Publications by authors named "Paco Bravo"

70 Publications

Multimodality imaging for the diagnosis of infiltrative cardiomyopathies.

Heart 2021 May 26. Epub 2021 May 26.

Radiology and Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA

Infiltrative cardiomyopathies result from the deposition or anomalous storage of specific substances in the heart, leading to impaired cardiac function and heart failure. In this review, we describe the utility of a variety of imaging modalities for the diagnosis of infiltrative cardiomyopathies and provide algorithms for clinicians to use to evaluate patients with these disorders. We have divided infiltrative cardiomyopathies into two different categories: (1) infiltrative cardiomyopathies characterised by increased wall thickness (eg, cardiac amyloidosis and Anderson-Fabry disease (AFD)) and (2) infiltrative cardiomyopathies that can mimic ischaemic or dilated cardiomyopathies (eg, cardiac sarcoidosis (CS) and iron overload cardiomyopathy). Echocardiography is the first modality of choice for the evaluation of cardiomyopathies in either category, and the differential can be narrowed using cardiac magnetic resonance (CMR) and nuclear imaging techniques. The diagnosis of cardiac amyloidosis is supported with key findings seen on echocardiography, CMR and nuclear imaging, whereas AFD can be suggested by unique features on CMR. CMR and nuclear imaging are also important modalities for the diagnosis of CS, while iron overload cardiomyopathy is mostly diagnosed using tissue characterisation on CMR. Overall, multimodality imaging is necessary for the accurate non-invasive diagnosis of infiltrative cardiomyopathies, which is important to ensure appropriate treatment and prognostication.
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http://dx.doi.org/10.1136/heartjnl-2020-318001DOI Listing
May 2021

Incremental prognostic value of visually estimated coronary artery calcium in patients undergoing positron emission tomography imaging.

Open Heart 2021 May;8(1)

Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA

Objective: Visually estimated coronary artery calcium (VECAC) from chest CT or attenuation correction (AC)/CT obtained during positron emission tomography (PET)-myocardial perfusion imaging (MPI) is feasible. Our aim was to determine the prognostic value of VECAC beyond conventional risk factors and PET imaging parameters, including coronary flow reserve (CFR).

Methods: We analysed 608 patients without known coronary artery disease who underwent PET-MPI between 2012 and 2016 and had AC/CT and/or chest CT images. We used Cox regression to estimate the association of VECAC categories (≤10, 11-400, >400 Agatston units (AU)) with the primary outcome of all-cause death, acute coronary syndrome or stroke (mean follow-up 4.3±1.8 years). C-statistics assessed the relationship between PET parameters and VECAC with the primary outcome.

Results: Mean age was 58±11 years, 65% were women and 67% were black. VECAC ≤10, 11-400 and >400 AU was observed in 68%, 12% and 20% of subjects, respectively. Compared with VECAC ≤10, VECAC categories 11-400 (HR 2.25, 95% CI 1.24 to 4.08) and >400 AU (HR 3.05, 95% CI 1.87 to 4.98) were associated with the primary outcome after adjusting for traditional risk factors, MPI findings and CFR. Adding VECAC to a model that included PET-MPI, CFR and clinical risk factors improved the prognostic value for the primary outcomes (c-statistic 0.71 to 0.75 with VECAC, p=0.01).

Conclusions: VECAC is a potent predictor of events beyond traditional risk factors and PET imaging markers, including CFR. These data further support the importance for routine VECAC implementation.
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http://dx.doi.org/10.1136/openhrt-2021-001648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8108688PMC
May 2021

Radionuclide Imaging of Cardiac Amyloidosis.

PET Clin 2021 Apr 12;16(2):285-293. Epub 2021 Feb 12.

Division of Cardiovascular Medicine, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Division of Nuclear Medicine and Clinical Molecular Imaging, Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Division of Cardiothoracic Imaging, Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address:

This article provides a review of the latest radiotracers for planar/single-photon emission computed tomography (SPECT) and positron emission tomography (PET)/computed tomography (CT) imaging of cardiac amyloidosis, detailing their affinity, specificity, and sensitivity for cardiac amyloidosis. There are several tracers available that have differing affinities for transthyretin (ATTR) and immunoglobulin light chain (AL), and new developments in technology have allowed for disease burden quantification. Bone scintigraphy is an excellent option for visualizing ATTR cardiac amyloidosis. Negative testing does not exclude the possibility of AL cardiac amyloidosis and absolute quantitation of amyloid burden is limited.
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http://dx.doi.org/10.1016/j.cpet.2020.12.010DOI Listing
April 2021

A Novel Mouse Model of Radiation-Induced Cardiac Injury Reveals Biological and Radiological Biomarkers of Cardiac Dysfunction with Potential Clinical Relevance.

Clin Cancer Res 2021 Apr 4;27(8):2266-2276. Epub 2021 Feb 4.

Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania.

Purpose: Radiation-induced cardiotoxicity is a significant concern in thoracic oncology patients. However, the basis for this disease pathology is not well characterized. We developed a novel mouse model of radiation-induced cardiotoxicity to investigate pathophysiologic mechanisms and identify clinically targetable biomarkers of cardiac injury.

Experimental Design: Single radiation doses of 20, 40, or 60 Gy were delivered to the cardiac apex of female C57BL/6 mice ages 9-11 weeks, with or without adjacent lung tissue, using conformal radiotherapy. Cardiac tissue was harvested up to 24 weeks post-radiotherapy for histologic analysis. Echocardiography and Technetium-99m sestamibi single photon emission computed tomography (SPECT) at 8 and 16 weeks post-radiotherapy were implemented to evaluate myocardial function and perfusion. Mouse cardiac tissue and mouse and human plasma were harvested for biochemical studies.

Results: Histopathologically, radiotherapy resulted in perivascular fibrosis 8 and 24 ( < 0.05) weeks post-radiotherapy. Apical perfusion deficits on SPECT and systolic and diastolic dysfunction on echocardiography 8 and 16 weeks post-radiotherapy were also observed ( < 0.05). Irradiated cardiac tissue and plasma showed significant increases in placental growth factor (PlGF), IL6, and TNFα compared with nonradiated matched controls, with greater increases in cardiac cytokine levels when radiotherapy involved lung. Human plasma showed increased PlGF ( = 0.021) and TNFα ( = 0.036) levels after thoracic radiotherapy. PlGF levels demonstrated a strong correlation ( = 0.89, = 0.0001) with mean heart dose.

Conclusions: We developed and characterized a pathophysiologically relevant mouse model of radiation-induced cardiotoxicity involving irradiation of the cardiac apex. The model can be used to integrate radiomic and biochemical markers of cardiotoxicity to inform early therapeutic intervention and human translational studies.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-3882DOI Listing
April 2021

Left ventricular mural thrombus appearing as a photopenic defect on myocardial viability PET imaging.

J Nucl Cardiol 2021 Jan 5. Epub 2021 Jan 5.

Division of Cardiology, Department of Medicine, Hospital of the University of Pennsylvania, 3400 Civic Center Blvd, 11-154 South Pavilion, Philadelphia, PA, 19104, USA.

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http://dx.doi.org/10.1007/s12350-020-02480-yDOI Listing
January 2021

Mechanical Dyssynchrony with Gated Myocardial Perfusion SPECT: Reproducibility is the Key.

J Nucl Cardiol 2021 Jan 3. Epub 2021 Jan 3.

Division of Cardiovascular Medicine, Department of Medicine, Hospital of the University of Pennsylvania, 3400 Civic Center Blvd, 11-154 South Pavilion, Philadelphia, PA, 19104, USA.

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http://dx.doi.org/10.1007/s12350-020-02463-zDOI Listing
January 2021

Potential Cardiovascular Applications of Total-body PET Imaging.

PET Clin 2021 Jan;16(1):129-136

Division of Nuclear Medicine and Clinical Molecular Imaging, Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Division of Cardiovascular Medicine, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Division of Cardiothoracic Imaging, Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address:

Cardiovascular conditions can exist as part of a systemic disorder (eg, sarcoidosis, amyloidosis, or vasculitis) or have systemic consequences as a result of the cardiovascular insult (eg, myocardial infarction). In other circumstances, multisystem evaluation of metabolism and blood flow might be key for evaluation of multisystemic syndromes or conditions. Long axial field-of-view PET/computed tomography systems hold the promise of transforming the investigation of such systemic disorders. This article aims at reviewing some of the potential cardiovascular applications of this novel instrumentation device.
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http://dx.doi.org/10.1016/j.cpet.2020.09.004DOI Listing
January 2021

Diagnostic accuracy of SPECT and PET myocardial perfusion imaging in patients with left bundle branch block or ventricular-paced rhythm.

J Nucl Cardiol 2020 Oct 20. Epub 2020 Oct 20.

Division of Cardiology, Department of Medicine, Hospital of the University of Pennsylvania, 3400 Civic Center Blvd, 11-154 South Pavilion, Philadelphia, PA, 19104, USA.

Background: The difference in diagnostic accuracy of coronary artery disease (CAD) between vasodilator SPECT and PET myocardial perfusion imaging (MPI) in patients with left bundle branch block (LBBB) or ventricular-paced rhythm (VPR) is unknown.

Methods: We identified patients with LBBB or VPR who underwent either vasodilator SPECT or PET MPI and subsequent coronary angiography. LBBB/VPR-related septal and anteroseptal defects were defined as perfusion defects involving those regions in the absence of obstructive CAD in the left anterior descending artery or left main coronary artery.

Results: Of the 55 patients who underwent coronary angiography, 38 (69%) underwent SPECT and 17 patients (31%) underwent PET. PET compared to SPECT demonstrated higher sensitivity (88% vs 60%), specificity (56% vs 14%), positive predictive value (64% vs 20%), negative predictive value (83% vs 50%), and overall superior diagnostic accuracy (AUC .72 (95% CI .50-.93) vs .37 (95% CI .20-.54), P = .01) to detect obstructive CAD. LBBB/VPR-related septal and anteroseptal defects were more common with SPECT compared to PET (septal: 72% vs 17%, P = .001; anteroseptal: 47% vs 8%, P = .02).

Conclusions: PET has higher diagnostic accuracy when compared to SPECT for the detection of obstructive CAD in patients with LBBB or VPR.
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http://dx.doi.org/10.1007/s12350-020-02398-5DOI Listing
October 2020

COVID-19 and the Heart.

Colomb Med (Cali) 2020 Jun 30;51(2):e4320. Epub 2020 Jun 30.

University of Pennsylvania, Departments of Medicine and Radiology, Philadelphia, United States.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which causes coronavirus disease 2019 (COVID-19) has resulted in a global health crisis. Prior to the arrival of this viral pandemic, the world was already plagued with a significant burden of cardiovascular disease. With the introduction of the novel virus, the world now faces a double jeapordy. Early reports have suggested an increased risk of death in individuals with underlying cardio-metabolic disorders. The exact effects of COVID-19 on the cardiovascular system are not well determined, however lessons from prior viral epidemics suggest that such infections can trigger acute coronary syndromes, arrhythmias and heart failure via direct and indirect mechanisms. In this article, we aimed to discuss the effects and potential underlying mechanisms of COVID -19 as well as potential implications of treatments targeted against this virus on the cardiovascular system.
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http://dx.doi.org/10.25100/cm.v51i2.4320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7518726PMC
June 2020

NaF-PET/CT global assessment in detecting and quantifying subclinical cardiac atherosclerosis and its association with blood pressure in non-dyslipidemic individuals.

Am J Cardiovasc Dis 2020 15;10(2):101-107. Epub 2020 Jun 15.

Department of Radiology, University of Pennsylvania Philadelphia, Pennsylvania, United States.

Background: We used F-sodium fluoride (NaF) to assess early atherosclerosis in the global heart in asymptomatic individuals with a coronary calcium score of zero and without a formal diagnosis of hypertension. We hypothesized that these individuals might present with subclinical atherosclerosis that correlates with systolic, diastolic and mean arterial pressure (SBP, DBP, and MAP).

Methods: We identified 20 asymptomatic individuals (41.6 ± 13.8 years, 8 females) from the CAMONA trial with C-reactive protein ≥3 mg/L, no smoking history, diabetes (fasting blood glucose <126 mg/dl) and dyslipidemia per the Adult Treatment Panel III Guidelines: untreated LDL <160 mg/dL, total cholesterol <240 mg/dL, HDL >40 mg/dL. All underwent PET/CT imaging 90 minutes after NaF injection (2.2 Mbq/Kg). The global cardiac average SUVmean (aSUVmean) was calculated for each individual. Correlation coefficients and linear regression models were employed for statistical analysis.

Results: Significant positive correlation was revealed between global cardiac NaF uptake and all blood pressures: SBP (r=0.44, P=0.05), DBP (r=0.64, P=0.002), and MAP (r=0.59, P=0.007). After adjusting for age and gender, DBP and MAP were independent predictors of higher global cardiac NaF uptake.

Conclusion: NaF-PET/CT for detecting and quantifying subclinical atherosclerosis in asymptomatic individuals revealed that cardiac NaF uptake correlated independently with DBP and MAP.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7364275PMC
June 2020

SPECT quantification of myocardial blood flow: Another step toward widespread availability.

J Nucl Cardiol 2020 May 31. Epub 2020 May 31.

Division of Cardiovascular Medicine, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

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http://dx.doi.org/10.1007/s12350-020-02207-zDOI Listing
May 2020

Improved Quantification of Cardiac Amyloid Burden in Systemic Light Chain Amyloidosis: Redefining Early Disease?

JACC Cardiovasc Imaging 2020 06 13;13(6):1325-1336. Epub 2020 May 13.

Department of Medicine, Division of Cardiology, Cardiac Amyloidosis Program, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Department of Radiology, Division of Nuclear Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Department of Medicine and Radiology, CV Imaging Program, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. Electronic address:

Objectives: The purpose of this study was to determine phenotypes characterizing cardiac involvement in AL amyloidosis by using direct (fluorine-18-labeled florbetapir {[F]florbetapir} positron emission tomography [PET]/computed tomography) and indirect (echocardiography and cardiac magnetic resonance [CMR]) imaging biomarkers of AL amyloidosis.

Background: Cardiac involvement in systemic light chain amyloidosis (AL) is the main determinant of prognosis and, therefore, guides management. The hypothesis of this study was that myocardial AL deposits and expansion of extracellular volume (ECV) could be identified before increases in N-terminal pro-B-type natriuretic peptide or wall thickness.

Methods: A total of 45 subjects were prospectively enrolled in 3 groups: 25 with active AL amyloidosis with cardiac involvement (active-CA), 10 with active AL amyloidosis without cardiac involvement by conventional criteria (active-non-CA), and 10 with AL amyloidosis with cardiac involvement in remission for at least 1 year (remission-CA). All subjects underwent echocardiography, CMR, and [F]florbetapir PET/CT to evaluate cardiac amyloid burden.

Results: The active-CA group demonstrated the largest myocardial AL amyloid burden, quantified by [F]florbetapir retention index (RI) 0.110 (interquartile range [IQR]: 0.078 to 0.139) min, and the lowest cardiac function by global longitudinal strain (GLS), median GLS -11% (IQR: -8% to -13%). The remission-CA group had expanded extracellular volume (ECV) and [F]florbetapir RI of 0.097 (IQR: 0.070 to 0.124 min), and abnormal GLS despite hematologic remission for >1 year. The active-non-CA cohort had evidence of cardiac amyloid deposition by advanced imaging metrics in 50% of the subjects; cardiac involvement was identified by late gadolinium enhancement in 20%, elevated ECV in 20%, and elevated [F]florbetapir RI in 50%.

Conclusions: Evidence of cardiac amyloid infiltration was found based on direct and indirect imaging biomarkers in subjects without CA by conventional criteria. The findings from [F]florbetapir PET imaging provided insight into the preclinical disease process and on the basis of interpretation of expanded ECV on CMR and have important implications for future research and clinical management of AL amyloidosis. (Molecular Imaging of Primary Amyloid Cardiomyopathy [MICA]; NCT02641145).
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http://dx.doi.org/10.1016/j.jcmg.2020.02.025DOI Listing
June 2020

Coronary Microvascular Dysfunction, Left Ventricular Remodeling, and Clinical Outcomes in Patients With Chronic Kidney Impairment.

Circulation 2020 01 29;141(1):21-33. Epub 2019 Nov 29.

Cardiovascular Imaging Program, Departments of Radiology and Medicine; Division of Nuclear Medicine and Molecular Imaging, Department of Radiology; and Divisions of Cardiovascular Medicine and Nephrology, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (N.S.B., A.S., W.Z., A.G., K.F., C.B., H.J.H., P.B., E.A., S.D., C.F.B., J.H., H.S., V.T., M.S., S.D., R.B., R.C.D., S.D.S., M.F.D.C.).

Background: Cardiac dysfunction and cardiovascular events are prevalent among patients with chronic kidney disease without overt obstructive coronary artery disease, but the mechanisms remain poorly understood. Coronary microvascular dysfunction has been proposed as a link between abnormal renal function and impairment of cardiac function and cardiovascular events. We aimed to investigate the relations between chronic kidney disease, coronary microvascular dysfunction, cardiac dysfunction, and adverse cardiovascular outcomes.

Methods: Patients undergoing cardiac stress positron emission tomography, echocardiogram, and renal function ascertainment at Brigham and Women's Hospital were studied longitudinally. Patients free of overt coronary (summed stress score <3 and without a history of ischemic heart disease), valvular, and end-organ disease were followed up for the adverse composite outcome of death or hospitalization for myocardial infarction or heart failure. Coronary flow reserve (CFR) was determined from positron emission tomography. Echocardiograms were used to measure cardiac mechanics: diastolic (lateral and septal E/e') and systolic (global longitudinal, radial, and circumferential strain). Image analyses and event adjudication were blinded. The associations between estimated glomerular filtration rate (eGFR), CFR, diastolic and systolic indices, and adverse cardiovascular outcomes were assessed in adjusted models and mediation analyses.

Results: Of the 352 patients (median age, 65 years; 63% female; 22% black) studied, 35% had an eGFR <60 mL·min·1.73 m, a median left ventricular ejection fraction of 62%, and a median CFR of 1.8. eGFR and CFR were associated with diastolic and systolic indices, as well as future cardiovascular events (all <0.05). In multivariable models, CFR, but not eGFR, was independently associated with cardiac mechanics and cardiovascular events. The associations between eGFR, cardiac mechanics, and cardiovascular events were partly mediated via CFR.

Conclusions: Coronary microvascular dysfunction, but not eGFR, was independently associated with abnormal cardiac mechanics and an increased risk of cardiovascular events. Coronary microvascular dysfunction may mediate the effect of chronic kidney disease on abnormal cardiac function and cardiovascular events in those without overt coronary artery disease.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.119.043916DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7117866PMC
January 2020

Feasibility of somatostatin receptor-targeted imaging for detection of myocardial inflammation: A pilot study.

J Nucl Cardiol 2019 Jun 13. Epub 2019 Jun 13.

Cardiovascular Imaging Program, Heart and Vascular Center, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Background: Gallium-68 Dotatate binds preferentially to somatostatin receptor (sstr) subtype-2 (sstr-2) on inflammatory cells. We aimed at investigating the potential clinical use of sstr-targeted imaging for the detection of myocardial inflammation.

Methods: Thirteen patients, with suspected cardiac sarcoidosis (CS) based on clinical history and myocardial uptake on recent fluorine-18 fluorodeoxyglucose (FDG) PET, were enrolled to undergo Dotatate PET after FDG-PET (median time 37 days [IQR 25-55]). Additionally, we investigated ex-vivo the immunohistochemistry expression of sstr-2 in 3 explanted sarcoid hearts.

Results: All FDG scans showed cardiac uptake (focal/multifocal = 6, focal on diffuse/heterogeneous = 7), and 46% (n = 6) extra-cardiac uptake (mediastinal/hilar). In comparison, Dotatate scans showed definite abnormal cardiac uptake (focal/multifocal) in 4 patients, probably abnormal (heterogenous/patchy) in 3, and negative uptake in 6 cases. Similarly, 6 patients had increased mediastinal/hilar Dotatate uptake. Overall concordance of FDG and Dotatate uptake was 54% in the heart and 100% for thoracic nodal activity. Quantitatively, FDG maximum standardized uptake value was 5.0 times [3.8-7.1] higher in the heart, but only 2.25 times [1.7-3.0; P = .019] higher in thoracic nodes relative to Dotatate. Ex-vivo, sstr-2 immunostaining was weakly seen within well-formed granulomas in all 3 examined sarcoid heart specimens with no significant staining of background myocardium or normal myocardium.

Conclusion: Our preliminary data suggest that, compared to FDG imaging, somatostatin receptor-targeted imaging may be less sensitive for the detection of myocardial inflammation, but comparable for detecting extra-cardiac inflammation.
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http://dx.doi.org/10.1007/s12350-019-01782-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6908775PMC
June 2019

Association between Nonalcoholic Fatty Liver Disease at CT and Coronary Microvascular Dysfunction at Myocardial Perfusion PET/CT.

Radiology 2019 05 5;291(2):330-337. Epub 2019 Mar 5.

From the Cardiovascular Imaging Program, Departments of Medicine (Cardiovascular Division) and Radiology (T.V., D.J.M., M.T.O., N.S.B., A.K., A.J.D.M., P.B., J.H., C.F.B., M.L.S., V.R.T., H.S., R.B., M.F.D.C., S.D.), Division of Nuclear Medicine and Molecular Imaging, Department of Radiology (S.J., A.N., J.H., C.F.B., V.R.T., M.F.D.C., S.D.), and Cardiovascular Division (V.R.T., H.S., R.B., M.F.D.C., S.D.), Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115; Department of Radiology, St Vincent's University Hospital, Dublin, Ireland (D.J.M.); Cardiac MR/PET/CT Program, Departments of Medicine and Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Mass (M.T.O.); and Division of Cardiology, Department of Internal Medicine and Radiology, University of Alabama at Birmingham, Birmingham, Ala (N.S.B.).

Background Cardiovascular disease is a major cause of mortality in patients with nonalcoholic fatty liver disease (NAFLD). However, the association of NAFLD with coronary microvascular dysfunction is, to our knowledge, unknown. Purpose To determine whether coronary microvascular dysfunction is more prevalent in patients with NAFLD and to determine whether coronary microvascular dysfunction predicts major adverse cardiac events (MACE) independently of NAFLD. Materials and Methods This retrospective study (2006-2014) included patients without evidence of obstructive epicardial coronary artery disease and healthy left ventricular ejection fraction (≥40%) at a clinical rest and stress myocardial perfusion PET/CT. NAFLD was defined by a mean hepatic attenuation of less than 40 HU at CT and coronary microvascular dysfunction as a coronary flow reserve (CFR) of less than 2.0. A composite of all-cause mortality, myocardial infarction, coronary revascularization, and hospitalization because of heart failure comprised MACE (130 of 886 patients; 14.7%). The relation between NAFLD and MACE was assessed by using multivariable Cox regression analysis. Results Among 886 patients (mean age, 62 years ± 12 [standard deviation]; 631 women [mean age, 62 years ± 12 years] and 255 men [mean age, 61 years ± 12]; and ejection fraction, 63% ± 9), 125 patients (14.1%) had NAFLD and 411 patients (46.4%) had coronary microvascular dysfunction. Coronary microvascular dysfunction was more prevalent (64.8% vs 43.4%; < .001) and CFR was lower (1.9 ± 1.1 vs 2.2 ± 0.7; < .001) in patients with NAFLD compared with those without NAFLD. NAFLD independently predicted coronary microvascular dysfunction ( = .01). The interaction of NAFLD and male sex predicted MACE (hazard ratio, 1.45; 95% confidence interval: 1.08, 1.69; = .008) and coronary microvascular dysfunction remained associated with MACE (adjusted hazard ratio, 1.46; 95% confidence interval: 1.02, 2.07; = .04). Conclusion Coronary microvascular dysfunction was more prevalent in patients with nonalcoholic fatty liver disease and predicted major adverse cardiac events independently of nonalcoholic fatty liver disease. © RSNA, 2019 See also the editorial by Ambale-Venkatesh and Lima in this issue.
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http://dx.doi.org/10.1148/radiol.2019181793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6492883PMC
May 2019

Precision Cardio-Oncology.

J Nucl Med 2019 04 17;60(4):443-450. Epub 2019 Jan 17.

Division of Cardiology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; and

Modern oncologic therapies and care have resulted in a growing population of cancer survivors with comorbid, chronic health conditions. As an example, many survivors have an increased risk of cardiovascular complications secondary to cardiotoxic systemic and radiation therapies. In response, the field of cardio-oncology has emerged as an integral component of oncologic patient care, committed to the early diagnosis and treatment of adverse cardiac events. However, as current clinical management of cancer therapy-related cardiovascular disease remains limited by a lack of phenotypic data, implementation of precision medicine approaches has become a focal point for deep phenotyping strategies. In particular, -omics approaches (a field of study in biology ending in -omic, such as genomics, proteomics, or metabolomics) have shown enormous potential in identifying sensitive biomarkers of cardiovascular disease, applying sophisticated, pattern-revealing technologies to growing databases of biologic molecules. Moreover, the use of -omics to inform radiologic strategies may add a dimension to future clinical practices. In this review, we present a paradigm for a precision medicine approach to the care of cardiotoxin-exposed cancer patients. We discuss the role of current imaging techniques; demonstrate how -omics can advance our understanding of disease phenotypes; and describe how molecular imaging can be integrated to personalize surveillance and therapeutics, ultimately reducing cardiovascular morbidity and mortality in cancer patients and survivors.
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http://dx.doi.org/10.2967/jnumed.118.220137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6448460PMC
April 2019

Advanced cardiovascular imaging for the evaluation of cardiac sarcoidosis.

J Nucl Cardiol 2019 02 2;26(1):188-199. Epub 2018 Nov 2.

Cardiovascular Imaging Program, Departments of Medicine (Cardiovascular Division) and Radiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Cardiac sarcoidosis (CS) remains an intriguing infiltrating disorder and one of the most important forms of inflammatory cardiomyopathy. Identification of patients with CS is of extreme importance because they are at higher risk of sudden death, and heart-failure progression. And while it remains a diagnostic conundrum, a great amount of experience has been accumulated over the last decade with the advent of fluorine-18 fluorodeoxyglucose positron emission tomography and cardiac magnetic resonance with late gadolinium enhancement imaging. They have both proven to be advanced imaging techniques that provide important, and often complementary, diagnostic and prognostic information for the management of CS. However, they have also shown to have limitations, and, thus, there is a continued need for developing more specific imaging probes for identifying cardiac inflammation. The aim of the present manuscript is to provide the reader with a better understanding of the histopathology of the disease, how this potentially relates to noninvasive imaging detection, and the best strategies available for the diagnosis and management of patients with CS.
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http://dx.doi.org/10.1007/s12350-018-01488-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6374180PMC
February 2019

Thick and thin: Bridging the gap to a better understanding of apical thinning.

J Nucl Cardiol 2020 04 4;27(2):461-464. Epub 2018 Oct 4.

Division of Cardiology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Boulevard, 11-154 South Pavilion, Philadelphia, PA, 19104, USA.

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http://dx.doi.org/10.1007/s12350-018-1451-0DOI Listing
April 2020

Cardiac sarcoidosis: Diagnosis confirmation by bronchoalveolar lavage and lung biopsy.

Respir Med 2018 11 16;144S:S13-S19. Epub 2018 Sep 16.

Center for Interstitial Lung Diseases, Division of Pulmonary, Critical Care, and Sleep Medicine, University of Washington, Seattle, WA, USA.

Introduction: The diagnosis of cardiac sarcoidosis (CS) is difficult to ascertain due to the insensitivity of endomyocardial biopsy. Current diagnostic criteria require a positive endomyocardial biopsy or extra-cardiac biopsy with clinical features suggestive of CS. Common tests for diagnosis of pulmonary sarcoidosis include bronchoalveolar lavage (BAL), lung and mediastinal lymph node (MLN) biopsies. Our objective was to determine the diagnostic utility of these tests in patients with suspected CS and without prior history of pulmonary involvement.

Methods: This retrospective cohort study included 37 patients without history of extra-cardiac sarcoidosis referred for suspected CS. All patients underwent chest computed tomography (CT) staged using the modified Scadding criteria, and had BAL, and/or lung or MLN biopsy. BAL cellular analyses with lymphocytes>15% and/or CD4/CD8 ratio≥ 4 were considered suggestive of sarcoidosis. The number of positive biopsies and BALs were compared between normal CT (Scadding stage 0) and abnormal CT (Scadding stage 1-4) groups.

Results: A definitive diagnosis of sarcoidosis was ascertained in 18/31 (58%) patients undergoing lung or lymph node biopsy, and a potential diagnosis in 18/27 (67%) patients with BAL CD4/CD8>4 or lymphocytes>15%. Of the 12 patients in the normal CT group, 4/10 (40%) had positive lung biopsies, and 9/12 (75%) patients had either positive biopsy or BAL criteria.

Conclusions: In suspected cardiac sarcoidosis, a diagnosis of extra-cardiac sarcoidosis was ascertained in a majority of patients irrespective of degree of lung involvement on chest CT. Our results support referral for pulmonary biopsy/bronchoalveolar lavage in suspected CS to confirm the diagnosis of sarcoidosis.
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http://dx.doi.org/10.1016/j.rmed.2018.09.008DOI Listing
November 2018

Myocardial Scar But Not Ischemia Is Associated With Defibrillator Shocks and Sudden Cardiac Death in Stable Patients With Reduced Left Ventricular Ejection Fraction.

JACC Clin Electrophysiol 2018 09 25;4(9):1200-1210. Epub 2018 Jul 25.

Division of Cardiovascular Medicine, Department of Medicine, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address:

Objectives: This study sought to investigate the association of myocardial scar and ischemia with major arrhythmic events (MAEs) in patients with left ventricular ejection fraction (LVEF) ≤35%.

Background: Although myocardial scar is a known substrate for ventricular arrhythmias, the association of myocardial ischemia with ventricular arrhythmias in stable patients with left ventricular dysfunction is less clear.

Methods: A total of 439 consecutive patients (median age, 70 years; 78% male; 55% with implantable cardioverter defibrillator [ICD]) referred for stress/rest positron emission tomography (PET) and resting LVEF ≤35% were included. Primary outcome was time-to-first MAE defined as sudden cardiac death, resuscitated sudden cardiac death, or appropriate ICD shocks for ventricular tachyarrhythmias ascertained by blinded adjudication of hospital records, Social Security Administration's Death Masterfile, National Death Index, and ICD vendor databases.

Results: Ninety-one MAEs including 20 sudden cardiac deaths occurred in 75 (17%) patients during a median follow-up of 3.2 years. Transmural myocardial scar was strongly associated with MAEs beyond age, sex, cardiovascular risk factors, beta-blocker therapy, and resting LVEF (adjusted hazard ratio per 10% increase in scar, 1.48 [95% confidence interval: 1.22 to 1.80]; p < 0.001). However, non transmural scar/hibernation or markers of myocardial ischemia on PET including global or peri-infarct ischemia, coronary flow reserve, and resting or hyperemic myocardial blood flows were not associated with MAEs in univariable or multivariable analysis. These findings remained robust in subgroup analyses of patients with ICD (n = 223), with ischemic cardiomyopathy (n = 287), and in patients without revascularization after the PET scan (n = 365).

Conclusions: Myocardial scar but not ischemia was associated with appropriate ICD shocks and sudden cardiac death in patients with LVEF ≤35%. These findings have implications for risk-stratification of patients with left ventricular dysfunction who may benefit from ICD therapy.
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http://dx.doi.org/10.1016/j.jacep.2018.06.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6201241PMC
September 2018

Relative Apical Sparing of Myocardial Longitudinal Strain Is Explained by Regional Differences in Total Amyloid Mass Rather Than the Proportion of Amyloid Deposits.

JACC Cardiovasc Imaging 2019 07 15;12(7 Pt 1):1165-1173. Epub 2018 Aug 15.

Noninvasive Cardiovascular Imaging Program, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; Division of Nuclear Medicine, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; Amyloidosis Program, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address:

Objectives: This study sought to test whether relative apical sparing (RELAPS) of left ventricular (LV) longitudinal strain (LS) in cardiac amyloidosis (CA) is explained by regional differences in markers of amyloid burden (F-florbetapir uptake by positron emission tomography [PET] and/or extracellular volume fraction [ECV] by cardiac magnetic resonance (CMR)].

Background: Further knowledge of the pathophysiological basis for RELAPS can help understand the adverse outcomes associated with apical LS impairment.

Methods: This was a prospective study of 32 subjects (age 62 ± 7 years; 50% males) with light chain CA. All subjects underwent two-dimensional echocardiography for LS estimation and F-florbetapir PET for quantification of LV florbetapir retention index (RI). A subset also underwent CMR (n = 22) for ECV quantification. Extracellular LV mass (LV mass*ECV) and total florbetapir binding (extracellular LV mass*florbetapir RI) were also calculated. All parameters were measured globally and regionally (base, mid, and apex).

Results: There was a significant base-to-apex gradient in LS (-7.4 ± 3.2% vs. -8.6 ± 4.0% vs. -20.8 ± 6.6%; p < 0.0001), maximal LV wall thickness (15.7 ± 1.9 cm vs. 15.4 ± 2.9 cm vs. 10.1 ± 2.4 cm; p < 0.0001), and LV mass (74.8 ± 21.2 g vs. 60.8 ± 17.3 g vs. 23.4 ± 6.2 g; p < 0.0001). In contrast, florbetapir RI (0.089 ± 0.03 μmol/min/g vs. 0.097 ± 0.03 μmol/min/g vs. 0.085 ± 0.03 μmol/min/g; p = 0.45) and ECV (0.53 ± 0.08 vs. 0.49 ± 0.08 vs. 0.49 ± 0.07; p = 0.15) showed no significant base-to-apex gradient in the tissue concentration or proportion of amyloid infiltration, whereas markers of total amyloid load, such as total florbetapir binding (3.4 ± 1.7 μmol/min vs. 2.8 ± 1.5 μmol/min vs. 0.93 ± 0.49 μmol/min; p < 0.0001) and extracellular LV mass (40.0 ± 15.6 g vs. 30.2 ± 10.9 g vs. 11.6 ± 3.9 g; p < 0.0001), did show a marked base-to-apex gradient.

Conclusions: Segmental differences in the distribution of the total amyloid mass, rather than the proportion of amyloid deposits, appear to explain the marked regional differences in LS in CA. Although these 2 matrices are clearly related concepts, they should not be used interchangeably.
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http://dx.doi.org/10.1016/j.jcmg.2018.06.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6377347PMC
July 2019

Coronary Microvascular Dysfunction and Cardiovascular Risk in Obese Patients.

J Am Coll Cardiol 2018 08;72(7):707-717

Cardiovascular Imaging Program, Departments of Medicine and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; Brigham and Women's Hospital Heart and Vascular Center, Harvard Medical School, Boston, Massachusetts. Electronic address:

Background: Besides body mass index (BMI), other discriminators of cardiovascular risk are needed in obese patients, who may or may not undergo consideration for bariatric surgery. Coronary microvascular dysfunction (CMD), defined as impaired coronary flow reserve (CFR) in the absence of flow-limiting coronary artery disease, identifies patients at risk for adverse events independently of traditional risk factors.

Objectives: The study sought to investigate the relationship among obesity, CMD, and adverse outcomes.

Methods: Consecutive patients undergoing evaluation for coronary artery disease with cardiac stress positron emission tomography demonstrating normal perfusion (N = 827) were followed for median 5.6 years for events, including death and hospitalization for myocardial infarction or heart failure.

Results: An inverted independent J-shaped relationship was observed between BMI and CFR, such that in obese patients CFR decreased linearly with increasing BMI (adjusted p < 0.0001). In adjusted analyses, CFR but not BMI remained independently associated with events (for a 1-U decrease in CFR, adjusted hazard ratio: 1.95; 95% confidence interval: 1.41 to 2.69; p < 0.001; for a 10-U increase in BMI, adjusted hazard ratio: 1.20; 95% confidence interval: 0.95 to 1.50; p = 0.125) and improved model discrimination (C-index 0.71 to 0.74). In obese patients, individuals with impaired CFR demonstrated a higher adjusted rate of events (5.7% vs. 2.6%; p = 0.002), even in those not currently meeting indications for bariatric surgery (6.4% vs. 2.6%; p = 0.04).

Conclusions: In patients referred for testing, CMD was independently associated with elevated BMI and adverse outcomes, and was a better discriminator of risk than BMI and traditional risk factors. CFR may facilitate management of obese patients beyond currently used markers of risk.
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http://dx.doi.org/10.1016/j.jacc.2018.05.049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6592712PMC
August 2018

Invasive Hemodynamics and Rejection Rates in Patients With Cardiac Sarcoidosis After Heart Transplantation.

Can J Cardiol 2018 08 6;34(8):978-982. Epub 2018 Apr 6.

Division of Cardiology, University of Washington Medical Center, Seattle, Washington, USA.

Background: Orthotopic heart transplant (OHT) is increasingly used for end-stage heart failure due to cardiac sarcoidosis (CS). However, concern regarding long-term outcomes in patients with CS after OHT persists because of multiorgan involvement.

Methods: Baseline demographics and invasive hemodynamics were measured in 12 patients with CS and 28 patients with nonischemic cardiomyopathy requiring OHT at the time of transplantation, 1 week after OHT, and in routine follow-up. Primary endpoints included changes in pulmonary artery pressure, right ventricular stroke work index, and pulmonary compliance. Secondary endpoints included degree of allograft rejection and death.

Results: During a mean follow-up of 73.8 months, no differences in pulmonary artery pressures, right ventricular stroke work index, or cardiac index were observed in patient with CS (n = 12) compared with those without CS (n = 28) between 1 week after OHT and the most recent follow-up. Long-term follow-up showed that pulmonary hemodynamics remained normal in the CS group. International Society for Heart and Lung Transplantation (ISHLT) 1990 grade ≥ 1a rejection occurred less frequently in the CS group (17% vs 68%, P = 0.006), and 0 of 12 patients in the CS group experienced histologic or clinical recurrence of sarcoidosis or ≥2 rejection. Patients with CS had excellent survival after OHT, with 0 deaths or significant rejection.

Conclusions: Patients with CS have similar post-transplant hemodynamics as patients without CS, without evidence of right ventricular dysfunction or pulmonary hypertension. Neither significant rejection nor recurrence of sarcoid in the allograft was observed in this cohort of patients with CS. Survival is similar between patients with CS and those without CS. Heart transplant is a viable strategy in selected patients with CS with excellent outcomes.
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http://dx.doi.org/10.1016/j.cjca.2018.03.021DOI Listing
August 2018

Is there a role for cardiac positron emission tomography in hypertrophic cardiomyopathy?

Authors:
Paco E Bravo

J Nucl Cardiol 2019 08 14;26(4):1125-1134. Epub 2018 May 14.

Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.

Coronary microvascular dysfunction and, its functional consequence, myocardial ischemia are common pathologic features in patients with hypertrophic cardiomyopathy (HCM). Both have been commonly invoked as potential triggers of and/or contributors to the underlying pathophysiological processes leading to heart failure, and malignant ventricular arrhythmias. Positron emission tomography (PET) with myocardial blood flow quantification provides a unique opportunity to evaluate the integrity and function of the coronary microcirculation in HCM. The purpose of the present review is to summarize all the pertinent literature and future perspectives of the role of PET in the evaluation and risk stratification of patients with HCM.
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http://dx.doi.org/10.1007/s12350-018-1298-4DOI Listing
August 2019

Complementary Value of Cardiac Magnetic Resonance Imaging and Positron Emission Tomography/Computed Tomography in the Assessment of Cardiac Sarcoidosis.

Circ Cardiovasc Imaging 2018 01;11(1):e007030

From the Cardiovascular Division, Department of Medicine, Cardiovascular Imaging Program (T.V., M.V.-C., P.E.B., E.M., E.H., V.R.T., M.S., H.S., R.Y.K., S.D., M.F.D.C., R.B.), Department of Radiology (T.V., M.V.-C., P.E.B., E.M., E.H., V.R.T., M.S., H.S., R.Y.K., S.D., M.F.D.C., R.B.), Division of Nuclear Medicine and Molecular Imaging, Department of Radiology (M.A., S.D., M.F.D.C., R.B.), Division of Thoracic Radiology, Department of Radiology (R.M.), and Cardiovascular Division (H.S., R.Y.K., G.S., M.F.D.C., R.B.), Brigham and Women's Hospital, Boston, MA; Division of Cardiology, Department of Medicine, Johns Hopkins Hospital, Baltimore, MD (D.R.O.); Division of Medicine, Cardiology Service, Walter Reed National Military Medical Center, Bethesda, MD (E.H.); and Uniformed Services University of Health Sciences, Bethesda, MD (E.H.).

Background: Although cardiac magnetic resonance (CMR) and positron emission tomography (PET) detect different pathological attributes of cardiac sarcoidosis (CS), the complementary value of these tests has not been evaluated. Our objective was to determine the value of combining CMR and PET in assessing the likelihood of CS and guiding patient management.

Methods And Results: In this retrospective study, we included 107 consecutive patients referred for evaluation of CS by both CMR and PET. Two experienced readers blinded to all clinical data reviewed CMR and PET images and categorized the likelihood of CS as no (<10%), possible (10%-50%), probable (50%-90%), or highly probable(>90%) based on predefined criteria. Patient management after imaging was assessed for all patients and across categories of increasing CS likelihood. A final clinical diagnosis for each patient was assigned based on a subsequent review of all available imaging, clinical, and pathological data. Among 107 patients (age, 55±11 years; left ventricular ejection fraction, 43±16%), 91 (85%) had late gadolinium enhancement, whereas 82 (76%) had abnormal F18-fluorodeoxyglucose uptake on PET, suggesting active inflammation. Among the 91 patients with positive late gadolinium enhancement, 60 (66%) had abnormal F18-fluorodeoxyglucose uptake. When PET data were added to CMR, 48 (45%) patients were reclassified as having a higher or lower likelihood of CS, most of them (80%) being correctly reclassified when compared with the final diagnosis. Changes in immunosuppressive therapies were significantly more likely among patients with highly probable CS.

Conclusions: Among patients with suspected CS, combining CMR and PET provides complementary value for estimating the likelihood of CS and guiding patient management.
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http://dx.doi.org/10.1161/CIRCIMAGING.117.007030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6381829PMC
January 2018

Diagnostic and prognostic value of myocardial blood flow quantification as non-invasive indicator of cardiac allograft vasculopathy.

Eur Heart J 2018 01;39(4):316-323

Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Cardiovascular Imaging Program, Heart and Vascular Center, Brigham and Women's Hospital and Harvard Medical School, ASB-L1 037-C, 75 Francis Street, Boston, MA 02115, USA.

Aims: Cardiac allograft vasculopathy (CAV) is a leading cause of death in orthotopic heart transplant (OHT) survivors. Effective non-invasive screening methods are needed. Our aim was to investigate the added diagnostic and prognostic value of myocardial blood flow (MBF) to standard myocardial perfusion imaging (MPI) with positron emission tomography (PET) for CAV detection.

Methods And Results: We studied 94 OHT recipients (prognostic cohort), including 66 who underwent invasive coronary angiography and PET within 1 year (diagnostic cohort). The ISHLT classification was used as standard definition for CAV. Positron emission tomography evaluation included semiquantitative MPI, quantitative MBF (mL/min/g), and left ventricular ejection fraction (LVEF). A PET CAV severity score (on a scale of 0-3) was modelled on the ISHLT criteria. Patients were followed for a median of 2.3 years for the occurrence of major adverse events (death, re-transplantation, acute coronary syndrome, and hospitalization for heart failure). Sensitivity, specificity, positive, and negative predictive value of semiquantitative PET perfusion alone for detecting moderate-severe CAV were 83% [52-98], 82% [69-91], 50% [27-73], and 96% [85-99], respectively {receiver operating characteristic (ROC area: 0.82 [0.70-0.95])}. These values improved to 83% [52-98], 93% [82-98], 71% [42-92], and 96% [97-99], respectively, when LVEF and stress MBF were added (ROC area: 0.88 [0.76-0.99]; P = 0.01). There were 20 major adverse events during follow-up. The annualized event rate was 5%, 9%, and 25% in patients with normal, mildly, and moderate-to-severely abnormal PET CAV grading (P < 0.001), respectively.

Conclusion: Multiparametric cardiac PET evaluation including quantification of MBF provides improved detection and gradation of CAV severity over standard myocardial perfusion assessment and is predictive of major adverse events.
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http://dx.doi.org/10.1093/eurheartj/ehx683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5837365PMC
January 2018

Integrated Noninvasive Physiological Assessment of Coronary Circulatory Function and Impact on Cardiovascular Mortality in Patients With Stable Coronary Artery Disease.

Circulation 2017 Dec 1;136(24):2325-2336. Epub 2017 Sep 1.

Division of Cardiovascular Medicine, Department of Medicine, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (A.G., V.R.T., N.S.B., P.E.B., S.B.S., T.V., C.F.B., M.H., J.H., S.D., R.B., M.F.D.C.)

Background: It is suggested that the integration of maximal myocardial blood flow (MBF) and coronary flow reserve (CFR), termed coronary flow capacity, allows for comprehensive evaluation of patients with known or suspected stable coronary artery disease. Because management decisions are predicated on clinical risk, we sought to determine the independent and integrated value of maximal MBF and CFR for predicting cardiovascular death.

Methods: MBF and CFR were quantified in 4029 consecutive patients (median age 66 years, 50.5% women) referred for rest/stress myocardial perfusion positron emission tomography scans from January 2006 to December 2013. The primary outcome was cardiovascular mortality. Maximal MBF <1.8 mL·g·min and CFR<2 were considered impaired. Four patient groups were identified based on the concordant or discordant impairment of maximal MBF or CFR. Association of maximal MBF and CFR with cardiovascular death was assessed using Cox and Poisson regression analyses.

Results: A total of 392 (9.7%) cardiovascular deaths occurred over a median follow-up of 5.6 years. CFR was a stronger predictor of cardiovascular mortality than maximal MBF beyond traditional cardiovascular risk factors, left ventricular ejection fraction, myocardial scar and ischemia, rate-pressure product, type of radiotracer or stress agent used, and revascularization after scan (adjusted hazard ratio, 1.79; 95% confidence interval [CI], 1.38-2.31; <0.001 per unit decrease in CFR after adjustment for maximal MBF and clinical covariates; and adjusted hazard ratio, 1.03; 95% CI, 0.84-1.27; =0.8 per unit decrease in maximal MBF after adjustment for CFR and clinical covariates). In univariable analyses, patients with concordant impairment of CFR and maximal MBF had high cardiovascular mortality of 3.3% (95% CI, 2.9-3.7) per year. Patients with impaired CFR but preserved maximal MBF had an intermediate cardiovascular mortality of 1.7% (95% CI, 1.3-2.1) per year. These patients were predominantly women (70%). Patients with preserved CFR but impaired maximal MBF had low cardiovascular mortality of 0.9% (95% CI, 0.6-1.6) per year. Patients with concordantly preserved CFR and maximal MBF had the lowest cardiovascular mortality of 0.4% (95 CI, 0.3-0.6) per year. In multivariable analysis, the cardiovascular mortality risk gradient across the 4 concordant or discordant categories was independently driven by impaired CFR irrespective of impairment in maximal MBF.

Conclusions: CFR is a stronger predictor of cardiovascular mortality than maximal MBF. Concordant and discordant categories based on integrating CFR and maximal MBF identify unique prognostic phenotypes of patients with known or suspected coronary artery disease.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.117.029992DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5726898PMC
December 2017

Role of PET to evaluate coronary microvascular dysfunction in non-ischemic cardiomyopathies.

Heart Fail Rev 2017 07;22(4):455-464

Division of Nuclear Medicine and Molecular Imaging, Brigham and Women's Hospital, 70 Francis Street, Shapiro 5th Floor, Room 128, Boston, MA, 02115, USA.

Coronary microvascular dysfunction (CMD) can result from structural and functional abnormalities at the intramural and small coronary vessel level affecting coronary blood flow autoregulation and consequently leading to impaired coronary flow reserve. CMD often co-exists with epicardial coronary artery disease but is also commonly seen in patients with various forms of heart disease, including dilated, hypertrophic, and infiltrative cardiomyopathies. CMD can go unnoticed without any symptoms, or manifest as angina, and/or dyspnea, and contribute to the development of heart failure, and even sudden death especially when co-existing with myocardial fibrosis. However, whether CMD in non-ischemic cardiomyopathy is a cause or an effect of the underlying cardiomyopathic process, or whether it can be potentially modifiable with specific therapies, remains incompletely understood.
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http://dx.doi.org/10.1007/s10741-017-9628-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6214157PMC
July 2017

Targeted Nuclear Imaging Probes for Cardiac Amyloidosis.

Curr Cardiol Rep 2017 07;19(7):59

Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, the Noninvasive Cardiovascular Imaging Program, Departments of Medicine (Cardiology) and Radiology, Cardiac Amyloidosis Program, Department of Medicine, Brigham and Women's Hospital, 70 Francis Street, Shapiro 5th Floor, Room 128, Boston, MA, 02115, USA.

Purpose Of Review: The aim of the present manuscript is to review the latest advancements of radionuclide molecular imaging in the diagnosis and prognosis of individuals with cardiac amyloidosis.

Recent Findings: Technetium labeled bone tracer scintigraphy had been known to image cardiac amyloidosis, since the 1980s; over the past decade, bone scintigraphy has been revived specifically to diagnose transthyretin cardiac amyloidosis. F labeled and C labeled amyloid binding radiotracers developed for imaging Alzheimer's disease, have been repurposed since 2013, to image light chain and transthyretin cardiac amyloidosis. Technetium bone scintigraphy for transthyretin cardiac amyloidosis, and amyloid binding targeted PET imaging for light chain and transthyretin cardiac amyloidosis, are emerging as highly accurate methods. Targeted radionuclide imaging may soon replace endomyocardial biopsy in the evaluation of patients with suspected cardiac amyloidosis. Further research is warranted on the role of targeted imaging to quantify cardiac amyloidosis and to guide therapy.
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http://dx.doi.org/10.1007/s11886-017-0868-4DOI Listing
July 2017