Philip A. Araoz

Characteristics and Clinical Significance of Late Gadolinium Enhancement by Contrast-Enhanced Magnetic Resonance Imaging in Patients with Hypertrophic Cardiomyopathy

Background—Myocardial late gadolinium enhancement (LGE) on contrast-enhanced magnetic resonance imaging (CE-MRI) of patients with hypertrophic cardiomyopathy (HCM) has been suggested to represent intramyocardial fibrosis and, as such, an adverse prognostic risk factor. We evaluated the characteristics of LGE on CE-MRI and explored whether LGE among patients with HCM was associated with genetic testing, severe symptoms, ventricular arrhythmias, or sudden cardiac death (SCD). Methods and Results—Four hundred twenty-four patients with HCM (age=55±16 years [range 2 to 90], 41% females), without a history of septal ablation/myectomy, underwent CE-MRI (GE 1.5 Tesla). We evaluated the relation between LGE and HCM genes status, severity of symptoms, and the degree of ventricular ectopy on Holter ECG. Subsequent SCD and appropriate implanted cardioverter defibrillator (ICD) therapies were recorded during a mean follow-up of 43±14 months (range 16 to 94). Two hundred thirty-nine patients (56%) had LGE on CE-MRI, ranging from 0.4% to 65% of the left ventricle. Gene-positive patients were more likely to have LGE (P<0.001). The frequencies of New York Heart Association class ≥3 dyspnea and angina class ≥3 were similar in patients with and without LGE (125 of 239 [52%] versus 94 of 185 [51%] and 24 of 239 [10%] versus 18 of 185 [10%], respectively, P=NS). LGE-positive patients were more likely to have episodes of nonsustained ventricular tachycardia (34 of 126 [27%] versus 8 of 94 [8.5%], P<0.001), had more episodes of nonsustained ventricular tachycardia per patient (4.5±12 versus 1.1±0.3, P=0.04), and had higher frequency of ventricular extrasystoles/24 hours (700±2080 versus 103±460, P=0.003). During follow-up, SCD occurred in 4 patients, and additional 4 patients received appropriate ICD discharges. All 8 patients were LGE positive (event rate of 0.94%/y, P=0.01 versus LGE negative). Two additional heart failure-related deaths were recorded among LGE-positive patients. Univariate associates of SCD or appropriate ICD discharge were positive LGE (P=0.002) and presence of nonsustained ventricular tachycardia (P=0.04). The association of LGE with events remained significant after controlling for other risk factors. Conclusions—In patients with HCM, presence of LGE on CE-MRI was common and more prevalent among gene-positive patients. LGE was not associated with severe symptoms. However, LGE was strongly associated with surrogates of arrhythmia and remained a significant associate of subsequent SCD and/or ICD discharge after controlling for other variables. If replicated, LGE may be considered an important risk factor for sudden death in patients with HCM.

Role of cardiac magnetic resonance imaging in the detection of cardiac amyloidosis.

OBJECTIVES Our aim was to evaluate the role and mechanism of late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) in identifying cardiac amyloidosis (CA) and to investigate associations between LGE and clinical, morphologic, functional, and biochemical features. BACKGROUND CA can be challenging to diagnose by echocardiography. Recent studies have demonstrated an emerging role for LGE-CMR. METHODS LGE-CMR was performed in 120 patients with amyloidosis. Cardiac histology was available in 35 patients. The remaining 85 patients were divided into those with and without echocardiographic evidence of CA. RESULTS Of the 35 patients with histologically verified CA, abnormal LGE was present in 34 (97%) patients and increased echocardiographic left ventricular wall thickness in 32 (91%) patients. Global transmural or subendocardial LGE (83%) was most common and was associated with greater interstitial amyloid deposition (p = 0.03). Suboptimal myocardial nulling (8%) and patchy focal LGE (6%) were also observed. LGE distribution matched the deposition pattern of interstitial amyloid. Among patients without cardiac histology, LGE was present in 86% of those with evidence of CA by echocardiography and in 47% of those without evidence of CA by echocardiography. In patients without echocardiographic evidence of CA, the presence of LGE was associated with worse clinical, electrocardiographic (ECG), and cardiac biomarker profiles. In all patients, LGE presence and pattern was associated with New York Heart Association functional class, ECG voltage, left ventricular mass index, right ventricular wall thickness, troponin-T, and B-type natriuretic peptide levels. CONCLUSIONS LGE is common in CA and detects interstitial expansion from amyloid deposition. Global transmural or subendocardial LGE is most common, but suboptimal myocardial nulling and focal patchy LGE are also observed. LGE-CMR may detect early cardiac abnormalities in patients with amyloidosis with normal left ventricular thickness. The presence and pattern of LGE is strongly associated with clinical, morphologic, functional, and biochemical markers of prognosis.

MR Elastography of Liver Tumors: Preliminary Results

OBJECTIVE The purpose of this study was to evaluate the potential value of MR elastography (MRE) in the characterization of solid liver tumors. MATERIALS AND METHODS Forty-four liver tumors (14 metastatic lesions, 12 hepatocellular carcinomas, nine hemangiomas, five cholangiocarcinomas, three cases of focal nodular hyperplasia, and one hepatic adenoma) were evaluated with MRE. MRE was performed with a 1.5-T system with a modified phase-contrast gradient-echo sequence to collect axial wave images sensitized along the through-plane motion direction. The tumors were identified on T2- and T1-weighted and gadolinium-enhanced T1-weighted images, and the MRE images were obtained through the tumor. A stiffness map (elastogram) was generated in an automated process consisting of an inversion algorithm. The mean shear stiffness of the tumor was calculated with a manually specified region of interest over the tumor in the stiffness map. The stiffness value of tumor-free hepatic parenchyma was calculated. Statistical analysis was performed on the stiffness values for differentiation of normal liver, fibrotic liver, benign tumors, and malignant tumors. RESULTS Malignant liver tumors had significantly greater mean shear stiffness than benign tumors (10.1 kPa vs 2.7 kPa, p < 0.001), fibrotic liver (10.1 kPa vs 5.9 kPa, p < 0.001), and normal liver (10.1 kPa vs 2.3 kPa, p < 0.001). Fibrotic livers had stiffness values overlapping both the benign and the malignant tumors. A cutoff value of 5 kPa accurately differentiated malignant tumors from benign tumors and normal liver parenchyma in this preliminary investigation. CONCLUSION MR elastography is a promising noninvasive technique for assessing solid liver tumors. Use of MRE may lead to new quantitative tissue characterization parameters for differentiating benign and malignant liver tumors.

Application of appropriateness criteria to stress single-photon emission computed tomography sestamibi studies and stress echocardiograms in an academic medical center.

OBJECTIVES The purpose of this study was to apply published appropriateness criteria for single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) in a single academic medical center. BACKGROUND The American College of Cardiology Foundation (ACCF) and the American Society of Nuclear Cardiology (ASNC) have developed appropriateness criteria for stress SPECT MPI to address concern about the growth in cardiac imaging studies. METHODS We retrospectively examined 284 patients who underwent stress SPECT MPI and 298 patients who underwent stress echocardiography before publication of these criteria. RESULTS The overall level of agreement in characterizing appropriateness between 2 experienced cardiovascular nurse abstractors was modest (kappa = 0.56), but noticeably poorer (kappa = 0.27) for patients with previous SPECT or echo studies. Similar percentages of each imaging modality were assigned to the 3 appropriateness categories: 64% of stress SPECT and 64% of stress echo studies were classified appropriate; 11% of stress SPECT and 9% of stress echo were of uncertain appropriateness; and 14% of stress SPECT and 18% of stress echo were inappropriate. Of the inappropriate studies, 88% were performed for 1 of 4 indications. Approximately 10% of the patients were unclassifiable. CONCLUSIONS Application of existing SPECT MPI appropriateness criteria is demanding and requires an established database or detailed data collection, as well as a number of assumptions. Fourteen percent of stress SPECT studies and 18% of stress echo studies were performed for inappropriate reasons. Quality improvement efforts directed at reducing the number of these inappropriate studies may improve efficiency in the health care system.

Helical CT pulmonary angiography predictors of in-hospital morbidity and mortality in patients with acute pulmonary embolism.

Purpose To determine if CT variables predict in-hospital morbidity and mortality in patients with pulmonary embolism (PE). Materials and Methods CT scans and charts of 173 patients with CT scans positive for PE were reviewed. CT scans were reviewed for leftward ventricular septal bowing, increased right ventricle (RV) to left ventricle (LV) diameter ratio, clot burden, increased pulmonary artery to aorta diameter ratio, and oligemia. Charts were reviewed for severe morbidity and mortality outcomes: death from pulmonary emboli or any cause, and cardiac arrest. Charts were also reviewed for milder morbidity outcomes: intubation, vasopressor use, or admission to an intensive care unit (ICU) and for multiple comorbidities. Results No CT predictor was significantly associated with severe morbidity or mortality outcomes. Ventricular septal bowing and increased RV/LV diameter ratio were both associated with subsequent admission to an ICU (P = 0.004 and P = 0.025, respectively). Oligemia (either lung) was associated with subsequent intubation; right lung oligemia was associated with the subsequent use of vasopressors. After controlling for history of congestive heart failure, ischemic heart disease, and pulmonary disease, both septal bowing and an increased RV/LV diameter ratio remained associated with admission to an ICU. Conclusion No CT variables predicted severe in-hospital morbidity and mortality (death from pulmonary embolism, death from any cause, or cardiac arrest) in patients with PE. However, ventricular septal bowing and increased RV/LV diameter ratio were both strongly predictive of less severe morbidity, namely, subsequent ICU admission, and oligemia was associated with subsequent intubation and vasopressor use.

Dynamic Tracking During Intracoronary Injection of 18F-FDG-Labeled Progenitor Cell Therapy for Acute Myocardial Infarction

We assessed the feasibility of dynamic 3-dimensional (3D) PET/CT tracking of 18F-FDG-labeled circulating progenitor cell (CPC) therapy during intracoronary injection, using a porcine model of acute myocardial infarction (MI). Methods: Human and porcine CPC were radiolabeled with 18F-FDG, with variation in temperature and incubation time to determine optimal conditions. For in vivo experiments, CPC were harvested before induction of infarction (using 90-min coronary balloon occlusion). At 48 h, animals underwent cardiac MRI to assess infarct size. A balloon catheter was placed in the infarct artery at the same location as that used for induction of MI, and during dynamic 3D PET/CT 3 × 107 autologous 18F-FDG progenitor cells were injected through the central lumen using either (a) 3 cycles of balloon occlusion and reperfusion or (b) high-concentration, single-bolus injection without balloon occlusion (n = 3 for both protocols). Peripheral blood was drawn at 1-min intervals during cell injection. Results: Labeling efficiency was optimized by 30-min incubation at 37°C (human CPC, 89.9% ± 4.8%; porcine CPC, 91.6% ± 6.4%). Cell-bound activity showed a nonsignificant decrease at 1 h (human, 74.3% ± 10.7%; porcine, 77.7% ± 12.8%; P > 0.05) and a significant decrease at 2 h (human, 62.1% ± 8.9%; porcine, 68.6% ± 5.4%; P = 0.009). Mean infarct size was similar for both injection protocols (16.3% ± 3.4% and 20.6% ± 2.7%; P > 0.05). Dynamic scanning demonstrated a sharp rise in myocardial activity during each cycle of balloon-occlusion cell delivery, with a significant fall in activity (around 80%) immediately after balloon deflation. The latter was associated with a transient spike in peripheral blood 18F-FDG activity, consistent with the first pass of labeled cells in the systemic circulation. A single spike and gradual fall in myocardial activity was observed with high-concentration, single-bolus therapy. At 1 h, myocardial activity was 8.7% ± 1.5% of total injected dose for balloon-occlusion delivery and 17.8% ± 7.9% for high-concentration, single-bolus delivery (P = 0.08). Conclusion: Dynamic tracking during intracoronary injection of 18F-FDG-labeled CPC is feasible and demonstrates significant cell washout from the myocardium immediately after balloon deflation. High-concentration, single-bolus therapy may be as effective as balloon-occlusion delivery. This tracking technique should facilitate development of improved delivery strategies for cardiac cell therapy.

Progression of Subclinical Coronary Atherosclerosis Does Obesity Make a Difference

Background—Obesity is associated with coronary artery calcification (CAC), a marker of the presence and extent of subclinical coronary atherosclerosis. Obesity adds incremental information in identifying those at higher risk of coronary heart disease to traditional risk factor assessment. The present study examined associations between obesity measures and progression of CAC in those at higher (≥10%) and lower (<10%) 10-year coronary heart disease risk according to the Framingham risk equation. Methods and Results—In this study, 443 asymptomatic white individuals >30 years of age (243 men) had baseline and follow-up CAC measurements an average of 8.9 years apart. Multivariable linear regression models were fit to determine associations of obesity measures at baseline with progression of CAC defined as loge of the difference between follow-up and baseline CAC area plus 1 divided by time (in years) between examinations, adjusting for baseline CAC quantity, age, sex, baseline hypertension status, and baseline cholesterol level. Among 329 participants (74.3%) in the lower-risk group, waist circumference (P=0.024), waist-to-hip ratio (P<0.001), body mass index (P=0.036), and being overweight compared with being underweight or of normal weight (P=0.008) were each significantly positively associated with progression of CAC. Among those at higher coronary heart disease risk, no baseline obesity measures were associated with CAC progression. Conclusions—Various measures of obesity were associated with increased progression of CAC in those at lower risk of coronary heart disease. Future studies examining the effectiveness of weight reduction strategies in reducing CAC progression among those with an otherwise favorable risk factor profile may be warranted.

Cardiac Magnetic Resonance Imaging Pericardial Late Gadolinium Enhancement and Elevated Inflammatory Markers Can Predict the Reversibility of Constrictive Pericarditis After Antiinflammatory Medical Therapy A Pilot Study

Background— Constrictive pericarditis (CP) is a disabling disease, and usually requires pericardiectomy to relieve heart failure. Reversible CP has been described, but there is no known method to predict the reversibility. Pericardial inflammation may be a marker for reversibility. As a pilot study, we assessed whether cardiac magnetic resonance imaging pericardial late gadolinium enhancement (LGE) and inflammatory biomarkers could predict the reversibility of CP after antiinflammatory therapy. Method and Results— Twenty-nine CP patients received antiinflammatory medications after cardiac magnetic resonance imaging. Fourteen patients had resolution of CP, whereas 15 patients had persistent CP after 13 months of follow-up. Baseline LGE pericardial thickness was greater in the group with reversible CP than in the persistent CP group (4±1 versus 2±1 mm, P=0.001). Qualitative intensity of pericardial LGE was moderate or severe in 93% of the group with reversible CP and in 33% of the persistent CP group (P=0.002). Cardiac magnetic resonance imaging LGE pericardial thickness ≥3 mm had 86% sensitivity and 80% specificity to predict CP reversibility. The group with reversible CP also had higher baseline C-reactive protein and erythrocyte sedimentation rate than the persistent CP group (59±52 versus 12±14 mg/L, P=0.04 and 49±25 versus 15±16 mm/h, P=0.04, respectively). Antiinflammatory therapy was associated with a reduction in C-reactive protein, erythrocyte sedimentation rate, and pericardial LGE in the group with reversible CP but not in the persistent CP group. Conclusions— Reversible CP was associated with pericardial and systemic inflammation. Antiinflammatory therapy was associated with a reduction in pericardial and systemic inflammation and LGE pericardial thickness, with resolution of CP physiology and symptoms. Further studies in a larger number of patients are needed.

Characterization of blood borne microparticles as markers of premature coronary calcification in newly menopausal women

While the risk for symptomatic atherosclerotic disease increases after menopause, currently recognized risk factors do not identify ongoing disease processes in low-risk women. This study tested the hypothesis that circulating cell-derived microparticles may reflect disease processes in women defined as low risk by the Framingham risk score. The concentration and phenotype of circulating microparticles were evaluated in a cross-sectional study of apparently healthy menopausal women, screened for enrollment into the Kronos Early Estrogen Prevention Study. Microparticles were evaluated by flow cytometry, and coronary artery calcification (CAC) was scored using 64-slice computed tomography scanners. The procoagulant activity of isolated microparticles was determined with a sensitive fluorescent thrombin generation assay. Chronological age, body mass index, serum lipids, systolic blood pressure (Framingham risk score < 10%, range 1-3%), and high-sensitivity C-reactive protein did not differ significantly among women with low (0 < 35; range, 0.3-32 Agatston units) or high (>50; range, 93-315 Agatston units) CAC compared with women without calcification. The total concentration and percentage of microparticles derived from platelets and endothelial cells were greatest in women with high CAC scores. The thrombin-generating capacity of the isolated microparticles correlated with phosphatidylserine expression, which also was greatest in women with high CAC scores. The percentages of microparticles expressing granulocyte and monocyte markers were not significantly different among groups. Therefore, the characterization of platelet and endothelial microparticles may identify early menopausal women with premature CAC who would not otherwise be identified by the usual risk factor analysis.

3 Tesla MR imaging provides improved contrast in first-pass myocardial perfusion imaging over a range of gadolinium doses

PURPOSE To compare myocardial enhancement during first-pass myocardial perfusion imaging at 3.0 Tesla (T) and 1.5T. MATERIALS AND METHODS First-pass myocardial perfusion imaging was performed on twelve normal subjects at 3T and 1.5T using an interleaved notched saturation recovery gradient echo pulse sequence. Subjects received either 0.10 mmol/kg for both scans (group 1), 0.075 mmol/kg for both scans (group 2), or 0.075 mmol/kg for the 3T scan and 0.10 mmol/kg for the 1.5T scan (group 3). RESULTS Contrast enhancement was significantly greater at 3T than at 1.5T for the 12 subjects whether enhancement was normalized to baseline signal intensity (2.58 +/- 0.76 vs. 1.52 +/- 0.37, p < 0.0001) or to noise (57.6 +/- 19.7 vs. 14.7 +/- 7.8, p < 0001). For each of the three groups, contrast enhancement was significantly greater at 3T versus 1.5T (p < 0.0001, p < 0.001, p < 0.008 when normalized to baseline signal; p < 0.0001 for all groups when normalized to noise). CONCLUSION 3T improves contrast in first-pass myocardial perfusion imaging at either 0.10 mmol/kg or 0.075 mmol/kg.