Rare Variants in Genes of the Cholesterol Pathway Are Present in 60% of Patients with Acute Myocardial Infarction.

Acute myocardial infarction (AMI) is a pandemic in which conventional risk factors are inadequate to detect who is at risk early in the asymptomatic stage. Although gene variants in genes related to cholesterol, which may increase the risk of AMI, have been identified, no studies have systematically screened the genes involved in this pathway. In this study, we included 105 patients diagnosed with AMI with an elevation of the ST segment (STEMI) and treated with primary percutaneous coronary intervention (PPCI). Using next-generation sequencing, we examined the presence of rare variants in 40 genes proposed to be involved in lipid metabolism and we found that 60% of AMI patients had a rare variant in the genes involved in the cholesterol pathway. Our data show the importance of considering the wide scope of the cholesterol pathway in order to assess the genetic risk related to AMI.

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.

Comparison of paclitaxel and everolimus-eluting stents in ST-segment elevation myocardial infarction and influence of thrombectomy on outcomes. ESTROFA-IM study.

INTRODUCTION AND OBJECTIVES: We sought to compare the long-term clinical outcome of with ST-segment elevation myocardial infarction treated with paclitaxel-eluting stents or everolimus-eluting stents and the influence of thrombectomy on outcomes. METHODS: The ESTROFA-IM is a multicenter retrospective registry collecting consecutive patients with infarction treated with these stents in 16 centers. Propensity-score matching was performed to select comparable stent groups and comparable groups with and without thrombectomy. RESULTS: After matching patients, 350 treated with everolimus-eluting stents and 350 with paclitaxel-eluting stents were included in the analysis. The clinical and angiographic characteristics were comparable in both groups. The 2-year incidence of death, infarction, and target lesion revascularization was 14.9% for paclitaxel-eluting stents and 11.5% for everolimus-eluting stents (P = .04) and the incidence of definite/probable thrombosis 4.3% and 1.4%, respectively (P = .01). The use of paclitaxel-eluting was an independent predictor for events (hazard ratio = 2.44, 95% confidence interval, 1.28-4.65; P = .006). The benefit of everolimus-eluting stents over paclitaxel-eluting stents regarding stent thrombosis was more evident in the nonthrombectomy subgroup (5.4% vs 1.4%; P = .01). A significant interaction was found in the subgroups with and without thombectomy in the comparison between paclitaxel-eluting stents and everolimus-eluting stents for the end-point of stent thrombosis (P = .039). CONCLUSIONS: The results of this multicenter registry suggest better clinical outcomes with the everolimus-eluting stents in ST-segment elevation myocardial infarction. The lower risk of thrombosis with these stents could be more relevant in the absence of thrombectomy.

Comparison of paclitaxel-eluting stents (Taxus) and everolimus-eluting stents (Xience) in left main coronary artery disease with 3 years follow-up (from the ESTROFA-LM registry).

Evidence regarding therapy with drug-eluting stents in the left main coronary artery (LM) is based mostly on trials performed with first-generation drug-eluting stents. The aim of this study was to evaluate long-term clinical outcomes after treatment for unprotected LM disease with paclitaxel-eluting stents (PES) and everolimus-eluting stents (EES). The ESTROFA-LM is a multicenter retrospective registry including consecutive patients with unprotected LM disease treated with PES or EES. A total of 770 patients have been included at 21 centers, 415 with treated PES and 355 with EES. Treatment with 2 stents was more frequent with PES (17% vs 10.4%, p = 0.007), whereas intravascular ultrasound was more frequently used with EES (35.2% vs 26%, p = 0.006). The 3-year death and infarction survival rates were 86.1% for PES and 87.3% for EES (p = 0.50) and for death, infarction, and target lesion revascularization were 83.6% versus 82% (p = 0.60), respectively. Definite or probable thrombosis was 1.6% for PES and 1.4% for EES (p = 0.80). The use of 2 stents, age, diabetes, and acute coronary syndromes were independent predictors of mortality. In the subgroup of distal lesions, the use of intravascular ultrasound was an independent predictor of better outcome. Comparison of propensity score-matched groups did not yield differences between the 2 stents. In conclusion, the results of this multicenter registry show comparable safety and efficacy at 3 years for PES and EES in the treatment of LM disease. The use of bifurcation stenting techniques in distal lesions was a relevant independent predictor for events. The use of intravascular ultrasound appears to have a positive impact on patients treated for LM distal disease.

Comparison of exercise echocardiography and the Duke treadmill score for risk stratification in patients with known or suspected coronary artery disease and normal resting electrocardiogram.

BACKGROUND: Although exercise echocardiography (EE) is not clearly indicated in patients with normal electrocardiogram (ECG) as the first evaluation, there is a lack of data regarding its superiority over the Duke score for prognosis. We investigate whether EE has incremental value over the Duke score for predicting outcome in patients with normal ECG. METHODS: One thousand six hundred forty-seven patients with interpretable ECG referred for EE were followed up for 2.5 +/- 1.4 years. There were 58 hard events (myocardial infarction or cardiovascular death). RESULTS: There were 38 events in 735 patients with abnormal EE versus 20 events in 912 with normal EE (P < .0001). The Duke score, resting wall motion score index, and ischemia were independently associated to events (incremental P value of EE = .03). The Duke score allowed stratification of patients with abnormal EE (P = .001) or ischemia (P = .01) into different risk categories but did not stratify patients without these characteristics. Exercise echocardiography variables stratified patients with the low Duke score (left anterior descending artery territory P = .04, left anterior descending artery ischemia P = .03) and with the intermediate Duke score (abnormal EE P = .005, necrosis P = .0009, ischemia P = .004, resting ejection fraction P < .00001, resting wall motion score index P < .00001, peak ejection fraction P < .00001, peak wall motion score index P < .0001, number of territories P = .002, left anterior descending artery territory P = .001, and left anterior descending artery ischemia P = .002) but did not with the high Duke score. CONCLUSIONS: Exercise echocardiography has incremental value over clinical variables, the Duke score, and resting echocardiography for the prediction of hard cardiovascular events in patients with normal resting ECG.

[Real time myocardial contrast echocardiography to predict left ventricular wall motion recovery after reperfused acute myocardial infarction]. / Ecocardiografía de perfusión miocárdica en tiempo real para la predicción de la recuperación de la función ventricular después del infarto agudo de miocardio reperfundido.

INTRODUCTION AND OBJECTIVES: Real time myocardial contrast echocardiography (RTMCE) is a recently developed method. We sought to determine: a) whether RTMCE predicts recovery of left ventricular function after acute myocardial infarction (AMI), and b) whether data obtained with this method are comparable to those obtained with 99mTc-sestamibi single photon emission computed tomography (SPECT) and magnetic resonance. PATIENTS AND METHOD: We studied 85 patients with AMI who underwent angioplasty. RTMCE was performed 7 (4) days after AMI. Two-dimensional echocardiography was performed at the time of the RTMCE study and at follow-up (10 [4] weeks). SPECT and magnetic resonance were performed after AMI in 18 and 32 patients, respectively. RESULTS: Follow-up two-dimensional echocardiography results were available for 82 patients, who were subdivided into 2 groups: recovery (n=49) and no recovery (n=33). Regional (AMI-related) wall motion score index improved from 1.75 (0.49) to 1.32 (0.36) (P< .001) in the recovery group, and worsened from 1.85 (0.39) to 1.95 (0.36) in the no recovery group (P< .001). RTMCE perfusion score was 0.8 (0.3) in the recovery group, and 0.6 (0.4) in the no recovery group (P< .001). Concordance between RTMCE and SPECT in a segmental analysis was 78% (P< .001; kappa=0.49), whereas concordance between RTMCE and hyperenhancement with delayed contrast magnetic resonance findings was 70% (P< .001; kappa =0.35). Independent predictors of recovery were peak creatine kinase (OR=1.4 per 1000 UI; 95% CI, 1.0-1.9; P< .05) and RTMCE score (OR=8.8; 95% CI, 1.9-39.3; P< .01). A RTMCE score > or = 0.60 had a positive predictive value of 73% and a negative predictive value of 69% (P< .001; area under the curve 0.70). CONCLUSION: RTMCE showed a modest predictive value for recovery of left ventricular function after reperfused AMI.

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.

Comparison of ischemia-modified albumin levels in patients undergoing percutaneous coronary intervention for unstable angina pectoris with versus without coronary collaterals.

This study compared ischemia-modified albumin levels, a marker of ischemia in patients undergoing percutaneous coronary intervention. Ischemia-modified albumin levels were significantly lower in patients with collateral circulation compared with those without collateral circulation.

[Clinical characteristics, prognosis, and variability in the management of non-ST-segment elevation acute coronary syndromes. Data from the PEPA registry]. / Perfil clínico, pronóstico y variabilidad en el tratamiento del síndrome coronario agudo sin elevación del segmento ST. Datos del registro PEPA.

OBJECTIVES: To assess the clinical characteristics and inter-hospital variability in the treatment and prognosis of patients with non-ST-segment elevation acute coronary syndromes. PATIENTS AND METHOD: Data from the PEPA study, a prospective registry that enrolled 4,115 patients in 18 Spanish hospitals, were analyzed. RESULTS: The mean age of the patients enrolled was 65 years, 33% were women, and 26% had diabetes. Large differences were observed in the clinical profile of patients admitted to different centers, especially relative the history of previous disease, prior coronary revascularization, and co-morbidity. Antiplatelet treatment was used in 93% of patients, heparin in 45%, beta-blockers in 42%, nitrates in 67%, and calcium antagonists in 46%. During hospitalization, exercise stress testing was performed in 37% of patients, coronary angiography in 32%, coronary angioplasty in 9%, and coronary surgery in 4%. Inter-hospital variability was minimal for the use of antiplatelet agents, wide for the use of heparin and beta-blockers, and huge for the use of revascularization procedures. Mortality and the incidence of death or myocardial infarction were 2.6% and 4.4% during hospitalization, and 4.6% and 8% at 3 months, with wide inter-hospital variability. These differences were not significant once adjusted for clinical characteristics and the treatment received at admission. CONCLUSIONS: Patients with non-ST-segment elevation acute coronary syndromes represent an heterogeneous group with a high incidence of complications. Pharmacologic and, especially, invasive treatment varies widely in different hospitals. These results underline the importance of correct initial risk stratification and uniform treatment following the recommendations of clinical guidelines.