rhythm and clinical outcomes of maze procedure in these patients. METHODS: Patients with severe tricuspid regurgitation and persistent atrial fibrillation who underwent tricuspid valve surgery between January 1994 and December 2017 at a single tertiary center were analyzed. The primary end point was sinus rhythm restoration. The key secondary end point was major adverse cardiovascular and cerebrovascular event rate, which is the composite event of stroke, cardiac death, major bleeding, and readmission for heart failure. Propensity score matching analysis was used. RESULTS: A total of 388 patients underwent tricuspid valve surgery, and among them 172 patients (44%) underwent concomitant maze procedure. The maze group had sinus rhythm restoration rate of 56% in 9 years. Further, in the matched cohort, the maze group had higher freedom from major adverse cardiovascular and cerebrovascular event rate at 10 years than the nonmaze group (55.6% vs 36.2%; P = .047). Preoperative left atrial diameter (hazard ratio, 1.022; 95% CI, 1.012-1.033; P < .001) and right atrial diameter (hazard ratio, 1.012; 95% CI, 1.003-1.022; P = .013) were independent risk factors for failure of sinus rhythm. CONCLUSIONS: Maze procedure in severe tricuspid regurgitation and persistent atrial fibrillation had acceptable rates of sinus rhythm restoration and reduced major adverse cardiovascular and cerebrovascular events in the long-term. Careful patient selection considering preoperative atrial diameters is needed to enhance maze success rate and long-term clinical outcomes.

Different characteristics of apical aneurysm in hypertrophic cardiomyopathy are related to difference in long-term prognosis.

BACKGROUND: Data regarding long-term cardiac and cerebrovascular adverse events in patients with hypertrophic cardiomyopathy (HCM) and apical aneurysm (AAn) are scarce and specific treatment strategies that include the use of anticoagulants have not yet been established. We aimed to evaluate the prevalence and long-term prognostic implication based on characteristics of AAn in patients with HCM. METHODS: A total of 458 consecutive patients diagnosed with HCM underwent cardiovascular magnetic resonance imaging and echocardiography from August 1, 2008 to December 31, 2015. AAn was classified into Grade 1 and Grade 2 based on size and morphology. The patients were followed up for a median duration of 6.3 years (range, 4.2-8.7 years) for major adverse cardiac and cerebral events (MACCEs); a composite of cardiac death, HCM-related hospitalization, cerebrovascular accident (CVA), heart transplantation, myocardial infarction, and implantable cardiac defibrillator/cardiac resynchronization therapy. RESULTS: AAn was detected in 9.2%. MACCEs developed more frequently in patients with AAn than in those without AAn (30.1% vs. 20.7%, P = 0.015), with the rate of CVA as the main difference (9.7% vs. 5.3%, P = 0.011). Grade 2 AAn group showed significantly higher MACCE than Grade 1 AAn group (41.8% vs. 21.9%, P < 0.001). In multivariate analysis, the presence of AAn was independently associated with increased risk of MACCEs (adjusted hazard ratio: 1.95; 95% confidence interval, CI: 1.16-3.28; P = 0.012). CONCLUSIONS: AAn is independently associated with increased risk of HCM-related adverse events, especially cerebral infarction, with significant relationship between aneurysm size and adverse events.