Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial.

BACKGROUND: Three different glucagon-like peptide-1 (GLP-1) receptor agonists reduce cardiovascular outcomes in people with type 2 diabetes at high cardiovascular risk with high glycated haemoglobin A1c (HbA1c) concentrations. We assessed the effect of the GLP-1 receptor agonist dulaglutide on major adverse cardiovascular events when added to the existing antihyperglycaemic regimens of individuals with type 2 diabetes with and without previous cardiovascular disease and a wide range of glycaemic control. METHODS: This multicentre, randomised, double-blind, placebo-controlled trial was done at 371 sites in 24 countries. Men and women aged at least 50 years with type 2 diabetes who had either a previous cardiovascular event or cardiovascular risk factors were randomly assigned (1:1) to either weekly subcutaneous injection of dulaglutide (1·5 mg) or placebo. Randomisation was done by a computer-generated random code with stratification by site. All investigators and participants were masked to treatment assignment. Participants were followed up at least every 6 months for incident cardiovascular and other serious clinical outcomes. The primary outcome was the first occurrence of the composite endpoint of non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes (including unknown causes), which was assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01394952. FINDINGS: Between Aug 18, 2011, and Aug 14, 2013, 9901 participants (mean age 66·2 years [SD 6·5], median HbA1c 7·2% [IQR 6·6-8·1], 4589 [46·3%] women) were enrolled and randomly assigned to receive dulaglutide (n=4949) or placebo (n=4952). During a median follow-up of 5·4 years (IQR 5·1-5·9), the primary composite outcome occurred in 594 (12·0%) participants at an incidence rate of 2·4 per 100 person-years in the dulaglutide group and in 663 (13·4%) participants at an incidence rate of 2·7 per 100 person-years in the placebo group (hazard ratio [HR] 0·88, 95% CI 0·79-0·99; p=0·026). All-cause mortality did not differ between groups (536 [10·8%] in the dulaglutide group vs 592 [12·0%] in the placebo group; HR 0·90, 95% CI 0·80-1·01; p=0·067). 2347 (47·4%) participants assigned to dulaglutide reported a gastrointestinal adverse event during follow-up compared with 1687 (34·1%) participants assigned to placebo (p<0·0001). INTERPRETATION: Dulaglutide could be considered for the management of glycaemic control in middle-aged and older people with type 2 diabetes with either previous cardiovascular disease or cardiovascular risk factors. FUNDING: Eli Lilly and Company.

Dulaglutide and renal outcomes in type 2 diabetes: an exploratory analysis of the REWIND randomised, placebo-controlled trial.

BACKGROUND: Two glucagon-like peptide-1 (GLP-1) receptor agonists reduced renal outcomes in people with type 2 diabetes at risk for cardiovascular disease. We assessed the long-term effect of the GLP-1 receptor agonist dulaglutide on renal outcomes in an exploratory analysis of the REWIND trial of the effect of dulaglutide on cardiovascular disease. METHODS: REWIND was a multicentre, randomised, double-blind, placebo-controlled trial at 371 sites in 24 countries. Men and women aged at least 50 years with type 2 diabetes who had either a previous cardiovascular event or cardiovascular risk factors were randomly assigned (1:1) to either weekly subcutaneous injection of dulaglutide (1·5 mg) or placebo and followed up at least every 6 months for outcomes. Urinary albumin-to-creatinine ratios (UACRs) and estimated glomerular filtration rates (eGFRs) were estimated from urine and serum values measured in local laboratories every 12 months. The primary outcome (first occurrence of the composite endpoint of non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes), secondary outcomes (including a composite microvascular outcome), and safety outcomes of this trial have been reported elsewhere. In this exploratory analysis, we investigate the renal component of the composite microvascular outcome, defined as the first occurrence of new macroalbuminuria (UACR >33·9 mg/mmol), a sustained decline in eGFR of 30% or more from baseline, or chronic renal replacement therapy. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01394952. FINDINGS: Between Aug 18, 2011, and Aug 14, 2013, 9901 participants were enrolled and randomly assigned to receive dulaglutide (n=4949) or placebo (n=4952). At baseline, 791 (7·9%) had macroalbuminuria and mean eGFR was 76·9 mL/min per 1·73 m2 (SD 22·7). During a median follow-up of 5·4 years (IQR 5·1-5·9) comprising 51 820 person-years, the renal outcome developed in 848 (17·1%) participants at an incidence rate of 3·5 per 100 person-years in the dulaglutide group and in 970 (19·6%) participants at an incidence rate of 4·1 per 100 person-years in the placebo group (hazard ratio [HR] 0·85, 95% CI 0·77-0·93; p=0·0004). The clearest effect was for new macroalbuminuria (HR 0·77, 95% CI 0·68-0·87; p<0·0001), with HRs of 0·89 (0·78-1·01; p=0·066) for sustained decline in eGFR of 30% or more and 0·75 (0·39-1·44; p=0·39) for chronic renal replacement therapy. INTERPRETATION: Long-term use of dulaglutide was associated with reduced composite renal outcomes in people with type 2 diabetes. FUNDING: Eli Lilly and Company.

Benefit of Four-Dimensional Computed Tomography Derived Ejection Fraction of the Left Atrial Appendage to Predict Thromboembolic Risk in the Patients with Valvular Heart Disease.

BACKGROUND AND OBJECTIVES: Decreased left atrial appendage (LAA) emptying velocity in transesophageal echocardiography (TEE) is related with higher incidence of thrombus and increased risk of stroke. Patients with valve disease are at higher risk of thrombus formation before and after surgery. The aim of this study was to investigate the role of 4-dimensional cardiac computed tomography (4DCT) to predict the risk of thrombus formation. METHODS: Between March 2010 to March 2015, total of 62 patients (mean 60±15 years old, male: 53.2%) who underwent 4DCT and TEE for cardiac valve evaluation before surgery were retrospectively included in the current study. Fractional area change in TEE view and emptying velocity at left atrial appendage in TEE view (VeTEE) were measured. Ejection fraction (EF) of left atrial appendage in computed tomography (EFCT) was calculated by 4DCT with full volume analysis. The best cut-off value of EFCT predicting presence of spontaneous echo contrast (SEC) or thrombus was evaluated, and correlation between the parameters were also estimated. RESULTS: SEC or thrombus was observed in 45.2%. EFCT and VeTEE were significantly correlated (r=0.452, p<0.001). However, fractional area change measured by TEE showed no correlation with VeTEE (r=0.085, p=0.512). EFCT <37.5% best predicted SEC or thrombus in the patients with valve disease who underwent 4DCT and TEE (area under the curve, 0.654; p=0.038). CONCLUSIONS: In the patients who underwent 4DCT for cardiac valve evaluation before surgery, EFCT by volume analysis might have additional role to evaluate LAA function and estimate the risk of thrombus.

Adverse effects of left ventricular electrical dyssynchrony on cardiac reverse remodeling and prognosis after aortic valve surgery.

BACKGROUND: Electrical dyssynchrony (ED) is one of the important contributing mechanisms in the progression of heart failure. We hypothesized that ED would interfere with cardiac reverse remodeling and affect prognosis after aortic valve surgery. METHODS: A total of 411 consecutive patients (233 males, mean age 65±11 years) who underwent aortic valve surgery were retrospectively analyzed. The patients were divided into two groups according to the presence of ED [Group 1: no ED (n=382, 93%), Group 2: ED (n=29, 7%)]. ED was defined as either left ventricular bundle branch block, or electrical pacing rhythm. Cardiac reverse remodeling was assessed at 1 year after surgery by the changes in left ventricular ejection fraction (LVEF), LV end-systolic volume (LVESV), and left atrial volume index (LAVI). The primary endpoint was a composite of hospitalization for heart failure, and all-cause mortality. RESULTS: At 1 year after surgery, group 2 showed lower LVEF (58±15% vs. 64±9%, p=0.044), and higher LAVI (42±18ml/m2 vs. 33±13ml/m2, p=0.018) than group 1. However, LVESV values (55±38ml vs. 42±24ml, p=0.076) were not significantly different. In particular, in patients with reduced preoperative LVEF, the LVEF was markedly increased in group 1 but not in group 2 after 1 year. During a median follow-up of 39 months, group 2 showed a worse clinical outcome than group 1 (20.7% vs. 7.6%, p=0.031). After adjusting for confounding factors in the multivariate analyses, age [hazard ratio (HR) 1.11, 95% confidence interval (CI) 1.06-1.16, p<0.001] and the presence of ED (HR 2.43, 95% CI 1.01-5.89, p=0.046) were found to be independent predictors of clinical outcomes. CONCLUSIONS: ED after aortic valve surgery negatively affected cardiac remodeling and prognosis.

Post-operative left atrial volume index is a predictor of the occurrence of permanent atrial fibrillation after mitral valve surgery in patients who undergo mitral valve surgery.

BACKGROUND: Atrial fibrillation (AF) can occur even after the correction of mitral valve (MV) pathology in patients who have pre-operative sinus rhythm and undergo MV surgery. However, the factors associated with the occurrence of AF after MV surgery are still unclear. The aim of this retrospective study was to investigate the factors determining the occurrence of permanent AF after MV surgery in patients with preoperative sinus rhythm who underwent MV surgery. METHODS: Four hundred and forty-two patients (mean age 46 ± 12, 190 men) who underwent MV surgery and sinus rhythm were investigated retrospectively. Transthoracic echocardiography was performed before and after MV surgery at the time of dismissal. RESULTS: Permanent post-operative AF occurred in 81 (18%) patients even after successful MV surgery and preoperative sinus rhythm. It was more common in rheumatic etiology, a presence of mitral stenosis, lower pre- and post-operative left ventricular ejection fraction, higher post-operative mean diastolic pressure gradient across mitral prosthesis, larger post-operative left atrial volume index (LAVI) and lesser degrees of reduction in LAVI after surgery. In multiple regression analysis, post-operative LAVI was found to be an independent predictor for occurrence of AF. Post-operative LAVI > 39 ml/m2 was the cut-off value for best prediction of new onset permanent AF (sensitivity: 79%, AUC: 0.762, SE: 0.051, p < 0.001). CONCLUSION: New-onset permanent post-operative AF is not uncommon, even after successful MV surgery despite pre-operative sinus rhythm. Larger post-operative LAVI was an independent predictor for the occurrence of AF.

Incremental predictive value of carotid arterial strain in patients with stroke.

Although increased carotid intima-media thickness (IMT) is a well-known risk factor for stroke, carotid IMT alone is not sufficient for risk stratification. The assessment of arterial properties using velocity vector imaging (VVI) represents a new method for quantifying structural changes. We sought to investigate the characteristics and the clinical value of carotid arterial mechanics using VVI in patients with stroke. Fifty male patients (55 ± 5 years) with stroke, 30 healthy age-matched volunteers (54 ± 8 years), and 30 healthy young male volunteers (29 ± 5 years) were evaluated. The peak circumferential strain, strain rate, and the standard deviation of the time to peak strain and strain rate, representing the synchronicity of the arterial expansion, were analyzed using VVI of the left common carotid artery. The circumferential strain and strain rate significantly decreased with age, and patients with stroke showed the lowest degree of strain and strain rate compared with healthy age-matched volunteers. In addition, patients with stroke showed decreased strain and strain rate even in participants with a normal carotid IMT (< 0.8 mm). Although carotid IMT did not improve the incremental predictive value of stroke over that of multiple clinical risk factors (diabetes mellitus, hypertension, coronary artery disease, smoking), adding carotid arterial strain and strain rate provided an incremental predictive value over both multiple risk factors and carotid IMT for stroke. Along with assessment of conventional risk factors, VVI analysis could provide improved risk stratification for stroke.

Design and baseline characteristics of participants in the Researching cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) trial on the cardiovascular effects of dulaglutide.

The aim was to determine the effects of dulaglutide, a synthetic once-weekly, injectable human glucagon-like peptide 1 analogue that lowers blood glucose, body weight, appetite and blood pressure, on cardiovascular outcomes. People with type 2 diabetes, aged ≥50 years, with glycated haemoglobin (HbA1c) ≤9.5%, and either a previous cardiovascular event, evidence of cardiovascular disease or ≥2 cardiovascular risk factors were randomly allocated to a weekly subcutaneous injection of either dulaglutide (1.5 mg) or placebo and followed within the ongoing Researching cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) trial every 3 to 6 months. The primary cardiovascular outcome is the first occurrence of the composite of cardiovascular death or non-fatal myocardial infarction or non-fatal stroke. Secondary outcomes include each component of the primary composite cardiovascular outcome, a composite clinical microvascular outcome comprising retinal or renal disease, hospitalization for unstable angina, heart failure requiring hospitalization or an urgent heart failure visit, and all-cause mortality. Follow-up will continue until the accrual of 1200 confirmed primary outcomes. Recruitment of 9901 participants (mean age 66 years, 46% women) occurred in 370 sites located in 24 countries over a period of 2 years. The mean duration of diabetes was 10 years, mean baseline HbA1c was 7.3%, and 31% had prior cardiovascular disease. The REWIND trial's international scope, high proportion of women, high proportion of people without prior cardiovascular disease and inclusion of participants whose mean baseline HbA1c was 7.3% suggests that its cardiovascular and safety findings will be directly relevant to the typical middle-aged patient seen in general practice throughout the world.

Associations of changes in body mass index with all-cause and cardiovascular mortality in healthy middle-aged adults.

BACKGROUND: Conflicting data exist regarding the association of body mass index (BMI) changes with all-cause and cardiovascular (CV) mortality. The current study investigated the association between changes in BMI and all-cause, CV, and non-CV mortality in a large cohort of middle-aged adults. METHODS: A total of 379,535 adults over 40 years of age without pre-existing CV disease or cancer at baseline were enrolled to undergo a series of at least three health examinations of biennial intervals. Changes in BMI between baseline, midpoint follow-up, and final health examination during mean 9.3 years were defined according to the pattern of BMI change as follows: stable, sustained gain, sustained loss, and fluctuation. The relationship between BMI change category and mortality was assessed by multivariate Cox regression reporting hazard ratio (HR) with 95% confidence interval (95% CI). RESULTS: During a mean follow-up of 10.7 years for mortality, 12,378 deaths occurred from all causes, of which 2,114 were CV and 10,264 were non-CV deaths. Sustained BMI gain was associated with the lower risk of all-cause (HR 0.89, 95% CI: 0.83-0.95), CV (HR 0.84, 95% CI 0.72-0.98), and non-CV mortality (HR 0.90, 95% CI 0.84-0.96) compared with stable BMI. Conversely, sustained BMI loss (HR 1.25, 95% CI 1.19-1.32) and fluctuation (HR 1.13, 95% CI 1.08-1.19) displayed a higher risk of all-cause mortality compared with stable BMI, which was mainly attributable to the increase in non-CV mortality. CONCLUSION: Sustained BMI gains were associated with reduced risk of all-cause, CV, and non-CV mortality in middle-aged healthy adults.

Incremental Value of Repeated Risk Factor Measurements for Cardiovascular Disease Prediction in Middle-Aged Korean Adults: Results From the NHIS-HEALS (National Health Insurance System-National Health Screening Cohort).

BACKGROUND: Increasing evidence suggests that repeatedly measured cardiovascular disease (CVD) risk factors may have an additive predictive value compared with single measured levels. Thus, we evaluated the incremental predictive value of incorporating periodic health screening data for CVD prediction in a large nationwide cohort with periodic health screening tests. METHODS AND RESULTS: A total of 467 708 persons aged 40 to 79 years and free from CVD were randomly divided into development (70%) and validation subcohorts (30%). We developed 3 different CVD prediction models: a single measure model using single time point screening data; a longitudinal average model using average risk factor values from periodic screening data; and a longitudinal summary model using average values and the variability of risk factors. The development subcohort included 327 396 persons who had 3.2 health screenings on average and 25 765 cases of CVD over 12 years. The C statistics (95% confidence interval [CI]) for the single measure, longitudinal average, and longitudinal summary models were 0.690 (95% CI, 0.682-0.698), 0.695 (95% CI, 0.687-0.703), and 0.752 (95% CI, 0.744-0.760) in men and 0.732 (95% CI, 0.722-0.742), 0.735 (95% CI, 0.725-0.745), and 0.790 (95% CI, 0.780-0.800) in women, respectively. The net reclassification index from the single measure model to the longitudinal average model was 1.78% in men and 1.33% in women, and the index from the longitudinal average model to the longitudinal summary model was 32.71% in men and 34.98% in women. CONCLUSIONS: Using averages of repeatedly measured risk factor values modestly improves CVD predictability compared with single measurement values. Incorporating the average and variability information of repeated measurements can lead to great improvements in disease prediction. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02931500.

Clinical Implications of Three-Dimensional Real-Time Color Doppler Transthoracic Echocardiography in Quantifying Mitral Regurgitation: A Comparison with Conventional Two-Dimensional Methods.

BACKGROUND: Automatic quantification of real-time three-dimensional (3D) full-volume color Doppler transthoracic echocardiography (FVCD) has been proposed as a feasible and accurate method for quantifying MR. We aimed to explore the clinical implications of real-time 3D-FVCD for mitral regurgitation (MR) with various clinical manifestations, in comparison with the conventional two-dimensional (2D) proximal isovelocity surface area (PISA) and volumetric method and cardiac magnetic resonance imaging (CMR) methods. METHODS: A total 186 patients with MR were enrolled prospectively. Based on exclusion criteria and image quality review, 152 patients were included in the final analysis for 3D-FVCD and 2D transthoracic echocardiography. Among them, 37 patients underwent subsequent CMR for the validation of 3D-FVCD. RESULTS: MR volume from 3D-FVCD demonstrated a better agreement (r = 0.94) with CMR than 2D-PISA or the 2D volumetric method (VM; r = 0.87 vs 0.56). Overall, 2D methods underestimated MR when compared with 3D-FVCD (35.4 ± 28.4 mL for 2D-VM vs 43.8 ± 24.6 mL for 2D-PISA vs 64.6 ± 35.1 mL for 3D-FVCD; P < .001). In subgroup analysis, multijet MR (odds ratio [OR], 6.30; 95% CI, 2.52-15.72) and dilated left ventricular end-systolic diameter ≥40 mm (OR, 2.90; 95% CI, 1.12-7.50) were predictors of significant difference in MR volume (>30 mL for primary MR and >15 mL for secondary MR) between 2D-PISA and 3D-FVCD. In identifying surgical candidates, patients with multijet MR (OR, 4.53, 95% CI, 1.99-10.35) demonstrated a higher risk of discrepancy between 2D-PISA and 3D-FVCD, which were consistent in both primary and secondary MR, respectively. CONCLUSIONS: MR quantification with 3D-FVCD showed better correlation and agreement than conventional 2D methods. MR was underestimated by 2D methods, especially in multijet and dilated left ventricle. Multijet MR demonstrated higher risk of discrepancy for the identification of surgical candidate, regardless of MR etiology.

Determinants and Prognostic Significance of Symptomatic Status in Patients with Moderately Dysfunctional Bicuspid Aortic Valves.

BACKGROUND: We aimed to identify the clinical and echocardiographic determinants of symptoms and their prognostic implications in patients with moderately dysfunctional bicuspid aortic valves (BAVs). METHODS: Among 1,019 subjects in the BAV registry treated in a single tertiary care center, the records of 127 patients (85 men, age 58±13 years) with moderately dysfunctional BAVs were comprehensively reviewed. The patients were divided into two groups based on symptom status: asymptomatic (n = 80) vs. symptomatic (n = 47). The primary end-point was defined as a composite of aortic valve surgery, hospitalization for heart failure, and any cause of death. RESULTS: The symptomatic group had a higher proportion of females, hypertension, aortic stenosis, and aortopathy than did the asymptomatic group. The symptomatic group showed lower e' (5.5±1.7 vs. 6.5±2.2 cm/s, p = 0.003), higher E/e' (13.3 ± 4.9 vs. 10.9±3.7, p = 0.002), and larger left atrial volume index (29.9±11.4 vs. 24.6±9.1 ml/m2, p = 0.006) than did the asymptomatic group. In multivariate logistic regression analysis, female gender (odds ratio [OR] 2.84, 95% confidence interval [CI] 1.10-7.36, p = 0.031), hypertension (OR 3.07, 95% CI 1.20-7.82, p = 0.019), moderate aortic stenosis (OR 5.33 5.78, 95% CI 1.99-16.83, p = 0.001), E/e' >15 (OR 3.82, 95% CI 1.03-11.19, p = 0.015), and aortopathy (OR 2.76, 95% CI 1.07-7.10, p = 0.035) were independently correlated with symptom status. The symptomatic group showed a significantly lower rate of event-free survival during the 8-year follow-up period (54±9% vs. 68±10%, p = 0.001). CONCLUSIONS: In patients with moderately dysfunctional BAVs, the presence of moderate aortic stenosis, aortopathy, and diastolic dysfunction determines symptom status, along with female gender and hypertension. Symptom status was associated with clinical outcomes.

Association of Thoracic Aorta Calcium Score With Left Ventricular Hypertrophy and Clinical Outcomes in Patients With Severe Aortic Stenosis After Aortic Valve Replacement.

BACKGROUND: Substantial aortic calcification is known to be associated with aortic stiffening and subsequent left ventricular (LV) hypertrophy. This study examined whether the thoracic aorta calcium score (TACS) is related to LV hypertrophy and whether it leads to an adverse prognosis in patients with severe aortic stenosis (AS) after aortic valve replacement (AVR). METHODS: We retrospectively reviewed 47 patients (mean age, 64 ± 11 years) with isolated severe AS who underwent noncontrast computed tomography of the entire thoracic aorta and who received AVR. TACS was quantified using the volume method with values becoming log transformed (log[TACS+1]). Transthoracic echocardiography was performed before and 1 year after the operation. RESULTS: Preoperative LV mass index (LVMI) displayed significant positive correlations with male gender (r = 0.430, p = 0.010) and log(TACS+1) (r = 0.556, p = 0.003). In multivariate linear regression analysis, only log(TACS+1) was independently associated with LVMI, even after adjusting for age, gender, transaortic mean pressure gradient, and coronary or valve calcium score. Independent determinants for postoperative LVMI included log(TACS+1) and preoperative LVMI after 1 year of follow-up echocardiography, adjusting for age, gender, indexed effective orifice area, and coronary or valve calcium score. During a median follow-up period of 54 months after AVR, there were 10 events (21%), which included 4 deaths from all-causes, 3 strokes, 2 inpatient admissions for heart failure, and 1 myocardial infarction. The event-free survival rate was significantly lower for patients with TACS of 2,257 mm3 or higher compared with those whose TACS was lower than 2,257 mm3 (log-rank p < 0.001). CONCLUSIONS: High TACS was associated with increased LVMI among patients with severe AS. Further, high TACS usefully predicted less regression of LVMI and poor clinical outcomes after AVR. TACS may serve as a useful proxy for predicting LV remodeling and adverse prognosis in patients with severe AS undergoing AVR.

Incidence, Predictors, and Clinical Outcomes of Postoperative Cardiac Tamponade in Patients Undergoing Heart Valve Surgery.

This study aimed to investigate the incidence, predictors, and clinical outcomes of cardiac tamponade after heart valve surgery. A total of 556 patients who underwent heart valve surgery in a single tertiary center between January 2010 and March 2012 were studied. All patients underwent transthoracic echocardiography (TTE) about 5 days after surgery and TTE was repeated regularly. Patients with suspected acute pericardial hemorrhage were excluded. Cardiac tamponade occurred in twenty-four (4.3%) patients and all underwent surgical or percutaneous pericardial drainage. The median time of pericardial drainage after surgery was 17 (interquartile range, IQR, 13-30) days. Infective endocarditis, mechanical valve replacement of aortic or mitral valve, and any amount of pericardial effusion (PE) on the first postoperative TTE were related to the occurrence of cardiac tamponade (all p<0.05). After multivariate adjustment, occurrence of cardiac tamponade was associated with any amount of PE on the first postoperative TTE (hazard ratio, HR, 14.00, p<0.001) and mechanical valve replacement (HR 2.69, p = 0.025). The mean hospital days in patients with cardiac tamponade was higher than those without (34.9 vs. 13.5, p = 0.031). After pericardial drainage, there was no echocardiographic recurrence of significant PE during a median of 34.8 (IQR 14.9-43.7) months after surgery. Cardiac tamponade after heart valve surgery is not uncommon. Patients with any amount of PE at the first postoperative TTE or mechanical valve replacement should receive higher attention with regard to the occurrence of cardiac tamponade. Although it prolongs hospital stay, cardiac tamponade exhibits a benign clinical course without recurrence after timely intervention.

Time course of left atrial reverse remodelling after mitral valve surgery and the impact of left ventricular global longitudinal strain in patients with chronic severe mitral regurgitation.

OBJECTIVES: We aimed to investigate the time course of left atrial (LA) reverse remodelling (LARR) after mitral valve (MV) surgery in patients with chronic severe mitral regurgitation (MR) and examine the impact of left ventricular (LV) mechanical function on LARR. METHODS: A total of 140 patients (73 males, age 54 ± 16 years) with chronic severe MR undergoing MV surgery were analysed. All patients underwent two-dimensional, Doppler and speckle-tracking echocardiography before and after surgery (1 week, 6 months and 12 months). RESULTS: There was a significant decrease in LA volume from 137.8 ± 85.5 to 89.7 ± 54.6 ml (-32.1 ± 16.7%, P < 0.001) at 1 week after surgery. LA volume further decreased to 77.4 ± 52.4 ml (-9.9 ± 13.4%, P < 0.001) at 6 months but increased to 79.7 ± 62.4 ml (3.6 ± 11.9%, P = 0.002) at 12 months after surgery. Patients with good LARR (a reduction of ≥25% in LA volume) showed lower LV global longitudinal strain (LV-GLS) than those with poor LARR (P = 0.032). In simple correlation, age (r = 0.19, P = 0.026), preoperative LA volume (r = -0.28, P = 0.001) and preoperative LV-GLS (r = 0.28, P = 0.001) showed significant correlations with the % change in LA volume, whereas no correlations were observed with preoperative LV ejection fraction, global circumferential and radial strain. In multivariate analyses, preoperative LV-GLS (ß = 0.24, P = 0.014) was an independent determinant for early LARR along with age and preoperative LA volume. CONCLUSIONS: The majority of LARR after MV surgery occurred during the early postoperative period. LV-GLS, age and LA volume at surgery determined the degree of early LARR after MV surgery in patients with chronic severe MR.

Effect of End-Stage Renal Disease on Rate of Progression of Aortic Stenosis.

This study aimed to investigate the progression of mild-to-moderate aortic stenosis (AS) in patients with end-stage renal disease (ESRD) and determine its metabolic and hemodynamic contributors and clinical outcomes. A total of 74 patients with ESRD (50 men, age 72 ± 11 years) with mild-to-moderate AS were compared with 79 age- and gender-matched controls with normal kidney function. Clinical, laboratory, and echocardiographic features and clinical outcomes including aortic valve (AV) intervention, hospitalization due to heart failure, and cardiovascular death were analyzed. Patients with ESRD were divided into 2 subgroups according to their rate of AV area changes (group 1 [n = 28], rapid progression; and group 2 [n = 46], slow progression). Progression in the degree of AS was noted in 38% of patients with ESRD and 18% of controls (p <0.01) during comparable echocardiographic follow-up durations (29 ± 15 vs 27 ± 24 months, respectively, p = 0.57). In ESRD, patients in group 1 were older (p <0.01) with higher baseline log parathyroid hormone (p <0.01) and larger stroke volume (p = 0.03) than those in group 2. During clinical follow-up (48 ± 23 months), patients in group 1 showed poorer clinical outcomes than those in group 2 and controls (log-rank p <0.01). Age, left atrial volume index ≥42 ml/m(2), and annual increases of peak pressure gradient across the AV (mm Hg/year) demonstrated additive predictive values for prognosis. AS in ESRD progresses in an accelerated manner along with higher metabolic and hemodynamic loads on AV compared with those with normal kidney function. Accelerated progression of mild-to-moderate AS in ESRD results in poor prognosis.

Fabry disease in patients with hypertrophic cardiomyopathy: a practical approach to diagnosis.

This study aimed to develop a new set of screening criteria that is easily applicable and highly sensitive for the detection of patients at high risk of Fabry disease (FD) among hypertrophic cardiomyopathy (HCM) patients. We prospectively studied 273 consecutive unrelated patients who were referred to HCM clinic for unknown left ventricular hypertrophy. Among the 273 patients, we selected 65 high-risk patients who fulfilled at least one of our newly proposed screening criteria. All 273 patients were assayed for plasma α-galactosidase A (α-GAL A) activity. The new screening criteria were: (1) atypical HCM, (2) history or presence of documented arrhythmia, (3) short PR interval defined as <120 ms on electrocardiogram, and (4) symptoms of autonomic dysfunction. From this screening study, three unrelated patients (4.6%; 2 females and 1 male) were newly diagnosed with FD using α-GAL A activity and mutation analysis of the GLA gene. Using the screening method based on the newly proposed criteria, the prevalence of FD in our HCM population was 4.6% if at least one criterion was met and 18.8% if ⩾3 criteria were met. Therefore, our proposed criteria are easily applicable and highly sensitive for classifying patients at high risk of FD from HCM patients.

Impact of D-Dimer for Prediction of Incident Occult Cancer in Patients with Unprovoked Venous Thromboembolism.

BACKGROUND: Unprovoked venous thromboembolism (VTE) is related to a higher incidence of occult cancer. D-dimer is clinically used for screening VTE, and has often been shown to be present in patients with malignancy. We explored the predictive value of D-dimer for detecting occult cancer in patients with unprovoked VTE. METHODS: We retrospectively examined data from 824 patients diagnosed with deep vein thrombosis or pulmonary thromboembolism. Of these, 169 (20.5%) patients diagnosed with unprovoked VTE were selected to participate in this study. D-dimer was categorized into three groups as: <2,000, 2,000-4,000, and >4,000 ng/ml. Cox regression analysis was employed to estimate the odds of occult cancer and metastatic state of cancer according to D-dimer categories. RESULTS: During a median 5.3 (interquartile range: 3.4-6.7) years of follow-up, 24 (14%) patients with unprovoked VTE were diagnosed with cancer. Of these patients, 16 (67%) were identified as having been diagnosed with metastatic cancer. Log transformed D-dimer levels were significantly higher in those with occult cancer as compared with patients without diagnosis of occult cancer (3.5±0.5 vs. 3.2±0.5, P-value = 0.009, respectively). D-dimer levels >4,000 ng/ml was independently associated with occult cancer (HR: 4.12, 95% CI: 1.54-11.04, P-value = 0.005) when compared with D-dimer levels <2,000 ng/ml, even after adjusting for age, gender, and type of VTE (e.g., deep vein thrombosis or pulmonary thromboembolism). D-dimer levels >4000 ng/ml were also associated with a higher likelihood of metastatic cancer (HR: 9.55, 95% CI: 2.46-37.17, P-value <0.001). CONCLUSION: Elevated D-dimer concentrations >4000 ng/ml are independently associated with the likelihood of occult cancer among patients with unprovoked VTE.

Differences in Characteristics, Left Atrial Reverse Remodeling, and Functional Outcomes after Mitral Valve Replacement in Patients with Low-Gradient Very Severe Mitral Stenosis.

BACKGROUND: The discrepancy between planimetered mitral valve area (MVA) and mean diastolic pressure gradient (MDPG) has not been studied extensively in patients with mitral stenosis. The purpose of the present study was to investigate differences in characteristics and outcomes after mitral valve replacement (MVR) between low- and high-MDPG groups in patients with very severe mitral stenosis (VSMS). The hypothesis was that the low-MDPG group would have different characteristics and would be associated with poor clinical outcomes after MVR. METHODS: In total, 140 patients who underwent isolated MVR because of pure VSMS (planimetered MVA ≤ 1.0 cm(2)) were retrospectively reviewed, and follow-up echocardiography was performed for ≥12 months after MVR. Patients were divided into two groups according to preoperative MDPG (low gradient [LG], <10 mm Hg; high gradient [HG], ≥10 mm Hg). Strain and strain rate analysis was performed using speckle-tracking echocardiography of the left ventricle before MVR in a subgroup of 56 patients. RESULTS: There were 82 patients (59%) in the LG group and 58 patients (41%) in the HG group. The LG group was older and demonstrated a higher prevalence of female gender, diabetes mellitus, and atrial fibrillation (P < .05 for all). When comparing the LG and HG groups, the left atrial volume index was larger (105.1 ± 51.9 vs 87.8 ± 42.9 mL/m(2), P < .001), and strain rate during isovolumic relaxation of the left ventricle was lower (0.17 ± 0.08 vs 0.29 ± 0.09 sec(-1), P < .001) in the LG group. After MVR, the percentage left atrial volume index reduction after MVR was significantly smaller in the LG group (-29.9 ± 15.1% vs -43.5 ± 16.4%, P < .001). Persistent symptoms after MVR were more common in the LG group compared with the HG group (P = .004), even though preoperative functional class was similar between the groups. CONCLUSIONS: Compared with those with HG VSMS, patients with LG VSMS were older, more often female, and more frequently had diabetes mellitus and atrial fibrillation. They also had greater impairment of isovolumic relaxation, less favorable left atrial reverse remodeling, and a greater risk for persistent symptoms after MVR. These data might suggest other concurrent mechanisms for left atrial enlargement and symptom development in LG VSMS, such as atrial fibrillation and diastolic dysfunction, as well as valvular stenosis.

Screening of Mechanical Complications of Dilated Pulmonary Artery Related to the Risk for Sudden Cardiac Death in Patients with Pulmonary Arterial Hypertension by Transthoracic Echocardiography.

BACKGROUND: In patients with pulmonary arterial hypertension (PAH), the mechanical complications of pulmonary artery (PA) enlargement are related to sudden cardiac death (SCD). The aim of this study was to investigate the prevalence of PA enlargement, the correlation of main PA (MPA) diameter with other echocardiographic parameters, and the role of transthoracic echocardiography in screening for such complications. METHODS: Among 298 patients who were followed for PAH, patients with PA enlargement (>40 mm) by transthoracic echocardiography were consecutively enrolled in a prospective manner. The presence of left main and airway compression, PA dissection, or PA thrombus was determined with cardiac computed tomography. RESULTS: Forty-six patients (15.4%; mean age, 49 ± 14 years; 32.6% men) with dilated MPAs were enrolled. Mechanical complications were present in 16 patients (34.8%). Those with complications had more dilated MPAs compared with patients without (mean PA diameter, 55.6 ± 12.2 vs 46.7 ± 4.3 mm; P = .012). Other echocardiographic parameters of the right heart, such as right ventricular systolic pressure, showed no differences (P > .05 for all). The area under the receiver operating characteristic curve for MPA diameter was 0.750 (95% CI, 0.577-0.923; P = .009), with the highest sensitivity and specificity values for the presence of complications being 85.7% and 58.6%, respectively, according to an MPA diameter of 46.5 mm. CONCLUSIONS: Mechanical complications related to sudden cardiac death in patients with PAH with dilated PAs are common. The overall performance of transthoracic echocardiography as a screening tool for predicting such complications appears reasonable. Given the burden of sudden cardiac death, measurement of PA diameter should be routinely included over the course of follow-up, especially in patients with PAH.

Differential Impact of Constrictive Physiology after Pericardiocentesis in Malignancy Patients with Pericardial Effusion.

BACKGROUND: Echocardiographic signs of constrictive physiology (CP) after pericardiocentesis are frequently observed in malignancy patients. The purpose of the current study was to explore whether features of CP after pericardiocentesis have prognostic impact in malignancy patients with pericardial effusion (PE). METHODS: We retrospectively reviewed 467 consecutive patients who underwent pericardiocentesis at our institution from January 2006 to May 2014. Among them, 205 patients with advanced malignancy who underwent comprehensive echocardiography after the procedure comprised the study population. Co-primary end points were all-cause mortality (ACM) and repeated drainage (RD) for PE. Patients were divided into four subgroups according to cytologic result for malignant cells and CP (positive cytology with negative CP, both positive, both negative, and negative cytology with positive CP). RESULTS: CP after pericardiocentesis was present in 106 patients (50%) at median 4 days after the procedure. During median follow-up of 208 days, ACM and RD occurred in 162 patients (79%) and 29 patients (14%), respectively. Cox regression analysis revealed that independent predictors for ACM were male gender and positive cytology (all, p < 0.05). For RD, predictors were positive cytology, the absence of cardiac tamponade, and negative CP after pericardiocentesis (all, p < 0.05). When the patients were divided into four subgroups, patients with negative cytology and positive CP demonstrated the most favorable survival (hazard ratio [HR]: 0.39, p = 0.005) and the lowest RD rates (HR: 0.07, p = 0.012). CONCLUSION: CP after pericardiocentesis is common, but does not always imply poor survival or the need for RD in patients with advanced malignancies. On the contrary, the presence of CP in patients with negative cytology conferred the most favorable survival and the lowest rate of RD. Comprehensive echocardiographic evaluation for CP after pericardiocentesis would be helpful for predicting prognosis in patients with advanced malignancies.