Javier Sanz

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.

Assessment of myocardial perfusion and viability from routine contrast-enhanced 16-detector-row computed tomography of the heart: preliminary results

To assess the diagnostic accuracy of 16-detector-row computed tomography (16DCT) of the heart in the assessment of myocardial perfusion and viability in comparison to stress perfusion magnetic resonance imaging (SP-MRI) and delayed-enhancement magnetic resonance imaging (DE-MRI). A number of 30 patients underwent both 16DCT and MRI of the heart. Contrast-enhanced 16DCT data sets were reviewed for areas of myocardium with reduced attenuation. Both CT and MRI data were examined by independent reviewers for the presence of myocardial perfusion defects or myocardial infarctions (MI). Volumetric analysis of the hypoperfusion areas in CT and the infarct sizes in DE-MRI were performed. According to MRI, myocardial infarctions were detected in 11 of 30 cases, and perfusion defects not corresponding to an MI were detected in six of 30 patients. CTA was able to detect ten of 11 MI correctly (sensitivity 91%, specificity 79%, accuracy 83%), and detected three of six hypoperfusions correctly (sensitivity 50%, specificity 92%, accuracy 79%). Assessing the volume of perfusion defects correlating to history of MI on the CT images, a systematic underestimation of the true infarct size as compared to the results of DE-MRI was found (P<0.01). Routine, contrast-enhanced 16-detector row CT of the heart can detect chronic myocardial infarctions in the majority of cases, but ischemic perfusion defects are not reliably detected under resting conditions.

Right ventriculo-arterial coupling in pulmonary hypertension: a magnetic resonance study

Objective To quantify right ventriculo-arterial coupling in pulmonary hypertension by combining standard right heart catheterisation (RHC) and cardiac magnetic resonance (CMR) and to estimate it non-invasively with CMR alone. Design Cross-sectional analysis in a retrospective cohort of consecutive patients. Setting Tertiary care centre. Patients 139 adults referred for pulmonary hypertension evaluation. Interventions CMR and RHC within 2 days (n=151 test pairs). Main outcome measures Right ventriculo-arterial coupling was quantified as the ratio of pulmonary artery (PA) effective elastance (Ea, index of arterial load) to right ventricular maximal end-systolic elastance (Emax, index of contractility). Right ventricular end-systolic volume (ESV) and stroke volume (SV) were obtained from CMR and adjusted to body surface area. RHC provided mean PA pressure (mPAP) as a surrogate of right ventricular end-systolic pressure, pulmonary capillary wedge pressure (PCWP) and pulmonary vascular resistance index (PVRI). Ea was calculated as (mPAP − PCWP)/SV and Emax as mPAP/ESV. Results Ea increased linearly with advancing severity as defined by PVRI quartiles (0.19, 0.50, 0.93 and 1.63 mm Hg/ml/m2, respectively; p<0.001 for trend) whereas Emax increased initially and subsequently tended to decrease (0.52, 0.67, 0.54 and 0.56 mm Hg/ml/m2; p=0.7). Ea/Emax was maintained early but increased markedly with severe hypertension (0.35, 0.72, 1.76 and 2.85; p<0.001), indicating uncoupling. Ea/Emax approximated non-invasively with CMR as ESV/SV was 0.75, 1.17, 2.28 and 3.51, respectively (p<0.001). Conclusions Right ventriculo-arterial coupling in pulmonary hypertension can be studied with standard RHC and CMR. Arterial load increases with disease severity whereas contractility cannot progress in parallel, leading to severe uncoupling.

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 BioImage Study: novel approaches to risk assessment in the primary prevention of atherosclerotic cardiovascular disease--study design and objectives.

The identification of asymptomatic individuals at risk for near-term atherothrombotic events to ensure optimal preventive treatment remains a challenging goal. In the BioImage Study, novel approaches are tested in a typical health-plan population. Based on certain demographic and risk characteristics on file with Humana Inc, a total of 7,687 men 55 to 80 years of age and women 60 to 80 years of age without evidence of atherothrombotic disease but presumed to be at risk for near-term atherothrombotic events were enrolled between January 2008 and June 2009. Those who met the prespecified eligibility criteria were randomized to a telephonic health survey only (survey only: n = 865), standard risk assessment (Framingham only: n = 718), or comprehensive risk assessment in a dedicated mobile facility equipped with advanced imaging tools (n = 6,104). Baseline examination included assessment of cardiovascular risk factors and screening for subclinical (asymptomatic) atherosclerosis with quantification of coronary artery calcification by computed tomography (CT), measurement of intima-media thickness, presence of carotid atherosclerotic plaques and abdominal aortic aneurysm by ultrasound, and ankle brachial index. Participants with one or more abnormal screening test results underwent advanced imaging with contrast-enhanced magnetic resonance imaging for carotid and aortic plaques, contrast-enhanced coronary CT angiography for luminal stenosis and noncalcified plaques, and 18F-fluorodeoxyglucose-positron emission tomography/CT for carotid and aortic plaque inflammation. Plasma, PAXgene RNA, and DNA samples were obtained, frozen, and stored for future biomarker discovery studies. All individuals will be followed until 600 major atherothrombotic events have occurred in those undergoing imaging. The BioImage Study will help identify those patients with subclinical atherosclerosis who are at risk for near-term atherothrombotic events and enable a more personalized management of care.

Detection of Left Atrial Appendage Thrombus by Cardiac Computed Tomography in Patients With Atrial Fibrillation: A Meta-Analysis

Background— Transesophageal echocardiogram (TEE) is considered the gold standard modality in detecting left atrial/LA appendage (LA/LAA) thrombi. However, this is a semi-invasive procedure with rare but potential life-threatening complications. Cardiac computed tomography has been proposed as an alternative method. The purpose of this meta-analysis was to evaluate the diagnostic accuracy of cardiac computed tomography assessing LA/LAA thrombi in comparison with TEE. Methods and Results— A systematic review of Medline, Cochrane, and Embase to look for clinical trials assessing detection of LA/LAA thrombi by cardiac computed tomography when compared with TEE in patients with a history of atrial fibrillation before electric cardioversion/pulmonary vein isolation or after cardioembolic cerebrovascular accident was performed using standard approach and bivariate analysis. Nineteen studies with 2955 patients (men, 71%; mean age, 61±4 years) fulfilled the inclusion criteria. Most studies (85%, 16 studies) used 64-slide multidetector computed tomography and 15 studies (79%) were electrocardiographic-gated. The incidence of LA/LAA thrombi was 8.9% (SD, ±7). The mean sensitivity and specificity were 96% and 92%, whereas the positive predictive value and negative predictive value were 41% and 99%, respectively. The diagnostic accuracy was 94%. In a subanalysis of studies in which delayed imaging was performed, the diagnostic accuracy significantly improved to a mean weighted sensitivity and specificity of 100% and 99%, respectively, whereas the positive predictive value and negative predictive value increased to 92% and 100%, respectively. The accuracy for this technique was 99%. Conclusions— Cardiac computed tomography, particularly when delayed imaging is performed, is a reliable alternative to TEE for the detection of LA/LAA thrombi/clot, avoiding the discomfort and risks associated with TEE.

Promoting mechanisms of vascular health: circulating progenitor cells, angiogenesis, and reverse cholesterol transport.

To understand and promote vascular health, we must reduce the aggression to the vessel wall and enhance the physiologic mechanisms leading to restoration of vessel wall function. Three main defense mechanisms are responsible for maintaining cardiovascular homeostasis: the regenerative production of endothelial progenitor cells, vessel wall angiogenesis, and macrophage-mediated reverse cholesterol transport. Endothelial progenitor cells can restore vessel wall function and reduce atherosclerosis. In patients with risk factors, high levels of circulating progenitor cells increase event-free survival from cardiovascular events. Mobilization of progenitor cells includes physical and pharmacological approaches, of which exercise and statin therapy have great potential. Angiogenesis is a pivotal defense mechanism to counteract hypoxia and is needed for plaque regression. However, neovessels are susceptible for intraplaque hemorrhage, particularly in diabetes mellitus. In these patients, the haptoglobin 2-2 genotype is the more affected, and may benefit from an antioxidant approach. Finally, the reverse cholesterol transport system is the main mechanism for plaque regression. In addition to high-density lipoprotein cholesterol, apolipoprotein A-I therapies and the promotion of cholesterol efflux from macrophages by the ABCA1 and ABCG1 transporter systems hold great promise and may be available for therapeutic application in the near future.

RV dysfunction in pulmonary hypertension is independently related to pulmonary artery stiffness.

OBJECTIVES This study investigated whether right ventricular (RV) adaptation to chronic pressure overload is associated with pulmonary artery (PA) stiffness beyond the degree of severity of pulmonary hypertension (PH). BACKGROUND Increased PA stiffness has been associated with reduced survival in PH. The mechanisms for this association remain unclear. METHODS Right heart catheterization and cardiac magnetic resonance were performed within 1 week in 124 patients with known or suspected chronic PH. Pulmonary vascular resistance index (PVRI) and PA pressures were quantified from right heart catheterization. Cardiac magnetic resonance included standard biventricular cine sequences and main PA flow quantification with phase-contrast imaging. Indexes of PA stiffness (elasticity, distensibility, capacitance, stiffness index beta, and pulse pressure) were quantified combining right heart catheterization and cardiac magnetic resonance data. RV performance and adaptation were measured by RV ejection fraction, right ventricular mass index (RVMI), RV end-systolic volume index, and right ventricular stroke work index (RVSWI). RESULTS All indexes of PA stiffness were significantly correlated with measures of RV performance (Spearman rho coefficients ranging from -0.20 to 0.61, p < 0.05). Using multivariate regression analysis, PA elasticity, distensibility, and index beta were independently associated with all measures of RV performance after adjusting PVRI (p ≤ 0.024). PA capacitance was independently associated with RV ejection fraction, RVMI, and RVSWI (p < 0.05), whereas PA pulse pressure was associated with RVMI and RVSWI (p ≤ 0.027). Compared with PVRI, PA elasticity, distensibility, capacitance, and index beta explained 15% to 68% of the variability in RV ejection fraction, RVMI, and RV end-systolic volume index. Relative contributions of PA stiffness for RVSWI were 1.2× to 18.0× higher than those of PVRI. CONCLUSIONS PA stiffness is independently associated with the degree of RV dysfunction, dilation, and hypertrophy in PH. RV adaptation to chronic pressure overload is related not only to the levels of vascular resistance (steady afterload), but also to PA stiffness (pulsatile load).

State-of-the-Art PaperPromoting Mechanisms of Vascular Health: Circulating Progenitor Cells, Angiogenesis, and Reverse Cholesterol Transport

To understand and promote vascular health, we must reduce the aggression to the vessel wall and enhance the physiologic mechanisms leading to restoration of vessel wall function. Three main defense mechanisms are responsible for maintaining cardiovascular homeostasis: the regenerative production of endothelial progenitor cells, vessel wall angiogenesis, and macrophage-mediated reverse cholesterol transport. Endothelial progenitor cells can restore vessel wall function and reduce atherosclerosis. In patients with risk factors, high levels of circulating progenitor cells increase event-free survival from cardiovascular events. Mobilization of progenitor cells includes physical and pharmacological approaches, of which exercise and statin therapy have great potential. Angiogenesis is a pivotal defense mechanism to counteract hypoxia and is needed for plaque regression. However, neovessels are susceptible for intraplaque hemorrhage, particularly in diabetes mellitus. In these patients, the haptoglobin 2-2 genotype is the more affected, and may benefit from an antioxidant approach. Finally, the reverse cholesterol transport system is the main mechanism for plaque regression. In addition to high-density lipoprotein cholesterol, apolipoprotein A-I therapies and the promotion of cholesterol efflux from macrophages by the ABCA1 and ABCG1 transporter systems hold great promise and may be available for therapeutic application in the near future.

Determinants of left ventricular mass in patients on hemodialysis: Frequent Hemodialysis Network (FHN) Trials.

Background— An increase in left ventricular mass (LVM) is associated with mortality and cardiovascular morbidity in patients with end-stage renal disease. Methods and Results— The Frequent Hemodialysis Network (FHN) Daily Trial randomized 245 patients to 12 months of 6 times per week daily in-center hemodialysis or conventional hemodialysis; the FHN Nocturnal Trial randomized 87 patients to 12 months of 6 times per week nocturnal hemodialysis or conventional hemodialysis. The main cardiac secondary outcome was change in LVM. In each trial, we examined whether several predefined baseline demographic or clinical factors as well as change in volume removal, blood pressure, or solute clearance influenced the effect of frequent hemodialysis on LVM. In the Daily Trial, frequent hemodialysis resulted in a significant reduction in LVM (13.1 g; 95% CI, 5.0–21.3 g; P=0.002), LVM index (6.9 g/m2; 95% CI, 2.4–11.3 g/m2; P=0.003), and percent change in geometric mean of LVM (7.0%; 95% CI, 1.0%–12.6; P=0.02). Similar trends were noted in the Nocturnal Trial but did not reach statistical significance. In the Daily Trial, a more pronounced effect of frequent hemodialysis on LVM was evident among patients with left ventricular hypertrophy at baseline. Changes in LVM were associated with changes in blood pressure (conventional hemodialysis: R=0.28, P=0.01, daily hemodialysis: R=0.54, P<0.001) and were not significantly associated with changes in other parameters. Conclusions— Frequent in-center hemodialysis reduces LVM. The benefit of frequent hemodialysis on LVM may be mediated by salutary effects on blood pressure. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00264758.Background— An increase in left ventricular mass (LVM) is associated with mortality and cardiovascular morbidity in patients with end-stage renal disease. Methods and Results— The Frequent Hemodialysis Network (FHN) Daily Trial randomized 245 patients to 12 months of 6 times per week daily in-center hemodialysis or conventional hemodialysis; the FHN Nocturnal Trial randomized 87 patients to 12 months of 6 times per week nocturnal hemodialysis or conventional hemodialysis. The main cardiac secondary outcome was change in LVM. In each trial, we examined whether several predefined baseline demographic or clinical factors as well as change in volume removal, blood pressure, or solute clearance influenced the effect of frequent hemodialysis on LVM. In the Daily Trial, frequent hemodialysis resulted in a significant reduction in LVM (13.1 g; 95% CI, 5.0–21.3 g; P =0.002), LVM index (6.9 g/m2; 95% CI, 2.4–11.3 g/m2; P =0.003), and percent change in geometric mean of LVM (7.0%; 95% CI, 1.0%–12.6; P =0.02). Similar trends were noted in the Nocturnal Trial but did not reach statistical significance. In the Daily Trial, a more pronounced effect of frequent hemodialysis on LVM was evident among patients with left ventricular hypertrophy at baseline. Changes in LVM were associated with changes in blood pressure (conventional hemodialysis: R =0.28, P =0.01, daily hemodialysis: R =0.54, P <0.001) and were not significantly associated with changes in other parameters. Conclusions— Frequent in-center hemodialysis reduces LVM. The benefit of frequent hemodialysis on LVM may be mediated by salutary effects on blood pressure. Clinical Trial Registration— URL: [http://www.clinicaltrials.gov][1]. Unique identifier: [NCT00264758][2]. [1]: http://www.clinicaltrials.gov. [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00264758&atom=%2Fcirccvim%2F5%2F2%2F251.atom