Circulating miR-323-3p and miR-652: Candidate markers for the presence and progression of acute coronary syndromes

Background

The prognostic utility of circulating plasma microRNA in patients with acute coronary syndromes (ACS) has been proposed but not yet demonstrated. We set out to investigate circulating microRNA levels in patients incurring recent ACS and examined associations with neurohormones, cardiac structure and function, and survival over 5 years of follow-up.

Methods

An initial screen of 375 microRNAs was performed in 35 ACS patients and 16 healthy controls. Candidates identified from the initial screen (miR-323-3p, miR-652, miR-27b, miR-103 and miR-208a) were validated in a further cohort of 200 patients at baseline (~ 30 days post-ACS) and at 4 and 12 months post-ACS, and compared with 100 controls.

Results

In the validation cohort, significantly higher levels in patients were replicated for miR-323-3p, miR-652 and miR-27b (10-fold, 2.3-fold and 2.3-fold, respectively, adjusted p < 0.05). Lower levels of miR-103 were not replicated and miR-208a was undetectable. From baseline to 4 months post-admission, miR-323-3p and miR-652 remained elevated in patients compared to controls (adjusted p < 0.01), with no further change in levels between 4 and 12 months; whereas miR-27b fell to control levels by 4 months. Baseline levels of miR-652 in the lowest tertile were significantly associated with readmission for heart failure (log-rank p < 0.001). In combination with NT-proBNP and LVEF, miR-652 significantly improved risk stratification (p < 0.001).

Conclusions

Our study identifies miR-652 as a novel candidate biomarker for post-ACS prognosis beyond existing biomarkers of LVEF and NT-proBNP. Moreover circulating miR-323-3p was markedly elevated in patients for at least a year post-ACS and may be a stable biomarker for ACS.     

Intravenous immunoglobulin does not reduce left ventricular remodeling in patients with myocardial dysfunction during hospitalization after acute myocardial infarction

Background

Left ventricular (LV) remodeling takes place after acute myocardial infarction (MI), potentially leading to overt heart failure (HF). Enhanced inflammation may contribute to LV remodeling. Our hypothesis was that the immunomodulating effects of intravenous immunoglobulin (IVIg) would be beneficial in patients with impaired myocardial function after MI by reducing myocardial remodeling and improving myocardial function.

Methods

Sixty-two patients with acute MI treated by percutaneous coronary intervention, with depressed LV ejection fraction (LVEF) were randomized in a double-blinded fashion to IVIg as induction therapy and thereafter as monthly infusions or placebo for 26 weeks. The primary end point was changes in LVEF from baseline to 6 months as assessed by MRI.

Results

Our main findings were: (i) LVEF increased significantly from 38 ± 10 (mean ± SD) to 45 ± 13% after IVIg and from 42 ± 9 to 49 ± 12% after placebo with no difference between the groups. (ii) The scar area decreased significantly by 3% and 5% in the IVIg and placebo group, respectively, with no difference between the groups. (iii) During the induction therapy (baseline to day 5), IVIg induced both inflammatory (e.g., increase in tumor necrosis factor α and monocyte chemoattractant protein-1) and anti-inflammatory (e.g., increase in interleukin-10 and decrease in leukocyte counts) variables, but during maintenance therapy there were no differences in changes of inflammatory mediators between IVIg and placebo.

Conclusions

IVIg therapy after ST elevation MI managed by primary PCI does not affect LV remodeling or function. This illustrates the challenges of therapeutic intervention directed against the cytokine network, to prevent post-MI remodeling.     

Expression of miR-126 and miR-508-5p in endothelial progenitor cells is associated with the prognosis of chronic heart failure patients

Background

MicroRNA (miRNA) expression profiles in endothelial progenitor cells (EPCs) contribute to EPC dysfunction in patients suffering from coronary artery disease. However, it remains unclear whether miRNA expression in EPCs is associated with the prognosis of chronic heart failure (CHF) secondary to ischemic cardiomyopathy (ICM) or non-ischemic cardiomyopathy (NICM).

Methods and results

One hundred six patients with CHF (55 ICM and 51 NICM) and 30 healthy controls were followed until the end of 24 months or when the end point was obtained (cardiovascular death). The miRNA expression profile was analyzed by TaqMan Human MicroRNA Array Set v2.0 in 30 randomly assigned samples (ICM = 10, NICM = 10, and healthy controls = 10). During the 24-month follow-up, 26 patients died from cardiovascular disease. Sixteen miRNAs (miR-126, miR-508-5p, miR-34a, miR-210, miR-490-3p, miR-513-5p, miR-517c, miR-518e, miR-589, miR-220c, miR-200a*, miR-186*, miR-7i*, miR-200b*, miR-595, and miR-662) were found to be differentially expressed between ICM and NICM patients. Survival analysis showed that miR-126 and miR-508-5p levels in EPCs were independent prognostic factors (P = 0.003; HR (hazard ratio): 0.19; 95% CI (confidence intervals): 0.06–0.58, P = 0.002; HR: 2.292; 95% CI: 1.37–3.84) for the outcome of ICM or NICM patients with CHF. Pathway enrichment analysis showed that the angiogenesis pathway was the most likely pathway regulated by miR-126 and miR-508-5p.

Conclusions

The miRNAs miR-126 and miR-508-5p are associated with the outcome of ICM and NICM patients with CHF. These two miRNAs could be useful in the diagnosis of CHF patients, and might provide novel targets for prevention and treatment of CHF.     

Direct implantation versus platelet-rich fibrin-embedded adipose-derived mesenchymal stem cells in treating rat acute myocardial infarction

Background

This study tested whether adipose-derived mesenchymal stem cells (ADMSC) embedded in platelet-rich fibrin (PRF) scaffold is superior to direct ADMSC implantation in improving left ventricular (LV) performance and reducing LV remodeling in a rat acute myocardial infarction (AMI) model of left anterior descending coronary artery (LAD) ligation.

Methods

Twenty-eight male adult Sprague Dawley rats equally divided into group 1 [sham control], group 2 (AMI only), group 3 (AMI + direct ADMSC implantation), and group 4 (AMI + PRF-embedded autologous ADMSC) were sacrificed on day 42 after AMI.

Results

LV systolic and diastolic dimensions and volumes, and infarct/fibrotic areas were highest in group 2, lowest in group 1 and significantly higher in group 3 than in group 4, whereas LV performance and LV fractional shortening exhibited a reversed pattern (p < 0.005). Protein expressions of inflammation (oxidative stress, IL-1β, MMP-9), apoptosis (mitochondrial Bax, cleaved PARP), fibrosis (Smad3, TGF-β), and pressure-overload biomarkers (BNP, MHC-β) displayed a pattern similar to that of LV dimensions, whereas anti-inflammatory (IL-10), anti-apoptotic (Bcl-2), and anti-fibrotic (Smad1/5, BMP-2) indices showed a pattern similar to that of LV performance among the four groups (all p < 0.05). Angiogenesis biomarkers at protein (CXCR4, SDF-1α, VEGF), cellular (CD31 +, CXCR4 +, SDF-1α +), and immunohistochemical (small vessels) levels, and cardiac stem cell markers (C-kit +, Sca-1 +) in infarct myocardium were highest in group 4, lowest in group 1, and significantly higher in group 3 than in group 2 (all p < 0.005).

Conclusion

PRF-embedded ADMSC is superior to direct ADMSC implantation in preserving LV function and attenuating LV remodeling.     

A pilot trial of autologous bone marrow mononuclear cell transplantation through grafting artery: A sub-study focused on segmental left ventricular function recovery and scar reduction

Background

Our preliminary study suggested that patients with chronic myocardial infarction (MI) and heart failure could potentially benefit from CABG combined with aBM-MNC by improving global left ventricular (LV) function. The purpose of this sub-study was to quantitatively evaluate the effectiveness of aBM-MNC transplantation during CABG in patients with chronic MI by intensively analyzing the global and segmental LV function, the scar, and the relationships between the function recovery and the scar transmural extent.

Methods

A randomized, double-blinded, placebo-controlled study was performed in 50 patients with chronic MI. The patients were randomly allocated into CABG with stem cell transplantation (group A) and CABG only (group B) groups. CMR assessments of global and segmental left ventricular function and scar tissue were performed before surgery and repeated at 12 months after CABG and aBM-MNC transplantation.

Results

The left ventricular ejection fraction (LVEF) improved by 13.5% and 8.0% in group A and B respectively (P = 0.04). Segmental analysis of regional LV function recovery indicated that more improvement in contractility was found in group A within the same degree of the infarct transmurality (P = 0.017) and showed a predominant interaction in the most severely affected segments (76–100%, P = 0.016). Decrease in infarct size between the two groups did not reach statistical difference (9.4% vs. 6.0%, P = 0.100).

Conclusions

CMR assessments revealed reversed ventricular remodeling and improved systolic function and scar reduction in patients who underwent aBM-MNC transplantation during CABG. And the conjunctional use of CABG and stem cell therapy could improve the left ventricular function in patients with chronic MI.     

Early pacing-induced systolic dyssynchrony is a strong predictor of left ventricular adverse remodeling: Analysis from the Pacing to Avoid Cardiac Enlargement (PACE) trial

Background

Right ventricular apical (RVA) pacing is associated with adverse left ventricular (LV) remodeling and biventricular (BiV) pacing may prevent it although the mechanisms remain unclear. The current study aimed to assess the role of early pacing-induced systolic dyssynchrony (DYS) to predict adverse LV remodeling.

Methods

Patients with standard pacing indications and normal LV ejection fraction were randomized either to BiV (n = 89) or RVA pacing (n = 88). Pacing-induced DYS, defined as the standard deviation of the time to peak systolic velocity (Dyssynchrony Index) > 33 ms in a 12-segmental model of LV, was measured by tissue Doppler echocardiography at 1 month.

Results

At 1 month, 59 patients (33%) had DYS which was more prevalent in RVA than BiV pacing group (52% vs. 15%, χ² = 28.3, p < 0.001), though Dyssynchrony Index was similar at baseline (30 ± 14 vs. 26 ± 11 ms, p = 0.06). At 12 months, those developing DYS had significantly lower LV ejection fraction (55.1 ± 9.7 vs. 62.2 ± 7.9%, p < 0.001) and larger LV end-systolic volume (35.3 ± 14.3 vs. 27.0 ± 10.4 ml, p < 0.001) when compared to those without DYS. Reduction of ejection fraction ≥ 5% occurred in 67% (39 out of 58) of patients with DYS, but only in 18% (21 out of 115) in those without DYS (χ² = 40.8, p < 0.001). Both DYS at 1 month (odds ratio [OR]: 4.725, p = 0.001) and RVA pacing (OR: 3.427, p = 0.009) were independent predictors for reduction of ejection fraction at 12 months.

Conclusion

Early pacing-induced DYS is a significant predictor of LV adverse remodeling and the observed benefit of BiV pacing may be related to the prevention of DYS.

Clinical trial registration

Centre for Clinical Trials number, CUHK_CCT00037 (URL: http://www.cct.cuhk.edu.hk/Registry/publictrialrecord.aspx?trialid=CUHK_CCT00037).     

Distal protection device aggravated microvascular obstruction evaluated by cardiac MR after primary percutaneous intervention for ST-elevation myocardial infarction

Background

Protection of distal embolization by balloon occlusion and thrombus aspiration has not improved microvascular circulation nor decreased myocardial injury during primary percutaneous intervention (PCI) for ST-elevation myocardial infarction (STEMI) in randomized trials. In a prospective randomized trial, we investigated the mechanism of the poor effect of distal protection and thrombus aspiration (DP–TA) in 126 patients with STEMI.

Methods

Patients with first-diagnosed STEMI were randomly assigned to DP–TA pretreatment or conventional PCI (c-PCI). Primary endpoint was reduced left ventricular end-diastolic volume (LVEDV) measured by MRI at post-PCI and 6 months after PCI. Secondary end points were infarct ratio (infarct size to entire LV size) by delayed enhancement (DE), area at risk (AAR) ratio (AAR to entire LV size) by T2 high signal, microvascular occlusion index (MVO) ratio (MVO to entire LV size) by DE, and myocardial salvage index (MSI: (AAR − infarct size) ∗ 100 / AAR) using cardiac magnetic resonance imaging (MRI) within 3 days after PCI.

Results

Baseline characteristics of the patients including cardiovascular risk factors and lesion characteristics were similar between the two groups. DT–PA failed to improve LV remodeling at 6 months (LVEDV 140 ± 39 vs 133 ± 37 in c-PCI group, p = 0.418). Infarct ratio, AAR ratio and MSI were not statistically different between DP–TA group and c-PCI group. However, MVO ratio was significantly larger in DP–TA group than in c-PCI group (2.4 ± 2.7 vs 1.1 ± 1.9, p = 0.045).

Conclusion

DP–TA was potentially hazardous in primary PCI for STEMI by increasing MVO. DP–TA should not be used in STEMI.     

Facilitation of left ventricular function recovery post percutaneous coronary intervention by levosimendan

Background

Efficiency of percutaneous revascularization and the utility of levosimendan for advanced ischemic heart failure (HF) is unclear. We examined the efficacy of revascularization and levosimendan on left ventricular ejection fraction (LVEF) and mortality of patients admitted with acute decompensated HF and severe left ventricular dysfunction.

Methods

A prospective case control study that enrolled 84 patients with ischemic decompensated HF with LVEF < 35% and preserved LV wall thickness. Group A: 42 patients whose LVEF improved post percutaneous coronary intervention (PCI). Group B1: 22 patients whose LVEF did not improve post-PCI alone but improved after levosimendan. Group B2: 20 patients whose LVEF did not improve neither post-PCI nor post levosimendan.

Results

LVEF increased in group A from 22 ± 5 to 29 ± 5% post PCI and continued to improve at the 6 month follow-up (36 ± 4%). In group B1 LVEF did not improve after PCI, but increased after levosimendan from 23 ± 4% to 32 ± 4% and remained constant at 6 months. In group B2 LVEF 26 ± 4% did not change following both interventions.Reverse remodeling with a decrease in end-diastolic and end-systolic diameters was observed only in groups A and B1.Group B2 had a dismal prognosis with 36% in-hospital and 43% six month mortality. Groups A and B1 had a lower in hospital (4.7%, 4.5%) and mid term (11%, 11%) mortality.

Conclusion

Improvement of LV size and function with better prognosis can be expected in the majority of patients undergoing PCI for decompensated ischemic HF. Levosimendan enhanced the recovery of LV function post PCI.     

Left ventricular geometry and outcomes in patients with atrial fibrillation: The AFFIRM Trial

Background

Echocardiographically determined left ventricular hypertrophy (LVH) is a marker of cardiovascular disease related to prognosis and clinical outcomes. We sought to determine if LVH is a measure of outcomes in atrial fibrillation (AF) patients.

Methods

We performed a post-hoc analysis of patients with echocardiographic data enrolled in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Trial. Patients were stratified based on gender-adjusted echocardiography derived interventricular septal (IVS) thickness, relative wall thickness (RWT), gender-adjusted LV mass, and type of LV remodeling (normal LV geometry, concentric hypertrophy, eccentric hypertrophy, and concentric remodeling).

Results

Of 4060 patients in AFFIRM, echocardiographic data were available in 2433 patients (60%). Multivariate analysis revealed that LVH defined as moderately or severely abnormal IVS thickness was an independent predictor of both all cause mortality (HR 1.46, 95%CI 1.14–1.86, p = 0.003) and stroke (HR 1.89, 95%CI 1.17–3.08, p = 0.01). This association was confirmed when IVS thickness was assessed as continuous or categorical variable. Concentric LV hypertrophy was associated with the highest rates of all cause mortality (HR 1.53; 95%CI 1.11–2.12; p = 0.009).

Conclusion

An easily obtained echocardiographic index of LVH (IVS thickness) may enhance risk stratification of patients with AF, and raise the possibility that LVH regression should be a therapeutic target in this population.     

Coronary artery bypass grafting in patients with left ventricular dysfunction: Predictors of long-term survival and impact of surgical strategies

Background

In the surgical management of ischemic cardiomyopathy, factors associated with long-term prognosis after coronary artery bypass grafting (CABG) in patients with severe left ventricular (LV) dysfunction are poorly understood. This study aimed to determine predictors of clinical outcomes in patients with severe LV dysfunction undergoing CABG.

Methods

Out of 6084 patients who underwent CABG between 1997 and 2011, 476 patients (aged 62.6 ± 9.3 years, 100 females) were identified as having severe LV dysfunction (ejection fraction ≤ 35%), preoperatively. All-cause mortality and adverse cardiac events (myocardial infarction, repeat revascularization, stroke and hospitalization due to cardiovascular causes) were evaluated during a median follow-up period of 55.2 months (inter-quartile range: 26.4–94.8 months).

Results

During the follow-up, 187 patients (39.3%) died and 126 cardiac events occurred in 104 patients (21.8%). Five-year survival and event-free survival rates were 72.1 ± 2.2% and 61.3 ± 2.4%, respectively. On Cox-regression analysis, old age (P < 0.001), recent MI (P < 0.001), history of coronary stenting (P = 0.023), decreased glomerular filtration rate (P < 0.001), and presence of mitral regurgitation (≥ moderate) (P = 0.012) or LV wall thinning (P = 0.007) emerged as significant and independent predictors of death. After adjustment for important covariates affecting outcomes, none of the pump strategy (off-pump vs. on-pump), concomitant mitral surgery or surgical ventricular reconstruction (SVR) affected survival or event-free survival (P = 0.082 to > 0.99).

Conclusions

Long-term survival following CABG in patients with severe LV dysfunction was affected by age, renal function, recent MI, prior coronary stenting, and presence of mitral regurgitation or LV wall thinning. Neither concomitant mitral surgery nor SVR, however, had significant influence on clinical outcomes.     

Indexed maximal left atrial volume predicts response to cardiac resynchronization therapy

Aims

Cardiac resynchronization therapy (CRT) has shown morbidity and mortality benefits in patients with advanced congestive heart failure (HF). Since about one-third of the patients did not appear to respond to CRT, it would seem reasonable to try to identify patients more accurately before implantation. Left atrial (LA) dimension has been proposed as a powerful outcome predictor in patients with heart disease. Accordingly, the aim of this study is to prospectively assess the predictive value of LA for selecting CRT responders.

Methods

Fifty two consecutive patients with refractory HF, sinus rhythm and left bundle branch block were enrolled in the study and planned for CRT implantation. Clinical and echocardiographic evaluations were performed before CRT implantation and after 6 months. Three LA volumes indexed to body surface area (iLAV) were computed to evaluate the LA complexity: maximal LAV (iLAVmax), LAV just before atrial systole (iLAVpre), and minimal LAV (iLAVpost). CRT responders were defined as those who presented a reduction of > 10% in LVESVi at 6-month follow-up.

Results

Responders (63%) and nonresponders (37%) had similar baseline clinical characteristics and pre-implantation LV volumes. However, baseline LA volumes were significantly associated with the extent of LV reverse remodeling: in particular, baseline iLAVmax was remarkably lower in responders than in nonresponders (50.2 ± 14.1 ml/m² vs 65.8 ± 15.7 ml/m², p = 0.001) resulting predictive for CRT response.

Conclusion

Patients with small iLAV result as better responders to CRT than larger one. iLAVmax is an independent predictor of LV reverse remodeling and allows to indentify the best candidates for CRT.     

Association of aortic stiffness with biomarkers of myocardial wall stress after myocardial infarction

Background

Aortic pulse wave velocity (PWV) was linked to LV-geometry and -function in patients with kidney disease and non-ischemic cardiomyopathy. The role of aortic compliance after acute STEMI is so far unknown. In the present study, we prospectively investigated the relationship of increased aortic stiffness with biomarkers of myocardial wall stress 4 months after STEMI.

Methods

48 STEMI patients who were reperfused by primary coronary angioplasty underwent cardiovascular magnetic resonance (CMR) at baseline and at 4-month follow-up. The CMR protocol comprised cine-CMR as well as gadolinium contrast-enhanced CMR. Aortic PWV was determined by velocity-encoded, phase-contrast CMR. Blood samples were routinely drawn at baseline and follow-up to determine N-terminal pro-B-type natriuretic peptide (NT-proBNP). In a subgroup of patients, mid-regional pro-adrenomedullin (MR-proADM) and mid-regional pro-A-type natriuretic peptide (MR-proANP) levels were determined.

Results

Patients with a PWV above median (> 7.0 m/s) had significantly higher NT-proBNP, MR-proADM and MR-proANP concentrations at 4-month follow-up than patients with a PWV below median (all p < 0.02). PWV showed moderate to good correlation with NT-proBNP, MR-proAMD and MR-proANP levels 4 months after STEMI (all p < 0.05). Multivariate analysis revealed PWV, beside myocardial infarct size, as an independent predictor of 4-month NT-proBNP levels after correction for age, creatinine and LV ejection fraction (model r: 0.781, p < 0.001).

Conclusion

Aortic stiffness is directly associated with biomarkers of myocardial wall stress 4 months after reperfused STEMI, suggesting a role for aortic stiffness in chronic LV-remodelling.     

A multi-biomarker risk score improves prediction of long-term mortality in patients with advanced heart failure

Background

Accurate risk prediction is important for an adequate management of heart failure (HF) patients. We assessed the incremental prognostic ability of a multi-biomarker approach in advanced HF.

Methods

In 349 patients with advanced HF (median 75 years, 66% male) we investigated the incremental prognostic value of 12 novel biomarkers involved in different pathophysiological pathways including inflammation, immunological activation, oxidative stress, cell growth, remodeling, angiogenesis and apoptosis.

Results

During a median follow-up of 4.9 years 55.9% of patients died. Using multivariable Cox regression and bootstrap variable-selection age, chronic obstructive pulmonary disease, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and the following 5 novel biomarkers were retained in the best mortality prediction model: the chemokine fractalkine, the angiogenic and mitogenic hepatocyte growth factor (HGF), the growth differentiation factor 15 (GDF-15) influencing cardiac remodeling and apoptosis, and the 2 pro-apoptotic molecules soluble apoptosis-stimulating fragment (sFAS) and soluble tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL). This multi-biomarker score had strong discriminatory power for 5-year mortality (area under the Receiver Operating Characteristic curve [AUC] = 0.81) and improved risk prediction beyond the prognostic power of a comprehensive conventional risk score including known clinical predictors and NT-proBNP (AUC = 0.77). Net reclassification confirmed a significant improvement of individual risk prediction (p = 0.003).

Conclusions

Risk prediction by a multi-biomarker score is superior to a conventional risk score including clinical parameters and NT-proBNP. Additional predictive information from different biological pathways reflects the multisystemic character of HF.     

Positive effect of intravenous iron-oxide administration on left ventricular remodelling in patients with acute ST-elevation myocardial infarction – A cardiovascular magnetic resonance (CMR) study

Objectives

This study investigated the safety profile and potential “therapeutic” effect of intravenous ultrasmall superparamagnetic iron-oxide (USPIO)-based iron administration regarding infarct healing in patients with ST-elevation myocardial infarction (STEMI). USPIO-administration was recently shown to enable an improved characterization of myocardial infarct pathology in acute STEMI patients.

Materials and Methods

Seventeen study patients (IRON, 54 ± 9 yrs, 88% male) and 22 matched controls (CONTROL, 57 ± 9 yrs, 77% male) both with primary reperfused STEMI underwent multi-parametric CMR studies in the first week and three months after acute MI. Only IRON patients received a single intravenous bolus of 510 mg elemental iron as ferumoxytol (Feraheme^TM) within four days following acute MI.

Results

Three months later, all patients were alive and there were no adverse cardiac events. Significant improvement in left ventricular (LV) ejection fraction (IRON: 53 ± 10% to 59 ± 9%, p = 0.002; CONTROL: 54 ± 6% to 57 ± 10%, p = 0.005) as well as shrinkage of infarct size were seen in both groups at follow-up. There was a more pronounced decrease in infarct size in the IRON group (IRON: − 10.3 ± 5.4% vs. CONTROL: − 7.0 ± 8.4%, p = 0.050) in addition to a significant decrease in both endocardial extent and prevalence of transmural infarctions in IRON but not in CONTROL patients. A significant decrease in LV end systolic volume was only seen in the IRON group (71 ± 25 mL to 59 ± 25 mL, p = 0.002).

Conclusions

Intravenous iron administration in acute STEMI patients seems to be associated with an improved infarct healing and a beneficial global left ventricular remodelling. These findings together with the good safety profile make USPIO-based iron administration a promising future candidate as a “diagnostic” and “therapeutic” adjunctive solution in acute MI management.     

Calreticulin overexpression correlates with integrin-α5 and transforming growth factor-β1 expression in the atria of patients with rheumatic valvular disease and atrial fibrillation

Objectives

The aim of this study was to determine whether altered calreticulin expression and distribution contribute to the pathogenesis of atrial fibrillation (AF) associated with valvular heart disease (VHD).

Background

AF affects electrophysiological and structural changes that exacerbate AF. Atrial remodeling reportedly underlies AF generation, but the precise mechanism of atrial remodeling in AF remains unclear.

Methods

Right and left atrial specimens were obtained from 68 patients undergoing valve replacement surgery. The patients were divided into sinus rhythm (SR; n = 25), paroxysmal AF (PaAF; n = 11), and persistent AF (PeAF; AF lasting > 6 months; n = 32) groups. Calreticulin, integrin-α5, and transforming growth factor-β1 (TGF-β1) mRNA and protein expression were measured. We also performed immunoprecipitation for calreticulin with either calcineurin B or integrin-α5.

Results

Calreticulin, integrin-α5, and TGF-β1 mRNA and protein expression were increased in the AF groups, especially in the left atrium in patients with mitral valve disease. Calreticulin interacted with both calcineurin B and integrin-α5. Integrin-α5 expression correlated with TGF-β1 expression, while calreticulin expression correlated with integrin-α5 and TGF-β1 expression. Despite similar cardiac function classifications, calreticulin expression was greater in the PeAF group than in the SR group.

Conclusions

Calreticulin, integrin-α5, and TGF-β1 expression was increased in atrial tissue in patients with AF and was related to AF type, suggesting that calreticulin is involved in the pathogenesis of AF in VHD patients.     

Sleep apnea prevalence in acute myocardial infarction — The Sleep Apnea in Post-acute Myocardial Infarction Patients (SAPAMI) Study

Background

While sleep apnea (SA) might be a modifiable cardiovascular risk factor, recent data suggest that SA is severely underdiagnosed in patients after acute myocardial infarction (MI). There is limited evidence about day–night variation of onset of MI on dependence of having SA. We therefore investigated the prevalence of SA and examined the day–night variation of onset of MI in acute MI patients.

Methods

We prospectively studied 782 consecutive patients admitted to the hospital with the diagnosis of acute MI. All subjects underwent sleep evaluations using a portable device after at least 48 h post-admission. Using the apnea–hypopnea index (AHI), groups were defined as patients without SA (< 5 events/h), mild SA (5–15 events/h), moderate SA (15–30 events/h), and severe SA (≥ 30 events/h).

Results

Almost all patients (98%) underwent urgent coronary angiography and 91% of patients underwent primary PCI. Using a threshold of AHI ≥5 events/h, SA was present in 65.7% of patients after acute MI. Mild SA was present in 32.6%, moderate in 20.4% and severe in 12.7%. The day–night variation in the onset of MI in all groups of SA patients was similar to that observed in non-SA patients. From 6 AM to 12 PM, the frequency of MI was higher in both SA and non-SA patients, as compared to the interval from 12 AM to 6 AM (all p < 0.05).

Conclusion

There is a high prevalence of SA in patients presenting with acute MI. Peak time of MI onset in SA patients was between 6 AM and noon, similar to that in the general population. Whether diagnosis and treatment of SA after MI will significantly improve outcomes in these patients remains to be determined.     

Triple-orifice valve repair in severe Barlow disease with multiple-jet mitral regurgitation: Report of mid-term experience

Objectives

Barlow disease represents a surgical challenge for mitral valve repair (MR) in the presence of mitral insufficiency (MI) with multiple regurgitant jets. We hereby present our mid-term experience using a modified edge-to-edge technique to address this peculiar MI.

Methods

From March 2003 till December 2010, 25 consecutive patients (mean age 54 ± 7 years, 14 males) affected by severe Barlow disease with multiple regurgitant jets were submitted to MR. Preoperative transesophageal echo (TEE) in all the cases showed at least 2 regurgitant jets, involving one or both leaflets in more than one segment. In all the patients, a triple orifice valve (TOV) repair with annuloplasty was performed. Intra-operative TEE and postoperative transthoracic echocardiography (TTE) were carried out to evaluate results of the TOV repair.

Results

There was no in-hospital death and one late death (non-cardiac related). At intra-operative TEE, the three orifices showed a mean total valve area of 2.9 ± 0.1 cm² (range 2.5–3.3 cm²) with no residual regurgitation (2 cases of trivial MI) and no sign of valve stenosis (mean transvalvular gradient 4.6 ± 1.5 mm Hg). At follow up (mean 38 ± 22 months), TTE showed favourable MR and no recurrence of significant MI (6 cases of trivial and 1 of mild MI). Stress TTE was performed in 5 cases showing persistent effective valve function (2 cases of trivial MI at peak exercise). All the patients showed significant NYHA functional class improvement.

Conclusions

This report indicates that the TOV technique is effective in correcting complex Barlow mitral valves with multiple jets. Further studies are required to confirm long-term applicability and durability in more numerous clinical cases.     

Early eicosapentaenoic acid treatment after percutaneous coronary intervention reduces acute inflammatory responses and ventricular arrhythmias in patients with acute myocardial infarction: A randomized,controlled study

Objective

We examined whether early loading of eicosapentaenoic acid (EPA) reduces clinical adverse events by 1 month, accompanied by a decrease in C-reactive protein (CRP) values in patients with acute myocardial infarction (MI).

Background

Acute MI triggers an inflammatory reaction, which plays an important role in myocardial injury. EPA could attenuate the inflammatory response.

Methods

This prospective, open-label, blinded endpoint, randomized trial consisted of 115 patients with acute MI. They were randomly assigned to the EPA group (57 patients) and the control group (58 patients). After percutaneous coronary intervention (PCI), 1800 mg/day of EPA was initiated within 24 h. The primary endpoint was composite events, including cardiac death, stroke, re-infarction, ventricular arrhythmias, and paroxysmal atrial fibrillation within 1 month.

Results

Administration of EPA significantly reduced the primary endpoint within 1 month (10.5 vs 29.3%, p = 0.01), especially the incidence of ventricular arrhythmias (7.0 vs 20.6%, p = 0.03). Peak CRP values after PCI in the EPA group were significantly lower than those in the control group (median [interquartile range], 8.2 [5.6–10.2] mg/dl vs 9.7 [7.6–13.9] mg/dl, p < 0.01). Logistic regression analysis showed that EPA use was an independent factor related to ventricular arrhythmia until 1 month, with an odds ratio of 0.29 (95% confidence interval, 0.09 to 0.96, p = 0.04).

Conclusions

Early EPA treatment after PCI in the acute stage of MI reduces the incidence of ventricular arrhythmias, and lowers CRP values.     

Correlation between vectorcardiographic measures and cardiac magnetic resonance imaging of the left ventricle in an implantable cardioverter defibrillator population

Background

Measures of vectorcardiographic changes and LV remodelling have been associated with arrhythmic risk. However the correlation between the two modalities is not well characterised.

Methods

We correlated spatial QRS-T angle and ventricular gradient with cardiac MRI derived LV global measures and scar pattern in 66 ICD recipients.

Results

Spatial QRS-T angle was significantly larger in patients with ischaemic scar than those without scar (150° ± 22° vs. 119° ± 46°, p = 0.01). Larger spatial QRS-T angle was also correlated with more depressed LV function, more dilated LV and larger LV mass. Ventricular gradient azimuth was significantly different between patients with no scar, non-ischaemic scar and ischaemic scar (20° ± 49° vs. 38° ± 62° vs. 65° ± 48°, p = 0.009), but independent of spatial QRS-T angle and LV structure.

Conclusions

Spatial QRS-T angle and ventricular gradient are partially related to LV structural properties. Further investigation is warranted to examine their comparative and combined prognostic value in risk stratification of ventricular arrhythmias.