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.

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.

Early Surgery or Conservative Care for Asymptomatic Aortic Stenosis.

BACKGROUND: The timing and indications for surgical intervention in asymptomatic patients with severe aortic stenosis remain controversial. METHODS: In a multicenter trial, we randomly assigned 145 asymptomatic patients with very severe aortic stenosis (defined as an aortic-valve area of ≤0.75 cm2 with either an aortic jet velocity of ≥4.5 m per second or a mean transaortic gradient of ≥50 mm Hg) to early surgery or to conservative care according to the recommendations of current guidelines. The primary end point was a composite of death during or within 30 days after surgery (often called operative mortality) or death from cardiovascular causes during the entire follow-up period. The major secondary end point was death from any cause during follow-up. RESULTS: In the early-surgery group, 69 of 73 patients (95%) underwent surgery within 2 months after randomization, and there was no operative mortality. In an intention-to-treat analysis, a primary end-point event occurred in 1 patient in the early-surgery group (1%) and in 11 of 72 patients in the conservative-care group (15%) (hazard ratio, 0.09; 95% confidence interval [CI], 0.01 to 0.67; P = 0.003). Death from any cause occurred in 5 patients in the early-surgery group (7%) and in 15 patients in the conservative-care group (21%) (hazard ratio, 0.33; 95% CI, 0.12 to 0.90). In the conservative-care group, the cumulative incidence of sudden death was 4% at 4 years and 14% at 8 years. CONCLUSIONS: Among asymptomatic patients with very severe aortic stenosis, the incidence of the composite of operative mortality or death from cardiovascular causes during the follow-up period was significantly lower among those who underwent early aortic-valve replacement surgery than among those who received conservative care. (Funded by the Korean Institute of Medicine; RECOVERY ClinicalTrials.gov number, NCT01161732.).

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.

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.

Predictor of atrial fibrillation recurrence in patients who underwent a tricuspid valve operation with modified Cox maze procedure.

BACKGROUND: Recurrence of any atrial arrhythmia after surgical ablation is known as a negative predictor of cardiovascular events and total mortality. However, there have been no focused studies for atrial fibrillation (AF) recurrence prediction in patients with significant tricuspid regurgitation (TR), and the risk-benefit estimation of surgical ablation in tricuspid valve (TV) surgery is not fully established. METHOD: We screened 385 patients who underwent a TV operation between 2001 and 2017. After excluding patients who did not undergo a maze operation, 158 patients were enrolled. Enrolled patients were divided by recurrence of AF. We analyzed the difference between the AF recurrence group and no AF recurrence group, and AF recurrence factors in terms of clinical risk factors and echocardiographic risk factors. The hazard ratio (HR) and 95% confidence intervals (CIs) were presented using a Cox proportional hazard model. RESULTS: Among 158 patients, AF recurred in 65 patients within 10 years. For AF prediction, age was most the important clinical factor and right atrium (RA) diameter was the most important echocardiographic parameters. In patients with a larger RA diameter over 49.2 mm, the prevalence of AF recurrence was higher (HR 4.322, 95% CI [2.185-8.549], log rank p value < .001). In clinical outcome, there was no significant difference between the AF recurrence group and the no recurrence group in terms of death, TR recurrence, heart failure, and stroke. However, the risk of permanent pacemaker (PPM) insertion was higher in the AF recurrence group (HR 10.240, 95% CI [1.257-83.480], log rank p value .007) compared to the no recurrence group. CONCLUSION: Age and RA enlargement are key predictors of AF recurrence after TV operation with the CM procedure in patients with significant TR.

Determinants of Exercise Capacity in Patients With Hypertrophic Cardiomyopathy.

BACKGROUND: Reduced exercise capacity reflects symptom severity and clinical outcomes in patients with hypertrophic cardiomyopathy (HCM). The present study aimed to identify factors that may affect exercise capacity in patients with HCM. METHODS: In 294 patients with HCM and preserved left ventricular (LV) ejection fraction, we compared peak oxygen consumption (peak VO2) evaluated by cardiopulmonary exercise testing as a representative parameter of exercise tolerance with clinical and laboratory data, including N-terminal pro-hormone of brain natriuretic peptide (NT-proBNP), diastolic parameters on echocardiography, and the grade of myocardial fibrosis on cardiac magnetic resonance imaging (CMR). RESULTS: Median peak VO2, was 29.0 mL/kg/min (interquartile range [IQR], 25.0-34.0). Age (estimated ß = -0.140, P < 0.001), female sex (ß = -5.362, P < 0.001), NT-proBNP (ß = -1.256, P < 0.001), and E/e' ratio on echocardiography (ß = -0.209, P = 0.019) were significantly associated with exercise capacity. Peak VO2 was not associated with the amount of myocardial fibrosis on CMR (mean of late gadolinium enhancement 12.25 ± 9.67%LV). CONCLUSION: Decreased exercise capacity was associated with age, female sex, increased NT-proBNP level, and E/e' ratio on echocardiography. Hemodynamic changes and increased filling pressure on echocardiography should be monitored in this population for improved outcomes.

Angiotensin Receptor Neprilysin Inhibitor for Functional Mitral Regurgitation.

BACKGROUND: The morbidity and mortality of patients with functional mitral regurgitation (MR) remain high, but no pharmacological therapy has been proven effective. The hypothesis of this study was that sacubitril/valsartan would be superior to valsartan alone in improving functional MR via dual inhibition of the renin-angiotensin system and neprilysin. METHODS: In this double-blind trial, we randomly assigned 118 patients with heart failure with chronic functional MR secondary to left ventricular (LV) dysfunction to receive either sacubitril/valsartan or valsartan, in addition to standard medical therapy for heart failure. The primary end point was the 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, LV end-systolic volume, LV end-diastolic volume, and incomplete mitral leaflet closure area. RESULTS: The decrease in effective regurgitant orifice area was significantly greater in the sacubitril/valsartan group than in the valsartan group (-0.058±0.095 versus -0.018±0.105 cm2; P=0.032) in an intention-to-treat analysis including 117 (99%) patients. Regurgitant volume was also significantly decreased in the sacubitril/valsartan group in comparison with the valsartan group (mean difference, -7.3 mL; 95% CI, -12.6 to -1.9; P=0.009). There were no significant between-group differences regarding the changes in incomplete mitral leaflet closure area and LV volumes, with the exception of LV end-diastolic volume index ( P=0.044). We noted no significant difference in the change of blood pressure between the treatment groups, and 7 patients (12%) in the sacubitril/valsartan group and 9 (16%) in the valsartan group had ≥1 serious adverse events ( P=0.54). CONCLUSIONS: Among patients with secondary functional MR, sacubitril/valsartan reduced MR to a greater extent than did valsartan. Our findings suggest that an angiotensin receptor-neprilysin inhibitor might be considered for optimal medical therapy of patients with heart failure and functional MR. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02687932.

Prevalence and clinical significance of cardiovascular magnetic resonance adenosine stress-induced myocardial perfusion defect in hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is thought to be associated with microvascular dysfunction. Adenosine stress-perfusion cardiovascular magnetic resonance imaging (CMR) is a sensitive method for assessing microvascular perfusion abnormalities. We evaluated the prevalence and clinical characteristics of HCM patients with adenosine-induced perfusion defects on CMR. METHODS: Among 189 consecutive patients with HCM who underwent adenosine-stress perfusion CMR, 115 patients who had clinical, echocardiography, 24-h Holter monitoring and treadmill exercise test data were analyzed. We calculated myocardial perfusion ratio index from the intensity-over-time curve to quantify perfusion defects. The presence and extent of the stress-induced perfusion defect were compared with clinical characteristics, presence and extent of late gadolinium enhancement (LGE), left ventricular (LV) mass index and volume, presence of non-sustained ventricular tachycardia (NSVT) and results of treadmill exercise test. RESULTS: The mean age of enrolled patients was 51.8 ± 11.3 years. Most patients were asymptomatic except 25 subjects presented with New York Heart Association Class II dyspnea and 16 patients with atypical non-exertional chest discomfort. LGE was present in 103 (89.6%) subjects. Adenosine stress-induced perfusion defects were present in 48 (42%) subjects. None of the perfusion defects corresponded with a single or multiple coronary artery territories, showing a multiple patchy pattern in 24 (50.0%), a concentric subendocardial pattern in 20 subjects (41.7%), and as a single blot-like defect in the remaining 4 (8.3%). A perfusion defect was associated with NSVT, LV apical aneurysm, higher LV mass index, and higher LGE volume on univariate analysis. Multivariate analysis revealed female gender (P = 0.008), presence of apical aneurysm and NSVT (P = 0.036 and 0.047, respectively), and LV mass index (P = 0.022) to be independently associated with adenosine stress-induced perfusion defects. CONCLUSIONS: In patients with HCM, adenosine-stress perfusion defects on CMR are present in more than 40% of subjects. This perfusion defect is associated with NSVT, higher LV mass index, and apical aneurysms. The prognostic value of this finding needs further elucidation.

Changes of echocardiographic parameters in primary mitral regurgitation and determinants of symptom: an assessment from the Asian Valve Registry data.

Clinicians often have a difficulty in determining the presence of mitral regurgitation (MR)-related symptoms because of subjectivity. However, there are few actual measurement data for echocardiographic left ventricular (LV) and left atrial (LA) size related to the severity of MR and the relationship between MR-related symptoms and these echocardiographic parameters. Among patients enrolled in the Asian Valve Registry, we investigated 778 consecutive patients with primary MR showing sinus rhythm. Symptoms were determined by New York Heart Association grade (≤ II or ≥ III). MR severity was mild in 106, moderate in 285, and severe in 387 patients. LA volume index, LV end-diastolic diameter, and LV mass index increased with increasing MR grade [LA volume index: 47.9 (mild), 56.2 (moderate), and 64.9 ml/m2 (severe) (p < 0.001), LV end-diastolic diameter: 51.2, 54.5, 58.1 mm (p < 0.001), and LV mass index: 101, 109, 123 g/m2 (p < 0.001)]. Regarding moderate and severe MR, 70 patients (10.4%) were symptomatic. In multivariable analysis, for being symptomatic in moderate and severe MR patients, LV mass index (odds ratio [OR] per 10 g/m2 increment; 1.09; 95% confidence interval [CI]: 1.005-1.18, p = 0.040), ejection fraction (OR per 1% increment; 0.96, 95%CI: 0.93-0.98, p < 0.001), female gender (OR 2.28; 95% CI: 1.31-3.98, p = 0.004), and heart rate (OR per 1 bpm increment; 1.03; 95%CI: 1.01-1.05, p = 0.007) were independent factors. LV and LA parameters on echocardiography worsened as MR severity progressed. Larger LV mass index and lower ejection fraction were independent determinant factors for MR-related symptoms. We should also pay attention to LV hypertrophy in patients with primary MR.

Comparison of global and regional myocardial strains in patients with heart failure with a preserved ejection fraction vs hypertension vs age-matched control.

BACKGROUND: With an increasing clinical importance of the treatment of the heart failure (HF) with preserved ejection fraction (HFpEF), it is important to be certain of the diagnosis of HF. We investigated global and regional left ventricular (LV) strains using speckle tracking echocardiography (STE) in patients with HFpEF and compared those parameters with that of patients with hypertension and normal subjects. METHODS: Peak longitudinal, circumferential and radial strains were assessed globally and regionally for each study groups using STE. Diastolic strain rate was also determined. RESULTS: There were 50 patients in HFpEF group, 56 patients in hypertension group and 46 age-matched normal subjects. In patients with HFpEF, global peak longitudinal, circumferential and radial strain and strain rate were reduced compared to both hypertension patients and normal controls (- 15.5 ± 5.3 vs - 17.7 ± 3.1 and - 19.9 ± 2.0; - 9.7 ± 2.2 vs - 19.3 ± 3.1 and - 20.5 ± 3.3; 17.7 ± 8.2 vs 38.4 ± 12.4 and 43.6 ± 11.9, respectively, P <  0.001, for all). The diagnostic performance of global circumferential strain to predict the HFpEF was greatest among strain parameters (area under the curve = 0.997). CONCLUSIONS: In the speckle tracking echocardiography, impaired peak global strain and homogeneously reduced regional strain was observed in HFpEF patients compared to the hypertension patients and normal subjects in decreasing order. This can provide early information on the initiation of LV deformation of HFpEF in patients with hypertension or normal subjects.

Clinical implications of exercise-induced regional wall motion abnormalities in significant aortic regurgitation.

BACKGROUND: Significant aortic regurgitation (AR) is sometimes accompanied by regional wall motion abnormalities (RWMA) during exercise stress echocardiography. The aim of this study was to estimate the association between RWMA after exercise and in the presence of significant AR in patients with coronary artery disease (CAD) or volume overload and to predict the eventual need for aortic valve replacement (AVR). METHODS AND RESULTS: We retrospectively reviewed 182 patients with significant AR who underwent exercise echocardiography. In addition, we investigated patients with AR who underwent coronary angiography (CAG) or coronary computed tomography angiography (CCTA) and were diagnosed with CAD. The presence of RWMA after exercise was defined as newly developed RWMA after exercise and included all changes in wall motion. Patients were divided into two groups according to the presence of RWMA after exercise: the RWMA group (n = 42) and non-RWMA group (n = 140). In the RWMA group, 31 patients (73.8%) underwent coronary artery evaluation by CAG or CCTA. Only two patients in the RWMA group were diagnosed with current CAD and underwent percutaneous coronary intervention. Patients with RWMA were older (61.6 ± 10.8 vs 52.0 ± 13.7 years, P < .001), had more severe AR (54.8% vs 32.9%), and underwent AVR more frequently (40.5% vs 14.3%, P = .001) than patients without RWMA. METs (odds ratio [OR], 0.796; P = .019), difference between rest and postexercise left ventricular end-diastolic volume (OR, 0.967; P = .001), and the difference between pre- and postexercise left ventricular end-systolic volume (OR, 1.113; P < .001) were identified as independent factors associated with RWMA after exercise according to multivariable logistic regression analysis. The majority of wall motion changes were seen in the lateral and inferior segments, and the locations of wall motion changes were relatively consistent with the direction of the AR jet. The relationship between RWMA after exercise and time to AVR was investigated by simple linear regression (hazard ratio [HR], 3.402; P < .001). After adjusting for baseline parameters of diastolic blood pressure, left ventricular end-systolic dimension (LVESD), aorta size, deceleration time, and METs, the presence of RWMA after exercise was not predictive of time to AVR (HR, 1.106; P = .81). On the other hand, without forcible entry of RWMA after exercise, LVESD (HR, 1.119; P < .001) and METs (HR, 0.828; P = .006) independently predicted the eventual need for AVR as an outcome. CONCLUSION: The degree of change in wall motion from rest to exercise in those with significant AR was not correlated with CAD, but was correlated with the severity of volume overload and exercise-induced preload changes, as well as the direction of the AR jet. In addition, RWMA after exercise had no role in predicting the need for AVR.

Prognostic Implications of Diastolic Dysfunction Change in Patients With Coronary Artery Disease Undergoing Percutaneous Coronary Intervention.

BACKGROUND: The association between a change in diastolic function (DF) and long-term clinical outcomes in patients undergoing percutaneous coronary intervention (PCI) is unknown. The aim of this study was to investigate the prognostic effect of changes in diastolic dysfunction in patients undergoing PCI.Methods and Results:Consecutive patients who underwent PCI and echocardiography before and after revascularization were prospectively included. Major adverse cardiac event (MACE) was defined as a composite of cardiac death, myocardial infarction, and repeat revascularization. A total of 1,235 patients were identified. Baseline diastolic dysfunction was present in 1,033 patients (83.6%). At follow-up echocardiography, DF had worsened in 219 (17.8%) patients and was unchanged in 623 patients (50.4%). The risk of MACE was significantly higher in the worsened DF group compared with the unchanged DF group (adjusted hazard ratio [aHR]: 2.15; 95% confidence interval [CI]: 1.59 to 2.90; P<0.001) and the improved or normal DF group (aHR: 2.20; 95% CI, 1.49 to 3.27; P<0.001). Patients with worsened DF consistently had a higher risk of MACE in various subgroups, especially irrespective of left ventricular systolic function. CONCLUSIONS: Aggravation of DF was independently associated with an increased risk of MACE in patients undergoing PCI. Evaluating changes in DF after PCI is a simple but useful method for predicting long-term clinical outcomes.

Assessment of reverse remodeling predicted by myocardial deformation on tissue tracking in patients with severe aortic stenosis: a cardiovascular magnetic resonance imaging study.

BACKGROUND: The technique of tissue tracking with balanced steady-state free precession cine sequences was introduced, and allowed myocardial strain to be derived directly, offering advantages over traditional myocardial tagging. The aim of this study was to evaluate the correlation between reverse remodeling as an outcome and left ventricular strain using cardiovascular magnetic resonance imaging (CMR) tissue tracking, and to evaluate prediction of reverse remodeling by myocardial deformation in patients with severe aortic stenosis (AS). METHODS: We enrolled 63 patients with severe AS and normal left ventricular (LV) systolic function (ejection fraction > 60%), who underwent both CMR and transthoracic echocardiography (Echo) before surgical aortic valve replacement (AVR). CMR at 1.5 T, including non and post-contrast T1 mapping for extracellular volume (ECV), was carried out to define the amount of myocardial fibrosis. Cardiac Performance Analysis software was used to derive myocardial deformation as strain parameters from three short-axis cine views (basal, mid and apical levels) and apical 2, 3, and 4 chamber views. The primary outcome was reverse remodeling, as evaluated by regression of left ventricular mass index (LVMI). RESULTS: Median follow-up was 28.8 months (interquartile range 11.3-38.3 months). As evaluated by LVMI between baseline and follow-up, mass regression was significantly improved after AVR (baseline 145.9 ± 37.0 [g/m2] vs. follow-up 97.7 ± 22.2[g/m2], p < 0.001). Statistically significant Pearson's correlations with LVMI regression were observed for longitudinal global strain (r = -0.461, p < 0.001), radial strain (r = 0.391, p = 0.002), and circumferential strain (r = -0.334, p = 0.009). A simple linear regression analysis showed that all strain parameters could predict the amount of LVMI regression (P < 0.05), as well as non-contrast T1 value (beta = -0.314, p < 0.001) and ECV (beta = -2.546, p = 0.038). However, ECV had the lowest predictive power (multiple r2 = 0.071). Multiple regression analysis showed strain could independently predict the amount of LVMI regression and the longitudinal global strain (beta = -3.335, p < 0.001). CONCLUSION: Longitudinal global strain measured by CMR tissue tracking as a technique was correlated with reverse remodeling as LVMI regression and was predictive of this outcome. As a simple and practical method, tissue tracking is promising to assess strain and predict reverse remodeling in severe AS, especially in patients with suboptimal Echo image quality.

Independent and incremental prognostic value of exercise stress echocardiography in low cardiovascular risk female patients with chest pain.

BACKGROUND: Exercise stress echocardiography (ESEcho) is sufficiently sensitive and has high enough specificity for the clinical detection of coronary artery disease (CAD) in women. However, there was little data about the ability of ESEcho to detect CAD and predict clinical outcomes in female patients with chest pain and low global cardiovascular (CV) risks. The purposes of this study were (1) to determine the diagnostic accuracy of ESEcho, (2) to evaluate the clinical outcomes of major cardiovascular outcome (MACE), and (3) to assess the incremental prognostic value of ESEcho for the prediction of MACE in Korean female patients with low CV risks. METHODS: Over a period of 15 years, 3396 patients (57±10 years) female patients with chest pain but no previous history of CAD undergoing ESEcho and exercise stress electrocardiography (ESECG) were assessed. RESULTS: During a median follow-up period of 4.8 years (2.8-6.2 years), there were 19 (0.61%) MACE. Positive results for ESEcho were seen in 134 patients (3.9%). The sensitivity and specificity of ESEcho were 66.7% and 84.8%, respectively. Positive ESEcho was an independent predictor of MACE (multivariate hazard ratio: 0.019, 95% CI: 0.004-0.081). ESEcho was incremental to clinical and ESECG parameters to predict the MACE in low CV risk women. CONCLUSIONS: ESEcho is effective for the diagnosis of CAD in Korean female patients with chest pain, a population characterized by low cardiovascular risk profiles. Positive ESEcho was an independent predictor of MACE, and negative results were associated with favorable clinical outcomes. ESEcho was incremental to clinical and ESECG parameters to predict the MACE in low CV risk women.

Effects of increased left ventricular wall thickness on the myocardium in severe aortic stenosis with normal left ventricular ejection fraction: Two- and three-dimensional multilayer speckle tracking echocardiography.

BACKGROUND: The aim of this study was to determine the capability of real time three-dimensional echocardiography (RT3DE) and two-dimensional (2D) multilayer speckle tracking echocardiography (MSTE) for evaluation of early myocardial dysfunction triggered by increased left ventricular (LV) wall thickness in severe aortic stenosis (AS) with normal LV ejection fraction (EF≥55%). METHODS: Conventional, RT3D STE and 2D MSTE were performed in 45 patients (mean 68.9±9.0 years) with severe AS (aortic valve area <1 cm2 , aortic velocity Vmax >4 m/s or mean PG >40 mm Hg) and normal left ventricular ejection fraction (LVEF) without overt coronary artery disease and in 18 age-, sex-matched healthy controls. Global longitudinal strain (GLS), global circumferential strain (GCS), global area strain (GAS), and global radial strain (GRS) were calculated using RT3DE and MSTE. RESULTS: The severe AS group had lower 3D GLS, GRS, GAS and 2D epicardium, and mid-wall and endocardium GLS compared to healthy controls. In MSTE analysis, 2D LS and CS values decreased from the endocardial layer toward the epicardial layer. Severe AS patients with increased LV wall thickness had lower 3D GLS and 2D epicardium, and mid-wall and endocardium GLS compared with severe AS patients without LV wall thickening. GLS on RT3D STE was correlated with GLS on 2D MSTE, left ventricular mass index, LVEF, left atrial volume index, and lnNT-proBNP. CONCLUSION: RT3DE and 2D MSTE can be used to identify subtle contractile dysfunction triggered by increased LV wall thickness in severe AS with normal LVEF. Therefore, RT3D STE and 2D MSTE may provide additional information that can facilitate decision-making regarding severe AS patients with increased LV wall thickness and normal LV function.

A protective role of early collateral blood flow in patients with ST-segment elevation myocardial infarction.

UNLABELLED: Conflict persists regarding whether the presence of early collateral blood flow to the infarct-related artery has an effective role in reducing infarct size and improving myocardial salvage in patients with ST-segment elevation myocardial infarction (STEMI). We sought to investigate the impact of the collateral circulation on myocardial salvage and infarct size in STEMI patients. METHODS: In 306 patients who were diagnosed with STEMI and underwent cardiac magnetic resonance within 1 week after revascularization, initial collateral flow to the infarct-related artery was assessed by coronary angiography. Using cardiac magnetic resonance imaging, myocardial infarct size and salvage were measured. RESULTS: Among 247 patients with preprocedural Thrombolysis in Myocardial Infarction flow 0/1, 54 (22%) patients had good collaterals (Rentrop grade ≥ 2, Collateral Connection Score ≥ 2). Infarct size and area at risk were significantly smaller in patients with good collaterals than those with poor collaterals (infarct size: 17.1 ± 10.1 %LV vs 21.8 ± 10.5 %LV, P = .003, area at risk: 33.8 ± 16.8 %LV vs 38.8 ± 15.5 %LV, P = .039). There was a significant difference of myocardial salvage index between 2 groups (50.9% ± 15.0% vs 43.8% ± 18.5%, P = .005). Poor collateralization was an independent predictor for large infarct size (odd ratio 2.48 [1.28-4.80], P = .007). CONCLUSIONS: In patients with STEMI, the presence of well-developed collaterals to occluded coronary artery from the noninfarct vessel and its extent were independently associated with reduced infarct burden and improved myocardial salvage. Our results help explain why MI patients with well-developed collateralization have reduced mortality and morbidity.

Identification of Factors that Predict whether the Right Parasternal View Is Required for Accurate Evaluation of Aortic Stenosis Severity.

BACKGROUND: To accurately assess aortic stenosis (AS) severity, multiple windows should be used to best align the Doppler beam with the flow direction of the stenotic jet. To evaluate: (1) the frequency at which the highest peak AV velocity is found in the right parasternal window (RPW), (2) the extent of correlation between aortic root angulation and the location of the highest peak AV jet velocity, and (3) which patients would benefit most from RPW-based assessment of AS severity. METHODS: We evaluated AS velocity in the apical window (AW) and RPW by continuous-wave Doppler (CWD) in 263 patients with more than moderate AS. If the AV was inaccessible by the left parasternal long-axis view, the aortoseptal angle was measured by echocardiography and a sagittal view of a computed tomography (CT). RESULTS: Patients were divided into two groups, the RPW group and the AW group. Significant differences were observed between the two groups regarding the sinus of Valsalva diameter, the aortoseptal angle as measured by echocardiography, and the type of valve. The aortoseptal angle as measured by echocardiography was larger in the AW group compared with the RPW group. Aortoseptal angle (P < 0.001) and valve type (P = 0.036) were independent predictors that the highest AV Vmax would be obtained from the RPW. CONCLUSIONS: The right parasternal window must be evaluated to achieve the most accurate assessment of AS severity, especially in patients with an aortoseptal angle <119° in the parasternal long-axis view as measured by echocardiography.

Aggravating factors associated with the severity of aortic regurgitation and clinical characteristics of patients with quadricuspid aortic valve.

BACKGROUND AND AIM OF THE STUDY: Quadricuspid aortic valve (QAV) is a rare congenital anomaly. Aortic regurgitation (AR) has been suggested to be the major functional abnormality of QAV. The study aim was to define the clinical characteristics of patients with QAV through echocardiography, thereby identifying factors related to the severity of AR. METHODS: Patients diagnosed with QAV by echocardiography were enrolled from electronic medical records obtained between November 1994 and May 2012. RESULTS: Twenty-six patients diagnosed with QAV were identified. AR was present in 20 of these patients (77%), among which 12 (46%) exhibited significant AR. Aortic stenosis was rare (n = 1; 4%). Patient age and severity of AR were weakly correlated. The most frequent valve morphology type was three equally sized cusps and one smaller cusp (n = 12; 46%), followed by two larger, equally sized cusps and two smaller, equally sized cusps (n = 6; 23%). The latter morphology type was accompanied by a high prevalence of significant AR (5/6; 83%). The initial clinical symptoms of the patients included dyspnea and chest pain (n = 14; 54%), other congenital abnormalities (n = 4; 15%), and arrhythmias (n = 4; 15%). Among the patients with significant AR, 10 were symptomatic. CONCLUSION: Approximately half of the patients with QAV had significant AR at the time of initial diagnosis by echocardiography. The severity of AR appeared to be correlated with patient age and valve morphology. These factors should be considered during echocardiographic assessment and follow up treatment for QAV.