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.

Coronary Obstruction After Transcatheter Aortic Valve Replacement: Insights From the Spanish TAVI Registry.

BACKGROUND: Coronary obstruction (CO) following transcatheter aortic valve replacement (TAVR) is a life-threatening complication, scarcely studied. OBJECTIVES: The authors analyzed the incidence of CO after TAVR, presentation, management, and in-hospital and 1-year clinical outcomes in a large series of patients undergoing TAVR. METHODS: Patients from the Spanish TAVI (Transcatheter Aortic Valve Implantation) registry who presented with CO in the procedure, during hospitalization or at follow-up were included. Computed tomography (CT) risk factors were assessed. In-hospital, 30-day, and 1-year all-cause mortality rates were analyzed and compared with patients without CO using logistic regression models in the overall cohort and in a propensity score-matched cohort. RESULTS: Of 13,675 patients undergoing TAVR, 115 (0.80%) presented with a CO, mainly during the procedure (83.5%). The incidence of CO was stable throughout the study period (2009-2021), with a median annual rate of 0.8% (range 0.3%-1.3%). Preimplantation CT scans were available in 105 patients (91.3%). A combination of at least 2 CT-based risk factors was less frequent in native than in valve-in-valve patients (31.7% vs 78.3%; P < 0.01). Percutaneous coronary intervention was the treatment of choice in 100 patients (86.9%), with a technical success of 78.0%. In-hospital, 30-day, and 1-year mortality rates were higher in CO patients than in those without CO (37.4% vs 4.1%, 38.3% vs 4.3%, and 39.1% vs 9.1%, respectively; P < 0.001). CONCLUSIONS: In this large, nationwide TAVR registry, CO was a rare, but often fatal, complication that did not decrease over time. The lack of identifiable predisposing factors in a subset of patients and the frequently challenging treatment when established may partly explain these findings.

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).

Assessment of diastolic function during exercise echocardiography: annulus mitral velocity or transmitral flow pattern?

OBJECTIVES: We hypothesize that the change in the left ventricular (LV) diastolic pattern (DP) may be measured with high reproducibility and correlates with exercise echocardiography (EE) better than the ratio of early LV inflow velocity to early diastolic annulus velocity (E/e' index). BACKGROUND: The E/e' index has been related to LV filling pressures but has not been compared with DP. METHODS: We selected 179 consecutive patients who were referred for EE. Early (E) and late (A) LV inflow velocities by conventional pulsed Doppler, and septal annulus e' velocity by pulsed Doppler myocardial imaging were measured at rest (R) and post-exercise (PE). RESULTS: Four LV-DPs were found: abnormal relaxation (AR) at R and PE (E < A) in 110 patients; AR at PE (E > A at R; E < A at PE) in 22 patients; restrictive pattern (RP) at R and PE (E > A) in 18 patients; and RP at PE (E < A at R; E > A at PE) in 29 patients. The more accurate PE cutoff E/e' values to predict abnormal EE, ischemic response, poor functional capacity (< 8 Mets in men; < 6 Mets in women), and lack of increase in left ventricular ejection fraction (LVEF) were 12, 12, 11, and 11 (areas under the curve were 0.53, 0.53, 0.63, and 0.57, respectively). Corresponding areas under the curve for an RP at R + PE or only at PE were 0.57, 0.55, 0.54, and 0.56 (P = not significant). The sensitivity of an RP at R + PE or only at PE was lower and the specificity was higher than those of the different E/e' cutoff values for predicting abnormal EE, functional capacity, ischemic response, and lack of increase in LVEF. Achieved Mets were lower in patients with an RP at R + PE or only at PE irrespectively of the E/e' values, whereas achieved Mets in patients with AR at R + PE or only at PE were lower if the E/e' was > or = 11 (8.2 +/- 2.9 vs. 9.8 +/- 3.1, P = .01). Interobserver and intraobserver concordance were 95% (kappa = 0.86) and 100% (kappa = 1.0) for an RP, and 86% (kappa = 0.73) and 92% (kappa = 0.78) for a PE-E/e' value of > or = 11. CONCLUSIONS: E/e' does not allow further stratification in patients with exercise RP. We propose both measurement of E/e' and determination of the LV-DP (a quickly assessable variable) for the assessment of diastolic function during EE. However, when an RP persists or develops with exercise, further assessment may not be more informative.

Comparison of 2- and 3-dimensional exercise echocardiography for the detection of coronary artery disease.

BACKGROUND: Although 3-dimensional echocardiography (3DE) has been applied during dobutamine echocardiography it has not been used during exercise echocardiography. We sought to compare feasibility and accuracy of 3DE and 2-dimensional echocardiography (2DE) during exercise echocardiography. METHODS: 100 patients underwent peak and postexercise (PEx) 2DE and 3DE on separate days. Coronary artery disease was detected in 58 patients. A quality score was calculated by assigning 0 to 3 points to each wall (apicoseptal, posterolateral, anterior, inferior). RESULTS: Feasibility of peak 2DE, peak 3DE, PEx 2DE, and PEx 3DE was 99%, 92%, 100%, and 95%, respectively (2DE at peak or PEx vs peak 3DE, P < .05). Agreement between 2DE and 3DE was 82% at peak (kappa = 0.62) and 78% at PEx (kappa = 0.55). Quality score less than 2 was seen in 4% of the walls with peak 2DE, in none with PEx 2DE, in 18% by peak 3DE, and in 14% by PEx 3DE. The mean quality score was lower with 3DE at peak and at PEx (2.4 +/- 0.9 vs 2.9 +/- 0.3; and 2.5 +/- 0.8 vs 3.0 +/- 0.1, both P < .0001). Acquisition time was shorter with 3DE at peak and PEx (22 +/- 8 vs 43 +/- 14 seconds; and 15 +/- 5 vs 31 +/- 14 seconds, both P < .0001). Sensitivity of peak 2DE, peak 3DE, PEx 2DE, and PEx 3DE was 84%, 78%, 71%, and 58%, respectively (P < .05 vs peak 3DE and peak 2DE). Specificity was 76%, 73%, 93%, and 88%, respectively. Accuracy for peak 2DE was 81% (area under the curve [AUC] 0.81, 95% confidence interval [CI] = 0.71-0.91); for peak 3DE was 76% (AUC 0.76, 95% CI = 0.65-0.86); for PEx 2DE was 80% (AUC 0.84, 95% CI = 0.75-0.92); and for PEx 3DE was 71% (AUC 0.73, 95% CI = 0.62-0.83). CONCLUSIONS: Three-dimensional echocardiography during exercise is comparable with 2DE in terms of sensitivity and specificity but feasibility is lower.

Global left ventricular systolic function based on the sum of regional myocardial velocities during exercise echocardiography.

OBJECTIVES: We sought to assess the relationship between global Doppler myocardial imaging (DMI) and left ventricular (LV) ejection fraction (LVEF) at both rest and exercise. BACKGROUND: We have previously demonstrated that global DMI correlates with LVEF at rest with low variability. METHODS: LVEF by 2-dimensional echocardiography, systolic global tissue Doppler velocity (s-TDV), strain (S) rate (SR), and S were assessed in 122 patients. LVEF was measured at rest and at peak exercise, whereas DMI was performed at rest and immediately postexercise. The region of interest by color DMI was set to enclose the external myocardial border when the LV achieved its maximal dimension. The means of the DMI assessments in the 4- and 2-chamber apical views at rest and postexercise were measured to correlate with LVEF. RESULTS: Significant correlations were found between the LVEF and global s-TDV, SR, and S either at rest (r = 0.32, r = 0.50, and r = 0.33, all P < .001) or at exercise (r = 0.47, r = 0.63, and r = 0.40, all P < .001). The best differentiation of an abnormal from a normal LVEF (>or=50%) at rest was provided by s-TDV less than 1.8 cm/s (sensitivity 63%, specificity 78%, area under the curve [AUC] 0.76, confidence interval [CI] 0.63-0.90), SR greater than -0.50/s (sensitivity 90%, specificity 76%, AUC 0.86, CI 0.76-0.97), and S greater than -9% (sensitivity 83%, specificity 75%, AUC 0.81, CI 0.70-0.91); whereas at exercise it was provided by s-TDV less than 3.5 cm/s (sensitivity 75%, specificity 74%, AUC 0.79, CI 0.69-0.89), SR greater than -0.80/s (sensitivity 83%, specificity 81%, AUC 0.91, CI 0.86-0.96), and S greater than -11% (sensitivity 67%, specificity 69%, AUC 0.74, CI 0.63-0.85). CONCLUSIONS: Global DMI is a valuable tool to assess global LV function during exercise.

[Value of resting and exercise mitral regurgitation during exercise echocardiography to predict outcome in patients with left ventricular dysfunction]. / Valor pronóstico de la regurgitación mitral en reposo y ejercicio durante la ecocardiografía de ejercicio en pacientes con disfunción ventricular izquierda.

INTRODUCTION AND OBJECTIVES: The relative value of exercise echocardiography (EE) over resting echocardiography when this last incorporates information on mitral regurgitation (MR) is unknown. Furthermore, limited data exists regarding to the value of MR worsening during exercise in patients with LV dysfunction. We investigated whether: a) EE has incremental value over a resting echo-Doppler study; and b) post-exercise MR increments the value of EE for predicting outcome in patients with LV dysfunction. METHODS: 388 consecutive patients with LV dysfunction (LV ejection fraction <50%) were followed for 2.1 (1.5) years. There were 46 hard events (myocardial infarction in 10 and cardiac death in 36). RESULTS: There were 43 events in 319 patients with abnormal EE vs 3 events in 69 patients with normal EE (13% vs 4%, P=.04), whereas there were 20 events in the 103 patients with at least moderate resting MR vs 26 events in the 288 with no/mild MR (19% vs 9%, P=.006). Resting MR, peak heart rate x blood pressure, and n masculine of diseased territories on EE were independently associated to hard events. The same variables and MR worsening were independently associated to cardiac death. CONCLUSIONS: EE maintains its higher prognostic value over resting echocardiography even when this last incorporates information on MR. MR worsening increments the value of EE for predicting cardiac death in patients with LV dysfunction.

[Clinical significance of late gadolinium enhancement on cardiovascular magnetic resonance in patients with hypertrophic cardiomyopathy]. / Significado clínico del realce tardío de gadolinio con resonancia magnética en pacientes con miocardiopatía hipertrófica.

INTRODUCTION AND OBJECTIVES: In patients with hypertrophic cardiomyopathy, myocardial fibrosis can be detected by late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging. We investigated the relationships between the extent of LGE, left ventricular morphology and function, and clinical characteristics. METHODS: Both cine and gadolinium-enhanced magnetic resonance imaging were performed in 104 patients with hypertrophic cardiomyopathy. RESULTS: Fifty patients (48%) showed LGE (range: 1-11 segments). The extent of LGE was positively correlated with maximum left ventricular wall thickness (r=0.53, P< .001), left ventricular mass (r=0.41, P< .001), and the number of hypokinetic segments (r=0.51, P< .001), and inversely correlated with ejection fraction (r=-0.32, P=.001), the magnitude of the subaortic gradient increase during exercise echocardiography (r=-0.26, P=.023), and age at diagnosis (r=-0.20, P=.04). Four of the five patients with an ischemic response on exercise echocardiography had > or =3 segments showing LGE (P=.003). Severe hypertrophy (i.e., > or =30 mm) and nonsustained ventricular tachycardia occurred more frequently as the number of LGE segments increased (P< .001 and P=.04, respectively). CONCLUSIONS: Extensive LGE reflects greater disease expression. It is associated with more severe myocardial damage (i.e., a lower ejection fraction and a larger number of hypokinetic segments) and with adverse clinical characteristics (e.g., young age at diagnosis, severe hypertrophy, nonsustained ventricular tachycardia, and an ischemic response on exercise), suggesting that it may be closely linked to prognosis.

[Beta-myosin heavy-chain gene mutations in patients with hypertrophic cardiomyopathy]. / Mutaciones en el gen de la cadena pesada de la betamiosina en pacientes con miocardiopatía hipertrófica.

INTRODUCTION AND OBJECTIVES: To determine the frequency of mutations in the beta-myosin heavy-chain gene (MYH7) in a cohort of patients with hypertrophic cardiomyopathy (HCM) and their families, and to investigate correlations between genotype and phenotype. METHODS: Single-strand conformation polymorphism analysis and sequencing of fragments with abnormal MYH7 gene mobility were carried out in 128 consecutive index patients with HCM. The phenotypes of patients with and without mutations were compared and the phenotypes of identified families were recorded. RESULTS: A total of 11 mutations were found in 13 families (10%); 7/11 had been previously described. The I736T mutation was found in three families and the A797T in two. One patient had two mutations (i.e., I736T and R787H). Mutations were more frequent in patients with a family history of sudden death (31%) and in those with severe hypertrophy (39% had a thickness > or = 30 mm). Mutations were found in 29 of 42 members of the 13 families, including six family members (20%) who were healthy carriers and aged < or = 36 years. Sudden death had occurred in eight members of four families: four in two families with the I736T mutation, one in a family with A797T, one in a family with R870H, and two in a family with A901P. CONCLUSIONS: MYH7 mutations were present in 10% of our families. Mutations were more frequent in patients with a family history of sudden death and in those with severe hypertrophy. Most mutations had been described previously. Some appeared in several families. For some mutations, the correlation between genotype and phenotype was stable, while for others, there were marked differences between the phenotypes of the index patients and their relatives, suggesting the presence of additional genetic factors that have yet to be identified.

Prognostic value of mitral regurgitation assessment during exercise echocardiography in patients with known or suspected coronary artery disease.

BACKGROUND: Although mitral regurgitation (MR) may be assessed during exercise echocardiography (EE) there are no data regarding its value for predicting outcome in large series of patients. We sought to determine whether the predictive value of EE is maintained over clinical variables and resting echocardiography when the latter included information on MR, and to verify whether postexercise MR may improve the value of EE for predicting outcome. METHODS: In all, 1916 patients (mean age +/- 1SD = 62 +/- 11 years; mean left ventricular ejection fraction +/- 1SD = 56 +/- 11) referred for EE were followed up for 1.9 +/- 1.4 years. RESULTS: There were 87 cardiac events before revascularization: 67 events occurred in 948 patients with abnormal EE and 20 events occurred in 968 patients with normal EE (P < .0001), whereas there were 24 events in the 218 patients with moderate or higher resting MR and 63 events in the 1698 patients with no or mild MR (P < .0001). Previous myocardial infarction, resting MR, peak double product, and peak left ventricular ejection fraction were independently associated to hard events (chi2 model = 144, P < .0001). The same variables were associated to cardiac death (chi2 model = 141, P < .0001). Predictors of cardiac events in patients with abnormal EE were resting MR, resting wall-motion score index, metabolic equivalents, peak double product, and MR worsening (incremental P value of MR worsening = .03). Predictors of cardiac death were resting MR, peak double product, peak left ventricular ejection fraction, and MR worsening (incremental P value of MR worsening = .03). CONCLUSIONS: EE maintains its higher prognostic value over resting echocardiography even when the latter incorporates information on resting MR. MR worsening provides significant incremental prognostic information in patients with abnormal EE.

Risk stratification by treadmill exercise echocardiography.

BACKGROUND: Although exercise echocardiography (EE) has value for the diagnosis of coronary artery disease (CAD), it's not clear whether it may be useful for risk assessment in all categories of patients. To determine whether: 1) there is an incremental value of EE over clinical, exercise and resting echocardiographic variables for the prediction of events according to the pre-test probability of CAD; and 2) the number, location of the diseased territories, and nature of the disease affect the risk stratification, we studied 2436 patients referred for EE that were followed for 2.1 +/- 1.5 years. METHODS: Based on a pre-test score, previous myocardial infarction (MI) or revascularizations, 1242 patients were considered as having high, 1038 moderate, and 156 low pre-test probability. RESULTS: There were 89 hard events (myocardial infarction or cardiovascular death) in the 1203 patients with abnormal EE vs. 31 events in the 1233 with normal EE (p < 0.0001). Gender, Mets, heart rate x blood pressure, resting wall motion score index and number of involved territories at exercise were independently associated to hard events (final Chi-square = 170, incremental p value of exercise echo <0.0001). The incremental value of exercise echo over other variables was found in patients with the different pre-test probabilities. CONCLUSIONS: Exercise echocardiography has incremental value over clinical, exercise and resting echocardiographic variables in patients with different pre-test probabilities of CAD.

[Inflammation, atherosclerosis and cardiovascular disease risk: PAPP-A, Lp-PLA2 and cystatin C. New insights or redundant information?]. / Inflamación, aterosclerosis y riesgo cardiovascular: PAPP-A, Lp-PLA2 y cistatina C. 'Nuevas aportaciones o información redundante?

It is well-known that inflammation plays a role in atherogenesis, atherosclerotic plaque progression, and acute coronary syndrome. Inflammatory cells, and cytokines and other biomolecules are implicated in these processes, and have, therefore, been investigated as potential markers of atherosclerotic plaque progression and cardiovascular disease risk. The best characterized and most widely studied is C-reactive protein. However, its role in the clinical setting is still debated. Emerging novel biomarkers that may provide information complementary to that derived from C-reactive protein include pregnancy-associated plasma protein A, lipoprotein-associated phospholipase A2, and cystatin C. This article focuses on the potential value of these three new markers in patients with coronary heart disease, and their use as markers of disease risk in apparently healthy individuals.

Humoral heart rejection (severe allograft dysfunction with no signs of cellular rejection or ischemia): incidence, management, and the value of C4d for diagnosis.

Severe allograft dysfunction after heart transplant (HT), without ischemia or evidence of cellular rejection upon endomyocardial biopsy (EMB), is a rare but potentially fatal condition that suggests humoral rejection (HR). Its incidence, and the methods of choice for its diagnosis and management, remain uncertain. We retrospectively studied 445 HT patients (April 1991-December 2003) to determine incidence of HR diagnosed by clinical and conventional histopathological criteria. We used immunofluorescence (IF) techniques to test archived frozen EMB issue for IgM, IgG, C1q, C3, fibrin and C4d. Twelve patients (2.7%) fulfilled the criteria for HR after a mean time post-HT of 21.3 +/- 24.7 months (range: 2-72 months). Patients were treated with high doses of steroids and plasmapheresis, with successful recovery in 11 cases. IF studies using classical markers were mainly negative for the six patients with enough EMB tissue for testing. All six patients showed positivity for C4d during the HR episode but not before or after. Humoral rejection was observed in less than 3% of HT patients. Plasmapheresis treatment was highly effective. Classical IF tests were not useful for diagnosis, but C4d appears to be useful both for confirmation of diagnosis and for monitoring response to treatment.