Susanna Prat-Gonzalez

Evaluation of pulmonary artery stiffness in pulmonary hypertension with cardiac magnetic resonance.

OBJECTIVES This study sought to evaluate indexes of pulmonary artery (PA) stiffness in patients with pulmonary hypertension (PH) using same-day cardiac magnetic resonance (CMR) and right heart catheterization (RHC). BACKGROUND Pulmonary artery stiffness is increased in the presence of PH, although the relationship to PH severity has not been fully characterized. METHODS Both CMR and RHC were performed on the same day in 94 patients with known or suspected PH. According to the RHC, patients were classified as having no PH (n = 13), exercise-induced PH (EIPH) only (n = 6), or PH at rest (n = 75). On CMR, phase-contrast images were obtained perpendicular to the pulmonary trunk. From CMR and RHC data, PA areas and indexes of stiffness (pulsatility, compliance, capacitance, distensibility, elastic modulus, and the pressure-independent stiffness index beta) were measured at rest. RESULTS All quantified indexes showed increased PA stiffness in patients with PH at rest in comparison with those with EIPH or no PH. Despite the absence of significant differences in baseline pressures, patients with EIPH had lower median compliance and capacitance than patients with no PH: 15 (interquartile range: 9 to 19.8) mm2/mm Hg versus 8.4 (interquartile range: 6 to 10.3) mm2/mm Hg, and 5.2 (interquartile range: 4.4 to 6.3) mm3/mm Hg versus 3.7 (interquartile range: 3.1 to 4.1) mm3/mm Hg, respectively (p < 0.05). The different measurements of PA stiffness, including stiffness index beta, showed significant correlations with PA pressures (r2 = 0.27 to 0.73). Reduced PA pulsatility (<40%) detected the presence of PH at rest with a sensitivity of 93% and a specificity of 63%. CONCLUSIONS Pulmonary artery stiffness increases early in the course of PH (even when PH is detectable only with exercise and before overt pressure elevations occur at rest). These observations suggest a potential contributory role of PA stiffness in the development and progression of PH.

Early Metoprolol Administration Before Coronary Reperfusion Results in Increased Myocardial Salvage Analysis of Ischemic Myocardium at Risk Using Cardiac Magnetic Resonance

Background— &bgr;-Blockers improve clinical outcome when administered early after acute myocardial infarction. However, whether &bgr;-blockers actually reduce the myocardial infarction size is still in dispute. Cardiac magnetic resonance imaging can accurately depict the left ventricular (LV) ischemic myocardium at risk (T2-weighted hyperintense region) early after myocardial infarction, as well as the extent of necrosis (delayed gadolinium enhancement). The aim of this study was to determine whether early administration of metoprolol could increase myocardial salvage, measured as the difference between the extent of myocardium at risk and myocardial necrosis. Methods and Results— Twelve Yorkshire pigs underwent a 90-minute left anterior descending coronary occlusion, followed by reperfusion. They were randomized to metoprolol (7.5 mg during myocardial infarction) or placebo. Global and regional LV function, extent of myocardium at risk, and myocardial necrosis were quantified by cardiac magnetic resonance imaging studies performed 4 and 22 days after reperfusion in 10 survivors. Despite similar extent of myocardium at risk in metoprolol- and placebo-treated pigs (30.9% of LV versus 30.6%; P=NS), metoprolol resulted in 5-fold-larger salvaged myocardium (32.4% versus 6.2% of myocardium at risk; P=0.015). The LV ejection fraction significantly improved in metoprolol-treated pigs between days 4 and 22 (37.2% versus 43.0%; P=0.037), whereas it remained unchanged in pigs treated with placebo (35.1% versus 35.0%; P=NS). The extent of myocardial salvage was related directly to LV ejection fraction improvement (P=0.031) and regional LV wall motion recovery (P=0.039) at day 22. Conclusions— Early metoprolol administration during acute coronary occlusion increases myocardial salvage. The extent of myocardial salvage, measured as the difference between myocardium at risk and myocardial necrosis, was associated with regional and global LV motion improvement.

The cardioprotection granted by metoprolol is restricted to its administration prior to coronary reperfusion

BACKGROUND Myocardial infarct size is a strong predictor of cardiovascular events. Intravenous metoprolol before coronary reperfusion has been shown to reduce infarct size; however, it is unknown whether oral metoprolol initiated early after reperfusion, as clinical guidelines recommend, is similarly cardioprotective. We compared the extent of myocardial salvage associated with intravenous pre-reperfusion-metoprolol administration in comparison with oral post-reperfusion-metoprolol or placebo. We also studied the effect on suspected markers of reperfusion injury. METHODS Thirty Yorkshire-pigs underwent a reperfused myocardial infarction, being randomized to pre-reperfusion-metoprolol, post-reperfusion-metoprolol or placebo. Cardiac magnetic resonance imaging was performed in eighteen pigs at day 3 for the quantification of salvaged myocardium. The amounts of at-risk and infarcted myocardium were quantified using T2-weighted and post-contrast delayed enhancement imaging, respectively. Twelve animals were sacrificed after 24h for reperfusion injury analysis. RESULTS The pre-reperfusion-metoprolol group had significantly larger salvaged myocardium than the post-reperfusion-metoprolol or the placebo groups (31 ± 4%, 13 ± 6%, and 7 ± 3% of myocardium at-risk respectively). Post-mortem analyses suggest lesser myocardial reperfusion injury in the pre-reperfusion-metoprolol in comparison with the other 2 groups (lower neutrophil infiltration, decreased myocardial apoptosis, and higher activation of the salvage-kinase phospho-Akt). Salvaged myocardium and reperfusion injury pair wise comparisons proved there were significant differences between the pre-reperfusion-metoprolol and the other 2 groups, but not among the latter two. CONCLUSIONS The intravenous administration of metoprolol before coronary reperfusion results in larger myocardial salvage than its oral administration initiated early after reperfusion. If confirmed in the clinical setting, the timing and route of β-blocker initiation could be revisited.

Cardiac CT: Indications and Limitations*

Cardiac CT (CCT) is rapidly evolving as a noninvasive imaging modality. Newer technologic developments in CCT allow the comprehensive assessment of cardiovascular anatomy, including the coronary arteries. There are special considerations regarding obtaining and accurately interpreting CCT studies. On completion of this article, the reader should be able to describe the issues related to adequate patient preparation and acquisition and interpretation of CCT studies, recognize specific limitations that impair image quality and subsequently the accuracy of diagnosis, and list the current indications and future potential applications of this technique.

Carvedilol administration in acute myocardial infarction results in stronger inhibition of early markers of left ventricular remodeling than metoprolol

BACKGROUND The structural secuelae of acute myocardial infarction (AMI) is mostly dictated by left ventricular (LV) remodelling, leading to heart failure. Monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play a critical role in LV remodelling. β-blockers are first line therapy for AMI and heart failure; however, the mechanisms responsible for their benefits remain poorly understood. Different β-blocker agents have been shown to exert beneficial activities both in AMI and heart failure, however, their role in early remodelling after ischemia/reperfusion is to be fully elucidated. We sought to compare the effect of 2 of the most prescribed β-blocker agents in early markers of LV remodelling after AMI. METHODS A reperfused AMI was induced in Yorshire pigs, being randomized to early intravenous carvedilol, metoprolol or placebo. Twenty-four hours after reperfusion markers of early remodelling were addressed in the LV. RESULTS The early administration of both β-blockers is able to significantly reduce macrophage infiltration as well as the expression and activity of MCP-1 and MMP-2 compared to placebo. The effects of carvedilol were much stronger than those of metoprolol. Conversely, carvedilol upregulated the expression TIMP-2 to a greater extent than metoprolol. CONCLUSIONS In an AMI model closely mimicking human pathophysiology, the early administration of carvedilol reduced the expression of markers associated with early LV remodelling to greater extent than metoprolol. These findings may explain the superior clinical benefits exerted by carvedilol in heart failure.

Quantification of serial changes in plaque burden using multi-detector computed tomography in experimental atherosclerosis

UNLABELLED Assessment of changes in plaque volume is increasingly used as a surrogate-endpoint in clinical trials testing the efficacy of anti-atherosclerotic interventions. Multi-detector computed tomography (MDCT) can detect and quantify non-calcified atherosclerotic plaques, but its ability to monitor changes in plaque volume has not yet been tested. We sought to test the ability of MDCT to detect and quantify serial changes in atheroma burden in comparison with magnetic resonance imaging (MRI). METHODS Rabbits (n=12) with experimentally induced abdominal atherosclerosis were randomized to receive a plaque-regressing agent (recombinant apoA-I(Milano), n=8) or placebo (n=4). All animals underwent two 64-slice MDCT angiography and MRI studies (pre- and post-treatment). The primary endpoint was the change in plaque burden (defined as vessel wall volume in the 5cm distal to the left renal artery) between pre- and post-treatment MDCT in comparison with MRI. RESULTS MDCT detected a significant decrease in plaque burden caused by recombinant apoA-I(Milano) (464 [423-535] to 405 [363-435]mm(3), p=0.03) that was confirmed by MRI (324 [286-412] to 298 [282-399]mm(3), p=0.03). No significant effect was noted in the placebo group either by MDCT or MRI. There were strong correlations between both modalities for the quantification of plaque burden (r=0.750, p<0.001) and change in plaque burden (r=0.657, p=0.020). MDCT overestimated plaque burden compared to MRI. On MDCT, the mean interobserver variability for plaque burden was 2.5+/-0.4%. CONCLUSIONS In an animal model of atherosclerosis, MDCT accurately documented serial changes in aortic plaque burden, demonstrating good correlation and agreement with MRI-derived measurements and low interobserver variability.

155 Quantification of pulse wave velocity in the pulmonary artery in patients with pulmonary hypertension

Introduction Pulmonary artery (PA) stiffness increases in pulmonary hypertension (PH). Pulse wave velocity (PWV) is an index of stiffness that provides prognostic information in systemic arterial disease, but its quantification in the pulmonary circulation is challenging. Harmonic analysis of the oscillatory variations in PA diameters and pressures measured invasively has been used in the past to determine that PWV is on average ~2 m/s in normal individuals and ~4.5 m/s in the presence of PH.