Andreea C. Popescu

Right ventricular functional recovery after acute myocardial infarction: relation with left ventricular function and interventricular septum motion. GISSI-3 echo substudy

Objective: To evaluate the pattern of right ventricular (RV) functional recovery and its relation with left ventricular (LV) function and interventricular septal (IVS) motion in low risk patients after acute myocardial infarction (AMI). Design and setting: Multicentre clinical trial carried out in 47 Italian coronary care units. Patients: 500 patients from the GISSI (Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico) -3 echo substudy, who underwent serial echocardiograms 24–48 hours after symptom onset and at discharge, six weeks, and six months after AMI. Results: Tricuspid annular plane systolic excursion (TAPSE) increased significantly during follow up (mean (SD) 1.79 (0.46) cm at 24–48 hours to 1.92 (0.46) cm at six months, p < 0.001) and the increase was already significant at discharge (1.88 (0.47) cm, p < 0.001). LV ejection fraction (LVEF) was the best correlate of TAPSE at 24–48 hours (r  =  0.15, p  =  0.001). TAPSE increased significantly in patients both with reduced (< 45%) and with preserved (⩾ 45%) LVEF, but the magnitude of increase was higher in patients with lower initial LVEF (p  =  0.001). Improvement in IVS wall motion score index (IVS-WMSI) was the only independent predictor of TAPSE changes during follow up (r  =  −0.12, p  =  0.007). Conclusions: In low risk patients after AMI, RV function recovered throughout six months of follow up and was already significant at discharge. TAPSE was significantly related to LVEF at 24–48 hours. The magnitude of RV functional recovery was higher in patients with lower initial LVEF. RV functional recovery is best related to IVS-WMSI improvement, suggesting that IVS motion has an important role in RV functional improvement in this setting.

MiR-486 and miR-92a Identified in Circulating HDL Discriminate between Stable and Vulnerable Coronary Artery Disease Patients

Small non-coding microRNAs (miRNAs) are implicated in gene regulation, including those involved in coronary artery disease (CAD). Our aim was to identify whether specific serum miRNAs present in the circulating lipoproteins (Lp) are associated with stable or vulnerable CAD patients. A cardiovascular disease-focused screening array was used to assess miRNAs distribution in sera collected from 95 CAD patients: 30 with stable angina (SA), 39 with unstable angina (UA), 26 at one month after myocardial infarction (MI) and 16 healthy control subjects. We found that miR-486, miR-92a and miR-122 presented the highest expression in CAD sera. These miRNA together with miR-125a, miR-146a and miR-33a were further individually analyzed by TaqMan assays. The results were consistent with PCR-array screening data that all of these miRNAs were significantly increased in CAD patients compared to controls. Using a binary logistic regression model, we established that miR-486 and miR-92a in association with some high-density lipoprotein (HDL) components can designate vulnerable CAD patients. Further, all classes of Lp were isolated from sera by density gradient ultracentrifugation. Analysis of the selected miRNAs in each Lp class showed that they were associated mainly with HDL, miR-486 and miR-92a having the highest levels. In UA and MI patients, miR-486 prevailed in HDL2, while miR-92a prevailed in HDL3, and their levels discriminate between stable and vulnerable CAD patients. We identified two circulating miRNAs that in association with some lipid metabolism biomarkers can be used as an additional tool to designate vulnerable CAD patients.

Left atrial remodelling early after mitral valve repair for degenerative mitral regurgitation

Objective: Left atrial (LA) size is an important predictor of outcome after mitral valve replacement in patients with symptomatic chronic mitral regurgitation (MR). Data on LA remodelling after mitral valve repair (MVr) for chronic non-ischaemic MR are scarce. The aim of this study was to assess changes in LA size early after MVr for chronic severe degenerative MR and to identify clinical and echocardiographic correlates of those changes. Methods: The study analysed 225 consecutive patients who underwent MVr and were echocardiographically evaluated in our hospital within 1 month before and 1–6 months after surgery. Patients with MR aetiology other than degenerative, associated aortic valve replacement, or congenital heart disease were excluded. The remaining 79 patients (aged 60 (SD 12) years, 55 men) with isolated chronic severe degenerative MR formed the study group. LA reverse remodelling was defined as a decrease in LA volume index (LAVi) ⩾15%. Results: LA dimensions significantly decreased after MVr (p<0.001). Mean LAVi reduction was 29% (SD 18%). LA reverse remodelling was observed in 63 patients (80%). Correlates of LAVi reduction were preoperative LAVi (p = 0.008), systolic and diastolic blood pressure (p = 0.032, p = 0.009), postoperative transmitral mean pressure gradient (p = 0.001) and residual MR (p = 0.043). LAVi reduction was lower in patients >45 years (p = 0.008) and in hypertensive patients (p = 0.031). Conclusion: LA reverse remodelling is common early after MVr for chronic severe degenerative MR. Preoperative LAVi, blood pressure, postoperative transmitral mean pressure gradient, residual MR and age >45 are related to LAVi reduction. The prognostic value of LA reduction in this setting needs further study.

Prognostic Role of Left Atrial Volume in Elderly Patients with Symptomatic Stable Chronic Heart Failure: Comparison with Left Ventricular Diastolic Dysfunction and B-Type Natriuretic Peptide

Background: Left atrial (LA) volume and B‐type natriuretic peptide (BNP) represent powerful outcome predictors in patients with heart failure (HF). Aim: To assess the comparative prognostic role of LA volume (indexed to body surface area, LAVi), left ventricular diastolic dysfunction (LVDD) and BNP levels on long‐term outcome in patients with symptomatic but stable chronic HF. Methods: We studied consecutively 46 patients with symptomatic stable chronic HF (73 ± 10 years, 30 men), in sinus rhythm, without significant valvular disease. Echocardiographic measurements included: LV mass, LV volumes and ejection fraction, and LAVi. LVDD was graded using a comprehensive Doppler algorithm. Blood taken before echocardiography was assayed for BNP levels. Primary end point was combined: all‐cause mortality and hospitalization for worsening HF. Results: During 20 ± 14 months of follow‐up 19 events occurred: 8 deaths, and 11 hospitalizations for HF. In univariate analyses LAVi, LVDD, BNP levels, LV ejection fraction, LV volumes, and LV mass were significant outcome predictors (P < 0.05). At multivariate regression LAVi was the only independent predictor of outcome (hazard ratio: 1.03 per 1 ml/m2 increase, 95% CI: 1.01–1.06, P = 0.02). Conclusion: Although directly related to LVDD and to BNP levels, only LAVi emerged as an independent outcome predictor in this cohort of elderly patients with symptomatic stable chronic HF.

Impact of associated significant aortic regurgitation on left ventricular remodeling and hemodynamic impairment in severe aortic valve stenosis.

Objectives: The left ventricular (LV) response to combined pressure and volume overload [aortic stenosis (AS) and aortic regurgitation (AR)] versus pressure overload (isolated AS) has not been systematically studied. We aimed to assess LV remodeling, functional and hemodynamic consequences in patients with mixed aortic valve disease versus patients with isolated AS. Methods: We enrolled 181 patients (67 ± 9 years, 109 men) with severe AS (aortic valve area indexed to body surface area <0.6 cm2/m2) who underwent preoperative cardiac catheterization and a complete echocardiogram. Pulmonary capillary wedge pressure (PCWP), LV end-diastolic pressure (LVEDP) and pulmonary artery pressure (PAP) were measured. Results: One hundred and ten patients (group A) had isolated severe AS (AR 0-1) and 71 patients (group B) had mixed aortic valve disease (severe AS plus AR 2-3). Patients in group B were younger and in a higher New York Heart Association class (p < 0.01). Severity of AS was similar in both groups. Patients in group B had a higher indexed LV mass, a lower LV ejection fraction, and higher PCWP, LVEDP and PAP (all p ≤ 0.01). Conclusions: Patients with severe AS and significant AR are more symptomatic than patients with isolated severe AS. The increased burden due to the combined lesion induces pronounced LV remodeling and more severe hemodynamic consequences.

Hyperglycemia Determines Increased Specific MicroRNAs Levels in Sera and HDL of Acute Coronary Syndrome Patients and Stimulates MicroRNAs Production in Human Macrophages.

We aimed to determine the levels of microRNAs (miRNAs) in sera and HDL of acute coronary syndrome (ACS) compared to stable angina (SA) patients with/without hyperglycemia, and evaluate comparatively the functional effect of these sera on the processing machinery proteins (Drosha, DGCR8, Dicer) and miRNAs production in human macrophages. MiRNAs levels in sera and HDL from 35 SA and 72 ACS patients and 30 healthy subjects were measured by using microRNA TaqMan assays. MiR-223, miR-92a, miR-486, miR-122, miR-125a and miR-146a levels were higher in the hyperglycemic ACS compared to normoglycemic sera. MiR-223 and miR-486 prevailed in HDL2, while miR-92a predominated in HDL3, all three miRNAs discriminating between ACS and SA patients; their levels were increased in HDL from hyperglycemic ACS patients versus normoglycemic ones. The incubation of human macrophages with sera from ACS and SA patients showed that all patients’ sera induced an increase of Drosha, DGCR8 and Dicer expressions and of selected miRNAs levels compared to control sera, the effect being higher in the case of hyperglycemic versus normoglycemic ACS sera. The addition of glucose to SA and ACS sera increased Drosha, DGCR8 and Dicer expression and miRNAs levels in the exposed macrophages. In conclusion, hyperglycemia is associated with increased miR-223, miR-92a, miR-486 levels in HDL, which discriminate between ACS and SA patients. Exposure of human macrophages to ACS compared to SA sera determines the upregulation of Drosha, DGCR8 and Dicer expression and the increase of selected miRNAs production, the effect being augmented by an increased glucose concentration.

Dysfunctional high-density lipoproteins have distinct composition, diminished anti-inflammatory potential and discriminate acute coronary syndrome from stable coronary artery disease patients

There is a stringent need to find means for risk stratification of coronary artery diseases (CAD) patients. We aimed at identifying alterations of plasma high-density lipoproteins (HDL) components and their validation as dysfunctional HDL that could discriminate between acute coronary syndrome (ACS) and stable angina (SA) patients. HDL2 and HDL3 were isolated from CAD patients’ plasma and healthy subjects. ApolipoproteinAI (apoAI), apoAII, apoCIII, malondialdehyde (MDA), myeloperoxidase (MPO), ceruloplasmin and paraoxonase1 (PON1) were assessed. The anti-inflammatory potential of HDL subfractions was tested by evaluating the secreted inflammatory molecules of tumor necrosis factor α-activated endothelial cells (EC) upon co-incubation with HDL2 or HDL3. We found in ACS versus SA patients: 40% increased MPO, MDA, apoCIII in HDL2 and HDL3, 35% augmented apoAII in HDL2, and in HDL3 increased ceruloplasmin, decreased apoAII (40%) and PON1 protein and activity (15% and 25%). Co-incubation of activated EC with HDL2 or HDL3 from CAD patients induced significantly increased levels of secreted inflammatory molecules, 15–20% more for ACS versus SA. In conclusion, the assessed panel of markers correlates with the reduced anti-inflammatory potential of HDL subfractions isolated from ACS and SA patients (mostly for HDL3 from ACS) and can discriminate between these two groups of CAD patients.

Management of Organic Mitral Regurgitation: Guideline Recommendations and Controversies

Mitral regurgitation (MR) represents the second most frequent valvular heart disease. The appropriate management of organic MR remains unclear in many aspects, especially in several specific clinical scenarios. This review aims to discuss the current guideline recommendations regarding the management of organic MR, while highlighting the controversial aspects encountered in daily clinical practice. The role of imaging is essential in establishing the most appropriate type of surgical treatment (repair or replace), which is based on morphological mitral valve (MV) characteristics (reparability of the valve) and local surgical expertise in valve repair. The potential advantages of 3-dimensional echocardiography in assessing the MV are discussed. Other modern imaging techniques (tissue Doppler and speckle tracking) may provide additional useful information in borderline cases. Exercise echocardiography (evaluating MR severity, pulmonary pressure, or right ventricular function) may have an important role in the management of difficult cases. Finally, the moment when surgery is no longer an option and alternative solutions should be sought is also discussed. Although in everyday clinical practice the timing of surgery is not always straightforward, some newer clinical and echocardiographic indicators can guide this decision and help improve the outcome of these patients.

New classification of geometric ventricular patterns in severe aortic stenosis: Could it be clinically useful?

In severe aortic stenosis, different left ventricle (LV) remodeling patterns as a response to pressure overload have distinct hemodynamic profiles, cardiac function, and outcomes. The most common classification considers LV relative wall thickness and LV mass index to create 4 different groups. A new classification including also end‐diastolic volume index has been recently proposed.

Mechanical dyssynchrony in heart failure with preserved ejection fraction: a treatment target or a dead end?

Heart failure with preserved ejection fraction (HFpEF) is a very prevalent condition and carries significant morbidity and mortality.1,2 Despite significant advances made during the last decades in treating patients with HF and reduced ejection fraction (HFrEF), no significant change in outcomes has been noted for HFpEF patients.3 The lack of efficacy for established HFrEF therapies in HFpEF patients underscores the incomplete understanding of the pathophysiology and mechanisms driving outcomes in the setting of HFpEF. Mechanical dyssynchrony in left ventricular (LV) contraction has been established as an important pathogenic mechanism, prognostic factor and potential treatment target (when associated with electrical dyssynchrony) in patients with HFrEF.3,4 Several authors have investigated lately the timing of systolic and diastolic events in patients with HFpEF hoping to ultimately extrapolate the benefits of cardiac resynchronization therapy (CRT) seen in HFrEF to the setting of HFpEF. Studies using conventional Doppler and tissue Doppler echocardiography parameters have found a high prevalence of mechanical dyssynchrony in patients with HFpEF, regardless of QRS duration.5,6 Recently, speckle tracking echocardiography (STE) has emerged as a useful technique for quantification of mechanical dyssynchrony, having the advantage of relative angle independence. Higher mechanical dyssynchrony was reported in patients with HFpEF compared to healthy controls, and this was seen even in patients with a narrow QRS complex (<100 ms) suggesting that dyssynchrony may play a pathophysiological role in HFpEF.7 However, even if QRS duration emerged as a phenotypic marker of adverse outcomes in patients with HFpEF,8 it remains unclear if mechanical dyssynchrony could be a clinically meaningful target for CRT.