Differentiating benign from malignant cardiac tumors with cardiac magnetic resonance imaging.

BACKGROUND: The purpose of this analysis is to describe the differences in cardiac magnetic resonance characteristics between benign and malignant tumors, which would be helpful for surgical planning. METHODS: This was a prospective cohort study of 130 patients who underwent cardiac magnetic resonance imaging for evaluation of a suspected cardiac mass. After excluding thrombi and tumors without definitive diagnosis, 66 tumors were evaluated for morphologic features and tissue composition. RESULTS: Of the 66 patients, 39 (59.0%) had malignant tumors and 27 (41.0%) had benign tumors. Patients with malignant tumors were younger when compared with those with benign tumors (age 51 years [42.8-60.0] vs 65 years [60.0-71.0] median). Malignant tumors more often demonstrated tumor invasion (69% vs 0% P < .001) and were more often associated with pericardial effusion (41% vs 7.4% P = .004). Presence of first-pass perfusion (100% vs 33% P < .001) and late gadolinium enhancement (100% vs 59.2%, P < .001) were significantly higher in malignant tumors. In logistic regression modeling, tumor invasion (P < .001) and first-pass perfusion (P < .001) were independently associated with malignancy. Furthermore, using classification and regression tree analysis, we developed a decision tree algorithm to help differentiate benign from malignant tumors (diagnostic accuracy ∼90%). The algorithm-weighted cost of misclassifying a malignant tumor as benign was twice that of classifying a benign tumor as malignant. CONCLUSIONS: Our study demonstrates that cardiac magnetic resonance imaging is a useful noninvasive method for differentiating malignant from benign cardiac tumors. Tumor size, invasion, and first-pass perfusion were useful imaging characteristics in differentiating benign from malignant tumors.

Mean Right Atrial Pressure for Estimation of Left Ventricular Filling Pressure in Patients with Normal Left Ventricular Ejection Fraction: Invasive and Noninvasive Validation.

BACKGROUND: There is a paucity of data on the utility of right atrial pressure (RAP) for estimating pulmonary capillary wedge pressure (PCWP) in patients with normal ejection fraction (EF), including patients with heart failure with preserved EF. METHODS: Mean RAP was compared with PCWP in 129 patients (mean age, 61 ± 11 years; 45% men) with exertional dyspnea enrolled in a multicenter study. Measurements included left ventricular volumes, EF, and mitral inflow velocities. RESULTS: Mean PCWP was 14 ± 7 mm Hg, and mean RAP was 8 ± 5 mm Hg. A significant relation was present between mean RAP and mean PCWP (r2 = 0.5, P < .001). RAP > 8 mm Hg had 76% sensitivity and 86% specificity in detecting mean PCWP > 12 mm Hg. In 101 patients with inconclusive mitral filling pattern (defined according to American Society of Echocardiography/European Association of Cardiovascular Imaging 2016 diastolic function recommendations), RAP by catheterization had sensitivity of 73% and specificity of 91%. In a subset of 59 patients with echocardiographic assessment of mean RAP, RAP by echocardiography had sensitivity of 76% and specificity of 89%. CONCLUSIONS: Mean RAP provides useful information about mean PCWP in many patients with normal left ventricular EF. There is good sensitivity and excellent specificity when combining invasive or noninvasive RAP and mitral velocities to determine if PCWP is elevated.

Risk Stratification of Patients With Current Generation Continuous-Flow Left Ventricular Assist Devices Being Bridged to Heart Transplantation.

Patients bridged to transplant (BTT) with continuous-flow left ventricular assist devices (CF-LVADs) have increased in the past decade. Decision support tools for these patients are limited. We developed a risk score to estimate prognosis and guide decision-making. We included heart transplant recipients bridged with CF-LVADs from the United Network for Organ Sharing (UNOS) database and divided them into development (2,522 patients) and validation cohorts (1,681 patients). Univariate and multivariate Cox proportional hazards models were performed. Variables that independently predicted outcomes (age, African American race, recipient body mass index [BMI], intravenous [IV] antibiotic use, pretransplant dialysis, and total bilirubin) were assigned weight using linear transformation, and risk scores were derived. Patients were grouped by predicted posttransplant mortality: low risk (≤ 38 points), medium risk (38-41 points), and high risk (≥ 42 points). We performed Cox proportional hazards analysis on wait-listed CF-LVAD patients who were not transplanted. Score significantly discriminated survival among the groups in the development cohort (6.7, 12.9, 20.7; p = 0.001), validation cohort (6.4, 10.1, 13.6; p < 0.001), and ambulatory cohort (6.4, 11.5, 17.2; p < 0.001). We derived a left ventricular assist device (LVAD) BTT risk score that effectively identifies CF-LVAD patients who are at higher risk for worse outcomes after heart transplant. This score may help physicians weigh the risks of transplantation in patients with CF-LVAD.

Hybrid approach to the management of infective endocarditis complicated by coronary artery embolism: a case report.

Septic coronary embolization in a patient with endocarditis is a rare and can be a devastating complication. The management of this clinical problem in the current era may be best served with a multi-modality approach. We present an interesting case of a patient with septic coronary embolization managed with the combined use of aspiration thrombectomy followed by surgical management of the infected valve.

Estimating Left Ventricular Filling Pressure by Echocardiography.

BACKGROUND: The diagnosis of heart failure may be challenging because symptoms are rather nonspecific. Elevated left ventricular (LV) filling pressure may be used to confirm the diagnosis, but cardiac catheterization is often not practical. Echocardiographic indexes are therefore used as markers of filling pressure. OBJECTIVES: This study investigated the feasibility and accuracy of comprehensive echocardiography in identifying patients with elevated LV filling pressure. METHODS: We conducted a multicenter study of 450 patients with a wide spectrum of cardiac diseases referred for cardiac catheterization. Left atrial volume index, in combination with flow velocities and tissue Doppler velocities, was used to estimate LV filling pressure. Invasively measured pressure was used as the gold standard. RESULTS: Mean left ventricular ejection fraction (LVEF) was 47%, with 209 patients having an LVEF <50%. Invasive measurements showed elevated LV filling pressure in 58% of patients. Clinical assessment had an accuracy of 72% in identifying patients with elevated filling pressure, whereas echocardiography had an accuracy of 87% (p < 0.001 vs. clinical assessment). The combination of clinical and echocardiographic assessment was incremental, with a net reclassification improvement of 1.5 versus clinical assessment (p < 0.001). CONCLUSIONS: Echocardiographic assessment of LV filling pressure is feasible and accurate. When combined with clinical data, it leads to a more accurate diagnosis, regardless of LVEF.

Doppler Echocardiography for the Estimation of LV Filling Pressure in Patients With Mitral Annular Calcification.

OBJECTIVES: This study sought to identify Doppler parameters useful for the assessment of left ventricular filling pressure (LVFP) in patients with mitral annular calcification (MAC) and to develop and validate a decision algorithm for assessing LVFP in such patients. BACKGROUND: Predicting LVFP in the presence of MAC is problematic. METHODS: Prospectively, 50 patients with MAC (mean 72 ± 11 years of age) underwent a complete Doppler echocardiographic study and right or left heart catheterization. Standard and nonstandard parameters of ventricular filling and relaxation were correlated with LVFP. Classification and regression tree analysis was used to develop a decision tree for prediction of LVFP. Validation was performed prospectively using an additional cohort with MAC and invasive hemodynamics (n = 21). RESULTS: In the initial study group, 26 patients had mild MAC, and 24 had moderate or severe MAC. Mean LVFP was 17.0 ± 8.1 mm Hg (range 4 to 50 mm Hg). Of the variables tested, the best predictor of LVFP was the ratio of early-to-late diastolic filling velocity (mitral E/A) (r = 0.66; p < 0.001). This finding was observed in subjects with mild as well as moderate-to-severe MAC. Importantly, the ratio of early diastolic filling velocity-to-mitral annulus velocity (E/e') demonstrated weak correlation (r = 0.42; p = 0.003). A clinical algorithm using mitral E/A and isovolumic relaxation time (IVRT) was associated with good specificity (100%) and positive predictive value (100%), and moderate sensitivity (81%) and negative predictive value (67%) for high LVFP. Validation of the clinical algorithm in a separate prospective cohort yielded a diagnostic accuracy of 94%. CONCLUSIONS: The E/e' ratio should not be used to estimate LVFP in subjects with significant MAC. However, mitral E/A ratio and IVRT are useful predictors of LVFP in this patient population. The proposed decision algorithm combining these Doppler parameters is accurate in estimating LVFP in patients with MAC.

Initial electrocardiogram as determinant of hospital course in ST elevation myocardial infarction.

BACKGROUND: A proportion of patients with ST elevation myocardial infarction (STEMI) have an initial electrocardiogram (ECG) that is nondiagnostic and are definitively diagnosed on a subsequent ECG. Our aim was to assess whether patients with a nondiagnostic initial ECG are different than those with a diagnostic initial ECG. METHODS: We collected demographic, ECG, medication, angiographic, and in-hospital clinical outcome data in consecutive patients undergoing primary percutaneous coronary intervention for STEMI at our institution from June 2009 to June 2013. RESULTS: A total of 334 patients were included, 285 (85%) diagnosed on the initial ECG and 49 (15%) on a subsequent ECG. Patients with a nondiagnostic initial ECG had more comorbidities including prior congestive heart failure (14% vs. 3%, p < .001), coronary artery disease (47% vs. 24%, p = .001), diabetes (37% vs. 16%, p = .001), and hyperlipidemia (55% vs. 40%, p = .048); higher rates of chronic medication use including aspirin (47% vs. 27%, p = .005), beta-blocker (47% vs. 22%, p < .001), and statins (53% vs. 28%, p = .001); longer door-to-balloon times (106 min vs. 45 min, p < .001); lower peak troponin levels (25 ng/ml vs. 50 ng/ml, p = .004), longer diagnostic ECG to balloon times (84 min vs. 75 min, p = .006); and higher rates of a patent infarct-related artery on baseline angiography (41% vs. 24%, p = .018) which remained significant in a multivariable logistic regression model. CONCLUSIONS: Approximately one in seven STEMI patients had an initial ECG that was nondiagnostic for STEMI. These patients had more comorbidities, higher rates of medication use, and received delayed intervention (even after the diagnosis was definitive).

Identification of cardiovascular risk factors associated with bone marrow cell subsets in patients with STEMI: a biorepository evaluation from the CCTRN TIME and LateTIME clinical trials.

Autologous bone marrow mononuclear cell (BM-MNC) therapy for patients with ST-segment elevation myocardial infarction (STEMI) has produced inconsistent results, possibly due to BM-MNC product heterogeneity. Patient-specific cardiovascular risk factors (CRFs) may contribute to variations in BM-MNC composition. We sought to identify associations between BM-MNC subset frequencies and specific CRFs in STEMI patients. Bone marrow was collected from 191 STEMI patients enrolled in the CCTRN TIME and LateTIME trials. Relationships between BM-MNC subsets and CRFs were determined with multivariate analyses. An assessment of CRFs showed that hyperlipidemia and hypertension were associated with a higher frequency of CD11b+ cells (P = 0.045 and P = 0.016, respectively). In addition, we found that females had lower frequencies of CD11b+ (P = 0.018) and CD45+CD14+ (P = 0.028) cells than males, age was inversely associated with the frequency of CD45+CD31+ cells (P = 0.001), smoking was associated with a decreased frequency of CD45+CD31+ cells (P = 0.013), glucose level was positively associated with the frequency of CD45+CD3+ cells, and creatinine level (an indicator of renal function) was inversely associated with the frequency of CD45+CD3+ cells (P = 0.015). In conclusion, the frequencies of monocytic, lymphocytic, and angiogenic BM-MNCs varied in relation to patients' CRFs. These phenotypic variations may affect cell therapy outcomes and might be an important consideration when selecting patients for and reviewing results from autologous cell therapy trials.

Bone marrow cell characteristics associated with patient profile and cardiac performance outcomes in the LateTIME-Cardiovascular Cell Therapy Research Network (CCTRN) trial.

BACKGROUND: Although several preclinical studies have shown that bone marrow cell (BMC) transplantation promotes cardiac recovery after myocardial infarction, clinical trials with unfractionated bone marrow have shown variable improvements in cardiac function. METHODS: To determine whether in a population of post-myocardial infarction patients, functional recovery after BM transplant is associated with specific BMC subpopulation, we examined the association between BMCs with left ventricular (LV) function in the LateTIME-CCTRN trial. RESULTS: In this population, we found that older individuals had higher numbers of BM CD133(+) and CD3(+) cells. Bone marrow from individuals with high body mass index had lower CD45(dim)/CD11b(dim) levels, whereas those with hypertension and higher C-reactive protein levels had higher numbers of CD133(+) cells. Smoking was associated with higher levels of CD133(+)/CD34(+)/VEGFR2(+) cells and lower levels of CD3(+) cells. Adjusted multivariate analysis indicated that CD11b(dim) cells were negatively associated with changes in LV ejection fraction and wall motion in both the infarct and border zones. Change in LV ejection fraction was positively associated with CD133(+), CD34(+), and CD45(+)/CXCR4(dim) cells as well as faster BMC growth rates in endothelial colony forming assays. CONCLUSIONS: In the LateTIME population, BM composition varied with patient characteristics and treatment. Irrespective of cell therapy, recovery of LV function was greater in patients with greater BM abundance of CD133(+) and CD34(+) cells and worse in those with higher levels of CD11b(dim) cells. Bone marrow phenotype might predict clinical response before BMC therapy and administration of selected BM constituents could potentially improve outcomes of other future clinical trials.

Treatment of Non-ST Elevation Myocardial Infarction: A Process Analysis of Patient and Program Factors in a Teaching Hospital.

As part of a quality improvement project, we performed a process analysis to evaluate how patients presenting with type 1 non-ST elevation myocardial infarction (STEMI) are diagnosed and managed early after the diagnosis has been made. We performed a retrospective chart review and collected detailed information regarding the timing of the first 12-lead electrocardiogram, troponin order entry and first positive troponin result, administration of anticoagulation and antiplatelet medications, and referral for coronary angiography to identify areas of treatment variability and delay. A total of 242 patients with type 1 non-STEMI were included. The majority of patients received aspirin early after presentation to the emergency department; however, there was significant variability in the time from presentation to administration of other medications, including anticoagulation and P2Y12 therapy, even after an elevated troponin level was documented in the chart. Lack of a standardized non-STEMI admission order set, inconsistency regarding whether the emergency department physician or the cardiology admitting team order these medications after the diagnosis is made, and per current protocol, the initial call regarding the patient made to the cardiology fellow, not the admitting house staff, were identified as possible contributors to the delay. Patients who presented during "nighttime" hours had higher rates of atypical symptoms (P = 0.036) and longer delays to coronary angiography (46.5 versus 24 hours, P < 0.001) even in those deemed intermediate to high risk. A process analysis revealed considerable variation in non-STEMI treatment in our teaching hospital and identified specific areas for quality improvement measures.

Functional Assessment of Bioprosthetic Aortic Valves by CMR.

OBJECTIVES: The aim of this study was to evaluate cardiac magnetic resonance (CMR) phase-contrast (PC) measures of a bioprosthetic aortic valve velocity time integral (PC-VTI) to derive the effective orifice area (PC-EOA) and to compare these findings with the clinical standard of Doppler echocardiography. BACKGROUND: Bioprosthetic aortic valve function can be assessed with CMR planimetry of the anatomic orifice area and PC measurement of peak transvalvular systolic velocity. However, bioprosthetic valves can create image artifact and data dropout, which makes planimetry measures a challenge for even experienced CMR readers. METHODS: From our institutional database, we identified 38 patients who had undergone 47 paired imaging studies (CMR and Doppler) within 46 days (median 3 days). Transvalvular forward flow volume by CMR was determined by 3 methods: ascending aorta flow, transvalvular flow, and left ventricular stroke volume. PC-EOA was derived as flow divided by PC-VTI, calculated with a semiautomated MATLAB (Mathworks, Natick, Massachusetts) application for integration of the instantaneous peak transvalvular velocity. Doppler EOA was assessed by the continuity method. RESULTS: PC-EOA by all 3 flow approaches demonstrated a strong correlation with Doppler EOA (r = 0.949, 0.947, and 0.874, respectively; all p < 0.001) and revealed good agreement (bias = 0.03, 0.03, and 0.28 cm(2), respectively). With Doppler-derived EOA as the reference standard, CMR was able to correctly characterize 24 of 26 valves as normal (EOA >1.2 cm(2)), 12 of 14 possibly stenotic valves (0.8 < EOA < 1.2 cm(2)), and 5 of 7 stenotic valves (EOA <0.8 cm(2); k = 0.826). CONCLUSIONS: We describe a new CMR-based method to derive the EOA for bioprosthetic aortic valves. This method compares favorably to traditional Doppler methods and might be an important additional parameter in the evaluation of prosthetic valves by CMR, particularly when Doppler methods are suboptimal or considered discordant with the clinical presentation.

Circulating fibrocytes as predictors of adverse events in unstable angina.

Half of the patients who present with unstable angina (UA) develop recurrent symptoms over the subsequent year. Identification of patients destined to develop such adverse events would be clinically valuable, but current tools do not allow for this discrimination. Fibrocytes are bone marrow-derived progenitor cells that co-express markers of leukocytes and fibroblasts and are released into the circulation in the context of tissue injury. We hypothesized that, in patients with UA, the number of circulating fibrocytes predicts subsequent adverse events. We enrolled 55 subjects with UA, 18 with chronic stable angina, and 22 controls and correlated their concentration of circulating fibrocytes to clinical events (recurrent angina, myocardial infarction, revascularization, or death) over the subsequent year. Subjects with UA had a >2-fold higher median concentration of both total and activated fibrocytes compared with subjects with chronic stable angina and controls. In UA subjects, the concentration of total fibrocytes identified those who developed recurrent angina requiring revascularization (time-dependent area under the curve 0.85) and was superior to risk stratification using thrombolysis in myocardial infarction risk score and N-terminal pro B-type natriuretic peptide levels (area under the curve, 0.53 and 0.56, respectively, P < 0.001). After multivariable adjustment for thrombolysis in myocardial infarction predicted death, MI, or recurrent ischemia, total fibrocyte level was associated with recurrent angina (hazard ratio, 1.016 per 10,000 cells/mL increase; 95% confidence interval, 1.007-1.024; P < 0.001). Circulating fibrocytes are elevated in patients with UA and successfully risk stratify them for adverse clinical outcomes. Fibrocytes may represent a novel biomarker of outcome in this population.

Identification of Bone Marrow Cell Subpopulations Associated With Improved Functional Outcomes in Patients With Chronic Left Ventricular Dysfunction: An Embedded Cohort Evaluation of the FOCUS-CCTRN Trial.

In the current study, we sought to identify bone marrow-derived mononuclear cell (BM-MNC) subpopulations associated with a combined improvement in left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), and maximal oxygen consumption (VO2 max) in patients with chronic ischemic cardiomyopathy 6 months after receiving transendocardial injections of autologous BM-MNCs or placebo. For this prospectively planned analysis, we conducted an embedded cohort study comprising 78 patients from the FOCUS-Cardiovascular Cell Therapy Research Network (CCTRN) trial. Baseline BM-MNC immunophenotypes and progenitor cell activity were determined by flow cytometry and colony-forming assays, respectively. Previously stable patients who demonstrated improvement in LVEF, LVESV, and VO2 max during the 6-month course of the FOCUS-CCTRN study (group 1, n = 17) were compared to those who showed no change or worsened in one to three of these endpoints (group 2, n = 61) and to a subset of patients from group 2 who declined in all three functional endpoints (group 2A, n = 11). Group 1 had higher frequencies of B-cell and CXCR4+ BM-MNC subpopulations at study baseline than group 2 or 2A. Furthermore, patients in group 1 had fewer endothelial colony-forming cells and monocytes/macrophages in their bone marrow than those in group 2A. To our knowledge, this is the first study to show that in patients with ischemic cardiomyopathy, certain bone marrow-derived cell subsets are associated with improvement in LVEF, LVESV, and VO2 max at 6 months. These results suggest that the presence of both progenitor and immune cell populations in the bone marrow may influence the natural history of chronic ischemic cardiomyopathy-even in stable patients. Thus, it may be important to consider the bone marrow composition and associated regenerative capacity of patients when assigning them to treatment groups and evaluating the results of cell therapy trials.

Heart Rate Variability as a Predictor of Death in Burn Patients.

Heart rate variability (HRV), a noninvasive technique used to quantify fluctuations in the interval between normal heart beats (NN), is a predictor of mortality in some patient groups. The aim of this study was to assess HRV in burn trauma patients as a predictor of mortality. The authors prospectively performed 24-hour Holter monitoring on burn patients and collected demographic information, burn injury details, and in-hospital clinical events. Analysis of HRV in the time and frequency domains was performed. A total of 40 burn patients with a mean age of 44 ± 15 years were enrolled. Mean %TBSA burn was 27 ± 22% for the overall population and was significantly higher in those who died compared with those who survived (55 ± 23% vs 19 ± 13%; P < .0001). There was a statistically significant inverse linear correlation between SD of NN intervals and %TBSA (r = -.337, R = 0.113, 95% CI = -0.587 to -0.028, two-tailed P = .034), as well as with ultra low frequency power and %TBSA burn (r = -0.351, R = 0.123, 95% CI = -0.152 to -0.009; P = .027). The receiver-operator characteristic showed the area under the curve for %TBSA as a predictor of death was 0.82 (P < .001), for SDANN was 0.94 (P < .0001), and for ultra low frequency power was 0.96 (P < .0001). Deranged HRV in the early postburn period is a strong predictor of death.

Replicating Patient-Specific Severe Aortic Valve Stenosis With Functional 3D Modeling.

BACKGROUND: 3D stereolithographic printing can be used to convert high-resolution computed tomography images into life-size physical models. We sought to apply 3D printing technologies to develop patient-specific models of the anatomic and functional characteristics of severe aortic valve stenosis. METHODS AND RESULTS: Eight patient-specific models of severe aortic stenosis (6 tricuspid and 2 bicuspid) were created using dual-material fused 3D printing. Tissue types were identified and segmented from clinical computed tomography image data. A rigid material was used for printing calcific regions, and a rubber-like material was used for soft tissue structures of the outflow tract, aortic root, and noncalcified valve cusps. Each model was evaluated for its geometric valve orifice area, echocardiographic image quality, and aortic stenosis severity by Doppler and Gorlin methods under 7 different in vitro stroke volume conditions. Fused multimaterial 3D printed models replicated the focal calcific structures of aortic stenosis. Doppler-derived measures of peak and mean transvalvular gradient correlated well with reference standard pressure catheters across a range of flow conditions (r=0.988 and r=0.978 respectively, P<0.001). Aortic valve orifice area by Gorlin and Doppler methods correlated well (r=0.985, P<0.001). Calculated aortic valve area increased a small amount for both methods with increasing flow (P=0.002). CONCLUSIONS: By combing the technologies of high-spatial resolution computed tomography, computer-aided design software, and fused dual-material 3D printing, we demonstrate that patient-specific models can replicate both the anatomic and functional properties of severe degenerative aortic valve stenosis.

Association of Left Ventricular Diastolic Dysfunction with Subclinical Coronary Atherosclerotic Disease Burden Using Coronary Artery Calcium Scoring.

AIM: Diastolic dysfunction is a common problem in patients with obesity, hypertension, diabetes, or coronary artery disease. The purpose of this study was to evaluate the association of left ventricular diastolic dysfunction with an abnormal coronary artery calcium score (CAC score). METHODS: This study considered a cohort of patients ≥ 18 years of age with normal ejection fraction who were admitted to the hospital with chest pain. All patients underwent regadenoson myocardial perfusion stress imaging and had no evidence of ischemia or infarction. Patients then underwent cardiac CT for measurement of CAC score. Patients were excluded if they had prior history of coronary artery disease, ECG findings diagnostic of an acute coronary syndrome, an elevated troponin level, or hemodynamic instability. RESULTS: A total of 114 patients were included and 52 (45.6%) patients had echocardiographic evidence of diastolic dysfunction. Patients with diastolic dysfunction were more likely to have an abnormal calcium score (79.6% vs 20%; OR 15.10, 95% CI 5.70 to 43.85; p ＜ 0.001). In multivariable analysis, the presence of diastolic dysfunction on echocardiogram was significantly associated with an abnormal calcium score (OR 13.82, 95% CI 5.57 to 37.37; p ＜ 0.001) after adjusting for Framingham Risk Score or clinical risk factors (age, gender, diabetes mellitus, dyslipidemia, and obesity; OR 19.06,95% CI 4.66 to 107.97; p ＜ 0.001). CONCLUSIONS: Our study demonstrates that left ventricular diastolic dysfunction is associated with an abnormal CAC score even after adjusting for Framingham Risk Score or clinical risk factors. Patients without known coronary artery disease that present with chest pain and have normal perfusion imaging with evidence of abnormal diastolic function on echocardiogram may warrant more thorough evaluation for coronary atherosclerotic disease with CAC score assessment.

Bone marrow characteristics associated with changes in infarct size after STEMI: a biorepository evaluation from the CCTRN TIME trial.

RATIONALE: Despite significant interest in bone marrow mononuclear cell (BMC) therapy for ischemic heart disease, current techniques have resulted in only modest benefits. However, selected patients have shown improvements after autologous BMC therapy, but the contributing factors are unclear. OBJECTIVE: The purpose of this study was to identify BMC characteristics associated with a reduction in infarct size after ST-segment-elevation-myocardial infarction. METHODS AND RESULTS: This prospective study comprised patients consecutively enrolled in the CCTRN TIME (Cardiovascular Cell Therapy Research Network Timing in Myocardial Infarction Evaluation) trial who agreed to have their BMCs stored and analyzed at the CCTRN Biorepository. Change in infarct size between baseline (3 days after percutaneous coronary intervention) and 6-month follow-up was measured by cardiac MRI. Infarct-size measurements and BMC phenotype and function data were obtained for 101 patients (mean age, 56.5 years; mean screening ejection fraction, 37%; mean baseline cardiac MRI ejection fraction, 45%). At 6 months, 75 patients (74.3%) showed a reduction in infarct size (mean change, -21.0±17.6%). Multiple regression analysis indicated that infarct size reduction was greater in patients who had a larger percentage of CD31(+) BMCs (P=0.046) and in those with faster BMC growth rates in colony-forming unit Hill and endothelial-colony forming cell functional assays (P=0.033 and P=0.032, respectively). CONCLUSIONS: This study identified BMC characteristics associated with a better clinical outcome in patients with segment-elevation-myocardial infarction and highlighted the importance of endothelial precursor activity in regenerating infarcted myocardium. Furthermore, it suggests that for these patients with segment-elevation-myocardial infarction, myocardial repair was more dependent on baseline BMC characteristics than on whether the patient underwent intracoronary BMC transplantation. CLINICAL TRIAL REGISTRATION INFORMATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00684021.