Diego Moguillansky

Quantification of plaque neovascularization using contrast ultrasound: a histologic validation.

AIMS The density of vasa vasorum within atherosclerotic plaque correlates with histologic features of plaque vulnerability in post-mortem studies. Imaging methods to non-invasively detect vasa vasorum are limited. We hypothesized that contrast ultrasound (CUS) can quantify vasa vasorum during atherosclerosis progression. METHODS AND RESULTS New Zealand white rabbits received a high-fat diet for 3 weeks, and bilateral femoral artery stenosis was induced by balloon injury. Contrast ultrasound femoral imaging was performed at baseline and 2, 4, and 6 weeks post injury to quantify adventitial videointensity. At each imaging time point 10 vessels were sectioned and stained with haematoxylin and eosin and von-Willebrand factor. Adventitial vasa vasorum density was quantified by counting the number of stained microvessels and their total cross-sectional area. Plaque size (per cent lumen area) progressed over time (P < 0.001), as did adventitial vasa vasorum density (P < 0.001). Plateau peak videointensity also progressed, demonstrating a strong linear correlation with histologic vasa vasorum density (P < 0.001). Receiver operating characteristic analysis indicated that a three-fold increase in median adventitial videointensity had a sensitivity of 100% and specificity of 88% for predicting abnormal neovascularization. CONCLUSION We have histologically validated that CUS quantifies the development of adventitial vasa vasorum associated with atherosclerosis progression. This imaging technique has the potential for characterizing prognostically significant plaque features.

Effectiveness of late gadolinium enhancement to improve outcomes prediction in patients referred for cardiovascular magnetic resonance after echocardiography

BackgroundEchocardiography (echo) is a first line test to assess cardiac structure and function. It is not known if cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE) ordered during routine clinical practice in selected patients can add additional prognostic information after routine echo. We assessed whether CMR improves outcomes prediction after contemporaneous echo, which may have implications for efforts to optimize processes of care, assess effectiveness, and allocate limited health care resources.Methods and resultsWe prospectively enrolled 1044 consecutive patients referred for CMR. There were 38 deaths and 3 cardiac transplants over a median follow-up of 1.0 years (IQR 0.4-1.5). We first reproduced previous survival curve strata (presence of LGE and ejection fraction (EF) < 50%) for transplant free survival, to support generalizability of any findings. Then, in a subset (n = 444) with contemporaneous echo (median 3 days apart, IQR 1–9), EF by echo (assessed visually) or CMR were modestly correlated (R2 = 0.66, p < 0.001), and 30 deaths and 3 transplants occurred over a median follow-up of 0.83 years (IQR 0.29-1.40). CMR EF predicted mortality better than echo EF in univariable Cox models (Integrated Discrimination Improvement (IDI) 0.018, 95% CI 0.008-0.034; Net Reclassification Improvement (NRI) 0.51, 95% CI 0.11-0.85). Finally, LGE further improved prediction beyond EF as determined by hazard ratios, NRI, and IDI in all Cox models predicting mortality or transplant free survival, adjusting for age, gender, wall motion, and EF.ConclusionsAmong those referred for CMR after echocardiography, CMR with LGE further improves risk stratification of individuals at risk for death or death/cardiac transplant.

Detection of elevated right atrial pressure using a simple bedside ultrasound measure

AIMS Accurate assessment of right atrial pressure (RAP) often requires invasive measurement. With normal RAP, Valsalva increases right internal jugular vein (RIJV) cross sectional area (CSA) 20% to 30%. With high RAP, when venous compliance is low, we hypothesized that the increase in CSA would be blunted and could be detected non-invasively with bedside ultrasound. METHODS AND RESULTS RIJV ultrasound images were obtained in 67 patients undergoing right heart catheterization. The median RAP at end-expiration was 7 mm Hg (interquartile range [IQR] 5-9 mm Hg) in patients with normal RAP (n = 47) versus 15 mm Hg (IQR 12-22 mm Hg) in patients with elevated RAP (n = 20). With Valsalva, the median percent change in RIJV CSA was 35% (IQR 19%-79%) versus 5% (IQR 3%-14%) for normal and high RAP, respectively. By receiver operating curve analysis, a <17% increase in RIJV CSA with Valsalva predicted elevated RAP (> or =12 mmHg) with 90% sensitivity, 74% specificity, 94% negative predictive value, and 60% positive predictive value (area under the curve 0.86, P < .001). CONCLUSIONS An increase in RIJV CSA >17% during Valsalva effectively rules out elevated RAP. This simple bedside technique may be useful to assess central venous pressure and reduce the need for invasive pressure measurement.

Role of high-pressure balloon valvotomy for resistant pulmonary valve stenosis.

BACKGROUND Pulmonary valve (PV) balloon valvotomy (BV) is considered the treatment of choice for isolated pulmonary valve stenosis (IPVS). While immediate and long-term results of PVBV are usually excellent, the reported results in dysplastic valves are variable. High-pressure (HP) PVBV in dysplastic valves that fail low-pressure (LP) PVBV may increase success rate, reducing the need for surgical interventions. METHODS We reviewed all cases of IPVS in patients <3 years old, who underwent PVBV between August 1999 and March 2004. Study outcomes were initial success rate (gradient post PVBV < 30 mm Hg) and freedom from reintervention. Possible predictors of failure to LP-PVBV were explored (age, hemodynamic data, PV leaflet maximal thickness, diameter/z-scores for PV annulus, sinotubular junction, and subvalvar area). RESULTS All 35 patients (16 neonates, 5 with critical IPVS) underwent LP-PVBV with immediate success in 27 (80%). All eight patients who failed LP-PVBV successfully underwent HP-PVBV. Upon follow-up (27 +/- 24 months), two patients (6.9%) required reintervention after LP-PVBV (LP-PVBV at 3 months, HP-PVBV at 2 months with success, both reintervention free thereafter), and one patient (12.5%) after HP-PVBV (surgical right ventricular outflow tract patch at 33 months) (Fishers exact test = 0.5). There were no major immediate or long-term complications. After nonparametric median regression, age (2 vs. 11 months, P < .001) and PV maximal thickness (0.13 vs. 0.24 cm, P= .026) were the only predictors of failure to LP-PVBV. CONCLUSION HP-PVBV can be performed safely in patients with IPVS that fail LP-PVBV, with high success rate and acceptable long-term results. Failure to LP-PVBV is difficult to predict.

Preoperative management in patients with single-ventricle physiology.

OBJECTIVE Advancements in the preoperative management of patients with single-ventricle physiology continue to evolve. Previous reports have questioned the benefit of using inhaled nitrogen in single-ventricle patients, suggesting that this therapeutic modality may not provide adequate systemic cardiac output. The objective of this study was to review our institutional experience managing preoperative patients with single-ventricle physiology using a combination of afterload reduction and inhaled hypoxemic therapy. DESIGN, SETTING, AND PATIENTS This is a retrospective review of 49 consecutive single-ventricle patients admitted preoperatively between July 2004 and January 2009, to the cardiac intensive care unit at Childrens Hospital of Pittsburgh who underwent single-ventricle palliation, and treated preoperatively with milrinone and inhaled nitrogen. Therapeutic interventions and indirect indicators of cardiac output were collected on day of admission (time 0) and compared with those collected on the morning of surgery (time 1); data included clinical assessment, hemodynamic measurements, and laboratory values. RESULTS When comparing time 0 to time 1, there was a statistically significant decrease in lactate (from 2.2 to 1.8 mEq/L [P < 0.001]) and an increase in pH (from 7.36 to 7.41 [P < 0.001]), serum bicarbonate (from 24.16 to 27.55 mmol/L [P < 0.001]) and arterial PaO2 (from 38.10 to 41.82 mm Hg [P = 0.027]). Preoperatively, there were no deaths, and only two patients had an evidence of multiorgan dysfunction on day of surgery (time 1). CONCLUSION Our results suggest that a combination of afterload reduction and hypoxemic therapy was able to maintain an appropriate distribution of the cardiac output in the majority of preoperative patients with single-ventricle physiology. An adequate balance of systemic and pulmonary blood flow was successfully achieved with an increase in arterial PaO2 values.

TOO MANY LEAKS, WHICH ONE TO FIX?

Echocardiography remains the mainstay of cardiac imaging in evaluating valvular heart disease. However, patients with ventricular dysfunction due to multi-valvular disease and/or intra-cardiac shunting will require accurate estimation of the individual contribution of each lesion. Cardiac magnetic

Cardiovascular magnetic resonance stress perfusion imaging predicts 1 year outcomes following equivocal stress testing

Summary We tested the hypothesis that cardiovascular magnetic resonance (CMR) stress perfusion can predict 1 year outcomes in individuals with equivocal or uncertain prior stress testing. Background Individuals with equivocal nuclear stress test results are at higher risk for cardiac events compared to those with normal studies. CMR stress perfusion imaging identifies individuals with coronary artery disease with high sensitivity and specificity, with excellent spatial resolution, and without ionizing radiation. The utility of CMR stress testing is uncertain in individuals with prior equivocal stress results. Methods We selected all participants in a CMR registry who were clinically referred for pharmacologic CMR perfusion testing due to recent nuclear stress perfusion study (6 months if outpatient, same admission if inpatient) from 2009-2010 with equivocal or uncertain results. Studies were defined as equivocal if the results were qualified by the mention of significant artifact or other technical difficulty. Studies were defined as uncertain if the referring physician documented suspicion of false positive or false negative results in the medi cal record. The presence of ischemia reported by each modality, as well as any description of uncertainty, was determined by a clinical nurse reviewer and 2 cardiologists (all blinded to the downstream clinical course of each subject). Any disagreement in assessment was arbitrated by majority vote. The clinical course of each subject was followed through chart review. Adverse outcome was defined as hospitalization for suspected or definite myocardial infarction.

Myocardial fibrosis quantified by the extracellular extravascular volume fraction is associated with the left ventricular sphericity index and the left atrial volume index

Summary The objective of this study is to test the hypothesis that quantitative measures of myocardial fibrosis such as the myocardial extravascular extracellular volume fraction (Ve) are associated with markers of adverse cardiac remodeling such as the left atrial volume index (LAVi) and left ventricular sphericity index (Si). Background LAVi and Si are intermediate phenotypes that precede adverse outcomes. Myocardial fibrosis is quantifiable with contemporary CMR techniques, is treatable, and may represent a therapeutic target when these intermediate phenotypes are present. Methods We measured myocardial Ve in 267 individuals referred for CMR without confounders such as myocardial infarction, where Ve= [ lr (1-Hct) - Vp]; the specific density of myocardial tissue, r=1.05; the myocardial plasma volume fraction, Vp=0.045, and l=ΔR1myocardium/ ΔR1blood. T1 was measured with an ECG-gated MOLLI sequence acquired before and 20 minutes after a gadolinium contrast bolus (0.2 mmol/kg). LAVi and Si were measured from standard SSFP cine images: LAVi = [8/3π [(A1)(A2)/L] where A1 and A2 are LA areas from end-systolic 2-chamber and 4-chamber views, L represents the shortest anteroposterior LA dimension from either view, and Si =EDV/[LAX^3 π /6), where EDV is the end-diastolic volume measured from short axis stacks and LAX^3 is the cube of the long axis diastolic dimension from a 4 chamber view. Multivariable linear regression models quantified the association of Ve with LAVi and Si, adjusting for key characteristics identified by stepwise selection. Results Ve was associated with LAVi (t value 4.5, p<0.001), and this association remained after adjusting for age, ejection fraction, EDV index, and left ventricular mass index (t value 2.8, p=0.005). Ve was also associated with Si (t value 5.6, p<0.001), and this association remained after adjusting for age, gender, EDV index, body mass index, and left ventricular mass index (t value 2.18, p=0.036). Conclusions Ve is associated with key intermediate phenotypes that indicate adverse cardiac remodeling such as LAVi and Si.

Cardiovascular magnetic resonance with late gadolinium enhancement improves mortality prediction beyond echocardiography: a comparative effectiveness study

Summary Adding information from CMR with LGE to ejection fraction measured by echocardiography significantly improves the prediction for all cause mortality and better classifies individuals at risk. Background We tested the hypotheses that 1) ejection fraction (EF) assessed by cardiovascular magnetic resonance (CMR) is a stronger predictor of all cause mortality than EF assessed by echocardiography; and 2) CMR with late gadolinium enhancement (LGE) improves risk stratification over echocardiography EF in Cox regression models as determined by net reclassification improvement (NRI). Echocardiography with EF measurement remains the initial noninvasive imaging modality for evaluation of patients, and it is used to individualize medical, surgical, and device-based therapy. Yet, if CMR with LGE improves risk stratification compared to echocardiography, then CMR would demonstrate a potential to optimize care through improved patient selection for interventions and more efficient allocation of healthcare resources.