lncRNA CDKN2B-AS1 is downregulated in patients with ventricular fibrillation in acute myocardial infarction.

Ventricular fibrillation (VF) in acute myocardial infarction (AMI) is the main cause of deaths occurring in the acute phase of an ischemic event. Although it is known that genetics may play an important role in this pathology, the possible role of long non-coding RNAs (lncRNA) has never been studied. Therefore, the aim of this work is to study the expression of 10 lncRNAs in patients with and without VF in AMI. For this purpose, the expression of CDKN2B-AS1, KCNQ1OT1, LIPCAR, MALAT1, MIAT, NEAT1, SLC16A1-AS1, lnc-TK2-4:2, TNFRSF14-AS1, and UCA1 were analyzed. After the analysis and Bonferroni correction, the lncRNA CDKN2B-AS showed a statistical significance lower expression (P values of 2.514 x 10-5). In silico analysis revealed that six proteins could be related to the possible effect of lncRNA CDKN2B-AS1: AGO3, PLD4, POU4F1, ZNF26, ZNF326 and ZNF431. These in silico proteins predicted to have a low cardiac expression, although there is no literature indicating a potential relationship with VF in AMI. Thus, the lncRNA CDKN2B-AS1 shows a significant lower expression in patients with VF in AMI vs patients without VF in AMI. Literature data suggest that the role of CDKN2B1-AS is related to the miR-181a/SIRT1 pathway.

Impact on mortality after implementation of a network for ST-segment elevation myocardial infarction care. The IPHENAMIC study.

INTRODUCTION AND OBJECTIVES: Little is known about the impact of networks for ST-segment elevation myocardial infarction (STEMI) care on the population. The objective of this study was to determine whether the PROGALIAM (Programa Gallego de Atención al Infarto Agudo de Miocardio) improved survival in northern Galicia. METHODS: We collected all events coded as STEMI between 2001 and 2013. A total of 6783 patients were identified and divided into 2 groups: pre-PROGALIAM (2001-2005), with 2878 patients, and PROGALIAM (2006-2013), with 3905 patients. RESULTS: In the pre-PROGALIAM period, 5-year adjusted mortality was higher both in the total population (HR, 1.22, 95%CI, 1.14-1.29; P <.001) and in each area (A Coruña: HR, 1.12; 95%CI, 1.02-1.23; P=.02; Lugo: HR, 1.34; 95%CI, 1.2-1.49; P <.001 and Ferrol: HR, 1.23; 95%CI, 1.1-1.4; P=.001). Before PROGALIAM, 5-year adjusted mortality was higher in the areas of Lugo (HR, 1.25; 95%CI, 1.05-1.49; P=.02) and Ferrol (HR, 1.32; 95%CI, 1.13-1.55; P=.001) than in A Coruña. These differences disappeared after the creation of the STEMI network (Lugo vs A Coruña: HR, 0.88; 95%CI, 0.72-1.06; P=.18, Ferrol vs A Coruña: HR, 1.04; 95%CI, 0.89-1.22; P=.58. CONCLUSIONS: For patients with STEMI, the creation of PROGALIAM in northern Galicia decreased mortality and increased equity in terms of survival both overall and in each of the areas where it was implemented. This study was registered at ClinicalTrials.gov (Identifier: NCT02501070).

A MicroRNA-Transcription Factor Blueprint for Early Atrial Arrhythmogenic Remodeling.

Spontaneous self-terminating atrial fibrillation (AF) is one of the most common heart rhythm disorders, yet the regulatory molecular mechanisms underlying this syndrome are rather unclear. MicroRNA (miRNA) transcriptome and expression of candidate transcription factors (TFs) with potential roles in arrhythmogenesis, such as Pitx2, Tbx5, and myocardin (Myocd), were analyzed by microarray, qRT-PCR, and Western blotting in left atrial (LA) samples from pigs with transitory AF established by right atrial tachypacing. Induced ectopic tachyarrhythmia caused rapid and substantial miRNA remodeling associated with a marked downregulation of Pitx2, Tbx5, and Myocd expression in atrial myocardium. The downregulation of Pitx2, Tbx5, and Myocd was inversely correlated with upregulation of the corresponding targeting miRNAs (miR-21, miR-10a/10b, and miR-1, resp.) in the LA of paced animals. Through in vitro transient transfections of HL-1 atrial myocytes, we further showed that upregulation of miR-21 did result in downregulation of Pitx2 in cardiomyocyte background. The results suggest that immediate-early miRNA remodeling coupled with deregulation of TF expression underlies the onset of AF.

Gene expression profiles following intracoronary injection of mesenchymal stromal cells using a porcine model of chronic myocardial infarction.

BACKGROUND AIMS: We evaluated the therapeutic potential of injection of in vitro differentiated bone marrow mesenchymal stromal cells (MSC) using a swine model. METHODS AND RESULTS: Myocardial infarction was induced by coronary occlusion. Three groups (n = 5 each) were analyzed: one group received an injection of 17.8 ± 9.3 × 10(6) 5-azacytidine-treated allogeneic MSC 1 month after infarction; a placebo group received an injection of medium; and controls were kept untreated. After 4 weeks, heart samples were taken from three infarcted areas, interventricular septa, ventricles and atria. Gene expression profiles of genes related to contractility (Serca2a), fibrosis (Col1a1), cardiomyogenesis (Mef2c, Gata4 and Nkx2.5) and mobilization of stem cells (Sdf1, Cxcr4 and c-kit) were compared by quantitative real-time PCR (qRT-PCR). Gene expression profiles varied in different heart areas. Thus Serca2a expression was reduced in infarcted groups in all heart regions except for the left ventricles, where Col1a1 was overexpressed. The expression of genes related to cardiomyogenesis decreased in the infarcted zones and left atria compared with healthy hearts. Interestingly, increased expression of Cxcr4 was detected in infarcted regions of MSC-treated pigs compared with the placebo group. CONCLUSIONS: Infarction induced changes in expression of genes involved in various biologic processes. Genes involved in cardiomyogenesis were downregulated in the left atrium. The intracoronary injection of MSC resulted in localized changes in the expression of Cxcr4.

Perventricular pulmonary valvuloplasty under echocardiographic guidance.

We report the case of a small neonate with a complex congenital heart disease who successfully underwent a perventricular pulmonary valvuloplasty during the early postoperative period, using echocardiographic guidance alone without fluoroscopy. We describe the technique and the advantages of this novel procedure.

Primary cardiac rhabdomyosarcoma causing obstruction to the right ventricular outflow.

A 72-year-old man presented with worsening shortness of breath and a systolic murmur. Transthoracic and transoesophageal echocardiograms revealed a huge mass (70 x 30 mm) obliterating the right ventricular outflow tract, with a peak transpulmonary gradient of 128 mmHg. Pathological examination confirmed the mass to be a primary cardiac rhabdomyosarcoma originating from the pulmonary valve.

Prognostic value of exercise echocardiography in patients with diabetes mellitus and known or suspected coronary artery disease.

To assess the prognostic value of exercise echocardiography in subjects who had diabetes, we studied 214 patients who had 28 hard cardiac events (cardiac death in 15, myocardial infarction in 13) during a follow-up of 44 +/- 16 months. Independent risk factors for predicting cardiac events were insulin therapy (odds ratio 2.313), peak left ventricular ejection fraction (odds ratio 0.973), and ischemia detected by exercise echocardiography (odds ratio 2.513).

A new simple method to assess global left ventricular systolic function based on the sum of regional myocardial velocities.

The relations between left ventricular (LV) function and global tissue Doppler velocity, strain rate, and strain were assessed in 99 studies. Significant correlations were found between the LV ejection fraction and global tissue Doppler velocity, strain, and strain rate (r = 0.50, r = 0.63, and r = 0.46, respectively, all p <0.001), suggesting that this global assessment may be useful in evaluating LV function.

Ischemia Modified Albumin for the assessment of patients presenting to the emergency department with acute chest pain but normal or non-diagnostic 12-lead electrocardiograms and negative cardiac troponin T.

BACKGROUND: The diagnosis of myocardial ischemia in patients with acute chest pain at rest but non-diagnostic electrocardiograms (ECG) is problematic. Ischemia Modified Albumin (IMA) is a new biochemical marker of ischemia, which may be useful to characterise acute coronary syndrome (ACS) patients. METHODS: We studied 131 patients (mean age 58.5 years; 95 male) presenting to the emergency department with symptoms suggestive of ACS but with normal or non-diagnostic ECGs. Cardiac troponin T (cTnT) and IMA were measured within 3 h of last chest pain episode. Based on hospital diagnostic test results, patients were classified as having ACS or non-ischemic chest pain (NICP), by two independent cardiologists unaware of IMA results. RESULTS: Mean IMA levels (U/ml) were higher in patients with ACS (98.3+/-11) compared to patients with NICP (85.5+/-15); p<0.0001. IMA levels >93.5 U/ml demonstrated a sensitivity and specificity of 75% for the diagnosis of ACS; area under the receiver operator characteristic curve 0.78 (95% CI: 0.70-0.85). If we applied the manufacturer cutoff point of 85 U/ml, the sensitivity of IMA increased to 90.6% with a specificity of 49.3% (negative predictive value=84.6%). In combination with cTnT (6-12 h) (>0.05 ng/ml), the sensitivity increased to 92.2%. After multivariate analysis, IMA levels >85 U/ml (odds ratio=14.6 [95% CI 4.4-48.4]; p<0.0001), age and prior myocardial infarction were independent predictors of ACS. CONCLUSION: IMA may be a useful biomarker for the identification of ACS in patients presenting with typical acute chest pain but normal or non-diagnostic ECGs.

Comparison of peak and postexercise treadmill echocardiography with the use of continuous harmonic imaging acquisition.

OBJECTIVES: We sought to compare the feasibility and accuracy of peak and postexercise treadmill echocardiography with the use of continuous harmonic imaging capture. BACKGROUND: Previous work has demonstrated the superiority of peak exercise echocardiography (EE) as compared with post-EE for the diagnosis of coronary artery disease (CAD). However, most of these studies used fundamental imaging and view-per-view acquisition systems. Technical advantages in stress echocardiography include harmonic imaging and continuous imaging capture. METHODS: The study group included 650 patients (423 men; 60 +/- 12 years) who were submitted to peak and postexercise treadmill echocardiography. RESULTS: Postexercise images were acquired within 55 seconds after exercise (28 +/- 10). The number of segments visualized in each view were similar at peak and post-EE except for the parasternal short-axis view, which was better qualified at postexercise. For analysis of diagnostic capability we included 312 patients: 195 were included on the basis of having had an EE and a coronary angiography, whereas 117 patients with pretest probability of CAD < 10% who had atypical chest pain or were asymptomatic were also included and considered as having no CAD. CAD (>/=50% stenosis) was confirmed in 159 patients. Positive EE was defined as ischemia or necrosis. Sensitivity for CAD was higher with peak imaging (92% vs 77%, P <.001), with similar specificity (78% vs 87%, P = not significant) and accuracy (85% vs 82%, P = not significant). CONCLUSION: Peak treadmill EE is technically feasible and has higher sensitivity for CAD than posttreadmill EE. Therefore, in the clinical setting, peak EE should be performed for diagnostic purposes.

Exercise echocardiography with addition of atropine.

Exercise echocardiography with the addition of atropine was performed in 31 patients who had a very small probability of achieving submaximal heart rate. Conclusive tests were obtained in 77% of the patients with this protocol.

Cardiac syndrome X. Diagnosis, pathogenesis and management.

Patients with cardiac syndrome X (typical chest pain and normal coronary arteriograms) represent a heterogeneous syndrome, which encompasses different pathogenic mechanisms. Although symptoms in most patients with cardiac syndrome X are non-cardiac, a sizable proportion of them have angina pectoris due to transient myocardial ischemia. Thus radionuclide myocardial perfusion defects, coronary sinus oxygen saturation abnormalities and pH changes, myocardial lactate production and stress-induced alterations of cardiac high energy phosphate suggest an ischemic origin of symptoms in at least a proportion of patients with cardiac syndrome X. Microvascular abnormalities, caused by endothelial dysfunction, appear to be responsible for myocardial ischemia in patients with cardiac syndrome X. Endothelial dysfunction is likely to be multifactorial in these patients and it is conceivable that risk factors such as hypertension, hypercholesterolemia, diabetes mellitus and smoking can contribute to its development. Most patients with cardiac syndrome X are postmenopausal women and estrogen deficiency has been therefore proposed as a pathogenic factor in female patients. Additional factors such as abnormal pain perception may contribute to the pathogenesis of chest pain in patients with angina pectoris and normal coronary angiograms. Although prognosis is good regarding survival, patients with cardiac syndrome X have an impaired quality of life. Management of this syndrome represents a major challenge to the treating physician. Understanding the mechanism underlying the condition is of vital importance for patient management. Thus diagnostic tests should aim at identifying the cause of the symptoms in the individual patient, i.e. myocardial ischemia, increased pain perception, abnormalities of adrenergic tone, non-cardiac mechanisms, etc. Moreover, it is important to bear in mind that treatment of cardiac syndrome X should be mainly directed towards improving quality of life, as prognosis is usually good in these patients. Conventional antianginal agents such nitrates, calcium channel antagonists, beta-adrenoceptor antagonists and nicorandil are effective particularly in patients in whom chest pain and ECG changes are clearly suggestive of myocardial ischemia and in those with objective documentation of ischemia. Angiotensin-converting enzyme inhibitors have been shown to be useful in syndrome X patients with increased adrenergic tone, borderline systemic hypertension, and those with documented endothelial dysfunction. Analgesic interventions of different sorts have been proposed based on the hypothesis that somatic and visceral perception of pain is altered in cardiac syndrome X patients. Pharmacological agents such as imipramine and aminophylline, and neural electrical stimulation techniques have been assessed in recent years with encouraging results. Psychological treatment, particularly cognitive therapy, appears to be useful in defined patient subsets. Relaxation techniques such as transcendental meditation have been successfully used in small studies and shown to improve not only chest pain but also exercise-induced ST segment changes. Reports indicate that these techniques improve quality of life.

C-reactive protein elevation and disease activity in patients with coronary artery disease.

AIMS: We sought to assess (1) whether C-reactive protein (CRP) is an independent predictor of future cardiovascular events after adjustment for coronary artery disease (CAD) severity and (2) whether CRP levels correlate with number of angiographically complex coronary artery stenosis. METHODS AND RESULTS: We studied 825 consecutive angina patients (mean age 63+/-10 years, 74% men), 700 with chronic stable angina (CSA) and 125 with acute coronary syndromes without ST-segment elevation (ACS). The composite endpoint of non-fatal acute myocardial infarction, hospital admission with class IIIb unstable angina and cardiac death was assessed at one year follow-up. Hs-CRP level was higher in CSA patients with the combined end-point (P=0.03) after adjustment for number of diseased coronary arteries. Hs-CRP was also significantly higher in patients with ACS compared to CSA ( P=0.004) and correlated with number of complex angiographic stenoses (r=0.36, P=0.01). Hs-CRP was also increased in patients with NYHA functional class III or IV compared to those in class I or II (p<0.0001). CONCLUSIONS: CRP levels predict future cardiovascular events independently of CAD severity and correlate with number of angiographically complex coronary artery stenosis in patients with ACS. Thus, CRP levels are a marker of atheromatous plaque vulnerability and CAD activity.

Effect of direct-current cardioversion on ischemia-modified albumin levels in patients with atrial fibrillation.

Ischemia-modified albumin (IMA), measured with the albumin cobalt binding test, is a marker of myocardial ischemia. We measured IMA concentrations after elective direct-current cardioversion for atrial fibrillation to determine whether transient myocardial ischemia occurs. Patients with electrocardiographic changes after cardioversion (ST-depression and/or T-wave inversion) had significantly higher IMA levels than those without these changes. Thus, elevated levels of IMA after cardioversion may reflect transient myocardial ischemia.