Browsing by Author "Selas, M"
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- Blunted Coronary Flow Velocity Reserve is Associated With Impairment in Systolic Function and Functional Capacity in Hypertrophic CardiomyopathyPublication . Aguiar Rosa, S; Rocha Lopes, L; Branco, L; Galrinho, A; Fiarresga, A; Thomas, B; Brás, P; Gonçalves, A; Cardoso, I; Papoila, A; Alves, M; Rio, P; Cruz, I; Selas, M; Silva, F; Silva, A; Cruz Ferreira, R; Mota Carmo, MBackground Coronary microvascular dysfunction constitutes an important pathophysiological feature in hypertrophic cardiomyopathy (HCM). We aimed to assess the association between impaired coronary flow velocity reserve (CFVR) and ventricular systolic function and functional capacity. Methods Eighty-three patients with HCM were enrolled in this prospective cohort study. Patients underwent echocardiogram to evaluate ventricular performance and CFVR in the left anterior descending artery (LAD) and posterior descending artery (PD). Diastolic coronary flow velocity was measured in basal conditions and in hyperemia. CFVR was calculated as the ratio of hyperemic and basal peak diastolic flow velocities. Functional capacity was evaluated by cardiopulmonary exercise testing (CPET). The link between CFVR and biventricular systolic function and peak VO2 was studied. Results Age was 55.0(14.4)years, 50 patients (60%) were male; 59 patients (71%) had nonobstructive HCM. Mean CFVR LAD was 1.81(0.49) and CFVR PD was 1.73(0.55). Lower CFVR PD was associated with impaired global longitudinal strain (GLS) 2D (β-estimate:-3.240,95%CI:-4.634;-1.846, p < 0.001), GLS 3D (β-estimate:-2.559,95%CI:-3.932;-1.186, p < 0.001) and area strain (β-estimate:-3.044,95%CI:-5.373;-0.716, p = 0.011). Lower values of CFVR PD related to worse global work index (β-estimate:267.824,95%CI:75.964;459.683, p = 0.007), global constructive work (β-estimate:217.300,95%CI:38.750;395.850, p = 0.018) and global work efficiency (β-estimate:5.656,95%CI:2.229;9.084, p = 0.002). Impaired CFVR LAD (β-estimate:2.826, 95%CI:0.913;4.739, p = 0.004) and CFVR PD (β-estimate:2.801,95%CI:0.657;4.945, p = 0.011) were associated with lower TAPSE. Lower values of CFVR LAD (β-estimate:2.580, 95%CI:0.169;4.991, p = 0.036) and CFVR PD (β-estimate:3.163, 95%CI: 0.721;5.606, p = 0.012) were associated with worse peak VO2. Conclusion Lower CFVR was associated with impairment in biventricular systolic function parameters and functional capacity assessed by pVO2.
- Changes of Soluble CD40 Ligand in the Progression of Acute Myocardial Infarction Associate to Endothelial Nitric Oxide Synthase Polymorphisms and Vascular Endothelial Growth Factor But Not to Platelet CD62P ExpressionPublication . Napoleão, P; Monteiro, MC; Cabral, L; Criado, MB; Ramos, C; Selas, M; Viegas-Crespo, AM; Saldanha, C; Mota Carmo, M; Cruz Ferreira, R; Pinheiro, TReported in vitro data implicated soluble CD40 ligand (sCD40L) in endothelial dysfunction and angiogenesis. However, whether sCD40L could exert that influence in endothelial dysfunction and angiogenesis after injury in acute myocardial infarction (AMI) patients remains unclear. In the present study, we evaluated the association of sCD40L with markers of platelet activation, endothelial, and vascular function during a recovery period early after AMI. To achieve this goal, the time changes of soluble, platelet-bound, and microparticle-bound CD40L levels over 1 month were assessed in AMI patients and correlated with endothelial nitric oxide synthase (eNOS) polymorphisms, vascular endothelial growth factor (VEGF) concentrations, and platelet expression of P-selectin (CD62P). The association of soluble form, platelet-bound, and microparticle-bound CD40L with CD62P expression on platelets, a marker of platelet activation, was also assessed to evaluate the role of CD40L in the thrombosis, whereas the association with eNOS and VEGF was to evaluate the role of CD40L in vascular dysfunction. This work shows for the first time that time changes of sCD40L over 1 month after myocardial infarct onset were associated with G894T eNOS polymorphism and with the VEGF concentrations, but not to the platelet CD62P expression. These results indicate that, in terms of AMI pathophysiology, the sCD40L cannot be consider just as being involved in thrombosis and inflammation but also as having a relevant role in vascular and endothelial dysfunction.
- Does Permanent Atrial Fibrillation Modify Response to Cardiac Resynchronization Therapy in Heart Failure Patients?Publication . Abreu, A; Oliveira, MM; Cunha, PS; Santa Clara, H; Portugal, G; Rodrigues, I; Santos, V; Almeida-Morais, L; Selas, M; Soares, R; Branco, LM; Cruz Ferreira, R; Mota Carmo, MINTRODUCTION: The benefits of cardiac resynchronization therapy (CRT) documented in heart failure (HF) may be influenced by atrial fibrillation (AF). We aimed to compare CRT response in patients in AF and in sinus rhythm (SR). METHODS: We prospectively studied 101 HF patients treated by CRT. Rates of clinical, echocardiographic and functional response, baseline NYHA class and variation, left ventricular ejection fraction, volumes and mass, atrial volumes, cardiopulmonary exercise test (CPET) duration (CPET dur), peak oxygen consumption (VO2max) and ventilatory efficiency (VE/VCO2 slope) were compared between AF and SR patients, before and at three and six months after implantation of a CRT device. RESULTS: All patients achieved ≥95% biventricular pacing, and 5.7% underwent atrioventricular junction ablation. Patients were divided into AF (n=35) and SR (n=66) groups; AF patients were older, with larger atrial volumes and lower CPET dur and VO2max before CRT. The percentages of clinical and echocardiographic responders were similar in the two groups, but there were more functional responders in the AF group (71% vs. 39% in SR patients; p=0.012). In SR patients, left atrial volume and left ventricular mass were significantly reduced (p=0.015 and p=0.021, respectively), whereas in AF patients, CPET dur (p=0.003) and VO2max (p=0.001; 0.083 age-adjusted) showed larger increases. CONCLUSION: Clinical and echocardiographic response rates were similar in SR and AF patients, with a better functional response in AF. Improvement in left ventricular function and volumes occurred in both groups, but left ventricular mass reduction and left atrial reverse remodeling were seen exclusively in SR patients
- Intracoronary Delivery of Human Mesenchymal/Stromal Stem Cells: Insights from Coronary Microcirculation Invasive Assessment in a Swine ModelPublication . Fiarresga, A; Mata, M; Cavaco-Gonçalves, S; Selas, M; Simões, I; Oliveira, E; Carrapiço, B; Cardim, N; Cabral, J; Cruz Ferreira, R; Silva, CBACKGROUND: Mesenchymal stem/stromal cells have unique properties favorable to their use in clinical practice and have been studied for cardiac repair. However, these cells are larger than coronary microvessels and there is controversy about the risk of embolization and microinfarctions, which could jeopardize the safety and efficacy of intracoronary route for their delivery. The index of microcirculatory resistance (IMR) is an invasive method for quantitatively assessing the coronary microcirculation status. OBJECTIVES: To examine heart microcirculation after intracoronary injection of mesenchymal stem/stromal cells with the index of microcirculatory resistance. METHODS: Healthy swine were randomized to receive by intracoronary route either 30x106 MSC or the same solution with no cells (1% human albumin/PBS) (placebo). Blinded operators took coronary pressure and flow measurements, prior to intracoronary infusion and at 5 and 30 minutes post-delivery. Coronary flow reserve (CFR) and the IMR were compared between groups. RESULTS: CFR and IMR were done with a variance within the 3 transit time measurements of 6% at rest and 11% at maximal hyperemia. After intracoronary infusion there were no significant differences in CFR. The IMR was significantly higher in MSC-injected animals (at 30 minutes, 14.2U vs. 8.8U, p = 0.02) and intragroup analysis showed a significant increase of 112% from baseline to 30 minutes after cell infusion, although no electrocardiographic changes or clinical deterioration were noted. CONCLUSION: Overall, this study provides definitive evidence of microcirculatory disruption upon intracoronary administration of mesenchymal stem/stromal cells, in a large animal model closely resembling human cardiac physiology, function and anatomy.
- Invasive Assessment of the Coronary Microcirculation Using the Index of Microcirculatory Resistance: Description and Validation of an Animal ModelPublication . Fiarresga, A; Selas, M; Oliveira, E; Cavaco-Gonçalves, S; Cacela, D; Carrapiço, B; Cardim, N; Cruz Ferreira, RINTRODUCTION: The index of microcirculatory resistance (IMR) enables/provides quantitative, invasive, and real-time assessment of coronary microcirculation status. AIMS: The primary aim of this study was to validate the assessment of IMR in a large animal model, and the secondary aim was to compare two doses of intracoronary papaverine, 5 and 10 mg, for induction of maximal hyperemia and its evolution over time. METHODS: Measurements of IMR were performed in eight pigs. Mean distal pressure (Pd) and mean transit time (Tmn) were measured at rest and at maximal hyperemia induced with intracoronary papaverine, 5 and 10 mg, and after 2, 5, 8 and 10 minutes. Disruption of the microcirculation was achieved by selective injection of 40-μm microspheres via a microcatheter in the left anterior descending artery. RESULTS: In each animal 14 IMR measurements were made. There were no differences between the two doses of papaverine regarding Pd response and IMR values - 11 ± 4.5 U with 5 mg and 10.6 ± 3 U with 10 mg (p=0.612). The evolution of IMR over time was also similar with the two doses, with significant differences from resting values disappearing after five minutes of intracoronary papaverine administration. IMR increased with disrupted microcirculation in all animals (41 ± 16 U, p=0.001). CONCLUSIONS: IMR provides invasive and real-time assessment of coronary microcirculation. Disruption of the microvascular bed is associated with a significant increase in IMR. A 5-mg dose of intracoronary papaverine is as effective as a 10-mg dose in inducing maximal hyperemia. After five minutes of papaverine administration there is no significant difference from resting hemodynamic status.
- Microvascular Dysfunction Is Associated With Impaired Myocardial Work in Obstructive and Nonobstructive Hypertrophic Cardiomyopathy: A Multimodality StudyPublication . Garcia Brás, P; Aguiar Rosa, S; Cardoso, I; Branco, L; Galrinho, A; Valentim Gonçalves, A; Thomas, B; Viegas, JM; Fiarresga, A; Branco, G; Pereira, R; Selas, M; Silva, F; Cruz, I; Baquero, L; Cruz Ferreira, R; Rocha Lopes, LBackground Two-dimensional speckle tracking echocardiography has been shown to correlate with microvascular dysfunction, a hallmark of hypertrophic cardiomyopathy (HCM). We hypothesized that there is an association between myocardial work and left ventricular ischemia, with incremental value to global longitudinal strain, in patients with HCM. Methods and Results We performed a prospective assessment of patients with HCM, undergoing 2-dimensional speckle tracking echocardiography and stress perfusion cardiac magnetic resonance. Results were stratified according to obstructive or nonobstructive HCM and the presence of significant replacement fibrosis (late gadolinium enhancement ≥15% of left ventricular mass). Seventy-five patients with HCM (63% men, age 55±15 years) were evaluated, 28% with obstructive HCM (mean gradient 89±60 mm Hg). Perfusion defects were found in 90.7%, involving 22.5±16.9% of left ventricular mass, and 38.7% had late gadolinium enhancement ≥15%. In a multivariable analysis, a lower global work index (r=-0.519, β-estimate -10.822; P=0.001), lower global work efficiency (r=-0.379, β-estimate -0.123; P=0.041), and impaired global constructive work (r=-0.532, β-estimate -13.788; P<0.001) significantly correlated with ischemia. A segmental analysis supported these findings, albeit with lower correlation coefficients. A global work index cutoff ≤1755 mm Hg% was associated with hypoperfusion with a sensitivity of 88% and a specificity of 71%, while the best cutoff for global longitudinal strain (>-15.5%) had a sensitivity of 64% and a specificity of 57%. The association between myocardial work and perfusion defects was significant independently of late gadolinium enhancement ≥15% and obstructive HCM. Conclusions Impaired myocardial work was significantly correlated with the extent of ischemia in cardiac magnetic resonance, independently of the degree of left ventricular hypertrophy or fibrosis, with a higher predictive power than global longitudinal strain.
- Percutaneous Treatment of Mitral Valve Regurgitation: Initial Experience with the MitraClip DevicePublication . Cacela, D; Fiarresga, A; Branco, LM; Galrinho, A; Rio, P; Selas, M; Cruz Ferreira, RINTRODUCTION: Mitral regurgitation (MR) is the most common valvular disease and has recently become the target of a number of percutaneous approaches. The MitraClip is virtually the only device for which there is considerable experience, with more than 20,000 procedures performed worldwide. OBJECTIVE: To describe our initial experience of the percutaneous treatment of MR with the MitraClip device. METHODS: We describe the first six MitraClip cases performed in this institution (mean age 58.5 ± 13.1 years), with functional MR grade 4+ and New York Heart Association (NYHA) heart failure class III or IV (n=3), with a mean follow-up of 290 ± 145 days. RESULTS: Procedural success (MR ≤ 2+) was 100%. Total procedure time was 115.8 ± 23.7 min, with no in-hospital adverse events and discharge between the fourth and eighth day, and consistent improvement in the six-minute walk test (329.8 ± 98.42 vs. 385.33 ± 106.95 m) and in NYHA class (three patients improved by two NYHA classes). During follow-up there were two deaths, in two of the four patients who had been initially considered for heart transplantation. CONCLUSION: In patients with functional MR the MitraClip procedure is safe, with both a high implantation and immediate in-hospital success rate. A longer follow-up suggests that the clinical benefit decreases or disappears completely in patients with more advanced heart disease, namely those denied transplantation or on the heart transplant waiting list.
- Prognostic Value of VEGF in Patients Submitted to Percutaneous Coronary InterventionPublication . Ramos, C; Napoleão, P; Selas, M; Freixo, C; Viegas Crespo, AM; Mota Carmo, M; Cruz Ferreira, R; Pinheiro, TWe examined the longitudinal changes of VEGF levels after percutaneous coronary intervention for predicting major adverse cardiac events (MACE) in coronary artery disease (CAD) patients. VEGF was measured in 94 CAD patients' serum before revascularization, 1-month and 1-year after. Independently of clinical presentation, patients had lower VEGF concentration than a cohort of healthy subjects (median, IQ: 15.9, 9.0-264 pg/mL versus 419, 212-758 pg/mL; P < 0.001) at baseline. VEGF increased to 1-month (median, IQ: 276, 167-498 pg/mL; P < 0.001) and remained steady to 1-year (median, IQ: 320, 173-497 pg/mL; P < 0.001) approaching control levels. Drug eluting stent apposition and previous medication intake produced a less steep VEGF evolution after intervention (P < 0.05). Baseline VEGF concentration <40.8 pg/mL conveyed increased risk for MACE in a 5-year follow-up. Results reflect a positive role of VEGF in recovery and support its importance in CAD prognosis.
- Proinflammatory Soluble CD40 Ligand Is Associated with the Systemic Extent of Stable AtherosclerosisPublication . Pereira da Silva, T; Napoleão, P; Pinheiro, T; Selas, M; Silva, F; Cruz Ferreira, R; Mota Carmo, MBackground and objectives: Polyvascular atherosclerosis is frequent and associated with a high cardiovascular risk, although the mechanisms regulating the atherosclerosis extent to single or multiple arterial territories are still poorly understood. Inflammation regulates atherogenesis and soluble CD40 ligand (sCD40L) is an inflammatory mediator associated with the presence of single-territorial atherosclerosis. We assessed whether the sCD40L expression is associated with the atherosclerosis extent to single or multiple arterial territories and with the atherosclerosis severity in different territories. Materials and Methods: We prospectively enrolled 94 participants with no atherosclerosis (controls, n = 26); isolated coronary atherosclerosis (group 1, n = 20); coronary and lower extremity (LE) atherosclerosis (group 2, n = 18); coronary and carotid atherosclerosis (group 3, n = 12); and coronary, LE, and carotid atherosclerosis (group 4, n = 18). Serum sCD40L levels were quantified. Results: The sCD40L levels (ng/mL, mean (standard deviation)) were 4.0 (1.5), 5.6 (2.6), 7.2 (4.2), 5.9 (3.7), and 5.1 (2.4) in controls and groups 1 to 4, respectively (ANOVA p = 0.012). In nonrevascularized patients, the sCD40L levels were significantly higher in group 2 than in group 1 and were correlated with the number of LE diseased segments. Prior LE bypass surgery was associated with lower sCD40L levels. Coexistence of coronary and LE atherosclerosis was independently associated with the sCD40L levels. Conclusions: The sCD40L levels were increased in stable atherosclerosis, particularly in polyvascular coronary and LE atherosclerosis. The number of LE diseased segments and prior LE revascularization were associated with sCD40L expression. To our knowledge, these are novel data, which provide insights into the mechanisms underlying multi-territorial atherosclerosis expression. sCD40L may be a promising noninvasive tool for refining the stratification of the systemic atherosclerotic burden.
- Serial Changes in Oxidized Low-Density Lipoprotein Associated with Culprit Vessel in ST - Elevation Myocardial Infarction - a Promising Marker?Publication . Napoleão, P; Selas, M; Toste, A; Turkman, A; Andreozzi, V; Viegas-Crespo, AM; Pinheiro, T; Cruz Ferreira, RThe aim of the present study was to investigate variations in oxidized LDL (oxLDL) at the onset of acute myocardial infarction (AMI) and over the recovery period, exploring their relationship with coronary disease severity. A follow-up of 50 AMI patients was evaluated against 25 healthy volunteers (reference group). The AMI patients were evaluated at three time points: at admission before the administration of IIb/IIIa inhibitors and angioplasty, and two and 40 days after intervention. Plasma oxLDL concentrations were measured by ELISA. oxLDL was found to be significantly higher in AMI patients in the acute phase relative to reference levels, decreasing progressively over the recovery period. The results also demonstrated that oxLDL levels were decreased in patients with the left circumflex artery (LCX) as culprit vessel compared to the left anterior descending coronary (LAD) or right coronary artery (RCA). The results highlight a significant increase in oxLDL concentration related to coronary artery disease severity, as conditions such as LCX lesions are usually associated with a favorable prognosis, contrasting with LAD-associated conditions that can compromise large areas of myocardium. The results thus suggest that oxLDL may constitute a promising marker in assessment of AMI evolution.