Person: Di Carli, Marcelo
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Publication Feasibility study of electrocardiographic and respiratory gated, gadolinium enhanced magnetic resonance angiography of pulmonary veins and the impact of heart rate and rhythm on study quality
(BioMed Central, 2014) Groarke, John; Waller, Alfonso H; Vita, Tomas S; Michaud, Gregory F.; Di Carli, Marcelo; Blankstein, Ron; Kwong, Raymond; Steigner, MichaelBackground: We aimed to assess the feasibility of 3 dimensional (3D) respiratory and ECG gated, gadolinium enhanced magnetic resonance angiography (MRA) on a 3 Tesla (3 T) scanner for imaging pulmonary veins (PV) and left atrium (LA). The impact of heart rate (HR) and rhythm irregularity associated with atrial fibrillation (AF) on image and segmentation qualities were also assessed. Methods: 101 consecutive patients underwent respiratory and ECG gated (ventricular end systolic window) MRA for pre AF ablation imaging. Image quality (assessed by PV delineation) was scored as 1 = not visualized, 2 = poor, 3 = good and 4 = excellent. Segmentation quality was scored on a similar 4 point scale. Signal to noise ratios (SNRs) were calculated for the LA, LA appendage (LAA), and PV. Contrast to noise ratios (CNRs) were calculated between myocardium and LA, LAA and PV, respectively. Associations between HR/rhythm and quality metrics were assessed. Results: 35 of 101 (34.7%) patients were in AF at time of MRA. 100 (99%) patients had diagnostic studies, and 91 (90.1%) were of good or excellent quality. Overall, mean ± standard deviation (SD) image quality score was 3.40 ± 0.69. Inter observer agreement for image quality scores was substantial, (kappa = 0.68; 95% confidence interval (CI): 0.46, 0.90). Neither HR adjusting for rhythm [odds ratio (OR) = 1.03, 95% CI = 0.98,1.09; p = 0.22] nor rhythm adjusting for HR [OR = 1.25, 95% CI = 0.20, 7.69; p = 0.81] demonstrated association with image quality. Similarly, SNRs and CNRs were largely independent of HR after adjusting for rhythm. Segmentation quality scores were good or excellent for 77.3% of patients: mean ± SD score = 2.91 ± 0.63, and scores did not significantly differ by baseline rhythm (p = 0.78). Conclusions: 3D respiratory and ECG gated, gadolinium enhanced MRA of the PVs and LA on a 3 T system is feasible during ventricular end systole, achieving high image quality and high quality image segmentation when imported into electroanatomic mapping systems. Quality is independent of HR and heart rhythm for this free breathing, radiation free, alternative strategy to current MRA or CT based approaches, for pre AF ablation imaging of PVs and LA.
Publication Obesity, metabolic syndrome and cardiovascular prognosis: from the Partners coronary computed tomography angiography registry
(BioMed Central, 2017) Hulten, Edward A.; Bittencourt, Marcio Sommer; Preston, Ryan; Singh, Avinainder; Romagnolli, Carla; Ghoshhajra, Brian; Shah, Ravi; Abbasi, Siddique; Abbara, Suhny; Nasir, Khurram; Blaha, Michael; Hoffmann, Udo; Di Carli, Marcelo; Blankstein, RonObjective: To investigate the relationship among body mass index (BMI), cardiometabolic risk and coronary artery disease (CAD) among patients undergoing coronary computed tomography angiography (CTA). Methods: Retrospective cohort study of 1118 patients, who underwent coronary CTA at two centers from September 2004 to October 2011. Coronary CTA were categorized as normal, nonobstructive CAD (<50%), or obstructive CAD (≥50%) in addition to segment involvement (SIS) and stenosis scores. Extensive CAD was defined as SIS > 4. Association of BMI with cardiovascular prognosis was evaluated using multivariable fractional polynomial models. Results: Mean age of the cohort was 57 ± 13 years with median follow-up of 3.2 years. Increasing BMI was associated with MetS (OR 1.28 per 1 kg/m2, p < 0.001) and burden of CAD on a univariable basis, but not after multivariable adjustment. Prognosis demonstrated a J-shaped relationship with BMI. For BMI from 20–39.9 kg/m2, after adjustment for age, gender, and smoking, MetS (HR 2.23, p = 0.009) was more strongly associated with adverse events. Conclusions: Compared to normal BMI, there was an increased burden of CAD for BMI > 25 kg/m2. Within each BMI category, metabolically unhealthy patients had greater extent of CAD, as measured by CCTA, compared to metabolically healthy patients.
Publication Anomalous origin of the coronary artery arising from the opposite sinus: prevalence and outcomes in patients undergoing coronary CTA
(Oxford University Press (OUP), 2016) Cheezum, Michael K.; Ghoshhajra, Brian; Bittencourt, Marcio S.; Hulten, Edward A.; Bhatt, Ami; Mousavi, Negareh; Shah, Nishant R.; Valente, Anne Marie; Rybicki, Frank John; Steigner, Michael; Hainer, Jon; MacGillivray, Thomas; Hoffmann, Udo; Abbara, Suhny; Di Carli, Marcelo; DeFaria Yeh, Doreen; Landzberg, Michael; Liberthson, Richard; Blankstein, RonAims The impact of coronary computed tomographic angiography (CTA) on management of anomalous origin of the coronary artery arising from the opposite sinus (ACAOS) remains uncertain. We examined the prevalence, anatomical characterization, and outcomes of ACAOS patients undergoing CTA. Methods and results Among 5991 patients referred for CTA at two tertiary hospitals between January 2004 and June 2014, we identified 103 patients (1.7% prevalence) with 110 ACAOS vessels. Mean age was 52 years (range 5–83, 63% male), with 55% previously known ACAOS and 45% discovered on CTA. ACAOS subtypes included: 39% interarterial (n = 40 anomalous right coronary artery, n = 3 anomalous left coronary artery), 38% retroaortic, 15% subpulmonic, 5% prepulmonic, and 2% other. ACAOS patients were assessed for symptoms, ischaemic test results, revascularization, all-cause or cardiovascular (CV) death, and myocardial infarction. CTAs were reviewed for ACAOS course, take-off height and angle, length and severity of proximal narrowing, intramural course, and obstructive coronary artery disease (CAD). In follow-up (median 5.8 years), there were 20 surgical revascularizations and 3 CV deaths. After adjusting for obstructive CAD (n = 21/103, 20%), variables associated with ACAOS revascularization included the following: CV symptoms, proximal vessel narrowing ≥50%, length of narrowing >5.4 mm, and an interarterial course. Conclusion The prevalence of ACAOS on CTA was 1.7%, including 45% of cases discovered incidentally. CTA provided excellent characterization of ACAOS features associated with coronary revascularization, including the length and severity of proximal vessel narrowing.
Publication Stress Cardiac Magnetic Resonance Imaging Provides Effective Cardiac Risk Reclassification in Patients With Known or Suspected Stable Coronary Artery Disease
(Ovid Technologies (Wolters Kluwer Health), 2013) Shah, Ravi; Heydari, Bobak; Coelho-Filho, O.; Murthy, Venkatesh; Abbasi, Siddique Akbar; Feng, J. H.; Pencina, M.; Neilan, Tomas; Meadows, J. L.; Francis, Sanjeev A.; Blankstein, Ron; Steigner, Michael; Di Carli, Marcelo; Jerosch-Herold, Michael; Kwong, RaymondBackground
A recent large-scale clinical trial found that an initial invasive strategy does not improve cardiac outcomes beyond optimized medical therapy in patients with stable coronary artery disease (CAD). Novel methods to stratify at-risk patients may refine therapeutic decisions to improve outcomes.
Methods and Results
In a cohort of 815 consecutive patients referred for evaluation of myocardial ischemia, we determined the net reclassification improvement of the risk of cardiac death or nonfatal MI (MACE) incremental to clinical risk models, using guideline–based low (<1%), moderate (1–3%), and high (>3%) annual risk categories. In the whole cohort, inducible ischemia demonstrated strong association with MACE (hazard ratio 14.66, P<0.0001) with low negative event rates of MACE and cardiac death (0.6% and 0.4%). This prognostic robustness maintained in patients with prior CAD (hazard ratio 8.17, P<0.0001, and 1.3% and 0.6%, respectively). Adding inducible ischemia to the multivariable clinical risk model (age and prior CAD adjusted) improved discrimination of MACE (C-statistic 0.81 to 0.86, P=0.04; Adjusted hazard ratio 7.37, P<0.0001) and reclassified 91.5% of patients at moderate pre-test risk (65.7% to low risk; 25.8% to high risk) with corresponding changes in the observed event rates (0.3%/year and 4.9%/year, for low and high risk post-test, respectively). Categorical net reclassification index was 0.229 (95% CI 0.063–0.391). Continuous NRI was 1.11 (95% CI 0.81–1.39).
Conclusions
Stress CMR effectively reclassifies patient risk beyond standard clinical variables, specifically in patients at moderate to high pre-test clinical risk and in patients with prior CAD.
Publication Identification of coronary heart disease in asymptomatic individuals with diabetes mellitus: to screen or not to screen
(Universidad del Valle, 2015) Bravo, Paco E; Psaty, Bruce M; Di Carli, Marcelo; Branch, Kelley RCoronary heart disease (CHD) is highly prevalent in patients with diabetes mellitus (DM), and remains the single most common cause of death among this population. Regrettably, a significant percentage of diabetics fail to perceive the classic symptoms associated with myocardial ischemia. Among asymptomatic diabetics, the prevalence of abnormal cardiac testing appears to be high, ranging between 10% and 62%, and mortality is significantly higher in those with abnormal scans. Hence, the potential use of screening for CHD detection among asymptomatic DM individuals is appealing and has been recommended in certain circumstances. However, it was not until recently, that this question was addressed in clinical trials. Two studies randomized a total of 2,023 asymptomatic diabetics to screening or not using cardiac imaging with a mean follow up of 4.4 ± 1.4 years. In combination, both trials showed lower than expected annual event rates, and failed to reduce major cardiovascular events in the screened group compared to the standard of care alone. The results of these trials do not currently support the use of screening tools for CHD detection in asymptomatic DM individuals. However, these studies have important limitations, and potential explanations for their negative results that are discussed in this manuscript.
Publication Presence of Late Gadolinium Enhancement by Cardiac Magnetic Resonance Among Patients With Suspected Cardiac Sarcoidosis Is Associated With Adverse Cardiovascular Prognosis: A Systematic Review and Meta-Analysis
(2017) Hulten, Edward; Agarwal, Vikram; Cahill, Michael; Cole, Geoff; Vita, Tomas S; Parrish, Scott; Bittencourt, Marcio Sommer; Murthy, Venkatesh L.; Kwong, Raymond; Di Carli, Marcelo; Blankstein, RonBackground: Individuals with cardiac sarcoidosis have an increased risk of ventricular arrhythmia and death. Several small cohort studies have evaluated the ability of late gadolinium enhancement (LGE) by cardiac magnetic resonance imaging (MRI) to predict adverse cardiovascular events. However, studies have yielded inconsistent results, and some analyses were underpowered. Therefore, we sought to systematically review and perform meta-analysis of the prognostic value of cardiac MRI for patients with known or suspected cardiac sarcoidosis. Methods and Results: We systematically searched for cohort studies of patients with known sarcoidosis with suspected cardiac involvement who underwent cardiac MRI with LGE with at least 12 months of either prospective or retrospective follow-up data regarding post-MRI adverse cardiovascular outcomes. We identified 7 studies of 694 subjects (mean age 53; 42% men). One hundred and ninety-nine patients (29%) were LGE positive. All-cause mortality occurred in 19 LGE-positive versus 17 LGE-negative subjects (annualized incidence, 3.1% versus 0.6%). The pooled relative risk was 3.38 (95% confidence interval, 1.07-10.7; P=0.04). Cardiovascular mortality occurred in 10 LGE-positive versus 2 LGE-negative subjects (annualized incidence, 1.9% versus 0.3%; relative risk 10.7 [95% confidence interval, 1.34–86.3]; P=0.03). Ventricular arrhythmia occurred in 41 LGE-positive versus 0 LGE-negative subjects (annualized incidence, 5.9% versus 0%; relative risk 19.5 [95% confidence interval, 2.68–143]; P=0.003). A combined end point of death or ventricular arrhythmia occurred in 64 LGE-positive versus 18 LGE-negative subjects (annualized incidence, 8.8% versus 0.6%; relative risk 6.20 [95% confidence interval, 2.47–15.6]; P<0.001). There was no significant heterogeneity for any outcomes. Conclusions: LGE is associated with future cardiovascular death and ventricular arrhythmia among patients referred to MRI for known or suspected cardiac sarcoidosis.
Publication Ranolazine in Symptomatic Diabetic Patients Without Obstructive Coronary Artery Disease: Impact on Microvascular and Diastolic Function
(John Wiley and Sons Inc., 2017) Shah, Nishant R.; Cheezum, Michael K.; Veeranna, Vikas; Horgan, Stephen J.; Taqueti, Viviany; Murthy, Venkatesh L.; Foster, Courtney; Hainer, Jon; Daniels, Karla M.; Rivero, Jose; Shah, Amil; Stone, Peter; Morrow, David; Steigner, Michael; Dorbala, Sharmila; Blankstein, Ron; Di Carli, MarceloBackground: Treatments for patients with myocardial ischemia in the absence of angiographic obstructive coronary artery disease are limited. In these patients, particularly those with diabetes mellitus, diffuse coronary atherosclerosis and microvascular dysfunction is a common phenotype and may be accompanied by diastolic dysfunction. Our primary aim was to determine whether ranolazine would quantitatively improve exercise‐stimulated myocardial blood flow and cardiac function in symptomatic diabetic patients without obstructive coronary artery disease. Methods and Results: We conducted a double‐blinded crossover trial with 1:1 random allocation to the order of ranolazine and placebo. At baseline and after each 4‐week treatment arm, left ventricular myocardial blood flow and coronary flow reserve (CFR; primary end point) were measured at rest and after supine bicycle exercise using 13N‐ammonia myocardial perfusion positron emission tomography. Resting echocardiography was also performed. Multilevel mixed‐effects linear regression was used to determine treatment effects. Thirty‐five patients met criteria for inclusion. Ranolazine did not significantly alter rest or postexercise left ventricular myocardial blood flow or CFR. However, patients with lower baseline CFR were more likely to experience improvement in CFR with ranolazine (r=−0.401, P=0.02) than with placebo (r=−0.188, P=0.28). In addition, ranolazine was associated with an improvement in E/septal e′ (P=0.001) and E/lateral e′ (P=0.01). Conclusions: In symptomatic diabetic patients without obstructive coronary artery disease, ranolazine did not change exercise‐stimulated myocardial blood flow or CFR but did modestly improve diastolic function. Patients with more severe baseline impairment in CFR may derive more benefit from ranolazine. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01754259.
Publication Use of Cardiac Computerized Tomography to Predict Neo–Left Ventricular Outflow Tract Obstruction Before Transcatheter Mitral Valve Replacement
(John Wiley and Sons Inc., 2017) Murphy, David; Ge, Yin; Don, Creighton W.; Keraliya, Abhishek; Aghayev, Ayaz; Morgan, Roisin; Galper, Benjamin; Bhatt, Deepak L.; Kaneko, Tsuyoshi; Di Carli, Marcelo; Shah, Pinak; Steigner, Michael; Blankstein, RonPublication Assessment of coronary vascular function with cardiac PET in relation to serum uric acid
(Public Library of Science, 2018) Kim, Seoyoung; Shah, Nishant R.; Rogers, James R.; Bibbo, Courtney F.; Di Carli, Marcelo; Solomon, DanielBackground: Elevated serum uric acid (SUA) levels have been independently associated with cardiovascular disease. Stress myocardial perfusion positron emission tomography (PET) allows for measurement of absolute myocardial blood flow (MBF) and quantification of global left ventricular coronary flow reserve (CFR). A CFR <2.0 is considered impaired coronary vascular function, and it is associated with increased cardiovascular risk. We evaluated the relationship between SUA and PET-measured markers of coronary vascular function. Methods: We studied adults undergoing a stress myocardial perfusion PET on clinical grounds (1/2006-3/2014) who also had ≥1 SUA measurement within 180 days from the PET date. Multivariable linear regression estimated the association between SUA and PET-derived MBF and CFR. We also stratified analyses by diabetes status. Results: We included 382 patients with mean (SD) age of 68.4 (12.4) years and mean (SD) SUA level of 7.2 (2.6) mg/dl. 36% were female and 29% had gout. Median [IQR] CFR was reduced at 1.6 [1.2, 2.0] and median [IQR] stress MBF was 1.5 [1.1, 2.1] ml/min/g. In the adjusted analysis, SUA was inversely associated with stress MBF (β = -0.14, p = 0.01) but not with CFR. Among patients without diabetes (n = 215), SUA had a negative association with CFR (β = -0.15, p = 0.02) and stress MBF (β = -0.19, p = 0.01) adjusting for age, sex, extent of myocardial scar and ischemia, serum creatinine and gout. In diabetic patients (n = 167), SUA was not associated with either CFR or MBF. Conclusions: In this cross-sectional study, higher SUA is modestly associated with worse CFR and stress MBF among patients without diabetes.